Aha 2018 Cir.0000000000000558 PDF

Circulation
AHA STATISTICAL UPDATE
Heart Disease and Stroke Statistics—

2018 Update
A Report From the American Heart Association
WRITING GROUP MEMBERS Each chapter listed in the Table of

Emelia J. Benjamin, MD, ScM, FAHA, Chair Khurram Nasir, MD, MPH, FAHA
Contents (see next page) is a hy-
Salim S. Virani, MD, PhD, FAHA, Co-Vice Chair Martin O’Flaherty, MD
perlink to that chapter. The reader
Clifton W. Callaway, MD, PhD Latha P. Palaniappan, MD, MS, FAHA
clicks the chapter name to access
Alanna M. Chamberlain, PhD, MPH Ambarish Pandey, MD
Alexander R. Chang, MD, MS Dilip K. Pandey, MBBS, MS, PhD, FAHA that chapter.
Susan Cheng, MD, MMSc, MPH Mathew J. Reeves, PhD
Stephanie E. Chiuve, ScD Matthew D. Ritchey, PT, DPT, OCS, MPH
Mary Cushman, MD, MSc, FAHA Carlos J. Rodriguez, MD, MPH, FAHA
Francesca N. Delling, MD, MPH Gregory A. Roth, MD, MPH, FAHA
Rajat Deo, MD, MTR Wayne D. Rosamond, PhD, MS, FAHA
Sarah D. de Ferranti, MD, MPH, FAHA Uchechukwu K.A. Sampson, MD, MBA, MPH, FAHA
Jane F. Ferguson, PhD Gary M. Satou, MD, FAHA
Myriam Fornage, PhD, FAHA Svati H. Shah, MD, MHS, FAHA
Cathleen Gillespie, MS Nicole L. Spartano, PhD
Carmen R. Isasi, MD, PhD, FAHA David L. Tirschwell, MD, MS, MSc
Downloaded from http://ahajournals.org by on May 19, 2019
Monik C. Jiménez, ScD, SM Connie W. Tsao, MD, MPH

Lori Chaffin Jordan, MD, PhD Jenifer H. Voeks, PhD
Suzanne E. Judd, PhD, MPH Joshua Z. Willey, MD, MS
Daniel Lackland, DrPH, FAHA John T. Wilkins, MD, MS, FAHA
Judith H. Lichtman, PhD, MPH, FAHA Jason HY. Wu, PhD, FAHA
Lynda Lisabeth, PhD, MPH, FAHA Heather M. Alger, PhD
Simin Liu, MD, ScD, FAHA Sally S. Wong, PhD, RD, CDN, FAHA
Chris T. Longenecker, MD Paul Muntner, PhD, MHS, FAHA, Co-Vice Chair
Pamela L. Lutsey, PhD, MPH, FAHA On behalf of the American Heart Association
Jason S. Mackey, MD Council on Epidemiology and Prevention
David B. Matchar, MD Statistics Committee and Stroke Statistics
Kunihiro Matsushita, MD, PhD, FAHA Subcommittee
Michael E. Mussolino, PhD, FAHA
Key Words: AHA Scientific

Statements ◼ cardiovascular diseases ◼
epidemiology ◼ risk factors ◼ statistics
◼ stroke
© 2018 American Heart Association, Inc.
http://circ.ahajournals.org
Circulation. 2018;137:e67–e492. DOI: 10.1161/CIR.0000000000000558 March 20, 2018 e67

Benjamin et al Heart Disease and Stroke Statistics—2018 Update: Summary
TABLE OF CONTENTS administrators, researchers, health advocates, and oth-

CLINICAL STATEMENTS
ers seeking the best available data on these factors and

Each chapter listed here is a hyperlink. Click on the chapter
AND GUIDELINES
name to be taken to that chapter. conditions. Cardiovascular disease (CVD) and stroke
produce immense health and economic burdens in the
Summary . . . . . . . . . . . . . . . . . . . . . . . . e68
United States and globally. The Update also presents
1. About These Statistics . . . . . . . . . . . . . . . . e78
the latest data on a range of major clinical heart and
2. Cardiovascular Health . . . . . . . . . . . . . . . . e81
circulatory disease conditions (including stroke, con-
Health Behaviors genital heart disease, rhythm disorders, subclinical ath-
3. Smoking/Tobacco Use . . . . . . . . . . . . . . . . e99
erosclerosis, coronary heart disease [CHD], heart failure
4. Physical Inactivity . . . . . . . . . . . . . . . . . . e112
5. Nutrition . . . . . . . . . . . . . . . . . . . . . . e128
[HF], valvular disease, venous disease, and peripheral
6. Overweight and Obesity . . . . . . . . . . . . . . e149 artery disease) and the associated outcomes (including
quality of care, procedures, and economic costs). Since
Health Factors and Other Risk Factors
7. High Blood Cholesterol and Other Lipids . . . . . . e169
2007, the annual versions of the Statistical Update have
8. High Blood Pressure . . . . . . . . . . . . . . . . e180 been cited >20 000 times in the literature. From January
9. Diabetes Mellitus . . . . . . . . . . . . . . . . . . e199 to July 2017 alone, the 2017 Statistical Update was
10. Metabolic Syndrome . . . . . . . . . . . . . . . . e214 accessed >106 500 times.
11. Kidney Disease . . . . . . . . . . . . . . . . . . . e233 Each annual version of the Statistical Update
Cardiovascular Conditions/Diseases undergoes revisions to include the newest nationally
12. Total Cardiovascular Diseases . . . . . . . . . . . . e247 representative data, add additional relevant published
13. Stroke (Cerebrovascular Disease) . . . . . . . . . . e270 scientific findings, remove older information, add
14. Congenital Cardiovascular Defects and new sections or chapters, and increase the number
Kawasaki Disease . . . . . . . . . . . . . . . . . e309 of ways to access and use the assembled information.
15. Disorders of Heart Rhythm . . . . . . . . . . . . . e325 This year-long process, which begins as soon as the
16. Sudden Cardiac Arrest . . . . . . . . . . . . . . . e355 previous Statistical Update is published, is performed
17. Subclinical Atherosclerosis . . . . . . . . . . . . . e373 by the AHA Statistics Committee faculty volunteers
18. Coronary Heart Disease, Acute Coronary and staff and government agency partners. This year’s
Syndrome, and Angina Pectoris . . . . . . . . . . e391
edition includes new data on the monitoring and
19. Cardiomyopathy and Heart Failure . . . . . . . . . e415
20. Valvular Diseases . . . . . . . . . . . . . . . . . . e430
benefits of cardiovascular health in the population,
new metrics to assess and monitor healthy diets, new
21. Venous Thromboembolism (Deep Vein

Thrombosis and Pulmonary Embolism), information on stroke in young adults, an enhanced
Chronic Venous Insufficiency, Pulmonary focus on underserved and minority populations, a
Hypertension . . . . . . . . . . . . . . . . . . . . e444 substantively expanded focus on the global burden
22. Peripheral Artery Disease and Aortic Diseases . . . e450 of CVD, and further evidence-based approaches to
Outcomes changing behaviors, implementation strategies, and
23. Quality of Care . . . . . . . . . . . . . . . . . . . e461 implications of the AHA’s 2020 Impact Goals. Below
24 . Medical Procedures . . . . . . . . . . . . . . . . e475 are a few highlights from this year’s Update.
25. Economic Cost of Cardiovascular Disease . . . . . e480
Supplemental Materials
26. At-a-Glance Summary Tables . . . . . . . . . . . . e486
Current State of Cardiovascular Health
27. Glossary . . . . . . . . . . . . . . . . . . . . . . e490 in the United States: What’s New?
(Chapter 2)
• Findings continue to accumulate from US and
SUMMARY international studies showing a strong protective
Each year, the American Heart Association (AHA), in association between ideal cardiovascular health
conjunction with the Centers for Disease Control and metrics (My Life Check - Life’s Simple 71) and
Prevention, the National Institutes of Health, and other many clinical and preclinical conditions, includ-
government agencies, brings together in a single docu- ing premature all-cause mortality, CVD mortal-
ment the most up-to-date statistics related to heart dis- ity, ischemic heart disease mortality, HF, carotid
ease, stroke, and the cardiovascular risk factors listed arterial wall stiffness, coronary artery calcium
in the AHA’s My Life Check - Life’s Simple 7 (Figure1), progression, impaired physical function, cogni-
which include core health behaviors (smoking, physi- tive decline, stroke, depression, end-stage renal
cal activity, diet, and weight) and health factors (cho- disease, chronic obstructive pulmonary disease,
lesterol, blood pressure [BP], and glucose control) that deep venous thromboembolism, and pulmonary
contribute to cardiovascular health. The Statistical embolism.
Update represents a critical resource for the lay public, • New data reported this year expand this list to
policy makers, media professionals, clinicians, healthcare include the positive association of cardiovascular
e68 March 20, 2018 Circulation. 2018;137:e67–e492. DOI: 10.1161/CIR.0000000000000558

CLINICAL STATEMENTS
AND GUIDELINES
Figure. Life’s Simple 7.
Seven approaches to staying heart healthy: be active, keep a healthy weight, learn about cholesterol, don’t smoke or use
smokeless tobacco, eat a heart-healthy diet, keep blood pressure healthy, and learn about blood sugar and diabetes mellitus.
health metrics with better leukocyte telomere other domains could provide substantial contribu-
length and reduced mean healthcare expenditures. tions to total physical activity, especially in minor-
• A recent major study in blacks found that the ity populations.
risk of incident HF was 61% lower among those • Community physical activity interventions and
with ≥4 ideal cardiovascular health metrics than strategies at worksites, schools, and the built
among those with 0 to 2 ideal metrics. environment have proven cost-effective in reduc-
ing medical spending. For example, nearly $3
in medical cost savings is realized for every $1
Smoking and Tobacco Use (Chapter 3) invested in building bike and walking trails.
• The prevalence of current smoking in the United • The current physical activity guidelines focus
States in 2015 was 15.1% for adults and 4.2% almost entirely on achieving moderate- and vigor-
for adolescents. Although there has been a con- ous-intensity physical activity, but recent evidence
sistent decline in tobacco use in the United States, suggests that substituting even 10 minutes of
significant disparities persist. Substantially higher sedentary time with 10 minutes of light-intensity
tobacco use prevalence rates are observed in activity is associated with a 9% lower mortality
American Indian/Alaska Natives and lesbian, gay, risk.
bisexual, and transgender populations, as well as • The prevalence of adolescents meeting the aero-
among individuals with low socioeconomic sta- bic physical activity guidelines is 27.1%, almost
tus, those with mental illness, individuals with HIV as low as their adult counterparts. Moreover, the
who are receiving medical care, and those who amount of time children spend sitting may be on
are active-duty military. the rise. From 2009 to 2015, the proportion of
• Tobacco use remains the leading cause of pre- youth who reported spending at least 3 hours per
ventable death in the United States and globally. day on computers for activities other than school
It was estimated to account for 7.2 million deaths work (eg, videogames or other computer games)
worldwide in 2015. increased from 24.9% to 41.7%.
• Over the past 5 years, there has been a sharp
increase in e-cigarette use among adolescents.
• Policy-level interventions such as Tobacco 21 Laws Nutrition (Chapter 5)
and MPOWER are being adopted and have been • A recent study using a comparative risk assess-
associated with reductions in tobacco use inci- ment model estimated that 45.4% of US deaths
dence and prevalence. caused by heart disease, stroke, and type 2 dia-
betes mellitus (DM) (cardiometabolic mortality)
in 2012 were attributable to poor dietary habits.
Physical Inactivity (Chapter 4) The top contributing poor dietary factors included
• According to the 2015 National Health Interview high sodium intake, low levels of nuts and seeds,
Survey, only 21.5% of American adults reported high intake of processed meats, low consumption
achieving adequate leisure-time aerobic and mus- of seafood omega-3 fats, low intake of vegeta-
cle-strengthening activities to meet the physical bles, low intake of fruits, and high consumption of
activity guidelines; however, the national survey sugar-sweetened beverages. Between 2002 and
did not record activity accumulated in occupa- 2012, diet-associated cardiometabolic death rates
tional, transport, and domestic domains. These decreased for polyunsaturated fats (−20.8%),

nuts and seeds (−18.0%), and sugar-sweetened for the management of blood cholesterol; how-
CLINICAL STATEMENTS
beverages (−14.5%) but increased for sodium ever, even after the guidelines were published,
AND GUIDELINES
(5.8%) and unprocessed red meats (14.4%). statin use and mean low-density lipoprotein cho-
• A report from the Global Burden of Disease lesterol level remained unchanged, which sug-
Study stated that an estimated 22.4% of all male gests that increased efforts to understand and
deaths and 20.7% of all female deaths in 2015 implement these guidelines are needed.
were attributable to poor dietary factors.
• Data from the US Department of Agriculture’s
Economic Research Service showed that the pro- High Blood Pressure (Chapter 8)
portion of food expenditures away from home • From 2005 to 2015, the death rate attributable
increased from 47.2% in 2004 to 50.1% in to high BP increased by 10.5%, and the actual
2014. number of deaths attributable to high BP rose by
37.5%.
• On the basis of data from 135 population-based
Overweight and Obesity (Chapter 6) studies (N=968 419 adults from 90 countries),
• Obesity prevalence increased in the National it was estimated that 31.1% (95% confidence
Health and Nutrition Examination Survey interval, 30.0%–32.2%) of the world’s adult pop-
(NHANES) 2013 to 2014 survey years in both ulation had hypertension in 2010.
adults and children compared with NHANES 2011 • There were 3.47 billion adults worldwide with sys-
to 2012 (Chart 6-11). In adults, the prevalence tolic BP of 110 to 115 mm Hg or higher in 2015.
increased from 34.9% in 2011 to 2012 to 37.7% In 2015, 874 million adults had systolic BP ≥140
in 2013 to 2014. In children (ages 2–19 years), mm Hg.
the prevalence of obesity increased from 16.9% • Between 1999 to 2000 and 2011 to 2012, the
in 2011 to 2012 to 17.2% in 2013 to 2014. prevalence of prehypertension decreased among
• Significant race and sex differences in obesity US adults, from 31.2% to 28.2%.
rates were still observed in the most recent sur-
vey years, with female and minority populations
more likely to be obese than their male and white Diabetes Mellitus (Chapter 9)
counterparts. • There is substantial heterogeneity in the preva-
• A meta-analysis from 2016 suggested that CVD lence of DM across US counties. In 2012, the
risk was higher (relative risk, 1.45) in obese indi- overall county-level prevalence of DM ranged
viduals without metabolic syndrome than in from 8.8% to 26.4%; the prevalence of diag-
metabolically healthy normal-weight participants, nosed DM was estimated to range from 5.6% to
which suggests that obesity is a risk factor even in 20.4%, and the prevalence of undiagnosed DM
the absence of high blood pressure, high choles- ranged from 3.2% to 6.8%.
terol, and DM. • In 2015, an estimated 5.2 million deaths globally
were attributed to DM.
• The prevalence of concurrent DM, hyperten-
High Blood Cholesterol and Other Lipids
sion, and hypercholesterolemia among US adults
(Chapter 7) increased over time from 3% in 1999 to 2000 to
• 21% of youths 6 to 19 years of age have at least 6.3% in 2011 to 2012.
1 abnormal cholesterol measure. • The incidence rate of DM per 1000 person-years
• The Healthy People 2010 target of an age- associated with having 0, 1, 2, 3, 4, and 5 or 6
adjusted mean total cholesterol level of ≤200 mg/ ideal cardiovascular health factors was 21.8, 18.6,
dL has been achieved in the overall adult popula- 13.0, 11.2, 4.7, and 3.6, respectively.
tion, in males, in females, and in all racial/ethnic
and sex subgroups. The Healthy People 2020 tar-
get is a mean total blood cholesterol of 178 mg/ Metabolic Syndrome (Chapter 10)
dL for adults, which has not yet been achieved for • On the basis of NHANES data from 2001 to 2012,
any subgroup. the prevalence of metabolic syndrome was higher
• An estimated 28.5 million adults ≥20 years of age among females (34.4%) than males (29%) and
have serum total cholesterol levels ≥240 mg/dL, increased with advancing age. The prevalence
with a prevalence of 11.9%. of metabolic syndrome was 17% among people
• 56.0 million (48.6%) US adults ≥40 years of age <40 years old, 29.7% for people 40 to 49 years
are eligible for statin therapy based on the 2013 old, 37.5% among those 50 to 59 years old, and
American College of Cardiology/AHA guidelines >44% among people ≥60 years of age.

• Isolated metabolic syndrome, which could be con- trillion in 2035, with direct medical costs pro-
CLINICAL STATEMENTS
sidered an earlier form of metabolic syndrome, jected to reach $748.7 billion and indirect costs
AND GUIDELINES
has been defined as the presence of ≥3 metabolic estimated to reach $368 billion.
syndrome components without overt hyperten-
sion or DM. In a community-based random sam-
ple of residents of Olmsted County, MN, those
Stroke (Cerebrovascular Disease)
with isolated metabolic syndrome were found to (Chapter 13)
be at increased risk of incident hypertension, DM, • Although there has been considerable reduction
diastolic dysfunction, and reduced renal function in stroke risks and stroke outcomes, the racial and
(glomerular filtration rate <60 mL/min) compared geographic disparities remain significant, with
with healthy control subjects (P<0.05). African Americans and residents of the south-
eastern United States experiencing the greatest
excess disease burden. According to data from
Kidney Disease (Chapter 11) the Centers for Disease Control and Prevention
• According to the Global Burden of Disease study, 2015 Behavioral Risk Factor Surveillance System,
the prevalence of chronic kidney disease is rising 2.6% of non-Hispanic whites, 4.1% of non-
in almost every country of the world, primarily Hispanic blacks, 1.5% of Asian/Pacific Islanders,
because of aging populations. In 2015, the total 2.3% of Hispanics (of any race), 5.2% of
estimated prevalence was 323 million people American Indian/Alaska Natives, and 4.7% of
(95% confidence interval, 313–330 million peo- other races or multiracial people had a history
ple), a 27% increase since 2005. of stroke. Stroke prevalence in adults is 2.7% in
• In the United States, Medicare spent more than the United States, with the lowest prevalence in
$50 billion in 2014 caring for people ≥65 years of Minnesota (1.9%) and the highest prevalence in
age with chronic kidney disease. More than 70% Alabama (4.3%).
of this spending was attributable to patients who • The impact of hypertension management on
had comorbid DM or congestive HF. stroke risk is evident with the greater risk reduc-
• CVD is the leading cause of death among people tion among those with more intense treatment.
with kidney disease. Among those with end-
stage renal disease, CVD accounts for more
than half of the deaths with known causes, with Congenital Cardiovascular Defects and
arrhythmias and sudden cardiac death accounting Kawasaki Disease (Chapter 14)
for nearly 40%. • Between 0.4 and 1 per 100 US infants are born
with congenital heart disease, ranging from
Total Cardiovascular Diseases mild asymptomatic lesions to severe life-threat-
ening conditions; approximately one fourth of
(Chapter 12) these lesions will require intervention during
• The mortality for males and females in the infancy.
United States declined from 1979 to 2015 • Kawasaki disease, an acquired acute inflammatory
(Chart 12-19). In 2015, 2 712 630 resident condition associated at its worst with coronary
deaths were registered in the United States, artery dilation, aneurysms, and coronary isch-
and 10 leading causes accounted for 74.2% of emia, is most common in Japanese, Taiwanese,
all registered deaths. The 10 leading causes of and Korean populations and is increasing in inci-
death were heart disease (No. 1), cancer (No. dence over time.
2), chronic lower respiratory diseases (No. 3),
unintentional injuries (No. 4), stroke (No. 5),
Alzheimer disease (No. 6), DM (No. 7), influenza Disorders of Heart Rhythm (Chapter 15)
and pneumonia (No. 8), kidney disease (No. 9), • There is increasing awareness that atrial fibrilla-
and suicide (No. 10). tion (AF) is frequently unrecognized. At present,
• CHD (43.8%) is the leading cause of deaths the detection of AF, even in an asymptomatic
attributable to CVD in the United States, followed stage, is the basis for risk stratification for stroke
by stroke (16.8%), high BP (9.4%), HF (9.0%), and appropriate decision making about the need
diseases of the arteries (3.1%), and other CVDs for anticoagulant therapy. Ongoing trials are
(17.9%). evaluating the risks and benefits of anticoagu-
• By 2035, >130 million adults in the US population lation therapy among patients at high risk for
(45.1%) are projected to have some form of CVD, stroke but without a prior history of AF. The find-
and total costs of CVD are expected to reach $1.1 ings from these studies will help to determine

optimal strategies for subclinical AF screening reporting data from 13 262 asymptomatic patients
CLINICAL STATEMENTS
and treatment. (mean age 60 years, 50% males) reported a nearly

AND GUIDELINES
• A prospective registry from 47 countries reported 3-fold higher risk of stroke with presence versus
substantial variability in annual AF mortality by absence of CAC.
region. Annual AF mortality in South America • Absence of CAC was a powerful negative marker
(17%) and Africa (20%) was double the mortal- for clinical atherosclerotic CVD in a study of
ity rate in North America, Western Europe, and African American adults with up to 10 years of
Australia (10%; P<0.001). In individuals with AF, follow-up. A significant proportion of those con-
HF deaths (30%) exceeded deaths caused by sidered statin eligible based on the current cho-
stroke (8%). lesterol guideline had no detectable CAC, and the
• Observational data have suggested that over- observed atherosclerotic CVD risk was below the
weight and obese individuals with symptomatic threshold for statin consideration.
AF who opted for weight loss and aggressive risk • A recent study from MESA (Multi-Ethnic Study
factor management had fewer hospitalizations, of Atherosclerosis) demonstrated that during a
cardioversions, and ablation procedures than median 10-year follow-up, among 12 negative
their counterparts who declined enrollment. The risk markers (CAC=0, carotid intima-media thick-
risk factor management group was associated ness, absence of carotid plaque, >5% change in
with a predicted 10-year cost savings of $12 094 brachial flow-mediated dilation, ankle-brachial
(in 2010 Australian dollars). index >0.9 and <1.3, high-sensitivity C-reactive
protein <2 mg/L, homocysteine <10 µmol/L,
Sudden Cardiac Arrest (Chapter 16) N-terminal pro-B-type natriuretic peptide <100
pg/mL, no microalbuminuria, no family history
• Sudden cardiac death appears among the mul- of CHD [any/premature], absence of metabolic
tiple causes of death on 13.5% of death certifi- syndrome, and healthy lifestyle), CAC=0 had
cates (366 807 of 2 712 630), which suggests that the lowest diagnostic likelihood ratio for all CHD
1 of every 7.4 people in the United States will die (0.41) and CVD (0.54).
of sudden cardiac death. Because some people
survive sudden cardiac arrest, the lifetime risk of
cardiac arrest is even higher. Coronary Heart Disease, Acute Coronary
• Survival after out-of-hospital cardiac arrest (2006– Syndrome, and Angina Pectoris
2015, Resuscitation Outcomes Consortium Epistry (Chapter 18)
data) and in-hospital cardiac arrest (2000–2015,
Get With The Guidelines data) has continued to • On the basis of data from NHANES 2011 to 2014,
improve over time. an estimated 16.5 million Americans ≥20 years of
• Large regional variations in survival to hospital age have CHD.
discharge (range, 3.4%–22.0%) and survival • This year, ≈720 000 Americans will have a new
with functional recovery (range, 0.8%–20.1%) coronary event (defined as first hospitalized
have been observed between 132 counties in the myocardial infarction [MI] or CHD death), and
United States. Differences in rates of layperson ≈335 000 will have a recurrent event.
cardiopulmonary resuscitation (CPR) explained • CHD mortality dropped by 34.4% from 2005 to
much of this variation. 2015, with a predicted continued decline (27%
• In a survey of 9022 people in the United States reduction by 2030); however, race disparities are
in 2015, 18% of participants reported current projected to persist.
training in CPR and 65% reported having CPR • Whites had a higher rate of recognized MI than
training at some point. The prevalence of CPR blacks (5.04 versus 3.24 per 1000 person-years)
training was lower among Hispanic/Latino peo- in the Atherosclerosis Risk in Communities
ple, older adults, individuals with less formal Study.
education, and lower-income groups. • In individuals ≥45 years of age, median survival (in
years) after a first MI is 8.4 for white males, 5.6
for white females, 7.0 for black males, and 5.5 for
Subclinical Atherosclerosis (Chapter 17) black females.
• Although the presence and a higher burden of • Individuals self-reporting low income and low
coronary artery calcification (CAC) are well estab- education have twice the incidence of CHD as
lished to be associated with an increased risk of those reporting high income and high education
CHD, there are few data highlighting the associa- (10.1 per 1000 person-years versus 5.2 per 1000
tions with risk of stroke. A recent meta-analysis person-years, respectively).

Cardiomyopathy and Heart Failure kidney injury; and higher incidence of vascular
CLINICAL STATEMENTS
(Chapter 19) complications, aortic regurgitation, and pace-
AND GUIDELINES
maker implantation.
• The prevalence of HF continues to rise over time • Percutaneous mitral valve repair techniques are
with the aging of the population. An estimated becoming a common treatment option for high-
6.5 million American adults ≥20 years of age had risk patients with mitral regurgitation who are
HF between 2011 and 2014 compared with an not deemed candidates for surgical repair. Data
estimated 5.7 million between 2009 and 2012. from the Society of Thoracic Surgeons/American
• Although survival of adults who develop HF after College of Cardiology’s TVT Registry (transcath-
an MI has improved over time, likely because of eter valve therapy registry) on patients commer-
secondary prevention therapies, CHD remains a cially treated with the MitraClip percutaneous
major risk factor for HF, along with hypertension mitral valve repair device showed a reduction in
and DM. the severity of mitral regurgitation and procedural
• Primary prevention of HF can be augmented by success in >90% of cases, although mitral valve
greater adherence to the AHA’s My Life Check - dysfunction at 12 months was more common
Life’s Simple 7 goals; optimal profiles in smoking, with percutaneous mitral valve repair than with
body mass index, physical activity, diet, choles- surgical repair.
terol, blood pressure, and glucose are associated
with a lower lifetime risk of HF and more favor-
able cardiac structure and functional parameters Venous Thromboembolism (Deep Vein
by echocardiography. Thrombosis and Pulmonary Embolism),
• Of incident hospitalized HF events, approximately Chronic Venous Insufficiency, Pulmonary
half are characterized by reduced ejection fraction
Hypertension (Chapter 21)
and the other half by preserved ejection fraction.
Black males had the highest proportion of pre- • Although there is no formal surveillance for deep
sentations with reduced ejection fraction (≈70%); vein thrombosis (DVT) or pulmonary embolism in
white females had the highest proportion of HF the United States, national hospitalization data
hospitalizations with preserved ejection fraction from 1996 to 2014 were compiled in this edition
(≈60%). of the update. From 2005 to 2014, there was a
34% increase in hospitalizations for DVT and a

53% increase in hospitalizations for pulmonary
Valvular Diseases (Chapter 20) embolism.
• Although rheumatic heart disease is uncommon in • Using 2014 data for DVT cases treated in the hos-
high-income countries such as the United States, pital (outlined above), if it is assumed that 30% of
it remains an important cause of morbidity and DVT cases were treated in the outpatient setting
mortality in low- and middle-income countries. in 2014, then an estimated 676 000 cases of DVT
• Both administrative and community-based data occurred in 2014.
report that the incidence of infective endocarditis
did not change after the publication of the 2007
Peripheral Artery Disease and Aortic
AHA guidelines for prevention of infective endo-
carditis,2 which restricted the indications for anti- Diseases (Chapter 22)
biotic prophylaxis before dental procedures. • A 2016 study using data from the Nationwide
• From the time of initial US Food and Drug Inpatient Sample demonstrated that admission
Administration approval in late 2011 through rates related to critical limb ischemia remained
2014, >26 000 transcatheter aortic valve replace- constant from 2003 to 2011.
ments for calcific aortic stenosis were performed • A few recent studies have demonstrated that
at 348 centers in 48 states. even individuals with low-normal ankle-brachial
• A recently published meta-analysis that included index (0.91–0.99) have reduced physical function
50 studies that enrolled >44 000 patients, with compared with those with normal ankle-brachial
a mean duration of follow-up of 21.4 months, index.
compared transcatheter to surgical aortic valve • US patients demonstrated higher rates of abdom-
replacement. Compared with surgical aortic valve inal aortic aneurysm repair, a smaller abdominal
replacement, balloon-expandable transcatheter aortic aneurysm diameter at the time of repair,
aortic valve replacement in symptomatic high-risk and lower rates of abdominal aortic aneurysm
patients had similar all-cause mortality; lower inci- rupture and abdominal aortic aneurysm–related
dence of stroke, AF, major bleeding, and acute death than patients in the United Kingdom.

Quality of Care (Chapter 23) Sally S. Wong, PhD, RD, CDN, FAHA, AHA Science and
CLINICAL STATEMENTS
Medicine Advisor
• Performance on inpatient measures of qual-
AND GUIDELINES
On behalf of the American Heart Association Council on

ity of care or measures at discharge in patients
Epidemiology and Prevention Statistics Committee
after MI or stroke exceeds 90% for most mea-
and Stroke Statistics Subcommittee
sures. Performance on outpatient measures was
<80% for body mass index assessment, counsel- Note: Population data used in the compilation of
ing for physical activity, and advising smokers and NHANES prevalence estimates are for the latest year
tobacco users to quit. available. Extrapolations for NHANES prevalence esti-
• Among patients who had out-of-hospital cardiac mates are based on the census resident population for
arrest, bystander CPR rates were 45.7% in adults 2014 because this is the most recent year of NHANES
and 61.4% in children. data used in the Statistical Update.
Medical Procedures (Chapter 24) ARTICLE INFORMATION

• The mean hospital charges for cardiovascular The views expressed in this manuscript are those of the authors and do not
necessarily represent the views of the National Heart, Lung, and Blood Institute;
procedures in 2014 ranged from $43 484 for the National Institutes of Health; the US Department of Health and Human
carotid endarterectomy to $808 770 for heart Services; or the US Department of Veterans Affairs.
transplantations. The findings and conclusions in this manuscript are those of the authors
and do not necessarily represent the official position of the Centers for Disease
• The total number of inpatient cardiovascular Control and Prevention.
operations and procedures decreased 6%, from The American Heart Association makes every effort to avoid any actual or
8 461 000 in 2004 to 7 971 000 in 2014. potential conflicts of interest that may arise as a result of an outside relationship
or a personal, professional, or business interest of a member of the writing pan-
• Of the 10 leading diagnostic groups in the United el. Specifically, all members of the writing group are required to complete and
States, the greatest number of surgical proce- submit a Disclosure Questionnaire showing all such relationships that might be
dures were conducted in the cardiovascular sys- perceived as real or potential conflicts of interest.
A copy of the document is available at http://professional.heart.org/state-
tem and obstetric procedures groups. ments by using either “Search for Guidelines & Statements” or the “Browse by
• In 2016, 3191 heart transplantations were per- Topic” area. To purchase additional reprints, call 843-216-2533 or e-mail kelle.
formed in the United States, the most ever. ramsay@wolterskluwer.com.
The American Heart Association requests that this document be cited as
follows: Benjamin EJ, Virani SS, Callaway CW, Chamberlain AM, Chang AR,
Cheng S, Chiuve SE, Cushman M, Delling FN, Deo R, de Ferranti SD, Ferguson JF,
Economic Cost of Cardiovascular Disease Fornage M, Gillespie C, Isasi CR, Jiménez MC, Jordan LC, Judd SE, Lackland D,
(Chapter 25) Lichtman JH, Lisabeth L, Liu S, Longenecker CT, Lutsey PL, Mackey JS, Matchar
DB, Matsushita K, Mussolino ME, Nasir K, O’Flaherty M, Palaniappan LP, Pandey
• In 2013 to 2014, the annual direct and indirect A, Pandey DK, Reeves MJ, Ritchey MD, Rodriguez CJ, Roth GA, Rosamond WD,
cost of CVD and stroke in the United States was Sampson UKA, Satou GM, Shah SH, Spartano NL, Tirschwell DL, Tsao CW, Voeks
JH, Willey JZ, Wilkins JT, Wu JHY, Alger HM, Wong SS, Muntner P; on behalf of
an estimated $329.7 billion. the American Heart Association Council on Epidemiology and Prevention Sta-
• CVD and stroke accounted for 14% of total tistics Committee and Stroke Statistics Subcommittee. Heart disease and stroke
health expenditures in 2013 to 2014, more than statistics—2018 update: a report from the American Heart Association. Circula-
tion. 2018;137:e67–e492. DOI: 10.1161/CIR.0000000000000558.
any major diagnostic group. Expert peer review of AHA Scientific Statements is conducted by the
AHA Office of Science Operations. For more on AHA statements and guide-
lines development, visit http://professional.heart.org/statements. Select the
Conclusions “Guidelines & Statements” drop-down menu, then click “Publication De-
velopment.”
The AHA, through its Statistics Committee, continuously Permissions: Multiple copies, modification, alteration, enhancement, and/
monitors and evaluates sources of data on heart disease or distribution of this document are not permitted without the express permis-
sion of the American Heart Association. Instructions for obtaining permission
and stroke in the United States to provide the most cur- are located at http://www.heart.org/HEARTORG/General/Copyright-Permis-
rent information available in the Statistical Update. The sion-Guidelines_UCM_300404_Article.jsp. A link to the “Copyright Permis-
2018 annual Statistical Update is the product of a full sions Request Form” appears on the right side of the page.
year’s worth of effort by dedicated volunteer physicians

and scientists, committed government professionals, Acknowledgments
and outstanding AHA staff members, without whom We wish to thank our colleagues: Dr David Goff, Dr Paul Sorlie, and Lucy Hsu,
publication of this valuable resource would be impos- National Heart, Lung, and Blood Institute; Dr Elizabeth B. Pathak, Dr Mary G.
sible. Their contributions are gratefully acknowledged. George, Dr Stuart K. Shapira, and Dr Tiffany J. Colarusso, Centers for Disease
Control and Prevention; Dr Fran F. Thorpe and Jim Beachy, American College
Emelia J. Benjamin, MD, ScM, FAHA, Chair of Cardiology; Dr Chris Shay, Ian Golnik, and Kathleen Smith, American Heart
Association; and all the dedicated staff of the Centers for Disease Control and
Paul Muntner, PhD, MHS, FAHA, Co-Vice Chair Prevention and the National Heart, Lung, and Blood Institute for their valuable
Salim S. Virani, MD, PhD, FAHA, Co-Vice Chair comments and contributions.

Disclosures
CLINICAL STATEMENTS
AND GUIDELINES
Writing Group Disclosures
Other Speakers’ Consultant/
Writing Group Research Bureau/ Expert Ownership Advisory
Member Employment Research Grant Support Honoraria Witness Interest Board Other
Emelia J. Benjamin Boston University School NIH None None None None None None
of Medicine (1R01HL128914;
2R01 HL092577;
1P50HL120163)†
Paul Muntner University of Alabama at Amgen Inc. None None None None Amgen Inc.* None
Birmingham (grant support)†
Salim S. Virani Michael E. DeBakey VA Medical Department of None None None None None None
Center, Baylor College of Veterans Affairs†;
Medicine American Heart
Association†;
American
Diabetes
Association†
Heather M. Alger American Heart Association None None None None None None None
Clifton W. Callaway University of Pittsburgh NIH (NHLBI None None None None None None
Emergency Medicine NINDS, NCATS)
(grants to study
emergency care)†
Alanna M. Mayo Clinic EpidStat None None None None None None
Chamberlain Institute†
Alexander R. Chang Geisinger Health System NIH None None None None None None
(epidemiology
research grants)*
Susan Cheng Brigham and Women’s Hospital NIH None None None None None None
(epidemiology
research grants)*
Stephanie E. Chiuve Harvard T.H. Chan School None None None None None None AbbVie,
of Public Health; Shire Inc (Salary,
Pharmaceuticals Associate
Director,
Epidemiology)†
Mary Cushman University of Vermont None None None None None None None
Francesca N. Delling University of California NIH (K23)† None None None None None None
San Francisco
Rajat Deo University of Pennsylvania None None None None None None None
Sarah D. de Ferranti Children’s Hospital Boston None None None None None None None
Jane F. Ferguson Vanderbilt University None None None None None None None
Medical Center
Myriam Fornage University of Texas Health Science None None None None None None None
Center at Houston Institute of
Molecular Medicine
Cathleen Gillespie Centers for Disease Control and None None None None None None None
Prevention DHDSP
Carmen R. Isasi Albert Einstein College None None None None None None None
of Medicine
Monik C. Jiménez Brigham and Women’s Hospital None None None None None None None
Lori Chaffin Jordan Vanderbilt University None None None None None None None
Medical Center
Suzanne E. Judd University of Alabama at None None None None None None None
Birmingham School of Public
Health
Daniel Lackland Medical University of South NIH (co- None None None None None None
Carolina investigator on
research/training
grant)†
(Continued )

Writing Group Disclosures Continued

CLINICAL STATEMENTS

AND GUIDELINES

Judith H. Lichtman Yale School of Public Health NIA (research None None None None None None
grant)*; AHA
(research grant)*
Lynda Lisabeth University of Michigan NIH (PI)† None None None None None None
Simin Liu Brown University None None None None None None None
Chris T. Case Western Reserve University Gilead Sciences*; None None None None None None
Longenecker School of Medicine Gilead Sciences
(immediate
family member)*
Pamela L. Lutsey University of Minnesota None None None None None None None
Jason S. Mackey Indiana University NIH None None None None None None
(R01NS30678)*;
NIH
(UL1TR001108)†
David B. Matchar Duke-NUS Graduate Medical None None None None None None None
School Health Services and
Systems Research
Kunihiro Matsushita Johns Hopkins Bloomberg School Kyowa Hakko None None None None Kyowa None
of Public Health Kirin†; Fukuda Hakko Kirin*
Denshi†
Michael E. NIH None None None None None None None
Mussolino
Khurram Nasir Baptist Health South Florida None None None None None None None
Martin O’Flaherty University of Liverpool (United NIH (CO-I in NIH None None None None None None
Kingdom) R021 grant)*;
British Heart
Foundation (UK)
(CO-I)*; NIHR
(UK) (PI in a
research grant)*
Latha P. Palaniappan Stanford University None None None None None None None
Ambarish Pandey University of Texas Southwestern None None None None None None None
Medical Center
Dilip K. Pandey University of Illinois at Chicago CDC (Principal None None None None None CDC (Salary-
Investigator)† Principal
Investigator)†
Mathew J. Reeves Michigan State University None None None None None None None
Matthew D. Ritchey Centers for Disease Control and None None None None None None None
Prevention
Carlos J. Rodriguez Wake Forest University None None None None None Amgen* None
Gregory A. Roth University of Washington None None None None None None None
Wayne D. Gillings School of Global Public None None None None None None None
Rosamond Health, University of North
Carolina
Uchechukwu K.A. National Institutes of Health, None None None None None None None
Sampson CTRIS
Gary M. Satou UCLA None None None None None None None
Svati H. Shah Duke DUMC None None None None None None None
Nicole L. Spartano Boston University None None None None None None None
David L. Tirschwell University of Washington None None None None None None None
Harborview Medical Center
Connie W. Tsao Beth Israel Deaconess Medical None None None None None None None
Center
(Continued )

Writing Group Disclosures Continued
CLINICAL STATEMENTS
AND GUIDELINES
Jenifer H. Voeks Medical University of South NIH None None None None None None
Carolina Neurology (Investigator)†
Joshua Z. Willey Columbia University None None None None None None None
John T. Wilkins Northwestern University Feinberg None None None None None None None
School of Medicine
Sally S. Wong American Heart Association None None None None None None None
Jason HY. Wu The George Institute for Global None None None None None None None
Health, The University of Sydney
(Australia)
This table represents the relationships of writing group members that may be perceived as actual or reasonably perceived conflicts of interest as reported on the
Disclosure Questionnaire, which all members of the writing group are required to complete and submit. A relationship is considered to be “significant” if (a) the
person receives $10 000 or more during any 12-month period, or 5% or more of the person’s gross income; or (b) the person owns 5% or more of the voting stock
or share of the entity, or owns $10 000 or more of the fair market value of the entity. A relationship is considered to be “modest” if it is less than “significant” under
the preceding definition.
*Modest.
†Significant.
infective endocarditis: guidelines from the American Heart Association:

REFERENCES a guideline from the American Heart Association Rheumatic
1. American Heart Association. My Life Check - Life’s Simple 7. http:// Fever, Endocarditis, and Kawasaki Disease Committee, Council on
www.heart.org/HEARTORG/Conditions/My-Life-Check—Lifes-Simple-7_ Cardiovascular Disease in the Young, and the Council on Clinical
UCM_471453_Article.jsp#.WBwQnvKQzio. Accessed June 30, 2016. Cardiology, Council on Cardiovascular Surgery and Anesthesia, and the
2. Wilson W, Taubert KA, Gewitz M, Lockhart PB, Baddour LM, Levison Quality of Care and Outcomes Research Interdisciplinary Working Group
M, Bolger A, Cabell CH, Takahashi M, Baltimore RS, Newburger JW, [published correction appears in Circulation. 2007;116:e376–e377].
Strom BL, Tani LY, Gerber M, Bonow RO, Pallasch T, Shulman ST, Rowley Circulation. 2007;116:1736–1754. doi:10.1161/CIRCULATIONAHA.
AH, Burns JC, Ferrieri P, Gardner T, Goff D, Durack DT. Prevention of 106.183095.

Benjamin et al Heart Disease and Stroke Statistics—2018 Update: Chapter 1
1. ABOUT THESE STATISTICS • NAMCS—physician office visits

CLINICAL STATEMENTS
• National Vital Statistics System—national and

AND GUIDELINES
Click here to return to the Table of Contents state mortality data

• NHAMCS—hospital outpatient and ED visits
The AHA works with the CDC’s Division for Heart Disease • NHANES—disease and risk factor prevalence and
and Stroke Prevention and the NCHS, the NHLBI, and nutrition statistics
other government agencies to derive the annual statis- • NHHCS—staff, services, and patients of home
tics in this Heart Disease and Stroke Statistics Update. health and hospice agencies
This chapter describes the most important sources and • NHIS—disease and risk factor prevalence
the types of data used from them. For more details, see • NIS of the AHRQ—hospital inpatient discharges,
Chapter 27 of this document, the Glossary. procedures, and charges
The surveys used are the following: • NNHS—nursing home residents
• ARIC—CHD and HF incidence rates • USRDS—kidney disease prevalence
• BRFSS—ongoing telephone health survey system • WHO—mortality rates by country
• GCNKSS—stroke incidence rates and outcomes • YRBSS—health-risk behaviors in youth and young
within a biracial population adults
• HCUP—hospital inpatient discharges and proce-
dures (discharged alive, dead, or status unknown) Disease Prevalence
• MEPS—data on specific health services that
Americans use, how frequently they use them, the Prevalence is an estimate of how many people have a
cost of these services, and how the costs are paid condition at a given point or period in time. The NCHS/
CDC conducts health examination and health interview
Abbreviations Used in Chapter 1 surveys that provide estimates of the prevalence of dis-
AHA American Heart Association
eases and risk factors. In this Update, the health inter-
AHRQ Agency for Healthcare Research and Quality view part of the NHANES is used for the prevalence of
AP angina pectoris CVDs. NHANES is used more than the NHIS because in
ARIC Atherosclerosis Risk in Communities Study NHANES, AP is based on the Rose Questionnaire; esti-
BP blood pressure mates are made regularly for HF; hypertension is based
BRFSS Behavioral Risk Factor Surveillance System
on BP measurements and interviews; and an estimate
CDC Centers for Disease Control and Prevention

CHD coronary heart disease
can be made for total CVD, including MI, AP, HF, stroke,
CHS Cardiovascular Health Study and hypertension.
CVD cardiovascular disease A major emphasis of this Statistical Update is to
DM diabetes mellitus present the latest estimates of the number of people
ED emergency department
in the United States who have specific conditions to
FHS Framingham Heart Study
GCNKSS Greater Cincinnati/Northern Kentucky Stroke Study
provide a realistic estimate of burden. Most estimates
HBP high blood pressure based on NHANES prevalence rates are based on data
HCUP Healthcare Cost and Utilization Project collected from 2011 to 2014. These are applied to
HD heart disease census population estimates for 2014. Differences in
HF heart failure population estimates cannot be used to evaluate pos-
ICD International Classification of Diseases
sible trends in prevalence because these estimates are
ICD-9-CM International Classification of Diseases, Clinical
Modification, 9th Revision based on extrapolations of rates beyond the data col-
ICD-10 International Classification of Diseases, 10th Revision lection period by use of more recent census population
MEPS Medical Expenditure Panel Survey estimates. Trends can only be evaluated by comparing
MI myocardial infarction prevalence rates estimated from surveys conducted in
NAMCS National Ambulatory Medical Care Survey
different years.
NCHS National Center for Health Statistics
NHAMCS National Hospital Ambulatory Medical Care Survey
A major enhancement in the 2018 Statistical Update
NHANES National Health and Nutrition Examination Survey is a greater emphasis on the global burden of CVD. The
NHHCS National Home and Hospice Care Survey Institute for Health Metrics and Evaluation contributed
NHIS National Health Interview Survey statistics and maps that characterize the distribution
NHLBI National Heart, Lung, and Blood Institute and prognosis of CVD and its risk factors.
NINDS National Institute of Neurological Disorders and Stroke
NIS Nationwide Inpatient Sample
NNHS National Nursing Home Survey Risk Factor Prevalence
PAD peripheral artery disease
USRDS US Renal Data System The NHANES 2011 to 2014 data are used in this
WHO World Health Organization Update to present estimates of the percentage of
YRBSS Youth Risk Behavior Surveillance System people with high lipid values, DM, overweight, and

obesity. The NHIS 2015 data are used for the preva- from the mortality tables of the NCHS/CDC website or
CLINICAL STATEMENTS
lence of cigarette smoking and physical inactivity. the CDC compressed mortality file. Any-mention num-
AND GUIDELINES
Data for students in grades 9 through 12 are obtained bers of deaths were tabulated from the electronic mor-
from the YRBSS. tality files of the NCHS/CDC website.
Incidence and Recurrent Attacks Population Estimates

An incidence rate refers to the number of new cases In this publication, we have used national population
of a disease that develop in a population per unit of estimates from the US Census Bureau for 20151 in
time. The unit of time for incidence is not necessarily 1 the computation of morbidity data. NCHS/CDC pop-
year, although incidence is often discussed in terms of ulation estimates2 for 2015 were used in the compu-
1 year. For some statistics, new and recurrent attacks tation of death rate data. The Census Bureau website
or cases are combined. Our national incidence esti- contains these data, as well as information on the file
mates for the various types of CVD are extrapolations layout.
to the US population from the FHS, the ARIC study,
and the CHS, all conducted by the NHLBI, as well as
the GCNKSS, which is funded by the NINDS. The rates
Hospital Discharges and Ambulatory
change only when new data are available; they are Care Visits
not computed annually. Do not compare the incidence Estimates of the numbers of hospital discharges and
or the rates with those in past editions of the Heart numbers of procedures performed are for inpatients
Disease and Stroke Statistics Update (also known as discharged from short-stay hospitals. Discharges
the Heart and Stroke Statistical Update for editions include those discharged alive, dead, or with unknown
before 2005). Doing so can lead to serious misinter- status. Unless otherwise specified, discharges are
pretation of time trends. listed according to the first-listed (primary) diagno-
sis, and procedures are listed according to all listed
procedures (primary plus secondary). These estimates
Mortality
are from HCUP 2014. Ambulatory care visit data
Mortality data are generally presented according to include patient visits to physician offices and hospi-
the underlying cause of death. “Any-mention” mor-
tal outpatient departments and EDs. Ambulatory care

tality means that the condition was nominally selected visit data reflect the first-listed (primary) diagnosis.
as the underlying cause or was otherwise mentioned These estimates are from the NAMCS and NHAMCS
on the death certificate. For many deaths classified as of the NCHS/CDC. Data for community health cen-
attributable to CVD, selection of the single most likely ters, which were included in estimates in previous
underlying cause can be difficult when several major years, were not available for 2014 NAMCS estimates
comorbidities are present, as is often the case in the included in this Update.
elderly population. It is useful, therefore, to know the
extent of mortality attributable to a given cause regard-
less of whether it is the underlying cause or a contribut- International Classification of Diseases
ing cause (ie, the “any-mention” status). The number Morbidity (illness) and mortality (death) data in the
of deaths in 2015 with any mention of specific causes United States have a standard classification system:
of death was tabulated by the NHLBI from the NCHS the ICD. Approximately every 10 to 20 years, the ICD
public-use electronic files on mortality. codes are revised to reflect changes over time in medi-
The first set of statistics for each disease in this cal technology, diagnosis, or terminology. If necessary
Update includes the number of deaths for which for comparability of mortality trends across the 9th and
the disease is the underlying cause. Two exceptions 10th ICD revisions, comparability ratios computed by
are Chapter 8 (High Blood Pressure) and Chapter 19 the NCHS/CDC are applied as noted.3 Effective with
(Cardiomyopathy and Heart Failure). HBP, or hyperten- mortality data for 1999, we are using the 10th revision
sion, increases the mortality risks of CVD and other (ICD-10).4
diseases, and HF should be selected as an underly-
ing cause only when the true underlying cause is not
known. In this Update, hypertension and HF death Age Adjustment
rates are presented in 2 ways: (1) as nominally clas- Prevalence and mortality estimates for the United States
sified as the underlying cause and (2) as any-mention or individual states comparing demographic groups
mortality. or estimates over time are either age specific or age
National and state mortality data presented accord- adjusted to the 2000 standard population by the direct
ing to the underlying cause of death were computed method.6 International mortality data are age adjusted

to the European standard.7 Unless otherwise stated, all Race/Ethnicity

CLINICAL STATEMENTS
death rates in this publication are age adjusted and are

Data published by governmental agencies for some
AND GUIDELINES
deaths per 100 000 population.

racial groups are considered unreliable because of the
small sample size in the studies. Because we try to
Data Years for National Estimates provide data for as many racial and ethnic groups as
possible, we show these data for informational and
In this Update, we estimate the annual number of comparative purposes.
new (incidence) and recurrent cases of a disease in
the United States by extrapolating to the US popula-
tion in 2014 from rates reported in a community- or Contacts
hospital-based study or multiple studies. Age-adjusted If you have questions about statistics or any points made
incidence rates by sex and race are also given in this in this Update, please contact the AHA National Center,
report as observed in the study or studies. For US Office of Science & Medicine. Direct all media inquiries
mortality, most numbers and rates are for 2015. For to News Media Relations at http://www.newsroom.
disease and risk factor prevalence, most rates in this heart.org/contacts or 214-706-1173.
report are calculated from the 2011 to 2014 NHANES. The AHA works diligently to ensure that this Update is
Because NHANES is conducted only in the noninsti- error free. If we discover errors after publication, we will
tutionalized population, we extrapolated the rates to provide corrections at http://www.heart.org/statistics
the total US population in 2014, recognizing that this and in Circulation.
probably underestimates the total prevalence, given
the relatively high prevalence in the institutionalized
population. The numbers and rates of hospital inpa- REFERENCES
tient discharges for the United States are for 2014. 1. US Census Bureau population estimates: historical data: 2000s. US Census
Numbers of visits to physician offices and hospital EDs Bureau website. http://www.census.gov/popest/. Accessed August 4,
2016.
are for 2014, whereas hospital outpatient department 2. Centers for Disease Control and Prevention. U.S. Census Populations With
visits are for 2011. Except as noted, economic cost Bridged Race Categories. http://www.cdc.gov/nchs/nvss/bridged_race.
estimates are for 2013 to 2014. htm. Accessed July 23, 2017.
3. National Center for Health Statistics. Health, United States, 2015: With
Special Feature on Racial and Ethnic Health Disparities. Hyattsville, MD:
National Center for Health Statistics; 2015. http://www.cdc.gov/nchs/

Cardiovascular Disease data/hus/hus15.pdf. Accessed June 15, 2016.
4. World Health Organization. International Statistical Classification of
For data on hospitalizations, physician office visits, Diseases and Related Health Problems, Tenth Revision. 2008 ed. Geneva,
and mortality, CVD is defined according to ICD codes Switzerland; World Health Organization; 2009.
given in Chapter 12. This definition includes all diseases 5. National Center for Health Statistics, Centers for Medicare and Medicaid
Services. ICD-9-CM Official Guidelines for Coding and Reporting, 2011.
of the circulatory system, as well as congenital CVD. http://www.cdc.gov/nchs/data/icd/icd9cm_guidelines_2011.pdf.
Unless otherwise specified, an estimate for total CVD Accessed October 29, 2012.
does not include congenital CVD. Prevalence of 6. Anderson RN, Rosenberg HM. Age standardization of death rates: implementa-
tion of the year 2000 standard. Natl Vital Stat Rep. 1998;47:1–16, 20.
CVD includes people with hypertension, HD, stroke, 7. World Health Organization. World Health Statistics Annual. Geneva,
PAD, and diseases of the veins. Switzerland: World Health Organization; 1998.

2. CARDIOVASCULAR HEALTH health can also be represented as being “ideal,” “inter-
CLINICAL STATEMENTS
mediate,” or “poor” for each of the health behaviors
See Tables 2-1 through 2-6 and Charts 2-1
AND GUIDELINES
and health factors.1 Table 2-1 provides the specific defi-
through 2-13
nitions for ideal, intermediate, and poor cardiovascular
health for each of the 7 metrics, both for adults and for
Click here to return to the Table of Contents
children.
This concept of cardiovascular health represented
In 2011, the AHA created a new set of central Strategic
a new focus for the AHA, with 3 central and novel
Impact Goals to drive organizational priorities for the
emphases:
current decade:
• An expanded focus on CVD prevention and pro-
By 2020, to improve the cardiovascular health motion of positive “cardiovascular health,” in
of all Americans by 20%, while reducing deaths addition to the treatment of established CVD.
from CVDs and stroke by 20%.1 • Efforts to promote both healthy behaviors (healthy
diet pattern, appropriate energy intake, PA, and
These goals introduced a new concept of cardiovas-
nonsmoking) and healthy biomarker levels (opti-
cular health, characterized by 7 metrics (Life’s Simple 72),
mal blood lipids, BP, glucose levels) throughout
including health behaviors (diet quality, PA, smoking,
the lifespan.
BMI) and health factors (blood cholesterol, BP, blood
• Population-level health promotion strategies to
glucose). Ideal cardiovascular health is defined by the
shift the majority of the public toward greater car-
absence of clinically manifest CVD together with the
diovascular health, in addition to targeting those
simultaneous presence of optimal levels of all 7 met-
individuals at greatest CVD risk, because healthy
rics, including not smoking and having a healthy diet
lifestyles in all domains are uncommon through-
pattern, sufficient PA, normal body weight, and nor-
out the US population.
mal levels of TC, BP, and fasting blood glucose, in the
Beginning in 2011, and recognizing the time lag in
absence of drug treatment (Table 2-1). Because a spec-
the nationally representative US data sets, this chap-
trum of cardiovascular health is possible and the ideal
ter in the annual Statistical Update has evaluated and
cardiovascular health profile is known to be rare in the
published metrics and information to provide insights
US population, a broader spectrum of cardiovascular
into both progress toward meeting the 2020 AHA
goals and areas that require greater attention to meet

Abbreviations Used in Chapter 2 these goals. The AHA has advocated for raising the
AHA American Heart Association visibility of patient-reported cardiovascular health sta-
BMI body mass index tus, which includes symptom burden, functional sta-
BP blood pressure
tus, and health-related quality of life, as an indicator
of cardiovascular health in future organizational goal
CI confidence interval setting.3
CVD cardiovascular disease
DASH Dietary Approaches to Stop Hypertension
DBP diastolic blood pressure Relevance of Ideal Cardiovascular Health
DM diabetes mellitus • Since the AHA announced its 2020 Impact Goals,
ESRD end-stage renal disease
F&V fruits and vegetables
multiple independent investigations (summaries
FPG fasting plasma glucose below) have confirmed the importance of these
HbA1c hemoglobin A1c (glycosylated hemoglobin) metrics and the concept of cardiovascular health.
HBP high blood pressure Findings include strong inverse, stepwise associa-
HF heart failure tions in the United States of the metrics and car-
HR hazard ratio diovascular health with all-cause mortality, CVD
IHD ischemic heart disease
mortality, and HF; with preclinical measures of
IMT intima-media thickness
NH non-Hispanic atherosclerosis such as carotid IMT arterial stiff-
NHANES National Health and Nutrition Examination Survey ness and coronary artery calcium prevalence and
PA physical activity progression; with physical functional impair-
REGARDS Reasons for Geographic and Racial Differences in Stroke ment and frailty4; and with cognitive decline and
RR relative risk
depression.4,5 Similar relationships have also been
SBP systolic blood pressure
SE standard error
seen in non-US populations.4,6–9
SFat saturated fat • A recent study in a large Hispanic/Latino cohort
SSB sugar-sweetened beverage study in the United States found that associations
svg servings of CVD and cardiovascular health metrics com-
TC total cholesterol pared favorably with existing national estimates;

however, some of the associations varied by sex • Data from the REGARDS cohort also demon-
CLINICAL STATEMENTS
and heritage.10 strated a stepwise association between cardiovas-

AND GUIDELINES
• A recent study in blacks found that risk of incident cular health metrics and incident stroke. Using a
HF was 61% lower among those with ≥4 ideal cardiovascular health score scale ranging from 0
cardiovascular health metrics than among those to 14, every unit increase in cardiovascular health
with 0 to 2 ideal metrics.11 was associated with an 8% lower risk of incident
• Ideal health behaviors and ideal health factors are stroke (HR, 0.92; 95% CI, 0.88–0.95), with a simi-
each independently associated with lower CVD lar effect size for white (HR, 0.91; 95% CI, 0.86–
risk in a stepwise fashion (Chart 2-1). In other 0.96) and black (HR, 0.93; 95% CI, 0.87–0.98)
words, across any level of health behaviors, health participants.16
factors are associated with incident CVD; con- • The Cardiovascular Lifetime Risk Pooling Project
versely, across any level of health factors, health showed that adults with all-optimal risk factor lev-
behaviors are still associated with incident CVD.12 els (similar to having ideal cardiovascular health
• Analyses from the US Burden of Disease factor levels of cholesterol, blood sugar, and BP,
Collaborators demonstrated that poor levels as well as not smoking) have substantially longer
of each of the 7 health factors and behaviors overall and CVD-free survival than those who have
resulted in substantial mortality and morbidity poor levels of ≥1 of these cardiovascular health
in the United States in 2010. The top risk factor factor metrics. For example, at an index age of 45
related to overall disease burden was suboptimal years, men with optimal risk factor profiles lived
diet, followed by tobacco smoking, high BMI, on average 14 years longer free of all CVD events,
raised BP, high fasting plasma glucose, and physi- and 12 years longer overall, than people with ≥2
cal inactivity.13 risk factors.17
• A stepwise association was present between the • Better cardiovascular health is associated with
number of ideal cardiovascular health metrics and less incident HF,18 less subclinical vascular dis-
risk of death based on NHANES 1988 to 2006 ease,19,20 better global cognitive performance and
data.14 The HRs for people with 6 or 7 ideal health cognitive function,21,22 lower prevalence23 and
metrics compared with 0 ideal health metrics were incidence24 of depressive symptoms, lower loss
0.49 (95% CI, 0.33–0.74) for all-cause mortality, of physical functional status,25 longer leukocyte
telomere length,26 less ESRD,27 and less pneumo-
0.24 (95% CI, 0.13–0.47) for CVD mortality, and

0.30 (95% CI, 0.13–0.68) for IHD mortality.14 nia, chronic obstructive pulmonary disease,27a and
• A recent meta-analysis of 9 prospective cohort venous thromboembolism/PE.27b
studies involving 12 878 participants reported • The AHA’s 2020 Strategic Impact Goals are
that achieving the most ideal cardiovascular to improve cardiovascular health among all
health metrics was associated with a lower risk of Americans. On the basis of NHANES 1999 to
all-cause mortality (RR, 0.55; 95% CI, 0.37–0.80), 2006 data, several social risk factors (low family
cardiovascular mortality (RR, 0.25; 95% CI, 0.10– income, low education level, minority race, and
0.63), CVD (RR, 0.20; 95% CI, 0.11–0.37), and single-living status) were related to lower likeli-
stroke (RR, 0.31; 95% CI, 0.25–0.38).15 hood of attaining better cardiovascular health as
• The adjusted population attributable fractions for measured by Life’s Simple 7 scores.28
CVD mortality were as follows14: • Cardiovascular health metrics are also associ-
— 40.6% (95% CI, 24.5%–54.6%) for HBP ated with lower healthcare costs. A recent report
— 13.7% (95% CI, 4.8%–22.3%) for smoking from a large, ethnically diverse insured population
— 13.2% (95% CI, 3.5%–29.2%) for poor diet found that people with 6 or 7 and those with 3 to
— 11.9% (95% CI, 1.3%–22.3%) for insuffi- 5 of the cardiovascular health metrics in the ideal
cient PA category had a $2021 and $940 lower annual
— 8.8% (95% CI, 2.1%–15.4%) for abnormal mean healthcare expenditure, respectively, than
glucose levels those with 0 to 2 ideal health metrics.29
• The adjusted population attributable fractions for
IHD mortality were as follows14: Cardiovascular Health: Current
— 34.7% (95% CI, 6.6%–57.7%) for HBP Prevalence
— 16.7% (95% CI, 6.4%–26.6%) for smoking
— 20.6% (95% CI, 1.2%–38.6%) for poor diet
(See Table 2-2 and Charts 2-2 through
— 7.8% (95% CI, 0%–22.2%) for insufficient 2-10)
PA • The most up-to-date data on national prevalence
— 7.5% (95% CI, 3.0%–14.7%) for abnormal of ideal, intermediate, and poor levels of each of
glucose levels the 7 cardiovascular health metrics are shown for

adolescents and teens (Chart 2-2) and for adults meet only 1 of 7 criteria. This is much worse
CLINICAL STATEMENTS
(Chart 2-3). than among children (12–19 years of age).
AND GUIDELINES
• For most metrics, the prevalence of ideal levels — Most US adults (≈65%) have 2, 3, or 4 crite-
of health behaviors and health factors is higher ria at ideal cardiovascular health, with ≈20%
in US children than in US adults. The main excep- adults within each of these categories.
tions are diet and PA, for which the prevalence — Approximately 13% of US adults have 5 cri-
of ideal levels in children is similar to (for PA) or teria, 5% have 6 criteria, and virtually 0%
worse (for diet) than in adults (unpublished AHA have 7 criteria at ideal levels.
tabulation). — Presence of ideal cardiovascular health is both
• Among US children aged 12 to 19 years (Chart age and sex related (Chart 2-5). Younger
2-2), the prevalence (unadjusted) of ideal levels of adults are more likely to meet greater num-
cardiovascular health behaviors and factors cur- bers of ideal metrics than are older adults.
rently varies from <1% for the healthy diet pat- More than 60% of Americans >60 years of
tern (ie, <1 in 100 US children meets at least 4 age have ≤2 metrics at ideal levels. At any
of the 5 dietary components or a corresponding age, females tend to have more metrics at
AHA diet score of at least 80) to >80% for the ideal levels than do males.
smoking, BP, and fasting glucose metrics (unpub- — Presence of ideal cardiovascular health
lished AHA tabulation). also varies by race (Chart 2-6). Blacks and
• Among US adults (Chart 2-3), the age-standard- Hispanics tend to have fewer metrics at
ized prevalence of ideal levels of cardiovascular ideal levels than whites or other races.
health behaviors and factors currently varies from Approximately 6 in 10 white adults and 7
<1% for having a healthy diet pattern to up to in 10 black or Hispanic adults have no more
77% for never having smoked or being a former than 3 of 7 metrics at ideal levels.
smoker who has quit for >12 months. • Chart 2-7 displays the age-standardized percent-
• Age-standardized and age-specific prevalence ages of US adults and the percentages of children
estimates for ideal cardiovascular health and for who have ≥5 of the metrics (of 7 possible) at ideal
ideal levels of each of its components are shown levels.
for 2011 to 2012 and 2013 to 2014 in Table 2-2. — Approximately 41% of US children 12 to 19
NHANES 2011 to 2012 data were used for some years of age have ≥5 metrics at ideal levels,
of the statistics that required nutritional data. The with similar prevalence in boys (42%) as in
prevalence of ideal levels across 7 health factors girls (41%).
and health behaviors generally was lower with — In comparison, only 17% of US adults have
age, with much lower prevalence among older ≥5 metrics at ideal levels, with lower preva-
versus younger age groups. The exception was lence in males (13%) than in females (21%).
diet, for which prevalence of ideal levels was — All populations have improved since baseline
highest in older adults. year 2007 to 2008.
• Chart 2-4 displays the prevalence estimates for • Chart 2-8 displays the age-standardized percent-
the population of US children (12–19 years of ages of US adults and percentages of children by
age) meeting different numbers of criteria for race/ethnicity who have ≥5 of the metrics (of 7
ideal cardiovascular health (of 7 possible) in 2011 possible) at ideal levels.
to 2012. — In both children and adults, NH Asians tend
— Few US children 12 to 19 years of age (≈5%) to have higher prevalence of having ≥5 met-
meet only 0, 1, or 2 criteria for ideal cardio- rics at ideal levels than other race/ethnic
vascular health. groups.
— Approximately half of US children (54%) — Approximately 4.7 in 10 NH Asian children,
meet 3 or 4 criteria for ideal cardiovascular 4.4 in 10 NH white children, 3.5 in 10 NH
health, and ≈41% meet 5 or 6 criteria. black children, and 3.7 in 10 Hispanic chil-
— <1% of children meet all 7 criteria for ideal dren have ≥5 metrics at ideal levels.
cardiovascular health. — By comparison, among adults, ≈2.6 in 10
• Charts 2-5 and 2-6 display the age-standardized NH Asians, 1.8 in 10 NH whites, 1.3 in 10
prevalence estimates of US adults meeting differ- Hispanics, and 1 in 10 NH blacks have ≥5
ent numbers of criteria for ideal cardiovascular metrics at ideal levels.
health (of 7 possible) in 2011 to 2012, overall and • Chart 2-9 displays the age-standardized percent-
stratified by age, sex, and race. ages of US adults who meet different numbers
— Approximately 3% of US adults have 0 of the of criteria for both poor and ideal cardiovascular
7 criteria at ideal levels, and another 15% health. Meeting the AHA 2020 Strategic Impact

Goals is predicated on reducing the relative per- not show consistent trends over time in
CLINICAL STATEMENTS
centage of those with poor levels while increasing adults.

AND GUIDELINES
the relative percentage of those with ideal levels • On the basis of NHANES data from 1988 to 2008,
for each of the 7 metrics. if current trends continue, estimated cardiovascu-
— Approximately 92% of US adults have ≥1 lar health is projected to improve by 6% between
metric at poor levels. 2010 and 2020, short of the AHA’s goal of 20%
— Approximately 34% of US adults have ≥3 improvement (Chart 2-13).31 On the basis of cur-
metrics at poor levels. rent trends among individual metrics, anticipated
— Few US adults (2.5%) have ≥5 metrics at declines in prevalence of smoking, high choles-
poor levels. terol, and HBP (in males) would be offset by sub-
— More US adults have 4 to 6 ideal metrics than stantial increases in the prevalence of obesity and
4 to 6 poor metrics. DM and smaller changes in ideal dietary patterns
• Using data from the BRFSS, Fang et al30 estimated or PA.31
the prevalence of ideal cardiovascular health by • On the basis of these projections in cardiovascu-
state (all 7 metrics at ideal level), which ranged lar health factors and behaviors, CHD deaths are
from 1.2% (Oklahoma) to 6.9% (District of projected to decrease by 30% between 2010 and
Columbia). Southern states tended to have higher 2020 because of projected improvements in TC,
percentages of poor cardiovascular health, lower SBP, smoking, and PA (≈167 000 fewer deaths),
percentages of ideal cardiovascular health, and offset by increases in DM and BMI (≈24 000 more
lower mean cardiovascular health scores than deaths).32
New England and Western states (Chart 2-10).
Achieving the 2020 Impact Goals1
Cardiovascular Health: Trends Over Time (See Tables 2-3 through 2-6)
(See Charts 2-11 through 2-13) • To achieve the AHA’s 2020 Impact Goals of reduc-
• The trends over the past decade in each of the ing deaths attributable to CVD and stroke by
7 cardiovascular health metrics (for diet, trends 20%, continued emphasis is needed on the treat-
from 1999–2000 through 2013–2014) are shown ment of acute CVD events and secondary pre-
in Chart 2-11 (for children 12–19 years of age) vention through treatment and control of health
and Chart 2-12 (for adults ≥20 years of age). behaviors and risk factors.
— The prevalence of both children and adults • Taken together, these data continue to demon-
meeting the dietary goals improved between strate both the tremendous relevance of the AHA
2003 to 2004 and 2011 to 2012. The preva- 2020 Impact Goals for cardiovascular health and
lence of ideal levels of diet (AHA diet score the progress that will be needed to achieve these
>80) increased from 0.2% to 0.6% in chil- goals by the year 2020.
dren and from 0.7% to 1.5% in adults. The • For each cardiovascular health metric, modest shifts
prevalence of intermediate levels of diet (AHA in the population distribution toward improved
diet score 40–79) increased from 30.6% health would produce appreciable increases in the
to 44.7% in children and from 49.0% to proportion of Americans in both ideal and inter-
57.5% in adults. These improvements were mediate categories. For example, on the basis of
largely attributable to increased whole grain NHANES 2013 to 2014, the current prevalence of
consumption and decreased SSB consump- ideal levels of BP among US adults is 45.4%. To
tion in both children and adults, as well as achieve the 2020 goals, a 20% relative improve-
small, nonsignificant trends in increased ment would require an increase in this proportion
fruits and vegetables (Chapter 5). No major to 54.4% by 2020 (45.4% × 1.20). On the basis
trends were evident in either children or of NHANES data, a reduction in population mean
adults meeting the target for consumption BP of just 5 mm Hg would result in 55.3% of US
of fish or sodium. adults having ideal levels of BP, which represents a
— Fewer children over time are meeting the 21.8% relative improvement in this metric (Table
ideal BMI metric, whereas more are meet- 2-3). Larger population reductions in BP would
ing the ideal smoking and TC metrics. Other lead to even greater numbers of people with ideal
metrics do not show consistent trends over levels of BP. Such small reductions in population BP
time in children. could result from small health behavior changes at
— More adults over time are meeting the smok- a population level, such as increased PA, increased
ing metric, whereas fewer are meeting the fruit and vegetable consumption, decreased
BMI and glucose metrics. Other metrics do sodium intake, decreased adiposity, or some

combination of these and other lifestyle changes, local communities, and states, as well as
CLINICAL STATEMENTS
with resulting substantial projected decreases in throughout the nation (Table 2-6).
AND GUIDELINES
CVD rates in US adults.33 • Such approaches can focus on both (1) improv-
• A range of complementary strategies and ing cardiovascular health among those who
approaches can lead to improvements in cardio- currently have less than optimal levels and
vascular health.32 These include the following: (2) preserving cardiovascular health among
— Individual-focused approaches that target those who currently have ideal levels (in par-
lifestyle and treatments at the individual level ticular, children, adolescents, and young adults)
(Table 2-4). as they age.
— Healthcare systems approaches that encour- • The metrics with the greatest potential for
age, facilitate, and reward efforts by provid- improvement in the United States are health
ers to improve health behaviors and health behaviors, including diet quality, PA, and body
factors (Table 2-5). weight. However, each of the 7 cardiovascular
— Population approaches that target lifestyle health metrics can be improved and deserves
and treatments in schools or workplaces, major focus.
Table 2-1. Definitions of Poor, Intermediate, and Ideal Cardiovascular Health for Each Metric in the AHA 2020 Goals
Level of Cardiovascular Health for Each Metric
Poor Intermediate Ideal
Current smoking
Adults ≥20 y of age Yes Former ≥12 mo Never or quit >12 mo
Children 12–19 y of age* Tried during the prior 30 d … Never tried; never smoked whole
cigarette
BMI†
Adults ≥20 y of age ≥30 kg/m2 25–29.9 kg/m2 <25 kg/m2
Children 2–19 y of age >95th percentile 85th–95th percentile <85th percentile

Physical activity
Adults ≥20 y of age None 1–149 min/wk moderate or ≥150 min/wk moderate or ≥75
1–74 min/wk vigorous or min/wk vigorous or ≥150 min/wk
moderate + 2× vigorous
1–149 min/wk moderate + 2×
vigorous
Children 12–19 y of age None >0 and <60 min of moderate or ≥60 min of moderate or vigorous
vigorous every day every day
Healthy diet pattern, No. of components (AHA diet score)‡
Adults ≥20 y of age <2 (0–39) 2–3 (40–79) 4–5 (80–100)
Children 5–19 y of age <2 (0–39) 2–3 (40–79) 4–5 (80–100)

Total cholesterol, mg/dL
Adults ≥20 y of age ≥240 200–239 or treated to goal <200
Children 6–19 y of age ≥200 170–199 <170
Blood pressure
Adults ≥20 y of age SBP ≥140 mm Hg or DBP ≥90 mm Hg SBP 120–139 mm Hg or DBP 80–89 <120 mm Hg/<80 mm Hg
mm Hg or treated to goal
Children 8–19 y of age >95th percentile 90th–95th percentile or SBP <90th percentile
≥120 mm Hg or DBP ≥80 mm Hg
Fasting plasma glucose, mg/dL
Adults ≥20 y of age ≥126 100–125 or treated to goal <100

Children 12–19 y of age ≥126 100–125 <100
AHA indicates American Heart Association; BMI, body mass index; DBP, diastolic blood pressure; ellipses (…), data not available; and SBP, systolic blood pressure.
*Age ranges in children for each metric depend on guidelines and data availability.
†Represents appropriate energy balance, that is, appropriate dietary quantity and physical activity to maintain normal body weight.
‡In the context of a healthy dietary pattern that is consistent with a Dietary Approaches to Stop Hypertension (DASH)–type eating pattern, to consume ≥4.5 cups/d
of fruits and vegetables, ≥2 servings/wk of fish, and ≥3 servings/d of whole grains and no more than 36 oz/wk of sugar-sweetened beverages and 1500 mg/d of
sodium. The consistency of one’s diet with these dietary targets can be described using a continuous AHA diet score, scaled from 0 to 100 (see chapter on Nutrition).
Modified from Lloyd-Jones et al.1 Copyright © 2010, American Heart Association, Inc.

Table 2-2. Prevalence of Ideal Cardiovascular Health and Its Components in the US Population in Selected Age
CLINICAL STATEMENTS
Strata: NHANES 2011 to 2012 and 2013 to 2014

AND GUIDELINES
NHANES Age Age Age Age Age

Cycle 12—19 y, % (SE) ≥20 y, % (SE)* 20–39 y, % (SE) 40–59 y, % (SE) ≥60 y, % (SE)
Ideal cardiovascular health profile (7/7) 2011–2012 0.0 (0.0) 0.0 (0.0) 0.0 (0.0) 0.0 (0.0) 0.0 (0.0)
≥6 Ideal 2011–2012 10.3 (1.7) 4.3 (0.6) 9.1 (1.4) 1.8 (0.4) 0.5 (0.3)
≥5 Ideal 2011–2012 41.3 (2.3) 16.9 (1.0) 32.7 (2.5) 8.9 (1.0) 3.2 (1.1)
Ideal health factors (4/4) 2013–2014 57.7 (2.1) 18.4 (0.9) 32.6 (2.1) 13.1 (1.2) 2.9 (0.5)
Total cholesterol <200 mg/dL 2013–2014 79.7 (0.9) 50.1 (1.5) 71.9 (2.2) 41.9 (1.6) 26.6 (1.8)
SBP <120/DBP <80 mm Hg 2013–2014 88.7 (1.1) 45.4 (0.9) 68.0 (1.6) 40.2 (2.0) 14.1 (1.1)
Nonsmoker 2013–2014 91.4 (1.4) 77.1 (1.2) 72.6 (1.4) 74.7 (2.1) 87.7 (1.2)
FPG <100 mg/dL and HbA1c <5.7% 2013–2014 87.6 (1.0) 60.8 (1.1) 78.5 (1.3) 57.7 (1.8) 35.4 (1.7)
Ideal health behaviors (4/4) 2011–2012 0.0 (0.0) 0.1 (0.1) 0.0 (0.0) 0.2 (0.1) 0.1 (0.1)
PA at goal 2013–2014 27.7 (1.2) 36.7 (1.1) 45.0 (2.0) 34.2 (1.6) 26.7 (1.5)
Nonsmoker 2013–2014 91.4 (1.4) 77.1 (1.2) 72.6 (1.4) 74.7 (2.1) 87.7 (1.2)
BMI <25 kg/m 2
2013–2014 63.1 (2.4) 29.6 (0.8) 36.3 (1.5) 25.4 (1.4) 25.6 (1.1)
4–5 Diet goals met† 2011–2012 0.0 (0.0) 0.4 (0.1) 0.1 (0.1) 0.2 (0.1) 0.8 (0.2)
F&V ≥4.5 C/d 2011–2012 3.9 (0.7) 12.1 (1.1) 7.9 (1.2) 13.9 (1.5) 17.1 (1.5)
Fish ≥2 svg/wk 2011–2012 10.0 (1.5) 18.5 (1.6) 16.3 (1.4) 18.3 (2.4) 22.5 (2.1)
Sodium <1500 mg/d 2011–2012 0.0 (0.0) 0.6 (0.2) 0.5 (0.3) 1.1 (0.5) 0.4 (0.2)
SSB <36 oz/wk 2011–2012 40.8 (2.4) 55.9 (1.9) 46.5 (2.5) 56.1 (2.0) 72.0 (2.1)
Whole grains ≥3 1-oz svg/d 2011–2012 4.1 (1.4) 7.7 (0.6) 5.7 (0.9) 6.6 (1.0) 12.3 (1.2)
Secondary diet metrics
Nuts/legumes/seeds ≥4 svg/wk 2011–2012 42.1 (2.6) 49.7 (0.9) 47.8 (2.0) 50.9 (1.7) 50.9 (2.1)
Processed meats ≤2 svg/wk 2011–2012 41.2 (2.1) 44.6 (1.4) 43.5 (1.9) 44.8 (2.0) 46.0 (2.3)
SFat <7% total kcal 2011–2012 6.4 (0.9) 10.4 (0.6) 10.1 (0.8) 10.5 (0.9) 11.6 (1.4)
BMI indicates body mass index; DBP, diastolic blood pressure; FPG, fasting plasma glucose; F&V, fruits and vegetables; HbA1c, hemoglobin A1c (glycosylated
hemoglobin); NHANES, National Health and Nutrition Examination Survey; PA, physical activity; SBP, systolic blood pressure; SFat, saturated fat; SSB, sugar-sweetened
beverages; and svg, servings.
*Standardized to the age distribution of the 2000 US standard population.
†Scaled to 2000 kcal/d and in the context of appropriate energy balance and a DASH (Dietary Approaches to Stop Hypertension)-type eating pattern.
Table 2-3. Reduction in BP Required to Increase

Prevalence of Ideal BP Among Adults ≥20 Years Old:
NHANES 2013 to 2014
%
Percent BP ideal among adults, 2013–2014 45.4
20% Relative increase 54.4
Percent whose BP would be ideal if population mean BP were lowered by*
2 mm Hg 49.5
3 mm Hg 51.7
4 mm Hg 52.9
5 mm Hg 55.3
Reduction in BP=(observed average systolic BP−X mm Hg) and (observed

average diastolic BP−X mm Hg). BP indicates blood pressure; and NHANES,
National Health and Nutrition Examination Survey.
*Standardized to the age distribution of the 2000 US standard population.

Table 2-4. Evidence-Based Individual Approaches for Table 2-5. Evidence-Based Healthcare Systems
CLINICAL STATEMENTS
Improving Health Behaviors and Health Factors in the Approaches to Support and Facilitate Improvements in
AND GUIDELINES
Clinic Setting Health Behaviors and Health Factors35-37
Set specific, shared, proximal goals (Class I; Level of Evidence A): Set Electronic systems for scheduling and tracking initial visits and regular
specific, proximal goals with the patient, including a personalized plan to follow-up contacts for behavior change and treatments
achieve the goals (eg, over the next 3 mo, increase fruits by 1 serving/d,
Electronic medical records systems to help assess, track, and report on
reduce smoking by half a pack/d, or walk 30 min 3 times/wk).
specific health behaviors (diet, PA, tobacco, body weight) and health
Establish self-monitoring (Class I; Level of Evidence A): Develop a strategy factors (BP, cholesterol, glucose), as well as to provide feedback and the
for self-monitoring, such as a dietary or physical activity diary or Web- latest guidelines to providers
based or mobile applications.
Practical paper or electronic toolkits for assessment of key health behaviors
Schedule regular follow-up (Class I; Level of Evidence A): Schedule regular and health factors, including during, before, and after provider visits
follow-up (in person, telephone, written, and/or electronic), with clear
Electronic systems to facilitate provision of feedback to patients on their
frequency and duration of contacts, to assess success, reinforce progress,
progress during behavior change and other treatment efforts
and set new goals as necessary.
Education and ongoing training for providers on evidence-based behavior
Provide feedback (Class I; Level of Evidence A): Provide feedback on
change strategies, as well as the most relevant behavioral targets,
progress toward goals, including using in-person, telephone, and/or
including training on relevant ethnic and cultural issues
electronic feedback.
Integrated systems to provide coordinated care by multidisciplinary teams
Increase self-efficacy (Class I; Level of Evidence A): Increase the patient’s
of providers, including physicians, nurse practitioners, dietitians, PA
perception that they can successfully change their behavior.*
specialists, and social workers
Use motivational interviewing† (Class I; Level of Evidence A): Use
Reimbursement guidelines and incentives that reward efforts to change
motivational interviewing when patients are resistant or ambivalent about
health behaviors and health factors. Restructuring of practice goals and
behavior change.
quality benchmarks to incorporate health behavior (diet, PA, tobacco,
Provide long-term support (Class I; Level of Evidence B): Arrange long-term body weight) and health factor (BP, cholesterol, glucose) interventions and
support from family, friends, or peers for behavior change, such as in other targets for both primary and secondary prevention
workplace, school, or community-based programs.
BP indicates blood pressure; and PA, physical activity.
Use a multicomponent approach (Class I; Level of Evidence A): Combine
≥2 of the above strategies into the behavior change efforts.
*Examples of approaches include mastery experiences (set a reasonable,

proximal goal that the person can successfully achieve); vicarious experiences
(have the person see someone with similar capabilities performing the behavior,
such as walking on a treadmill or preparing a healthy meal); physiological
feedback (explain to the patient when a change in their symptoms is related to
worse or improved behaviors); and verbal persuasion (persuade the person that
you believe in their capability to perform the behavior).
†Motivational interviewing represents use of individual counseling to explore
and resolve ambivalence toward changing behavior. Major principles include
fostering the person’s own awareness and resolution of their ambivalence, as
well as their own self-motivation to change, in a partnership with the counselor
or provider.
Modified from Artinian et al.34 Copyright © 2010, American Heart
Association, Inc.

Table 2-6. Summary of Evidence-Based Population Approaches for Improving Diet, Increasing Physical Activity,
CLINICAL STATEMENTS
and Reducing Tobacco Use*

AND GUIDELINES
Diet
Media and education Sustained, focused media and educational campaigns, using multiple modes, for increasing consumption of specific healthful
foods or reducing consumption of specific less healthful foods or beverages, either alone (Class IIa; Level of Evidence B) or as
part of multicomponent strategies (Class I; Level of Evidence B)†‡§
On-site supermarket and grocery store educational programs to support the purchase of healthier foods (Class IIa; Level
of Evidence B)†
Labeling and information Mandated nutrition facts panels or front-of-pack labels/icons as a means to influence industry behavior and product
formulations (Class IIa; Level of Evidence B)†
Economic incentives Subsidy strategies to lower prices of more healthful foods and beverages (Class I; Level of Evidence A)†
Tax strategies to increase prices of less healthful foods and beverages (Class IIa; Level of Evidence B)†
Changes in both agricultural subsidies and other related policies to create an infrastructure that facilitates production,
transportation, and marketing of healthier foods, sustained over several decades (Class IIa; Level of Evidence B)†
Schools Multicomponent interventions focused on improving both diet and physical activity, including specialized educational
curricula, trained teachers, supportive school policies, a formal physical education program, healthy food and beverage
options, and a parental/family component (Class I; Level of Evidence A)†
School garden programs, including nutrition and gardening education and hands-on gardening experiences (Class IIa; Level
of Evidence A)†
Fresh fruit and vegetable programs that provide free fruits and vegetables to students during the school day (Class IIa; Level
of Evidence A)†
Workplaces Comprehensive worksite wellness programs with nutrition, physical activity, and tobacco cessation/prevention components
(Class IIa; Level of Evidence A)†
Increased availability of healthier food/beverage options and/or strong nutrition standards for foods and beverages
served, in combination with vending machine prompts, labels, or icons to make healthier choices (Class IIa; Level of
Evidence B)†
Local environment Increased availability of supermarkets near homes (Class IIa; Level of Evidence B)†‡‖
Restrictions and mandates Restrictions on television advertisements for less healthful foods or beverages advertised to children (Class I; Level of
Evidence B)†
Restrictions on advertising and marketing of less healthful foods or beverages near schools and public places frequented by
youths (Class IIa; Level of Evidence B)†
General nutrition standards for foods and beverages marketed and advertised to children in any fashion, including
on-package promotion (Class IIa; Level of Evidence B)†
Regulatory policies to reduce specific nutrients in foods (eg, trans fats, salt, certain fats) (Class I; Level of Evidence B)†§
Physical activity
Labeling and information Point-of-decision prompts to encourage use of stairs (Class IIa; Level of Evidence A)†
Economic incentives Increased gasoline taxes to increase active transport/commuting (Class IIa; Level of Evidence B)†
Schools Multicomponent interventions focused on improving both diet and physical activity, including specialized educational
curricula, trained teachers, supportive school policies, a formal physical education program, serving of healthy food and
beverage options, and a parental/family component (Class IIa; Level of Evidence A)†
Increased availability and types of school playground spaces and equipment (Class I; Level of Evidence B)†
Increased number of physical education classes, revised physical education curricula to increase time in at least
moderate activity, and trained physical education teachers at schools (Class IIa; Level of Evidence A/Class IIb; Level of
Evidence A¶)†
Regular classroom physical activity breaks during academic lessons (Class IIa; Level of Evidence A)†§
Physical activity
Workplaces Comprehensive worksite wellness programs with nutrition, physical activity, and tobacco cessation/prevention components
Structured worksite programs that encourage activity and also provide a set time for physical activity during work hours
(Class IIa; Level of Evidence B)†
Improving stairway access and appeal, potentially in combination with “skip-stop” elevators that skip some floors (Class IIa;
Level of Evidence B)†
Adding new or updating worksite fitness centers (Class IIa; Level of Evidence B)†
(Continued )

Table 2-6. Continued
CLINICAL STATEMENTS
Physical activity Continued
AND GUIDELINES
Local environment Improved accessibility of recreation and exercise spaces and facilities (eg, building of parks and playgrounds, increasing
operating hours, use of school facilities during nonschool hours) (Class IIa; Level of Evidence B)†
Improved land-use design (eg, integration and interrelationships of residential, school, work, retail, and public spaces) (Class
IIa; Level of Evidence B)†
Improved sidewalk and street design to increase active commuting (walking or bicycling) to school by children (Class IIa; Level
of Evidence B)†
Improved traffic safety (Class IIa; Level of Evidence B)†
Improved neighborhood aesthetics (to increase activity in adults) (Class IIa; Level of Evidence B)†
Improved walkability, a composite indicator that incorporates aspects of land-use mix, street connectivity, pedestrian
infrastructure, aesthetics, traffic safety, and crime safety (Class IIa; Level of Evidence B)†
Smoking
Media and education Sustained, focused media and educational campaigns to reduce smoking, either alone (Class IIa; Level of Evidence B) or as
part of larger multicomponent population-level strategies (Class I; Level of Evidence A)†
Labeling and information Cigarette package warnings, especially those that are graphic and health related (Class I; Level of Evidence B)†‡§
Economic incentives Higher taxes on tobacco products to reduce use and fund tobacco control programs (Class I; Level of Evidence A)†‡§
Schools and workplaces Comprehensive worksite wellness programs with nutrition, physical activity, and tobacco cessation/prevention components
Local environment Reduced density of retail tobacco outlets around homes and schools (Class I; Level of Evidence B)†
Development of community telephone lines for cessation counseling and support services (Class I; Level of Evidence A)†
Restrictions and mandates Community (city, state, or federal) restrictions on smoking in public places (Class I; Level of Evidence A)†
Local workplace-specific restrictions on smoking (Class I; Level of Evidence A)†‡§
Stronger enforcement of local school-specific restrictions on smoking (Class IIa; Level of Evidence B)†
Local residence-specific restrictions on smoking (Class IIa; Level of Evidence B)†§
Partial or complete restrictions on advertising and promotion of tobacco products (Class I; Level of Evidence B)†
*The specific population interventions listed here are either a Class I or IIa recommendation with a Level of Evidence grade of either A or B.
†At least some evidence from studies conducted in high-income Western regions and countries (eg, North America, Europe, Australia, New Zealand).
‡At least some evidence from studies conducted in high-income non-Western regions and countries (eg, Japan, Hong Kong, South Korea, Singapore).
§At least some evidence from studies conducted in low- or middle-income regions and countries (eg, Africa, China, Pakistan, India).
‖Based on cross-sectional studies only; only 2 longitudinal studies have been performed, with no significant relations seen.
¶Class IIa; Level of Evidence A for improving physical activity; Class IIb; Level of Evidence B for reducing adiposity.
Reprinted from Mozaffarian et al.35 Copyright © 2012, American Heart Association, Inc.

CLINICAL STATEMENTS
AND GUIDELINES
Chart 2-1. Incidence of cardiovascular disease according to the number of ideal health behaviors and health
factors.
Reprinted from Folsom et al12 with permission from the American College of Cardiology Foundation. Copyright © 2011, the
American College of Cardiology Foundation.
Chart 2-2. Prevalence (unadjusted) estimates of poor, intermediate, and ideal cardiovascular health for each of the 7
metrics of cardiovascular health in the American Heart Association 2020 goals, among US children aged 12 to 19 years.
*Healthy Diet Score reflects 2011 to 2012 National Health and Nutrition Examination Survey (NHANES).
Source: National Center for Health Statistics, NHANES 2013 to 2014.

CLINICAL STATEMENTS
AND GUIDELINES
Chart 2-3. Prevalence (unadjusted) estimates of poor, intermediate, and ideal cardiovascular health for each of the
7 metrics of cardiovascular health in the American Heart Association 2020 goals among US adults aged 20 to 49
and ≥50 years.
*Healthy Diet Score reflects 2011 to 2012 National Health and Nutrition Examination Survey (NHANES).
Source: National Center for Health Statistics, NHANES 2013 to 2014.
Chart 2-4. Proportion (unadjusted) of US children aged 12 to 19 years meeting different numbers of criteria for
ideal cardiovascular health, overall and by sex.
Source: National Center for Health Statistics, National Health and Nutrition Examination Survey 2011 to 2012.

CLINICAL STATEMENTS
AND GUIDELINES
Chart 2-5. Age-standardized prevalence estimates of US adults aged ≥20 years meeting different numbers of crite-
ria for ideal cardiovascular health, overall and by age and sex subgroups.
Chart 2-6. Age-standardized prevalence estimates of US adults aged ≥20 years meeting different numbers of crite-
ria for ideal cardiovascular health, overall and in selected race subgroups.

CLINICAL STATEMENTS
AND GUIDELINES
Chart 2-7. Prevalence of meeting ≥5 criteria for ideal cardiovascular health among US adults aged ≥20 years
(age standardized) and US children aged 12 to 19 years, overall and by sex.
Source: National Center for Health Statistics, National Health and Nutrition Examination Survey 2007 to 2008 and 2011 to
2012.
Chart 2-8. Prevalence of meeting ≥5 criteria for ideal cardiovascular health among US adults aged ≥20 years (age
standardized) and US children aged 12 to 19 years, by race/ethnicity.
NH indicates non-Hispanic.

CLINICAL STATEMENTS
AND GUIDELINES
Chart 2-9. Age-standardized prevalence estimates of US adults meeting different numbers of criteria for ideal and
poor cardiovascular health for each of the 7 metrics of cardiovascular health in the American Heart Association
2020 goals among US adults aged ≥20 years.

CLINICAL STATEMENTS
AND GUIDELINES
Chart 2-10. Age-standardized cardiovascular health status by US states, BRFSS, 2009.

A, Age-standardized prevalence of population with ideal cardiovascular health by states. B, Age-standardized percentage
of population with 0 to 2 cardiovascular health metrics by states. C, Age-standardized mean score of cardiovascular health
metrics by states.
BRFSS indicates Behavioral Risk Factor Surveillance System.
Reprinted from Fang et al30 with permission. Copyright © 2013, The Authors. This is an Open Access article distributed under
the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any
medium, provided the original author and source are credited.

CLINICAL STATEMENTS
AND GUIDELINES
Chart 2-11. Trends in prevalence (unadjusted) of meeting criteria for ideal cardiovascular health for each of the
7 metrics among US children aged 12 to 19 years.
Data for the Healthy Diet Score, based on a 2-day average intake, were only available for the 2003 to 2004, 2005 to 2006,
2007 to 2008, 2009 to 2010, and 2011 to 2012 NHANES cycles at the time of this analysis.
NHANES indicates National Health and Nutrition Examination Survey.
*Because of changes in the physical activity questionnaire between different cycles of NHANES, trends over time for this indicator
should be interpreted with caution, and statistical comparisons should not be attempted.
Source: National Center for Health Statistics, NHANES 1999 to 2000 through 2013 to 2014.
Chart 2-12. Age-standardized trends in prevalence of meeting criteria for ideal cardiovascular health for each of
the 7 metrics among US adults aged ≥20 years.
Data for the Healthy Diet Score, based on a 2-day average intake, were only available for the 2003 to 2004, 2005 to 2006,
2007 to 2008, 2009 to 2010, and 2011 to 2012 NHANES cycles at the time of this analysis.
*Because of changes in the physical activity questionnaire between different cycles of NHANES, trends over time for this
indicator should be interpreted with caution, and statistical comparisons should not be attempted.
Source: National Center for Health Statistics, NHANES 1999 to 2000 through 2013 to 2014.

CLINICAL STATEMENTS
AND GUIDELINES
Chart 2-13. Prevalence of ideal, intermediate, and poor cardiovascular health metrics in 2006 (American Heart
Association 2020 Strategic Impact Goals baseline year) and 2020 projections assuming current trends continue.
The 2020 targets for each cardiovascular health metric assume a 20% relative increase in ideal cardiovascular health prevalence
metrics and a 20% relative decrease in poor cardiovascular health prevalence metrics for males and females.
Reprinted from Huffman et al.31 Copyright © 2012, American Heart Association, Inc.
from the American Heart Association. Circulation. 2013;127:2233–2249.

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2016;91:649–670. doi: 10.1016/j.mayocp.2016.01.019. cident end-stage renal disease in a community-based longitudinal cohort
10. González HM, Tarraf W, Rodríguez CJ, Gallo LC, Sacco RL, Talavera GA, study: the Kailuan Study. BMJ Open. 2016;6:e012486. doi: 10.1136/
Heiss G, Kizer JR, Hernandez R, Davis S, Schneiderman N, Daviglus ML, bmjopen-2016-012486.
Kaplan RC. Cardiovascular health among diverse Hispanics/Latinos: 27a. Fan W, Lee H, Lee A, Kieu C, Wong ND. Association of lung function and
Hispanic Community Health Study/Study of Latinos (HCHS/SOL) results. chronic obstructive pulmonary disease with American Heart Association
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JE, Das S, Kociol R, de Ferranti S, Mohebali D, Mwasongwe S, Tucker KL, 27b. Olson NC, Cushman M, Judd SE, McClure LA, Lakoski SG, Folsom AR,
Murthy VL, Shah RV. Ideal cardiovascular health, cardiovascular remodel- Safford MM, Sakai MA. American Heart Association’s Life’s Simple 7
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2017;10:e003682. doi: 10.1161/CIRCHEARTFAILURE.116.003682. and Racial Differences in Stroke (REGARDS) Study. J Am Heart Assoc.
12. Folsom AR, Yatsuya H, Nettleton JA, Lutsey PL, Cushman M, Rosamond 2015;4:e001494. doi: 10.1161/JAHA.114.001494.
WD; ARIC Study Investigators. Community prevalence of ideal car- 28. Caleyachetty R, Echouffo-Tcheugui JB, Muennig P, Zhu W, Muntner P,
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2011;57:1690–1696. doi: 10.1016/j.jacc.2010.11.041. 2015;191:296–300. doi: 10.1016/j.ijcard.2015.05.007.
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burden of diseases, injuries, and risk factors. JAMA. 2013;310:591–606. Guzman H, Younus A, Ogunmoroti O, Feldman T, Agatston AS, Veledar
doi: 10.1001/jama.2013.13805. E, Katzen B, Calitz C, Sanchez E, Lloyd-Jones DM, Nasir K. Favorable car-
14. Yang Q, Cogswell ME, Flanders WD, Hong Y, Zhang Z, Loustalot F, diovascular health is associated with lower health care expenditures and
Gillespie C, Merritt R, Hu FB. Trends in cardiovascular health metrics and resource utilization in a large US employee population: the Baptist Health
associations with all-cause and CVD mortality among US adults. JAMA. South Florida Employee Study [published online ahead of print March
2012;307:1273–1283. doi: 10.1001/jama.2012.339. 13, 2017]. Mayo Clin Proc. 2017. doi: 10.1016/j.mayocp.2016.12.026.
15. Fang N, Jiang M, Fan Y. Ideal cardiovascular health metrics and risk https://www.ncbi.nlm.nih.gov/pubmed/28365099.
of cardiovascular disease or mortality: a meta-analysis. Int J Cardiol. 30. Fang J, Yang Q, Hong Y, Loustalot F. Status of cardiovascular
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16. Kulshreshtha A, Vaccarino V, Judd SE, Howard VJ, McClellan WM, Muntner P, Columbia, 2009. J Am Heart Assoc. 2012;1:e005371. doi: 10.1161/
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Stroke. 2013;44:1909–1914. doi: 10.1161/STROKEAHA.111.000352. Cardiovascular health behavior and health factor changes (1988-2008)
17. Wilkins JT, Ning H, Berry J, Zhao L, Dyer AR, Lloyd-Jones DM. Lifetime risk and projections to 2020: results from the National Health and Nutrition
and years lived free of total cardiovascular disease. JAMA. 2012;308:1795– Examination Surveys. Circulation. 2012;125:2595–2602. doi: 10.1161/
1801. doi: 10.1001/jama.2012.14312. CIRCULATIONAHA.111.070722.
18. Folsom AR, Shah AM, Lutsey PL, Roetker NS, Alonso A, Avery CL, 32. Huffman MD, Lloyd-Jones DM, Ning H, Labarthe DR, Guzman Castillo
Miedema MD, Konety S, Chang PP, Solomon SD. American Heart M, O’Flaherty M, Ford ES, Capewell S. Quantifying options for reducing
Association’s Life’s Simple 7: avoiding heart failure and preserving cardiac coronary heart disease mortality by 2020. Circulation. 2013;127:2477–
structure and function. Am J Med. 2015;128:970–976.e2. doi: 10.1016/j. 2484. doi: 10.1161/CIRCULATIONAHA.112.000769.
amjmed.2015.03.027. 33. Bibbins-Domingo K, Chertow GM, Coxson PG, Moran A, Lightwood JM,
19. Robbins JM, Petrone AB, Carr JJ, Pankow JS, Hunt SC, Heiss G, Arnett Pletcher MJ, Goldman L. Projected effect of dietary salt reductions on
DK, Ellison RC, Gaziano JM, Djoussé L. Association of ideal cardiovascular future cardiovascular disease. N Engl J Med. 2010;362:590–599. doi:
health and calcified atherosclerotic plaque in the coronary arteries: the 10.1056/NEJMoa0907355.
National Heart, Lung, and Blood Institute Family Heart Study. Am Heart J. 34. Artinian NT, Fletcher GF, Mozaffarian D, Kris-Etherton P, Van Horn L,
2015;169:371–378.e1. doi: 10.1016/j.ahj.2014.12.017. Lichtenstein AH, Kumanyika S, Kraus WE, Fleg JL, Redeker NS, Meininger
20. Saleem Y, DeFina LF, Radford NB, Willis BL, Barlow CE, Gibbons LW, JC, Banks J, Stuart-Shor EM, Fletcher BJ, Miller TD, Hughes S, Braun
Khera A. Association of a favorable cardiovascular health profile with LT, Kopin LA, Berra K, Hayman LL, Ewing LJ, Ades PA, Durstine JL,
the presence of coronary artery calcification. Circ Cardiovasc Imaging. Houston-Miller N, Burke LE; on behalf of the American Heart Association
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21. Crichton GE, Elias MF, Davey A, Alkerwi A. Cardiovascular health and Interventions to promote physical activity and dietary lifestyle changes
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Howard VJ, Cushman M. The American Heart Association Life’s Simple 35. Mozaffarian D, Afshin A, Benowitz NL, Bittner V, Daniels SR, Franch
7 and incident cognitive impairment: the REasons for Geographic HA, Jacobs DR Jr, Kraus WE, Kris-Etherton PM, Krummel DA, Popkin
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2014;3:e000635. doi: 10.1161/JAHA.113.000635. Council on Epidemiology and Prevention, Council on Nutrition, Physical
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24. España-Romero V, Artero EG, Lee DC, Sui X, Baruth M, Ruiz JR, Pate RR, Blair American Heart Association. Circulation. 2012;126:1514–1563. doi:
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JAHA.114.001322. 2009;123(suppl 5):S301–S307. doi: 10.1542/peds.2008-2780I.

3. SMOKING/TOBACCO USE Other forms of tobacco use are becoming increas-
CLINICAL STATEMENTS
ingly common. Electronic cigarette (e-cigarette) use,
See Table 3-1 and Charts 3-1 through 3-8
AND GUIDELINES
which involves inhalation of a vaporized liquid that
includes nicotine, solvents, and flavoring (“vaping”),
has risen dramatically, particularly among young peo-
ple. The variety of e-cigarette–related products has
Tobacco use is one of the leading preventable causes increased exponentially, giving rise to the more general
of death in the United States and globally.1 Tobacco term electronic nicotine delivery systems.5 Use of ciga-
smoking, the most common form of tobacco use, is rillos and other mass market cigars, hookahs, and water
a major risk factor for CVD and stroke.2 The AHA has pipes also has become increasingly common in recent
identified never having tried smoking or never having years. Thus, each section below will address the most
smoked a whole cigarette (for children) and never hav- recent statistical estimates for combustible cigarettes,
ing smoked or having quit >12 months ago (for adults) electronic nicotine delivery systems, and other forms of
as 1 of the 7 components of ideal cardiovascular health tobacco use if such estimates are available.
in Life’s Simple 7.3 Life’s Simple 7 uses NHANES data.
According to the most recently available NHANES data,
which sampled from 2013 to 2014, 91.4% of adoles- Prevalence
cents and 77.1% of adults met these criteria. Unless (See Charts 3-1 through 3-5)
otherwise stated, throughout the rest of the chapter
we will report tobacco use and smoking estimates from Youth
the NSDUH1 for adolescents (12–17 years of age) and • According to the NSDUH 2015 data, for adoles-
from the NHIS for adults (≥18 years of age), because cents aged 12 to 17 years1:
— 6.0% (1 492 000) used tobacco products,
these data sources have more recent data.4
and 4.2% (1 039 000) smoked cigarettes in
the past month.
Abbreviations Used in Chapter 3 — 1.5% (367 000) used smokeless tobacco in
ACS acute coronary syndrome the past month.
AHA American Heart Association — Of adolescents who smoked, 20%
AIAN American Indian or Alaska Native
(208 000) smoked cigarettes daily, and 5%
AMI acute myocardial infarction

(52 000) smoked ≥1 pack per day in the
CDC Centers for Disease Control and Prevention past month.
CHD coronary heart disease — 2.1% (517 000) were current cigar smokers,
CI confidence interval 0.3% (84 000) were current pipe tobacco
CVD cardiovascular disease smokers, and 1.5% (367 000) used smoke-
DALY disability-adjusted life-year
less tobacco.
DM diabetes mellitus
EAGLES Study Evaluating the Safety and Efficacy of Varenicline and
• In 2015, tobacco use within the past month for
Bupropion for Smoking Cessation in Subjects With and youth 12 to 17 years of age varied modestly
Without a History of Psychiatric Disorders by region: 6.2% in the Northeast, 7.0% in the
EVITA Evaluation of Varenicline in Smoking Cessation for Patients
Midwest, 6.0% in the South, and 4.9% in the
Post-Acute Coronary Syndrome
GBD Global Burden of Disease West.1
GU Guam • In 2015, 21.6% of adults aged 18 to 20 years
HD heart disease were current cigarette smokers compared with
HIV human immunodeficiency virus 8.7% of adolescents aged 16 to 17 years.1
HR hazard ratio
• In most states, the minimum age for purchasing
NH non-Hispanic
NHANES National Health and Nutrition Examination Survey
tobacco products is 18 years.
NHIS National Health Interview Survey
Adults
NNT number needed to treat
NSDUH National Survey on Drug Use and Health • According to the NHIS 2015 data, among adults
PAF population attributable fraction ≥18 years of age6:
PAR population attributable risk — 15.1% of adults (36.5 million) are current
PR Puerto Rico smokers.
RCT randomized controlled trial
— 16.7% of males and 13.6% of females are
RR relative risk
SAH subarachnoid hemorrhage
current smokers.
SBP systolic blood pressure — 13% of those 18 to 24 years of age, 17.7%
UI uncertainty interval of those 25 to 44 years of age, 17.0% of
VI Virgin Islands those 45 to 64 years of age, and 8.4% of
WHO World Health Organization those ≥65 years old are current smokers.

— 21.9% of American Indians or Alaska — The number of new smokers 12 to 17 years

CLINICAL STATEMENTS
Natives, 16.7% of blacks, 7% of Asians (with of age (823 000) was down from 2002 (1.3
AND GUIDELINES
the highest rates in Vietnamese [16.3%] million); new smokers 18 to 25 years of age
and Filipinos [12.6%]), 10.1% of Hispanics increased from ≈600 000 in 2002 to 1.05
(highest rates in Puerto Ricans [28.5%] and million in 2015.
Cubans [19.8%]), and 16.6% of whites are • In the NHIS4:
current smokers. — In 2015, the average age for initiation of
— 26.1% of people below the poverty level are cigarette use was 17.9 years.
current smokers.
• 20.6% of lesbian/gay/bisexual/transgender indi-
viduals were current smokers.7 Lifetime Risk and Cumulative Incidence
• By region, the prevalence of current cigarette
smokers was highest in the Midwest (18.7%) and
in Youth (12 to 17 Years Old) in 2015
lowest in the West (12.4%).7 (NSDUH Data)
• In 2009, 42.4% of adults with HIV receiving med- • Per NSDUH data for individuals aged 12 to 17
ical care were current smokers.8 years, overall the lifetime use of tobacco products
• Using data from BRFSS 2015, the state with the declined from 18.5% to 17.3%, with lifetime cig-
highest age-adjusted percentage of current cigarette use declining from 14.2% to 13.2% during
arette smokers was West Virginia (17.3%). The the same time period (P<0.05 for both).1
state with the lowest age-adjusted percentage of • The lifetime use of tobacco products among
current cigarette smokers was Utah (9.0%) (Chart adolescents 12 to 17 years old varied by the
3-5).9 following1:
• In 2015, smoking prevalence was higher among — Sex: Lifetime use was higher among boys
adults ≥18 years of age who reported having (19.1%) than girls (15.3%).
a disability or activity limitation (21.5%) than — Race/ethnicity: Lifetime use was high-
among those reporting no disability or limitation est among whites (19.9%), followed by
(13.8%).7 American Indians or Alaskan Natives (19.6%),
— 40% of males and 34% of females with Hispanics or Latinos (14.5%), African
mental illness were current smokers.7 Americans (13.8%), and Asians (7.7%).
— Geographic division: The highest lifetime use
• In 2012 to 2013, among females 15 to 44 years
was observed in the South (East South Central
of age, past-month cigarette use was lower
22.8%), and the lowest was observed in the
among those who were pregnant (15.4%) than
among those who were not pregnant (24.0%). Pacific West (13.0%).
Rates were higher among females 18 to 25 years
of age (21.0% versus 26.2% for pregnant and Adults
nonpregnant females, respectively) than among
• According to NSDUH data, the lifetime use of
women 26 to 44 years of age (11.8% versus
tobacco products in individuals aged ≥18 years
25.4%, respectively). Smoking declines by preg-
declined significantly (P<0.01) between 2014
nancy trimester, from 19.9% of females 15 to 44
and 2015, from 71.1% to 68.7%, with cigarette
years of age in the first trimester of pregnancy to
use declining in the same interval from 65.9% to
12.8% in the third trimester (NSDUH).10
63.1% (both P<0.01).1 Similar to the patterns in
youth, lifetime risk of tobacco products varied by
Incidence demographic factors:
• According to 2015 NSDUH1: — Sex: Lifetime use was higher in men (78.1%)
— Approximately 1.96 million people ≥12 years than women (60.0%).
of age smoked cigarettes for the first time — Race/ethnicity: Lifetime use was high-
within the past 12 months, down from 2.3 est in American Indians or Alaskan Natives
million in 2012. The 2015 estimate aver- (75.9%) and whites (75.9%), followed by
ages out to ≈5390 new cigarette smokers blacks (58.4%), Native Hawaiian or Other
every day. Of new smokers in 2015, 823 000 Pacific Islander (56.8%), Hispanics or Latinos
(42.1%) were 12 to 17 years old, 762 000 (56.7%), and Asians (37.9%).
(39%) were 18 to 20 years old, and 287 000 — Geographic division: The highest lifetime
(14.7%) were 21 to 25 years old, and only use was observed in the South (East South
84 000 (4.3%) were ≥26 years when they Central 19.8%), and the lowest was observed
first smoked cigarettes. in New England (10.6%).

• In 2015, the lifetime use of smokeless tobacco for hypertension and high cholesterol), is a contributing
CLINICAL STATEMENTS
adults ≥18 years of age was 17.4%. factor in the sharp decline in the HD death rate during
AND GUIDELINES
• Lifetime tobacco use for people with psychiatric this period.17
diagnoses was 56.1%, 55.6%, and 70.1% in • On the basis of weighted NHIS data, the current
patients with mood disorders, anxiety disorders, smoking status among 18- to 24-year-old men
and schizophrenia, respectively.11 declined 46.5%, from 28.0% in 2005 to 15.0%
in 2015, and for 18- to 24-year-old women,
smoking declined 47.0%, from 20.7% to 11.0%,
Mortality over the same time period.7 On the basis of age-
• Tobacco use is the largest preventable cause adjusted estimates in 2015, among people ≥65
of death in the United States, killing >480 000 years of age, 9.7% of men and 8.3% of women
Americans per year; 41 000 of these deaths were were current smokers.
attributed to secondhand smoke exposure.12 • From 2005 to 2015, adjusted prevalence rates for
• Overall mortality among US smokers is 3 times tobacco use in individuals with serious psycholog-
higher than that for never-smokers.13 ical distress (according to the Kessler Scale) went
• On average, male smokers die 13.2 years earlier from 41.9% to 40.6%, which represents a non-
than male nonsmokers, and female smokers die significant 3.1% decline; however, rates for peo-
14.5 years earlier than female nonsmokers.2 ple without serious psychological stress declined
• Increased CVD mortality risks persist for older significantly, from 20.3% to 14.0%.7
(≥60 years old) smokers as well. A meta-analysis
comparing CVD risks in 503 905 cohort partici-
pants ≥60 years of age reported an HR for car-
Cardiovascular Health Impact
diovascular mortality of 2.07 (95% CI, 1.82–2.36) • A 2010 report of the US Surgeon General on how
compared with never-smokers and 1.37 (95% CI, tobacco causes disease summarized an extensive
1.25–1.49) compared with former smokers.14 body of literature on smoking and CVD and the
• In a sample of Native Americans (Strong Heart mechanisms through which smoking is thought
Study), among whom the prevalence of tobacco to cause CVD.12 There is a sharp increase in CVD
use is highest in the United States, the PAR for risk with low levels of exposure to cigarette
smoke, including secondhand smoke, and a less
total mortality was 18.4% for males and 10.9%

for females.15 rapid further increase in risk as the number of cig-
• Since the first report on the dangers of smoking arettes per day increases. Similar health risks for
was issued by the US Surgeon General in 1964, CHD events are reported with regular cigar smok-
tobacco control efforts have contributed to a ing as well.18
reduction of 8 million premature smoking-attrib- • Smoking is an independent risk factor for CHD
utable deaths.16 and appears to have a multiplicative effect with
• If current smoking trends continue, 5.6 million US the other major risk factors for CHD: high serum
children will die of smoking prematurely during levels of lipids, untreated hypertension, and
adulthood.17 DM.12
• Cigarette smoking and other traditional CHD risk
factors may have a synergistic interaction in HIV-
Secular Trends positive individuals.19
(See Charts 3-2 and 3-3) • A meta-analysis of 75 cohort studies (≈2.4 million
Youth individuals) demonstrated a 25% greater risk for
The percentage of adolescents (12–17 years old) who CHD in female smokers than in male smokers (RR,
1.25; 95% CI, 1.12–1.39).20
reported smoking in the past month declined from
• Cigarette smoking is an independent risk factor
13% in 2003 to 4.2% in 2013.10
for both ischemic stroke and SAH and has a syn-
Adults ergistic effect on other stroke risk factors such as
Since the US Surgeon General’s first report on the SBP21 and oral contraceptive use.22,23
health dangers of smoking, age-adjusted rates of smok- • A meta-analysis comparing pooled data of ≈3.8
ing among adults have declined, from 51% of males million smokers and nonsmokers found a similar
smoking in 1965 to 16.7% in 2015 and from 34% of risk of stroke associated with current smoking in
females in 1965 to 13.6% in 2015, according to NHIS females and males.21
data.4,7 The decline in smoking, along with other fac- • Current smokers have a 2 to 4 times increased risk
tors (including improved treatment and reductions of stroke compared with nonsmokers or those
in the prevalence of risk factors such as uncontrolled who have quit for >10 years.24,25

• Short-term exposure to water pipe smoking is • As of May 5, 2017, the states of California and
CLINICAL STATEMENTS
associated with a significant increase in SBP and Hawaii and at least 230 communities in Arizona,
AND GUIDELINES
heart rate compared with nonsmoking control Arkansas, Illinois, Kansas, Maine, Massachusetts,
subjects,26 but long-term effects remain unclear. Michigan, Minnesota, Mississippi, Missouri, New
Current use of smokeless tobacco is associated Jersey, New York, Ohio, Oregon, Rhode Island,
with an increased risk of CVD events in cigarette and Washington, DC, have set the minimum age
nonsmokers.27 for the purchase of tobacco to 21 years.32,33
• The CVD risks associated with e-cigarette use are • A federal Tobacco 21 law was introduced to the
not known. Congress in September 2015; review and a vote
are pending.
Healthcare Utilization: Hospital
Discharges/Ambulatory Care Visits Awareness, Treatment, and Control
Cost Smoking Cessation
• Each year from 2005 to 2009, US smoking-attrib- • According to NHIS 2015 data, 59.1% of adult
utable economic costs were between $289 billion ever-smokers had stopped smoking.34
and $333 billion, including $133 billion to $176 — The majority (68.0%) of adult smokers
billion for direct medical care of adults and $151 wanted to quit smoking, 55.4% had tried
billion for lost productivity related to premature in the past year, 7.4% had stopped recently,
death.17 and 57.2% had received healthcare provider
• In the United States, cigarette smoking was asso- advice to quit.
ciated with 8.7% of annual aggregated health- — Receiving advice to quit smoking was lower
care spending from 2006 to 2010.28 in uninsured smokers and varied by race,
• In 2014, $9 billion was spent on marketing with a lower prevalence in Asian (34.2%),
cigarettes and smokeless tobacco in the United American Indian/Alaska Native (38.1%),
States.29 and Hispanic (42.2%) smokers than in white
• 258 billion cigarettes were sold in the United smokers (60.2%).
States in 2016, which is a 2.5% decrease from — The period from 2000 to 2015 revealed sig-
nificant increases in the prevalence of smok-
the number sold in 2015.29

• Cigarette prices in the United States have ers who had tried to quit in the past year, had
increased 283% between the early 1980s and stopped recently, had a health professional
2011, in large part because of excise taxes on recommend quitting, or had used cessation
tobacco products. Higher taxes have decreased counseling or medication.
cigarette consumption, which fell from ≈30 mil- — In 2015, less than one third of smokers
lion packs sold in 1982 to ≈14 million packs sold attempting to quit used evidence-based ther-
in 2011.29 apies: 4.7% used counseling and medica-
tion, 6.8% used counseling, and 29.0% used
Smoking Prevention medication (16.6% nicotine patch, 12.5%
Tobacco 21 Laws increase the minimum age of sale for gum/lozenges, 2.4% nicotine spray/inhaler,
tobacco products from 18 to 21 years old. 2.7% bupropion, and 7.9% varenicline).
• Such legislation would likely reduce the rates • Smoking cessation reduces the risk of cardiovas-
of smoking during adolescence, a time during cular morbidity and mortality for smokers with
which the majority of smokers start smoking, and without CHD.
by limiting access, because most people who — There is no convincing evidence to date that
buy cigarettes for adolescents are <21 years of smoking fewer cigarettes per day reduces
age.30 the risk of CVD, although in several studies,
• In several towns where Tobacco 21 laws have a dose-response relationship has been seen
been enacted, 47% reductions in smoking preva- among current smokers between the num-
lence among high school students have been ber of cigarettes smoked per day and CVD
reported.30 incidence.12
• Furthermore, the Institute of Medicine estimates — Quitting smoking at any age significantly
that a nationwide Tobacco 21 law would result lowers mortality from smoking-related dis-
in 249 000 fewer premature deaths, 45 000 fewer eases, and the risk declines more the longer
lung cancer deaths, and 4.2 million fewer lost life- the time since quitting smoking.35 Cessation
years among Americans born between 2010 and appears to have both short-term (weeks to
2019.31 months) and long-term (years) benefits for

lowering CVD risk. Overall, CVD risk appears • Despite states having collected $25.6 billion in
CLINICAL STATEMENTS
to approach that of nonsmokers after ≈10 2012 from the 1998 Tobacco Master Settlement
AND GUIDELINES
years of cessation. Agreement and tobacco taxes, <2% of those
— Smokers who quit smoking at 25 to 34 years funds are spent on tobacco prevention and cessa-
of age gained 10 years of life compared with tion programs.43
those who continued to smoke. Those aged
35 to 44 years gained 9 years and those aged
45 to 54 years gained 6 years of life, on aver-
Electronic Cigarettes
age, compared with those who continued to (See Charts 3-6 and 3-7)
smoke.13 • Electronic nicotine delivery systems, more com-
• Cessation medications (including sustained- monly called electronic cigarettes or e-cigarettes,
release bupropion, varenicline, and nicotine gum, are battery-operated devices that deliver nicotine,
lozenge, nasal spray, and patch) are effective for flavors, and other chemicals to the user in an
helping smokers quit.36 aerosol. Although e-cigarettes were introduced
• EVITA was an RCT that examined the efficacy less than a decade ago, there are currently >450
of varenicline versus placebo for smoking ces- e-cigarette brands on the market, and sales in the
sation among smokers who were hospitalized United States were projected to be $2 billion in
for ACS. At 24 weeks, rates of smoking absti- 2014.44
nence and reduction were significantly higher • Teenagers are increasingly trying e-cigarettes.
among patients randomized to varenicline. Point- According to the National Youth Tobacco Survey,
prevalence abstinence rates were 47.3% in the in 2015, e-cigarettes were the most commonly
varenicline group and 32.5% in the placebo used tobacco products in youth: in the prior
group (P=0.012; NNT=6.8). Continuous absti- 30 days, 5.3% of middle school and 16.0% of
nence rates and reduction rates (≥50% of daily high school students endorsed use (Charts 3-3
cigarette consumption) were also higher in the and 3-4).45 In 2015, ever use of e-cigarettes was
varenicline group.37 reported by 13.5% of middle school students and
• The EAGLES trial demonstrated efficacy and 37.7% of high school students,46 which was a
safety of 12 weeks of varenicline, bupropion, substantial increase from 2011 (1.4% of middle
or nicotine patch in motivated-to-quit smoking
and 4.7% of high school students)47 (Charts 3-6

patients with major depressive disorder, bipolar and 3-7).
disorder, anxiety disorders, posttraumatic stress • In 2014, 18.3 million US middle and high school
disorder, obsessive-compulsive disorder, social students (68.9%) were exposed to e-cigarette
phobia, psychotic disorders including schizophre- advertising.48
nia and schizoaffective disorders, and borderline • Among US adults during 2010 to 2013, aware-
personality disorder. Of note, these participants ness and use of e-cigarettes increased con-
were all clinically stable from a psychiatric per- siderably, and more than one third of current
spective and were believed not to be at high risk cigarette smokers reported ever having used
for self-injury.38 e-cigarettes.49
• Extended use of a nicotine patch (24 weeks com- • According to NHIS 2014 data, among US work-
pared with 8 weeks) has been demonstrated to ing adults, 3.8% (≈5.5 million) currently used
be safe and efficacious in recent randomized clini- e-cigarettes. The use of e-cigarettes was signifi-
cal trials.39 cantly higher among current smokers (16.2%)
• An RCT demonstrated the effectiveness of indi- than among past smokers (4.3%) or never-smok-
vidual- and group-oriented financial incentives for ers (0.5%). Similarly, prevalence was significantly
tobacco abstinence through at least 12 months of higher among males (4.5%), NH whites (4.5%),
follow-up.40 younger adults (18–24 years; 5.1%), individu-
• In addition to medications, smoke-free policies, als without health insurance (5.9%), individuals
increases in tobacco prices, cessation advice with incomes <$35 000, and those residing in the
from healthcare professionals, and quit-lines and Midwest (4.5%).50
other counseling have contributed to smoking • As of June 30, 2017, 46 states, the District of
cessation.41 Columbia, Guam, Puerto Rico, and the US Virgin
• Mass media antismoking campaigns, such as Islands have passed legislation prohibiting the
the CDC’s Tips campaign (Tips From Former sale of e-cigarettes to minors. Four states (Maine,
Smokers), have been shown to reduce smoking- Massachusetts, Michigan, and Pennsylvania) do
attributable morbidity and mortality and are not have any legislation requiring a minimum age
cost-effective.42 restriction on the purchase of e-cigarettes.51

Secondhand Smoke Global Burden of Smoking

CLINICAL STATEMENTS
• Data from the US Surgeon General on the con- (See Table 3-1 and Chart 3-8)
AND GUIDELINES
sequences of secondhand smoke indicate the • Although tobacco use in the United States has
following: been declining, the absolute number of tobacco
— Nonsmokers who are exposed to secondhand users worldwide has climbed steeply.43
smoke at home or at work increase their risk • Based on the GBD synthesis of >2800 data
of developing CHD by 25% to 30%.12 sources, the daily smoking age-standardized
— Short exposures to secondhand smoke can global prevalence of smoking in 2015 was 25.0%
cause blood platelets to become stickier, (95% UI, 24.2%–25.7%) in males and 5.4%
damage the lining of blood vessels, and (95% UI, 5.1%–5.7%) in females. The investiga-
decrease coronary flow velocity reserves, tors estimate that since 1990, smoking rates have
potentially increasing the risk of an AMI.12 declined globally by 28.4% in males and 34.4%
— Exposure to secondhand smoke increases in females.57
the risk of stroke by 20% to 30%, and it is • The GBD 2015 study used statistical models and
associated with increased mortality (adjusted data on incidence, prevalence, case fatality, excess
mortality rate ratio, 2.11) after a stroke.52 mortality, and cause-specific mortality to estimate
▪ A meta-analysis of 23 prospective and disease burden for 315 diseases and injuries in
17 case-control studies of cardiovascular
195 countries and territories. Greenland had the
risks associated with secondhand smoke
highest mortality rates attributable to tobacco
exposure demonstrated 18%, 23%,
(Chart 3-8).58
23%, and 29% increased risks for total
• The number of smokers was estimated to have
mortality, total CVD, CHD, and stroke,
grown from 721 million in 1980 to 967 million in
respectively, in those exposed to second-
2012.59
hand smoke.53
• Worldwide, ≈80% of smokers live in low- and
▪ A meta-analysis of 24 studies demon- middle-income countries.60
strates that secondhand smoke can
• Tobacco smoking (including secondhand smoke)
increase risks for preterm birth by 20%.54
caused an estimated 7.2 million deaths in 2015.
• As of June 30, 2017, 8 states (California,
Among the leading risk factors for death, smok-
Delaware, Hawaii, New Jersey, North Dakota,

Oregon, Utah, and Vermont), the District of ing ranked fifth in DALYs in 109 countries.57
Columbia, and Puerto Rico have passed compre- • The WHO estimated that the economic cost
hensive smoke-free indoor air laws that include of smoking-attributable diseases accounted
e-cigarettes. These laws prohibit smoking and the for $422 billion US dollars, which represented
use of e-cigarettes in indoor areas of private work ≈5.7% of global health expenditures.61 The total
sites, restaurants, and bars.51 economic costs, including both health expendi-
• Pooled data from 17 studies in North America, tures and lost productivity, amounted to approx-
Europe, and Australia suggest that smoke-free imately US $1436 billion, which was roughly
legislation can reduce the incidence of acute cor- equal to 1.8% of the world’s annual gross
onary events by 10%.55 domestic product. The WHO further estimated
• The percentage of the US nonsmoking population that 40% of the expenditures were in developing
with serum cotinine ≥0.05 ng/mL (which indicates countries.
exposure to secondhand smoke) declined from • To help combat the global problem of tobacco
52.5% in 1999 to 2000 to 25.3% in 2011 to 2012, exposure, in 2003 the WHO adopted the
with declines occurring for both children and adults. Framework Convention on Tobacco Control
During 2011 to 2012, the percentage of nonsmok- treaty. From this emerged a set of evidence-based
ers with detectable serum cotinine was 40.6% for policies with the goal of reducing the demand
those 3 to 11 years of age, 33.8% for those 12 to for tobacco, entitled MPOWER. MPOWER poli-
19 years of age, and 21.3% for those ≥20 years of cies outline the following strategies for nations to
age. The percentage was also higher for NH blacks reduce tobacco use: (1) monitor tobacco use and
(46.8%) than for NH whites (21.8%) and Mexican prevention policies; (2) protect individuals from
Americans (23.9%). People living below the pov- tobacco smoke; (3) offer to help with tobacco
erty level (43.2%) and those living in rental hous- cessation; (4) warn about tobacco-related dan-
ing (36.8%) had higher rates of secondhand smoke gers; (5) enforce bans on tobacco advertising; (6)
exposure than their counterparts (21.1% of those raise taxes on tobacco; and (7) reduce the sale
living above the poverty level and 19.0% of those of cigarettes. More than half of all nations have
who owned their homes; NHANES).56 implemented at least 1 MPOWER policy.‍62

Table 3-1. Deaths Caused by Tobacco Smoke Worldwide, by Sex58
CLINICAL STATEMENTS
Males and Females Males Females
AND GUIDELINES
Total number of deaths in 2015, millions 7.2 (6.5 to 7.8) 5.2 (4.7 to 5.7) 1.9 (1.7 to 2.2)
Percent change in total number from 1990 to 2015 21.5 (15.8 to 27.2) 26.4 (20.4 to 32.9) 9.9 (1.2 to 19.1)
Percent change in total number from 2005 to 2015 4.2 (0.9 to 7.6) 6.8 (3.1 to 10.7) -2.3 (-7.5 to 3.7)
Mortality rate per 100 000 in 2015 110.7 (101.0 to 120.3) 177.2 (160.2 to 193.7) 55.2 (48.8 to 61.9)
Percent change in rate from 2005 to 2015 −20.3 (−22.8 to −17.7) −18.9 (−21.7 to −16.0) −25.2 (−29.1 to −20.5)
Percent change in rate from 1990 to 2015 −33.3 (−36.4 to −30.1) −32.8 (−35.8 to −29.5) −38.4 (−43.7 to −33.2)
PAF in 2015, % 12.8 (11.7 to 13.9) 16.9 (15.4 to 18.4) 7.8 (6.9 to 8.7)
Percent change in PAF from 1990 to 2015 4.4 (−0.1 to 8.5) 3.7 (−0.1 to 7.4) −0.4 (−7.9 to 7.0)
Percent change in PAF from 2005 to 2015 0.1 (−2.4 to 2.6) −0.1 (−2.4 to 2.2) −3.0 (−7.4 to 2.2)
Rates are most current data available as of 2015. Rates are per 100 000 people.
PAF indicates population attributable fraction.
Source: Global Burden of Disease Study 2015, Institute of Health Metrics and Evaluation.58
10
9 8.6
2014 2015
8
7
6.3
6
Prevalence (%)
5.4
5.1
4.9 4.8
5 4.6 4.6
4.2
4 3.8 3.8
3 2.6 2.7
2.2
2
1.3
1.1
1
0
Total Male Female NH White NH Black NH AIAN NH Asian Hispanic
Chart 3-1. Prevalence (%) of cigarette use in the past month for adolescents aged 12 to 17 years by sex and race/
ethnicity (NSDUH, 2014 and 2015).
Because of methodological differences among the NSDUH, the Youth Risk Behavior Survey, the National Youth Tobacco Survey,
and other surveys, percentages of cigarette smoking measured by these surveys are not directly comparable. Notably, school-
based surveys may include students who are 18 years old, who are legally permitted to smoke and have higher rates of smoking.
AIAN indicates American Indian or Alaska Native; NH, non-Hispanic; and NSDUH, National Survey on Drug Use and Health.
Data derived from Substance Abuse and Mental Health Services Administration, National Survey on Drug Use and Health.63

CLINICAL STATEMENTS
Males Females
AND GUIDELINES
50 50
40 40
12-17 years
18-44 years
30 30
45-64 years
65 years and over
20 20
10 10
0 0
2003 2009 2015 2003 2009 2015
Chart 3-2. Prevalence (%) of cigarette smoking for adolescents (past month) and adults (current) by sex and age
(NHIS, 2003–2015; NSDUH, 2003–2015).
NSDUH indicates National Survey on Drug Use and Health; and NHIS, National Health Interview Survey.
Data derived from the Centers for Disease Control and Prevention/National Center for Health Statistics and the Substance
Abuse and Mental Health Services Administration (NSDUH).63
Chart 3-3. Estimated percentage of middle school students who have used any tobacco products,* ≥2 tobacco
products,†‡ and select tobacco products§ in the past 30 days (National Youth Tobacco Survey, 2011–2015).
*Any tobacco use is defined as past 30-day use of cigarettes, cigars, smokeless tobacco, electronic cigarettes (e-cigarettes), hoo-
kahs, pipe tobacco, and/or bidis. †Use of ≥2 tobacco products is defined as past 30-day use of ≥2 of the following product types:
cigarettes, cigars, smokeless tobacco, e-cigarettes, hookahs, pipe tobacco, or bidis. ‡Use of ≥2 tobacco products demonstrated a
nonlinear change (P<0.05). §E-cigarettes and hookahs demonstrated a linear increase (P<0.05). Cigarettes, cigars, and smokeless
tobacco demonstrated a linear decrease (P<0.05). Pipe tobacco and bidis demonstrated a nonlinear decrease (P<0.05).
Data derived from the Centers for Disease Control and Prevention, National Youth Tobacco Survey.47

CLINICAL STATEMENTS
AND GUIDELINES
Chart 3-4. Estimated percentage of high school students who have used any tobacco products,* ≥2 tobacco prod-
ucts,†‡ and select tobacco products§ in the past 30 days (National Youth Tobacco Survey, 2011–2015).
*Any tobacco use is defined as past 30-day use of cigarettes, cigars, smokeless tobacco, electronic cigarettes (e-cigarettes), hoo-
kahs, pipe tobacco, and/or bidis. †Use of ≥2 tobacco products is defined as past 30-day use of ≥2 of the following product types:
cigarettes, cigars, smokeless tobacco, e-cigarettes, hookahs, pipe tobacco, or bidis. ‡Use of ≥2 tobacco products demonstrated a
nonlinear change (P<0.05). §E-cigarettes and hookahs demonstrated a linear increase (P<0.05). Cigarettes, cigars, and smoke-
less tobacco demonstrated a linear decrease (P<0.05). Pipe tobacco and bidis demonstrated a nonlinear decrease (P<0.05).
Chart 3-5. Age-adjusted prevalence (%) of current cigarette smoking for adults, by state: United States (BRFSS, 2015).
BRFSS indicates Behavior Risk Factor Surveillance System; GU, Guam; PR, Puerto Rico; and VI, Virgin Islands.
Data derived from the Centers for Disease Control and Prevention.64

CLINICAL STATEMENTS
AND GUIDELINES
Chart 3-6. Percentage of US middle school students who have ever used tobacco, by type of product (National
Youth Tobacco Survey, 2011–2015).
a
lncludes those who reported having tried at least one other tobacco product in their lives.
b
Includes exclusive use of only e-cigarettes. It does not include use of any other product. Ever e-cigarette use includes those
who responded “electronic cigarettes or e-cigarettes, such as Ruyan or NJOY” to the following question: “Which of the following
tobacco products have you ever tried, even just one time?”
c
Includes exclusive use of only cigarettes, cigars, pipes, bidis, kreteks, and/or hookahs. It does not include use of noncombus-
tible products or e-cigarettes. They were defined using the following questions: Conventional cigarettes: “Have you ever tried
cigarette smoking, even one or two puffs?” and “During the past 30 days, on how many days did you smoke cigarettes?”;
cigars: “Have you ever tried smoking cigars, cigarillos, or little cigars, such as Black and Milds, Swisher Sweets, Dutch Masters,
While Owl, or Phillies Blunts, even one or two puffs?” and “During the past 30 days, on how many days did you smoke cigars,
cigarillos, or little cigars?”; pipes: “Have you ever tried smoking tobacco in a pipe, even one or two puffs?” and “During the
past 30 days, on how many days did you smoke tobacco in a pipe?”; and hookahs, kreteks, and bidis: “Which of the follow-
ing tobacco products have you ever tried, even just one time? (CHOOSE ALL THAT APPLY)” and “During the past 30 days,
which of the following products have you used on at least 1 day? (CHOOSE ALL THAT APPLY).”
d
lncludes exclusive use of only smokeless tobacco, sous, and/or dissolvable tobacco. It does not include use of combustible
products or e-cigarettes. They were defined using the following questions: Smokeless tobacco: “Have you ever used chew-
ing tobacco, snuff, or dip, such as Red Man, Levi Garrett, Beechnut, Skoal, Skoal Bandits, or Copenhagen, even just a small
amount?” and “During the past 30 days, on how many days did you use chewing tobacco, snuff, or dip?”; and dissolvables
and snus: “Which of the following tobacco products have you ever tried, even just one time? (CHOOSE ALL THAT APPLY)” and
“During the past 30 days, which of the following products have you used on at least 1 day? (CHOOSE ALL THAT APPLY).”

CLINICAL STATEMENTS
AND GUIDELINES
Chart 3-7. Percentage of US high school students who have ever used tobacco, by type of product (National Youth
Tobacco Survey, 2011–2015).
a
lncludes those who reported having tried at least one other tobacco product in their lives.
b
Includes exclusive use of only e-cigarettes. It does not include use of any other product. Ever e-cigarette use includes those
who responded “electronic cigarettes or e-cigarettes, such as Ruyan or NJOY” to the following question: “Which of the fol-
lowing tobacco products have you ever tried, even just one time?”
c
Includes exclusive use of only cigarettes, cigars, pipes, bidis, kreteks, and/or hookahs. It does not include use of noncombus-
tible products or e-cigarettes. They were defined using the following questions: Conventional cigarettes: “Have you ever tried
cigarette smoking, even one or two puffs?” and “During the past 30 days, on how many days did you smoke cigarettes?”;
cigars: “Have you ever tried smoking cigars, cigarillos, or little cigars, such as Black and Milds, Swisher Sweets, Dutch Masters,
While Owl, or Phillies Blunts, even one or two puffs?” and “During the past 30 days, on how many days did you smoke cigars,
cigarillos, or little cigars?”; pipes: “Have you ever tried smoking tobacco in a pipe, even one or two puffs?” and “During the
past 30 days, on how many days did you smoke tobacco in a pipe?”; and hookahs, kreteks, and bidis: “Which of the follow-
ing tobacco products have you ever tried, even just one time? (CHOOSE ALL THAT APPLY)” and “During the past 30 days,
which of the following products have you used on at least 1 day? (CHOOSE ALL THAT APPLY).”
d
lncludes exclusive use of only smokeless tobacco, sous, and/or dissolvable tobacco. It does not include use of combustible
products or e-cigarettes. They were defined using the following questions: Smokeless tobacco: “Have you ever used chew-
ing tobacco, snuff, or dip, such as Red Man, Levi Garrett, Beechnut, Skoal, Skoal Bandits, or Copenhagen, even just a small
amount?” and “During the past 30 days, on how many days did you use chewing tobacco, snuff, or dip?”; and dissolvables
and snus: “Which of the following tobacco products have you ever tried, even just one time? (CHOOSE ALL THAT APPLY)”
and “During the past 30 days, which of the following products have you used on at least 1 day? (CHOOSE ALL THAT APPLY).”
Data derived from the Centers for Disease Control, National Youth Tobacco Survey.47
Chart 3-8. Age-standardized global mortality rates attributable to tobacco per 100 000, both sexes, 2015.
Please click here to view the chart and its legend.
4. National Center for Health Statistics. National Health Interview Survey, 2015.
REFERENCES Public-use data file and documentation: NCHS tabulations. http://www.cdc.
gov/nchs/nhis/nhis_2015_data_release.htm. Accessed July 18, 2016.
1. Bose J, Hedden SL, Lipari RN, Park-Lee E; Center for Behavioral Health
5. Centers for Disease Control and Prevention (CDC). Electronic Nicotine
Statistics and Quality. Key Substance Use and Mental Health Indicators
Delivery Systems Key Facts. 2014. https://chronicdata.cdc.gov/Policy/
in the United States: Results From the 2015 National Survey on Drug
Electronic-Nicotine-Delivery-Systems-Key-Facts-Inf/nwhw-m4ki. Accessed
Use and Health. September 2016. HHS publication No. SMA 16-4984,
June 8, 2016.
NSDUH series H-51. https://www.samhsa.gov/data/sites/default/files/
6. Ward BW, Clarke TC, Nugent CN, Schiller JS. Early Release of Selected
NSDUH-FFR1-2015/NSDUH-FFR1-2015/NSDUH-FFR1-2015.pdf. Accessed Estimates Based on Data From the 2015 National Health Interview
May 18, 2017. Survey. 2016. https://www.cdc.gov/nchs/data/nhis/earlyrelease/early
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AND GUIDELINES
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journal.pone.0147848. Accessed July 18, 2016.

4. PHYSICAL INACTIVITY adults get at least 150 minutes of moderate-intensity or

CLINICAL STATEMENTS
75 minutes of vigorous-intensity aerobic activity (or an

See Charts 4-1 through 4-11
AND GUIDELINES
equivalent combination) per week and perform muscle-

strengthening activities at least 2 days per week.6 In a
nationally representative sample of adults,7 only 21.5%
reported participating in adequate leisure-time aerobic
Physical inactivity is a major risk factor for CVD and and muscle-strengthening activity to meet these crite-
stroke.1 Meeting the guidelines for PA is one of the ria, but they were not asked to report activity accumu-
AHA’s 7 components of ideal cardiovascular health for lated during occupational, transportation, or domestic
both children and adults.2 The AHA and 2008 federal duties. Being physically active is an important aspect of
guidelines on PA recommend that children get at least overall health.6 PA not only reduces premature mortality
60 minutes of PA daily (including aerobic and muscle- but also improves risk factors for CVD (such as HBP and
and bone-strengthening activity). In 2015, on the basis high cholesterol) and reduces the likelihood of diseases
of survey interviews,3 only 27.1% of high school stu- related to CVD, including CHD, stroke, type 2 DM, and
dents reported achieving at least 60 minutes of daily PA, sudden heart attacks.6 Benefits from PA are seen for
which is likely an overestimation of those actually meet- all ages and groups, including older adults, pregnant
ing the guidelines.4,5 The guidelines recommend that females, and people with disabilities and chronic con-
ditions. Therefore, the federal guidelines recommend
Abbreviations Used in Chapter 4 being as physically active as abilities and conditions
AF atrial fibrillation allow and, if not currently meeting the recommenda-
AHA American Heart Association tions, increasing PA gradually.
BMI body mass index
BP blood pressure
CAD coronary artery disease Defining and Measuring PA
CARDIA Coronary Artery Risk Development in Young Adults
CHD coronary heart disease There are 4 dimensions of PA (mode or type, fre-
CI confidence interval quency, duration, and intensity) and 4 common
CVD cardiovascular disease domains for adults (occupational, domestic, transpor-
DBP diastolic blood pressure tation, and leisure time).4 For children, there are addi-
tional considerations of structured PA in schools and
EF ejection fraction
communities. The federal guidelines specify the sug-
GBD Global Burden of Disease gested frequency, duration, and intensity of activity.
GED General Educational Development Historically, recommendations on PA for health pur-
HbA1c hemoglobin A1c poses have focused on leisure-time activity. However,
HBP high blood pressure because all domains of PA could have an impact on
HDL-C high-density lipoprotein cholesterol
health, and because an increase in 1 domain may
HF heart failure
HR hazard ratio
sometimes be compensated for by a decrease in
LDL-C low-density lipoprotein cholesterol another domain, ideally data will be collected on all
MET metabolic equivalent dimensions and domains of PA.4
MI myocardial infarction There are 2 broad categories of methods to assess
MSA metropolitan statistical area PA: (1) subjective methods that use questionnaires
NAVIGATOR Long-term Study of Nateglinide + Valsartan to Prevent or Delay
Type II Diabetes Mellitus and Cardiovascular Complications
and diaries/logs and (2) objective methods that use
NH non-Hispanic wearable monitors (pedometers, accelerometers, etc).
NHANES National Health and Nutrition Examination Survey Studies that compare the findings between subjective
NHIS National Health Interview Survey and objective methods have found that there is marked
PA physical activity discordance between self-reported and measured PA,
with respondents often overstating their PA, especially
PAR population attributable risk
QALY quality-adjusted life-year the intensity.4,5
RCT randomized controlled trial Another consideration in the measurement of PA is
RR relative risk that surveys often ask only about leisure-time PA, which
SBP systolic blood pressure represents PA obtained from a single domain. People
SD standard deviation
who get a lot of PA in other domains may be less likely
SES socioeconomic status
TC total cholesterol
to engage in leisure-time PA. Although they may meet
VTE venous thromboembolism the federal PA guidelines, people who spend consider-
WHI Women’s Health Initiative able time and physical effort in occupational, domestic,
WHO World Health Organization or transportation activities/domains may be less likely to
YRBSS Youth Risk Behavior Surveillance System be identified as meeting the guidelines.

PA and cardiorespiratory fitness provide distinct — Only 8% of 12- to 19-year-olds accumulated
CLINICAL STATEMENTS
metrics in assessment of CVD risk.8 Poor cardiorespira- ≥60 minutes of moderate to vigorous PA on
AND GUIDELINES
tory (or aerobic) fitness may be a stronger predictor of ≥5 days per week, whereas 42% of 6- to
adverse cardiometabolic and cardiovascular outcomes 11-year-olds achieved similar activity levels.5
than traditional risk factors.9 Although many studies — More boys than girls met PA recommenda-
have shown that increasing the amount and quality of tions (≥60 minutes of moderate to vigorous
PA can improve cardiorespiratory fitness, other factors activity) on ≥5 days per week.5
can contribute, such as a genetic predisposition to per- • With regard to objectively measured cardiorespi-
form aerobic exercise.10 Because cardiorespiratory fit- ratory fitness (NHANES, 2012)11:
ness is directly measured and reflects both participation — For adolescents aged 12 to 15 years, boys
in PA and the state of physiological systems affecting in all age groups were more likely to have
performance, the relationship between cardiorespira- adequate levels of cardiorespiratory fitness
tory fitness and clinical outcomes is stronger than the than girls (Chart 4-3).11
relationship of PA to a series of clinical outcomes.8
Unlike health behaviors such as PA and risk factors • With regard to self-reported muscle strengthen-
that are tracked by federally funded programs (NHIS, ing activities (YRBSS, 2015):3
NHANES, etc),5,7 there are no national data on adult — The proportion of high school students who
cardiorespiratory fitness, although the development participated in muscle-strengthening activi-
of a national cardiorespiratory fitness registry has been ties on ≥3 days of the week was 53.4%
proposed.8 Such additional data on the cardiorespira- nationwide and declined from 9th (males
tory fitness levels of Americans could give a fuller and 64.9%, females 48.2%) to 12th (males
more accurate picture of physical fitness levels.8 59.9%, females 39.9%) grades.
— More high school boys (63.7%) than girls
(42.7%) reported having participated in
Prevalence muscle-strengthening activities on ≥3 days
Youth of the week.
Meeting the Activity Recommendations Structured Activity Participation in Schools and Sport
(See Charts 4-1 through 4-3) • In 2015, only 29.8% of students attended physi-
• On the basis of self-reported PA (YRBSS, 2015)3:
cal education classes in school daily (33.8% of

— The prevalence of high school students who boys and 25.5% of girls) (YRBSS).3
met aerobic activity recommendations of • Daily physical education class participation
≥60 minutes of PA on all 7 days of the week declined from the 9th grade (44.6% for boys,
was 27.1% nationwide and declined from 39.5% for girls) through the 12th grade (27.9%
9th (31.0%) to 12th (23.5%) grades. At for boys, 16.0% for girls) (YRBSS).3
each grade level, the prevalence was higher • Just over half (57.6%) of high school students
in boys than in girls. played on at least 1 school or community sports
— More than double the percentage of high
team in the previous year: 53.0% of girls and
school–aged boys (36.0%) than girls (17.7%)
62.2% of boys (YRBSS).3
reported having been physically active ≥60
minutes per day on all 7 days. Television/Video/Computers
— The prevalence of students meeting activ- (See Chart 4-4)
ity recommendations on ≥5 days per week Research suggests that screen time (watching television
was higher among NH white boys (62.0%), or using a computer) may lead to less PA among chil-
NH black boys (52.2%), and Hispanic boys dren.12 In addition, television viewing time is associated
(53.5%) than NH white girls (43.5%), with poor nutritional choices, overeating, and weight
NH black girls (33.4%), and Hispanic girls gain (Chapter 5, Nutrition).
(33.1%) (Chart 4-1). • In 2015 (YRBSS)3:
— 14.3% of students reported that they did — Nationwide, 41.7% of high school students
not participate in ≥60 minutes of any kind used a computer for activities other than
of PA on any 1 of the previous 7 days (Chart school work (eg, videogames or other com-
4-2). Girls were more likely than boys to puter games) for ≥3 hours per day on an
report this level of inactivity (17.5% versus average school day.
11.1%). — The prevalence of using computers ≥3 hours
• With regard to objectively measured moderate per day (for activities other than school work)
to vigorous PA (accelerometer counts per minute was highest among NH black girls (48.4%),
>2020; NHANES, 2003–2004)5: followed by Hispanic girls (47.4%), Hispanic

boys (45.1%), NH black boys (41.2%), NH the federal guidelines for aerobic PA through
CLINICAL STATEMENTS
white boys (38.9%), and NH white girls leisure-time activities (Chart 4-7).
AND GUIDELINES
(38.3%) (Chart 4-4). • Adults residing in urban areas (metropolitan sta-

— The prevalence of watching television ≥3 tistical areas) are more likely to meet the federal
hours per day was highest among NH black aerobic PA guidelines through leisure-time activi-
girls (41.5%) and boys (37.0%), followed by ties than those residing in rural areas (51.4% ver-
Hispanic girls (29.2%) and boys (27.4%) and sus 41.1%) (Chart 4-8).7
NH white boys (21.4%) and girls (18.8%). • Adults living below 200% of the poverty level
• A report from the Kaiser Family Foundation (using are less likely to meet the federal PA guidelines
data from 2009) reported that 7th to 12th grad- through leisure-time activities than adults living at
ers spent an average of 90 minutes per day text >200% above the poverty level (Chart 4-9).7
messaging, 33 minutes talking on the phone, and • 30.4% of adults report that they do not engage
49 minutes using their phone to access media in leisure-time PA (no sessions of PA of ≥10 min-
(music, games, or videos).13 Surveys such as YRBSS utes’ duration).7
have not historically asked about cell phone use • With regard to objectively measured moderate
specifically and are thus likely underestimates of to vigorous PA (accelerometer counts per minute
total screen-time use. >2020; NHANES, 2003–2004)5:
— Among those ≥60 years of age, adherence to
Adults PA recommendations was 2.5% in males and
Meeting the Activity Recommendations 2.3% in females.5
(See Charts 4-5 through 4-9) — In contrast to self-reported PA, which suggested
• With regard to self-reported leisure-time aerobic that NH whites had the higher levels of PA,7
and muscle-strengthening PA (NHIS, 2015)7: data from objectively measured PA revealed that
— 21.5% of adults met the 2008 federal PA Hispanic participants had higher total PA and
guidelines for both aerobic and strength- moderate to vigorous PA compared with NH
ening activity, an important component of white or black participants (≥20 years old).5,14
overall physical fitness, based on only report- • Among adults 20 to 59 years of age, 3.8% of
ing leisure-time activity (Chart 4-5). males and 3.2% of females met recommenda-
— 30.4% do not engage in any leisure-time PA
tions to engage in moderate to vigorous PA for

(“no leisure time PA/inactivity” refers to no 30 minutes (in sessions of ≥10 minutes) on ≥5 of
sessions of light/moderate or vigorous PA of 7 days.5 It is also important to consider that using
≥10 minutes’ duration). data accumulated only in ≥10-minute bouts could
• For self-reported leisure time aerobic PA (NHIS, remove up to 75% of moderate activity.15
2015)7: • Levels of activity declined sharply after the age of
— The age-adjusted proportion who reported 50 years in all groups.15
meeting the 2008 aerobic PA guidelines for • These data also revealed that rural US residents
Americans (≥150 minutes of moderate PA or performed less moderate to vigorous PA than
75 minutes of vigorous PA or an equivalent urban residents, but rural residents spent more
combination each week) through leisure- time in lighter-intensity activities (accelerometer
time activities was 49.7%, with 52.9% of counts per minute >760) than their urban resi-
males and 46.7% of females meeting the dent counterparts.16
aerobic guidelines. • In a review examining self-reported versus actual
— Age-adjusted prevalence was 50.9% for NH measured PA (eg, accelerometers, pedometers,
whites, 41.7% for NH blacks, and 43.3% for indirect calorimetry, doubly labeled water, heart
Hispanics. Among both males and females, rate monitor), 60% of respondents self-reported
NH whites were more likely to meet the PA higher values of activity than what was measured
aerobic guidelines with leisure-time activity by use of direct methods.17 Among males, self-
than NH blacks and Hispanics (Chart 4-6). reported PA was 44% greater than actual mea-
— Education was positively associated with sured values; among females, self-reported activity
meeting the federal guidelines. Among was 138% greater than actual measured PA.17
adults ≥25 years of age, 30.0% of partici-
pants with no high school diploma, 38.9% Structured Activity Participation in Leisure-Time,
of those with a high school diploma or GED Domestic, Occupational, and Transportation
high school equivalency credential, 46.8% Activities
of those with some college, and 62.8% of • Individuals from urban areas who participated in
those with a bachelor’s degree or higher met NHANES 2003 to 2006 reported participating in

more transportation activity, but rural individuals • A meta-analysis of 9 cohort studies, represent-
CLINICAL STATEMENTS
reported spending more time in household PA ing 122 417 patients, found that as little as 15
AND GUIDELINES
and more total PA than urban individuals, pos- minutes of daily moderate to vigorous PA reduced
sibly explaining the higher levels of light activ- all-cause mortality in adults ≥60 years of age. This
ity of rural individuals observed by objective protective effect of PA was dose dependent; the
methods.16 most rapid reduction in mortality per minute of
• NH whites and blacks were more likely to report added PA was for those at the lowest levels of
meeting the PA guidelines through leisure-time PA. These findings suggest that older adults can
PA but had lower objectively measured PA than benefit from PA time far below the amount rec-
Hispanic individuals.16 At this time, it is unclear ommended by the federal guidelines.24
which construct of PA (domestic, occupational, or • A pooled study of >600 000 participants found
transportation) contributes to the higher observed that even low levels of leisure-time PA (up to 75
PA for Hispanic individuals or whether these dif- minutes of brisk walking per week) were associ-
ferences are caused by overreporting or underre- ated with a reduced risk of mortality compared
porting leisure-time PA. with participants with no PA. If this is a causal
• A 1-day assessment indicated that the mean prev- relationship, this low level of PA would confer a
alence of any active transportation was 10.3%. 1.8-year gain in life expectancy after age 40 years
NH whites reported the lowest active transport, compared with no PA. For participants meeting
only 9.2%, of any racial/ethnic group. Roughly the PA guidelines, the gain in life expectancy was
11.0% of Hispanics, 13.4% of blacks, and 15.0% 3.4 years over those with no PA.25
of other NH individuals reported participating • In further analysis of this pooled sample, an
in any active transportation on the previous day inverse dose-response relationship was observed
(Active Transportation Surveillance, 2012).18 between level of leisure-time PA (HR, 0.80 for less
than the recommended minimum of the PA guide-
lines; HR, 0.69 for 1–2 times the recommended
Mortality minimum; and HR, 0.63 for 2–3 times the mini-
• Physical inactivity is the fourth-leading risk factor mum) and mortality, with the upper threshold for
for global death, responsible for 1 to 2 million mortality benefit occurring at 3 to 5 times the PA
deaths annually.19,20 recommendations (HR, 0.61). Furthermore, there
• A study of US adults that linked a large, nation- was no evidence of harm associated with per-
ally representative sample of 10 535 participants forming ≥10 times the recommended minimum
(NHANES) to death records found that meeting (HR, 0.69).26
the aerobic PA guidelines reduced all-cause mor- • Similarly, a population-based cohort in New South
tality, with an HR of 0.64, after adjustment for Wales, Australia, of 204 542 adults followed up
potential confounding factors. Furthermore, for for an average of 6.5 years evaluated the relation-
adults not meeting the aerobic PA guidelines, ship of PA to mortality risk. It found that com-
engaging in muscle-strengthening activity ≥2 pared with those who reported no moderate to
times a week was associated with a 44% lower vigorous PA, the adjusted HRs for all-cause mor-
adjusted HR for all-cause mortality.21 tality were 0.66 for those reporting 10 to 149
• In smaller samples of NHANES (participants with min/wk, 0.53 for those reporting 150 to 299 min/
objectively measured PA and between the ages of wk, and 0.46 for those reporting ≥300 min/wk of
50 and 79 years [n=3029]), models that replaced activity.27
sedentary time with 10 minutes of moderate to • A meta-analysis of 17 eligible studies on PA in
vigorous PA were associated with lower all-cause patients with DM revealed that the highest PA
mortality (HR, 0.70; 95% CI, 0.57–0.85) after 5 to category in each study was associated with a
8 years of follow-up. Even substituting in 10 min- lower RR (0.61) for all-cause mortality and CVD
utes of light activity was associated with lower all- (0.71) than the lowest PA category. Although
cause mortality (HR, 0.91; 95% CI, 0.86–0.96).22 more PA was associated with larger reductions
• Adults ≥40 years of age who reported participat- in future all-cause mortality and CVD, in patients
ing in moderate to vigorous PA once a week or with DM, any amount of habitual PA was better
more had a lower mortality risk than those who than inactivity.28
were inactive. Furthermore, older adults who • Meta-analysis has also revealed an association
engaged in moderate to vigorous PA ≥5 times between participating in more transportation-
per week had a significantly lower mortality risk related PA and lower all-cause mortality risk.29 In
than those who participated in a lower frequency contrast, higher occupational PA has recently been
of PA.23 associated with higher mortality in males (but not

females).30 It is unclear whether confounding fac- reporting having participated in muscle-strength-

CLINICAL STATEMENTS
tors such as fitness, SES, or other domains of PA ening activities on ≥3 days per week, from 47.8%
AND GUIDELINES
might impact this relationship. in 1991 to 53.4% in 2015; however, the preva-
• In a study involving 55 137 adults followed up lence did not change substantively from 2013
over an average of 15 years, running even 5 to 10 (51.7%) to 2015 (53.4%).
min/d and at slow speeds (<6 mph) was associ- • A significant increase occurred in the number of
ated with a markedly reduced risk of CVD and of youth reporting having used computers not for
death attributable to all causes.31 school work for ≥3 hours per day compared with
• The Cooper Center Longitudinal Study, an analy- 2003 (22.1% versus 41.7% in 2015). The preva-
sis conducted on 16 533 participants, revealed lence increased from 2003 to 2009 (22.1% ver-
that across all risk factor strata, the presence of sus 24.9%) and then increased more rapidly from
low cardiorespiratory fitness was associated with 2009 to 2015 (24.9% versus 41.7%).
a greater risk of CVD death over a mean follow- — From 2004 to 2009, the Kaiser Family Foun-
up of 28 years.32
dation reported that the proportion of 8- to
• In a retrospective cohort study of 57 085 individu-
18-year-olds who own their own cell phone
als who were clinically referred for stress testing
has increased from 39% to 66%,13 which
(but without established CAD or HF), cardiorespi-
could also contribute to higher exposure to
ratory fitness–associated “biological age” was a
screen time in children.
stronger predictor of mortality over 10 years of
follow-up than chronological age.33 • Nationwide, the number of high school students
• In the Southern Community Cohort Study of who reported attending physical education classes
63 308 individuals followed up for >6.4 years, more at least once per week did not change substantively
time spent being sedentary (>12 h/d versus <5.76 between 2013 (48.0%) and 2015 (51.6%).
h/d) was associated with a 20% to 25% increased — The number of high school students re-
risk of all-cause mortality in both black and white porting attending daily physical education
adults. Both PA (beneficial) and sedentary time classes changed in nonlinear ways over
(detrimental) were associated with mortality risk.34 time. Attendance initially decreased from
• A study that prospectively assessed the association 1991 to 1995 (from 41.6% to 25.4%)
of continuous inactivity and of changes in sitting and did not substantively change between
time for 2 years with subsequent long-term all- 1995, 2013, and 2015 (25.4%, 29.4%, and
cause mortality found that compared with people 29.8%, respectively).
who remained consistently sedentary, the HRs for
• The prevalence of high school students playing
mortality were 0.91 in those who were newly sed-
≥1 team sport in the past year did not substan-
entary, 0.86 in formerly sedentary individuals, and
tively change between 2013 (54.0%) and 2015
0.75 in those who remained consistently nonsed-
(57.6%).
entary. Thus, participants who reduced their sit-
ting time over 2 years experienced a reduction in — In 2012, the prevalence of adolescents
mortality.35 aged 12 to 15 years with adequate levels of
• A meta-analysis including >1 million participants cardiorespiratory fitness (based on age- and
across 16 studies compared the risk associated sex-specific standards) was 42.2% in 2012
with sitting time and television viewing in physi- (Chart 4-3), down from 52.4% in 1999 to
cally active and inactive study participants. For 2000.11
inactive individuals (defined as the lowest quartile
of PA), those sitting >8 h/d had a higher all-cause Adults
mortality risk than those sitting <4 h/d. For active (See Chart 4-10)
individuals (top quartile for PA), sitting time was • The age-adjusted percentage of US adults who
not associated with all-cause mortality, but active reported meeting both the muscle-strengthening
people who watched television ≥5 h/d did have and aerobic guidelines increased from 14.4% in
higher mortality risk.36 1998 to 21.4% in 2015 (Chart 4-10).7 The per-
centage of US adults who reported meeting the
aerobic guideline increased from 40.1% in 1998
Secular Trends to 49.7% in 2015.7,37
Youth • Also, the number of adults reporting no leisure-
In 2015 (YRBSS)3: time PA decreased from 36.2% in 2008 to 30.0%
• Among students nationwide, there was a sig- in 2014,38 surpassing the target for Healthy People
nificant increase in the number of individuals 2020, which was 32.6%.

• A 2.3% decline in physical inactivity between • A total of 120 to 150 min/wk of moderate-inten-
CLINICAL STATEMENTS
1980 and 2000 was estimated to have prevented sity activity, compared with none, can reduce the
AND GUIDELINES
or postponed ≈17 445 deaths (≈5%) attributable risk of developing metabolic syndrome.6
to CHD in the United States.39 • Even lighter-intensity activities, such as yoga,
were reported to improve BMI, BP, triglycerides,
LDL-C, and HDL-C but not fasting blood glucose
Complications of Physical Inactivity: The in a meta-analysis of 32 RCTs comparing yoga to
Cardiovascular Health Impact nonexercise control groups.45
Youth • In CARDIA, females who maintained high PA
• Among children aged 4 to 18 years, both higher through young adulthood gained 6.1 fewer
activity levels and lower sedentary time measured kilograms of weight and 3.8 fewer centimeters
by accelerometry were associated with more in waist circumference in middle age than those
favorable metabolic risk factor profiles.40 with lower activity. Highly active males gained 2.6
• Among children 4 to 18 years of age, more time fewer kilograms and 3.1 fewer centimeters than
spent engaging in moderate to vigorous PA was their lower-activity counterparts.46
associated with higher HDL-C and lower waist cir- • In 3 US cohort studies, males and females who
cumference, SBP, fasting triglycerides, and insulin. increased their PA over time gained less weight
These findings were significant regardless of the in the long term, whereas those who decreased
amount of children’s sedentary time.40 their PA over time gained more weight.47
• For elementary school children, engagement in • Among US males and females, every hour per
organized sports for ≈1 year was associated with day of increased television watching was associ-
lower clustered cardiovascular risk.41 ated with 0.3 lb of greater weight gain every
4 years.47
Adults • In a sample of 466 605 participants in the China
Cardiovascular and Metabolic Risk Kadoorie Biobank study, a 1-SD (1.5 h/d) increase
• A review of the US Preventive Services Task in sedentary time was associated with a 0.19-U
Force recommendations examined the evidence higher BMI, a 0.57-cm larger waist circumference,
on whether relevant counseling interventions and 0.44% more body fat. Both higher sedentary
for a healthful diet and PA in primary care leisure time and lower PA were independently
modify self-reported behaviors, intermediate associated with an increased BMI.48
physiological outcomes, DM incidence, and Cardiovascular Events
cardiovascular morbidity or mortality in adults • In the WHI observational study (N=71 018), sitting
with CVD risk factors. It was concluded that for ≥10 h/d compared with ≤5 h/d was associated
after 12 to 24 months, intensive lifestyle coun- with increased CVD risk (HR, 1.18) in multivari-
seling for individuals selected because of risk able models that included PA. Low PA was also
factors reduced TC levels by an average of 0.12 associated with higher CVD risk. It was concluded
mmol/L, LDL-C levels by 0.09 mmol/L, SBP by that both low PA and prolonged sitting augment
2.03 mm Hg, DBP by 1.38 mm Hg, fasting glu- CVD risk.49
cose by 0.12 mmol/L, DM incidence by an RR of • In a meta-analysis of longitudinal studies among
0.58, and weight outcomes by a standardized females, RRs of incident CHD were 0.83 (95%
difference of 0.25.42 CI, 0.69–0.99), 0.77 (95% CI, 0.64–0.92), 0.72
• Results from NHANES 2011 to 2014 demon- (95% CI, 0.59–0.87), and 0.57 (95% CI, 0.41–
strated that the prevalence of low HDL-C was 0.79) across increasing quintiles of PA compared
higher among adults who reported not meeting with the lowest quintile.50
PA guidelines (21.0%) than among adults meet- • A study of the factors related to declining CVD
ing guidelines (17.7%).43 among Norwegian adults ≥25 years of age found
• Engaging in active transport to work has been that increased PA (≥1 hour of strenuous PA per
associated with lower cardiovascular risk factors. week) accounted for 9% of the decline in hos-
— In a large Swedish cohort of 23 732 indi- pitalized and nonhospitalized fatal and nonfatal
viduals, bicycling to work at baseline was CHD events.51
associated with a lower odds of developing • In the Health Professionals Follow-Up Study, for
incident obesity, hypertension, hypertriglyc- every 3-hour-per-week increase in vigorous-inten-
eridemia, and impaired glucose tolerance at sity activity, the multivariate RR of MI was 0.78
10 years’ follow-up than among those using (95% CI, 0.61–0.98) for males. This 22% reduc-
passive modes of transportation.44 tion of risk can be explained in part by beneficial

effects of PA on HDL-C, vitamin D, apolipoprotein • Using data from a registry of stable outpatients
CLINICAL STATEMENTS
B, and HbA1c.52 with symptomatic coronary disease, cerebrovas-

AND GUIDELINES
• A 2003 meta-analysis of 23 studies on the asso- cular disease, or PAD, the mortality rate of patients
ciation of PA with stroke indicated that compared with a recent MI was significantly lower in patients
with low levels of activity, high (RR, 0.73; 95% who participated in supervised (N=593) versus
CI, 0.67–0.79) and moderate (RR, 0.80; 95% CI, unsupervised (N=531) exercise programming.63
0.74–0.86) levels of activity were inversely associ- • Early mortality after a first MI was lower for
ated with the likelihood of developing total stroke patients who had higher exercise capacity before
(ischemic and hemorrhagic).53 the MI event. Every 1-MET-higher exercise capac-
• In a study involving 1.1 million females without ity before the MI was associated with an 8% to
prior vascular disease and followed up over an 10% lower risk of mortality at 28 days, 90 days,
average of 9 years, those who reported moderate and 365 days after MI.64
activity were found to be at lower risk of CHD, a
cerebrovascular event, or a first thrombotic event.
Costs
However, strenuous PA was not found to be as
beneficial as moderate PA.54 • The economic consequences of physical inactivity
• Domains of PA, other than leisure time, are under- are substantial. Using data derived primarily from
studied and often overlooked. A meta-analysis WHO publications and data warehouses, one
reported a protective relation of transportation study estimated that economic costs of physical
activity to cardiovascular risk, which was greater inactivity account for 1.5% to 3.0% of total direct
in females.55 However, occupational PA has healthcare expenditures in developed countries
recently been associated with higher MI incidence such as the United States.65
in men 19 to 70 years old.30,56 These relationships • A global analysis of 142 countries (93.2% of
require further investigation, because a protective the world’s population) concluded that physical
association of occupational activity with MI has inactivity cost healthcare systems $53.8 billion
been reported in young men (19–44 years).56 in 2013, including $9.7 billion paid by individual
• In a Swedish cohort of 773 925 young males with- households.66
out history of VTE, cardiorespiratory fitness was • A study of American adults reported that inad-
equate levels of aerobic PA (after adjusting for
associated with a reduced risk of VTE (HR, 0.81;

95% CI, 0.78–0.85) at ≥20 years of follow-up.57 BMI) were associated with an estimated 11.1%
• In 5962 veterans, lower exercise capacity was of aggregate healthcare expenditures (including
associated with a higher risk of developing AF. For expenditures for inpatient, outpatient, ED, office-
every 1-MET increase in exercise capacity, the risk based, dental, vision, home health, prescription
of developing AF was 21% lower (HR, 0.79; 95% drug, and other services).67
CI, 0.76–0.82).58 • An evaluation of healthcare costs based on the
• In a large clinical trial (NAVIGATOR) involving cardiovascular risk factor profile (including ≥30
9306 people with impaired glucose tolerance, minutes of moderate to vigorous PA ≥5 times per
ambulatory activity as assessed by pedometer at week) found that among adults aged ≥40 years
baseline and 12 months was found to be inversely with CVD, the highest marginal expenditures
associated with risk of a cardiovascular event.59 ($2853 in 2012) were for those not meeting the
• Self-reported low lifetime recreational activity has PA guidelines. Healthcare costs included hospital-
been associated with increased PAD.60 izations, prescribed medications, outpatient visits
(hospital outpatient visits and office-based visits),
Secondary Prevention ED visits, and other expenditures (dental visits,
• A Cochrane systematic review of 63 studies con- vision aid, home health care, and other medical
cluded that exercise-based cardiac rehabilitation supplies).68
programs for CHD patients reduced cardiovas- • A systematic review of population-based inter-
cular mortality and hospital admissions, but not ventions to encourage PA found that improving
overall mortality.61 biking trails, distributing pedometers, and school-
• In a prospective study that monitored 902 HF based PA were most cost-effective.69
patients (with preserved or reduced EF) for 3 • Interventions and community strategies to
years, reporting participation in any PA (≥1 min/ increase PA have been shown to be cost-effective
wk) was associated with a lower risk of cardiac in terms of reducing medical costs70:
death and all-cause death than no PA. Less televi- — Nearly $3 in medical cost savings is realized
sion screen time (<2 versus >4 h/d) was also asso- for every $1 invested in building bike and
ciated with lower all-cause death.62 walking trails.

— Incremental cost and incremental effective- • In 2012, the School Health Policies and Practices
CLINICAL STATEMENTS
ness ratios range from $14 000 to $69 000 Study also reported that 58.9% of school districts
AND GUIDELINES
per QALY gained from interventions such as required regular elementary school recess.38
pedometer or walking programs compared • Healthy afterschool programs and active school
with no intervention, especially in high-risk day policies have been shown to be cost-effective
groups. solutions to increase PA and prevent childhood
obesity.75
Strategies to Prevent Physical Inactivity Worksites
The US Surgeon General has introduced “Step It Up!, • Worksites can offer access to on-site exercise
a Call to Action to Promote Walking and Walkable facilities or employer-subsidized off-site exercise
Communities” in recognition of the importance of PA.71 facilities to encourage PA among employees.
There are roles for communities, schools, and worksites. • Worksite interventions for sedentary occupations,
such as providing “activity-permissive” worksta-
Communities tions and e-mail contacts that promote breaks,
• Community-level interventions have been shown have reported increased occupational light activ-
to be effective in promoting increased PA. ity, and the more adherent individuals observed
Communities can encourage walking with street improvements in cardiometabolic outcomes.76
design that includes sidewalks, improved street
lighting, and landscaping design that reduces
traffic speed to improve pedestrian safety. Moving Global Burden
to a walkable neighborhood was associated with • Physical inactivity is responsible for 12.2% of
a lower risk for incident hypertension in the the global burden of MI after accounting for
Canadian Community Health Survey.72 other CVD risk factors such as cigarette smok-
• Community-wide campaigns: Such campaigns ing, DM, hypertension, abdominal obesity, lipid
include a variety of strategies, such as media profile, excessive alcohol intake, and psychosocial
coverage, risk factor screening and education, factors.77
community events, and policy or environmental • Worldwide, the prevalence of physical inactiv-
changes. ity (35%) is now greater than the prevalence of
• Educating the public on the recommended PA smoking (26%). On the basis of the HRs associ-
guidelines may increase adherence. In a study ated with these 2 behaviors (1.57 for smoking
examining awareness of current US PA guidelines, and 1.28 for inactivity), it was concluded that
only 33% of respondents had direct knowledge the PAR was greater for inactivity (9%) than for
of the recommended dosage of PA (ie, frequency/
smoking (8.7%). Inactivity was estimated to be
duration).73
responsible for 5.3 million deaths compared with
Schools 5.1 million deaths for smoking.78
• Schools can provide opportunities for PA through • The GBD 2015 Study used statistical models
physical education, recess, before- and after- and data on incidence, prevalence, case fatal-
school activity programs, and PA breaks.74 ity, excess mortality, and cause-specific mortality
• According to the School Health Policies and to estimate disease burden for 315 diseases and
Practices Study, <5% of elementary schools and injuries in 195 countries and territories. Mortality
junior and senior high schools required daily phys- rates attributable to low PA are high in the Pacific
ical education in 2014.38 Island countries (Chart 4-11).79

CLINICAL STATEMENTS
AND GUIDELINES
Chart 4-1. Prevalence of students in grades 9 to 12 who report meeting currently recommended levels of physical
activity on at least 5 of the past 7 days by race/ethnicity and sex.
“Currently recommended levels” was defined as activity that increased their heart rate and made them breathe hard some of
the time for a total of ≥60 min/d on 5 of the 7 days preceding the survey.
Source: Youth Risk Behavior Surveillance Survey 2015.3
30
25.2
25
20 19.2
Percent of Population
16.2
15 14.3
11.9
10 8.8
0
Male Female
NH White NH Black Hispanic
Chart 4-2. Prevalence of students in grades 9 to 12 who did not participate in ≥60 minutes of physical activity on
any day in the past 7 days by race/ethnicity and sex.

CLINICAL STATEMENTS
60
AND GUIDELINES
50.2 51.2
50 49.1
43.6
42.2
40.6
Percent of Youths 40
35.7
33.8
31.8
30
20
10
0
Total (12-15 Years) 12-13 Years 14-15 Years
Total Boys Girls
Chart 4-3. Prevalence of children 12 to 15 years of age who had adequate levels of cardiorespiratory fitness by sex
and age (NHANES, National Youth Fitness Survey: 2012).
Source: NHANES, National Youth Fitness Survey 2012.11
Chart 4-4. Percentage of students in grades 9 to 12 who used a computer for ≥3 hours on an average school day
by race/ethnicity and sex.

CLINICAL STATEMENTS
AND GUIDELINES
Chart 4-5. Met 2008 federal aerobic and strengthening physical activity (PA) guidelines for adults.
“Met 2008 federal aerobic and strengthening physical activity guidelines for adults” is defined as engaging in ≥150 minutes of
moderate or 75 minutes of vigorous aerobic leisure-time PA per week (or an equivalent combination) and engaging in leisure-
time strengthening PA at least twice per week. Data are age adjusted for adults ≥18 years of age.
Source: National Health Interview Survey 2015 (National Center for Health Statistics).7
60
55.2
50.3 50.9
50
45.7
41.0
40
35.0
30
20
10
0
Males Females
NH White NH Black Hispanic or Latino
Chart 4-6. Prevalence of meeting the aerobic guidelines of the 2008 Federal Physical Activity Guidelines for
Americans through leisure-time activity only among adults ≥18 years of age by race/ethnicity and sex (NHIS, 2015).
Percentages are age adjusted. The aerobic guidelines of the 2008 Federal Physical Activity Guidelines for Americans recom-
mend engaging in moderate leisure-time physical activity for ≥150 min/wk or vigorous activity ≥75 min/wk or an equivalent
combination.
NH indicates non-Hispanic; and NHIS, National Health Interview Survey.
Source: NHIS 2015 (National Center for Health Statistics).7

CLINICAL STATEMENTS
AND GUIDELINES
Americans through leisure-time activity only among adults ≥25 years of age by educational attainment (NHIS,
2015).
combination.
GED indicates General Educational Development; and NHIS, National Health Interview Survey.
Americans through leisure-time activity only among adults ≥18 years of age by location of residence (NHIS, 2015).
combination.
MSA indicates metropolitan statistical area; and NHIS, National Health Interview Survey.

CLINICAL STATEMENTS
AND GUIDELINES
Chart 4-9. Percent distribution of meeting the 2008 Federal Physical Activity Guidelines for Americans through
leisure-time activity only among adults ≥18 years of age by poverty level and type of activity (NHIS, 2015).
combination and performing muscle-strengthening activities at least 2 days per week.
NHIS indicates National Health Interview Survey.
Chart 4-10. Trends in meeting the physical activity guidelines of the 2008 Federal Physical Activity Guidelines for
Americans through leisure-time activity only among adults ≥18 years of age by type of activity (NHIS, 1998–2015).
Percentages are age adjusted. The aerobic guidelines of the 2008 Federal Physical Activity Guidelines for Americans recommend
engaging in moderate leisure-time physical activity for ≥150 min/wk or vigorous activity ≥75 min/wk or an equivalent combination.
NHIS indicates National Health Interview Survey.
Source: NHIS 1998 to 2015 (National Center for Health Statistics).7

Chart 4-11. Age-standardized global mortality rates attributable to low physical activity per 100 000, both sexes, 2015.
CLINICAL STATEMENTS
AND GUIDELINES
11. Gahche J, Fakhouri T, Carroll DD, Burt VL, Wang CY, Fulton JE.
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CIR.0b013e3181e8edf1. J. Kaiser Family Foundation; 2010.
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GC, Ho PM, Lauer MS, Masoudi FA, Robertson RM, Roger V, Schwamm age, and racial/ethnic groups: a cross-sectional study. Int J Behav Nutr Phys
LH, Sorlie P, Yancy CW, Rosamond WD; on behalf of the American Heart Act. 2009;6:31. doi: 10.1186/1479-5868-6-31.
Association Strategic Planning Task Force and Statistics Committee. 15. Luke A, Dugas LR, Durazo-Arvizu RA, Cao G, Cooper RS. Assessing physical
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Goal through 2020 and beyond. Circulation. 2010;121:586–613. doi: 16. Fan JX, Wen M, Kowaleski-Jones L. Rural-urban differences in objective
10.1161/CIRCULATIONAHA.109.192703. and subjective measures of physical activity: findings from the National
3. Kann L, McManus T, Harris WA, Shanklin SL, Flint KH, Hawkins J, Queen Health and Nutrition Examination Survey (NHANES) 2003-2006. Prev
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AND GUIDELINES
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1 million men and women. Lancet. 2016;388:1302–1310. doi: 10.1016/ tive study of women in the United Kingdom. Circulation. 2015;131:721–
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AND GUIDELINES
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5. NUTRITION The AHA scoring system for ideal, intermediate, and

CLINICAL STATEMENTS
poor diet patterns uses a binary-based scoring system,

AND GUIDELINES
which awards 1 point for meeting the ideal target for

each metric and 0 points otherwise.2 For better consis-
tency with other dietary pattern scores such as DASH,
an alternative continuous scoring system has been
This chapter of the Update highlights national dietary developed to measure small improvements over time
habits, focusing on key foods, nutrients, dietary pat- toward the AHA ideal target levels (Table 5-1). The
terns, and other dietary factors related to cardiometa- dietary targets remain the same, and progress toward
bolic health. It is intended to examine current intakes, each of these targets is assessed by use of a more gran-
trends and changes in intakes, and estimated effects ular range of 1 to 10 (rather than 0 to 1).
on disease to support and further stimulate efforts to Using the alternative scoring system, the mean
monitor and improve dietary habits in relation to car- AHA healthy diet score improved between 2003 to
diovascular health. 2004 and 2011 to 2012 in the United States in both
children and adults (Chart 5-1). The prevalence of an
Prevalence and Trends in the AHA 2020 ideal healthy diet score (>80) increased from 0.2% to
0.6% in children (Chart 5-2) and from 0.7% to 1.5%
Healthy Diet Metrics
in adults (Chart 5-3). The prevalence of an intermedi-
(See Table 5-1 and Charts 5-1 through 5-4) ate healthy diet score (40–79) increased from 30.6%
The AHA’s 2020 Impact Goals prioritize improving car- to 44.7% in children and from 49.0% to 57.5% in
diovascular health,1 which includes following a healthy adults.3 These improvements were largely attributable
diet pattern characterized by 5 primary and 3 second- to increased whole grain consumption and decreased
ary metrics (Table 5-1) that should be consumed within SSB consumption in both children and adults.3 Among
the context that is appropriate in energy balance and adults, other significant changes between 1999 and
consistent with a DASH-type eating plan.1 2012 included increased consumption of nuts, seeds,
and legumes (from 0.54 to 0.81 servings/d) and
Abbreviations Used in Chapter 5 decreased consumption of 100% fruit juice (from 0.43
to 0.32 servings/d) and white potatoes (from 0.39 to
BMI body mass index 0.32 servings/d) among adults between 2003 to 2004
BP blood pressure and 2011 to 2012 (Chart 5-4).3 No major trends were
CHD coronary heart disease evident in progress toward the targets for consumption
CI confidence interval of sodium, fish, fruits and vegetables, processed meats,
CRP C-reactive protein
and saturated fat.
DASH Dietary Approaches to Stop Hypertension
Although AHA healthy diet scores tended to improve
DBP diastolic blood pressure in all categories of age, race/ethnicity, income, and
DM diabetes mellitus education level, many disparities present in earlier years
GBD Global Burden of Disease widened over time, with generally smaller improve-
HbA1c hemoglobin A1c (glycosylated hemoglobin) ments seen in minority groups and those with lower
HD heart disease
income or education.3 For example, among Americans
HF heart failure
with the highest family income (income-to-poverty
HR hazard ratio ratio ≥3.0), the proportion with a poor diet decreased
IHD ischemic heart disease from 50.5% to 35.7%, whereas among those with the
LDL-C low-density lipoprotein cholesterol lowest family income (income-to-poverty ratio <1.3),
MI myocardial infarction the proportion with a poor diet decreased from 67.8%
NH non-Hispanic
to only 60.6%.
PA physical activity
PREDIMED
RCT
Prevención con Dieta Mediterránea
randomized controlled trial
Global Trends in Key Dietary Factors
REGARDS Reasons for Geographic and Racial Differences in Stroke Globally, between 1999 and 2010, SSB intake increased
RR relative risk in several countries.4 Among adults, mean global intake
was highest in males aged 20 to 39 years, at 1.04 8-oz
SCD sudden cardiac death
servings per day. In comparison, globally, females >60
SSB sugar-sweetened beverage years of age had the lowest mean consumption at 0.34
TC total cholesterol servings per day. SSB consumption was highest in the
WHI Women’s Health Initiative Caribbean, with adults consuming on average 2 serv-
WWEIA What We Eat In America ings per day, and lowest in East Asia, at 0.20 servings

per day. Adults in the United States had the 26th-high- servings per day by NH black males and females,
CLINICAL STATEMENTS
est consumption among 187 countries. and 0.6 to 0.8 servings by Mexican American
AND GUIDELINES
Worldwide in 2010, mean sodium intake among males and females. For each of these groups,
adults was 3950 mg/d, which corresponds to salt intake <10% of adults in 2011 to 2012 met guidelines
of ≈10 g/d.5 Across world regions, mean sodium intakes of ≥3 servings per day.
were highest in Central Asia (5510 mg/d) and lowest in • Fruit consumption ranged from 1.0 to 1.6 serv-
Eastern sub-Saharan Africa (2180 mg/d). Across coun- ings per day in these sex and racial or ethnic sub-
tries, the lowest observed mean national intakes were groups: ≈9% of NH whites, 7% of NH blacks,
≈1500 mg/d. Between 1990 and 2010, global mean and 6% of Mexican Americans met guidelines of
sodium intake appeared to remain relatively stable, ≥2 cups per day. When 100% fruit juices were
although data on trends in many world regions were included, the number of servings increased and
suboptimal.5 the proportions of adults consuming ≥2 cups
In a systematic review of population-level sodium per day nearly doubled in NH whites, doubled in
initiatives (10 initiatives, 64 798 participants with suf- NH blacks, and more than doubled in Mexican
ficient data), reduction in mean sodium intake occurred Americans.
in 5 initiatives, whereas there was no change in 3 initia- • Nonstarchy vegetable consumption ranged from
tives and an increase in 2 initiatives.6 Successful pop- 1.7 to 2.7 servings per day. Across all racial/eth-
ulation-level sodium initiatives tended to use multiple nic subgroups, NH white females were the only
strategies and included structural activities, such as group meeting the target of consuming ≥2.5
food product reformulation. For example, Finland initi- cups per day.
ated a nationwide campaign in the late 1970s through • Consumption of fish and shellfish was lowest
public education, collaboration with the food industry, among Mexican American females and white
and salt labeling legislation. From 1979 to 2002, mean females (0.8 and 1.0 servings per week, respec-
24-hour urine sodium excretion in population-based tively) and highest among NH black females and
samples decreased in Finnish males (5.1 g/d to 3.9 NH black and Mexican American males (1.9 and
g/d) and females (4.1 g/d to 3.0 g/d); mean SBP and 1.7 servings per week, respectively). Generally,
prevalence of hypertension also decreased over that only 15% to 27% of adults in each sex and racial
time period.7,8 Similarly, the United Kingdom initiated or ethnic subgroup consumed at least 2 servings
per week.
a nationwide salt reduction program in 2003 to 2004

that included consumer awareness campaigns, pro- • Weekly consumption of nuts and seeds was
gressively lower salt targets for various food categories, ≈3.5 servings among NH whites and 2.5 serv-
clear nutritional labeling, and working with industry to ings among NH blacks and Mexican Americans.
reformulate foods. The UK initiative appears to have Approximately 1 in 4 whites, 1 in 6 NH blacks,
been successful in reducing the average sodium intake and 1 in 8 Mexican Americans met guidelines of
of the population by 15% from 2003 to 2011.6 Over ≥4 servings per week.
the same time period, there were also parallel decreases • Consumption of unprocessed red meats was
in blood pressure of 3.0/1.4 mm Hg in patients not tak- higher in males than in females, up to 4.8 serv-
ing antihypertensive medication (P<0.001), in stroke ings per week in Mexican American males.
mortality by 42% (P<0.001), and in IHD mortality by • Consumption of processed meats was lowest
40% (P<0.001); these findings remained statistically among Mexican American females (1.1 servings
significant after adjustment for changes in demograph- per week) and highest among NH black and NH
ics, BMI, and other dietary factors. white males (≈2.5 servings per week). Between
57% (NH white males) and 79% (Mexican
American females) of adults consumed ≤2 serv-
Dietary Habits in the United States: ings per week.
Current Intakes • Consumption of SSBs ranged from 6.8 servings
per week among NH white females to nearly
Foods and Nutrients
12 servings per week among Mexican American
Adults males. Females generally consumed less than
(See Chart 5-5) males. Some adults, from 33% of Mexican
The average dietary consumption by US adults of American males to 65% of NH white females,
selected foods and nutrients related to cardiometabolic consumed <36 oz/wk.
health based on data from 2011 to 2012 NHANES data • Consumption of sweets and bakery desserts
is detailed below: ranged from 3.9 servings per week (Mexican
• Consumption of whole grains was 1.1 servings American males) to >7 servings per week (white
per day by NH white males and females, 0.8 to 0.9 females). Approximately 1 in 3 adults (1 in 2

Mexican American males) consumed <2.5 serv- <1.5% of children in different age and sex
CLINICAL STATEMENTS
ings per week. subgroups meeting guidelines of ≥2.5 cups

AND GUIDELINES
• Consumption of eicosapentaenoic acid and doco- per day.

sahexaenoic acid ranged from 0.058 to 0.117 g/d — Consumption of fish and shellfish was low,
in each sex and racial or ethnic subgroup. Fewer ranging between 0.3 and 1.0 servings per
than 8% of NH whites, 14% of NH blacks, and week in all age and sex groups. Among all
11% of Mexican Americans consumed ≥0.250 ages, only 7% to 14% of youths consumed
g/d. ≥2 servings per week.
• One third to one half of adults in each sex and — Consumption of nuts, seeds, and beans
racial or ethnic subgroup consumed <10% of ranged from 1.1 to 2.7 servings per week
total calories from saturated fat, and approxi- among different age and sex groups, and
mately one half to two thirds consumed <300 mg generally <15% of children in different age
of dietary cholesterol per day. and sex subgroups consumed ≥4 servings
• Only ≈7% to 10% of NH whites, 4% to 5% of per week.
blacks, and 13% to 14% of Mexican Americans — Consumption of unprocessed red meats was
consumed ≥28 g of dietary fiber per day. higher in boys than in girls and increased
• Only approximately 6% to 8% of adults in each with age, up to 3.6 and 2.5 servings per
age and racial or ethnic subgroup consumed week in 15- to 19-year-old boys and girls,
less than the recommended 2.3 g of sodium per respectively.
day. Sodium is widespread in the US food supply, — Consumption of processed meats ranged
with top food categories of sodium intake listed from 1.4 to 2.3 servings per week, and the
in Chart 5-5. Top sources of sodium intake var- majority of children consumed no more than
ied by race/ethnicity, with the largest contributor 2 servings per week of processed meats.
being yeast breads for NH whites, sandwiches for — Consumption of SSBs was higher in boys
NH blacks, burritos and tacos for Hispanics, and than in girls in the 5- to 9-year-old (7.7±6.2
soups for NH Asians.9 versus 6.0±3.8 servings per week) and 10- to
14-year-old (11.6±5.3 versus 9.7±7.9 serv-
Foods and Nutrients
ings per week) groups, but it was higher in
Children and Teenagers girls than in boys in the 15- to 19-year-old
• The average dietary consumption by US children group (14±6.0 versus 12.4±5.8 servings
and teenagers of selected foods and nutrients per week). Only about half of children 5 to
related to cardiometabolic health is detailed below: 9 years of age and one quarter of boys 15
— Whole grain consumption was low, <1 serving to 19 years of age consumed <4.5 servings
per day in all age and sex groups, with <5% of per week.
all children in different age and sex subgroups — Consumption of sweets and bakery desserts
meeting guidelines of ≥3 servings per day.10 was higher among 5- to 9-year-old and 10-
— Fruit consumption was low and decreased to 14-year-old boys and girls and modestly
with age: 1.7 to 1.9 servings per day in lower (4.7 to 6 servings per week) among
younger boys and girls (5–9 years of age), 1.4 15- to 19-year-olds. A minority of children
servings per day in adolescent boys and girls in all age and sex subgroups consumed <2.5
(10–14 years of age), and 0.9 to 1.3 serv- servings per week.
ings per day in teenage boys and girls (15–19 — Consumption of eicosapentaenoic acid and
years of age). The proportion meeting guide- docosahexaenoic acid was low, ranging
lines of ≥2 cups per day was also low and from 0.034 to 0.065 g/d in boys and girls in
decreased with age: ≈8% to 14% in those all age groups. Fewer than 7% of children
5 to 9 years of age, 3% to 8% in those 10 and teenagers at any age consumed ≥250
to 14 years of age, and 5% to 6% in those mg/d.
15 to 19 years of age. When 100% fruit — Consumption of saturated fat was ≈11% of
juices were included, the number of servings calories in boys and girls in all age groups,
consumed increased by ≈50%, and propor- and average consumption of dietary cho-
tions consuming ≥2 cups per day increased lesterol ranged from ≈210 to 270 mg/d,
to nearly 25% of those 5 to 9 years of age, increasing with age. Approximately 25%
20% of those 10 to 14 years, and 15% of to 40% of youths consumed <10% energy
those 15 to 19 years of age. from saturated fat, and ≈70% to 80%
— Nonstarchy vegetable consumption was low, consumed <300 mg of dietary cholesterol
ranging from 1.1 to 1.5 servings per day, with per day.

— Consumption of dietary fiber ranged from Cost of a Healthy Diet
CLINICAL STATEMENTS
≈14 to 16 g/d. Fewer than 3% of children • A meta-analysis of price comparisons of healthy
AND GUIDELINES
in all age and sex subgroups consumed versus unhealthy diet patterns found that
≥28 g/d. the healthiest diet patterns cost, on average,
— Consumption of sodium ranged from 3.1 approximately $1.50 more per person per day to
to 3.5 g/d. Only 2% to 11% of children in consume.14
different age and sex subgroups consumed • In an assessment of snacks served at YMCA after-
<2.3 g/d. school programs from 2006 to 2008, healthful
— In children and teenagers, average daily snacks were ≈50% more expensive ($0.26 per
caloric intake is higher in boys than in girls snack) than less healthful snacks.15 Higher snack
and increases with age in boys. costs were driven by serving fruit juice compared
with water; serving refined grains without trans
fat compared with refined grains with trans fat;
Impact on US Mortality and serving fruit and canned or frozen vegeta-
(See Chart 5-6) bles. Serving fresh vegetables (mostly carrots or
A recent report used comparable risk assessment celery) or whole grains did not alter price.
methods and nationally representative data to estimate
Cost-Benefit of a Healthy Diet
the impact of 10 specific dietary factors on cardiomet-
• An overview of the costs of various strategies
abolic mortality (eg, deaths attributable to heart dis-
for primary prevention of CVD determined that
ease, stroke, type 2 DM) in the United States in 2002
the estimated costs per year of life gained were
and 2012 (Chart 5-6).11 In 2012, 318 656 (45.4%)
between $9800 and $18 000 for statin therapy,
of 702 308 cardiometabolic deaths were estimated
$1500 for nurse screening and lifestyle advice,
to be attributable to poor dietary habits. The larg-
$500 to $1250 for smoking cessation, and $20 to
est numbers of deaths attributable to diet were esti-
$900 for population-based healthy eating.16
mated to be from high sodium intake (66 508; 9.5%
• Each year, more than $33 billion in medical costs
of all cardiometabolic deaths), low consumption of
and $9 billion in lost productivity resulting from
nuts/seeds (59 374; 8.5%), high consumption of pro-
HD, cancer, stroke, and DM are attributed to poor
cessed meats (57 766; 8.2%), low intake of seafood
nutrition.10,17–19
omega-3 fats (54 626; 7.8%), low consumption of

• Two separate cost-effectiveness analyses esti-
vegetables (53,410; 7.6%) and fruits (52 547; 7.5%),
mated that population reductions in dietary salt
and high consumption of SSBs (51 694; 7.4%) (Chart
would not only be cost-effective but actually
5-5). Between 2002 and 2012, population-adjusted
cost-saving. In one analysis, a 1.2-g/d reduc-
US cardiometabolic deaths decreased by 26.5% ,with
tion in dietary sodium was projected to reduce
declines in estimated diet-associated cardiometabolic
US annual cases of incident CHD by 60 000 to
deaths for polyunsaturated fats (−20.8%), nuts/seeds
120 000, stroke by 32 000 to 66 000, and total
(−18.0%), and SSBs (−14.5%) and increases in diet-
mortality by 44 000 to 92 000.20 If accomplished
associated cardiometabolic deaths for sodium (5.8%)
through a regulatory intervention, estimated sav-
and unprocessed red meats (14.4%). Estimated cardio-
ings in healthcare costs would be $10 to $24 bil-
metabolic mortality related to whole grains, fruits, veg-
lion annually.20 Such an intervention would be
etables, seafood, omega-3 fats, and processed meats
more cost-effective than using medications to
remained relatively stable.
lower BP in all people with hypertension.
Cost Secular Trends

(See Chart 5-7) Trends in Dietary Patterns
The US Department of Agriculture reported that the In addition to individual foods and nutrients, overall
Consumer Price Index for all food decreased 0.3% from dietary patterns can be another useful tool for assess-
August 2016 to July 2017.12 Prices for foods eaten at ing diet quality.21 Different dietary patterns have been
home decreased by 1.3% in 2016, whereas prices for defined, such as Mediterranean, DASH-type, Healthy
foods eaten away from home increased by 2.6%.12 Eating Index–2010, Alternate Healthy Eating Index,
Total food expenditures as a share of personal dispos- Western, prudent, and vegetarian patterns. The origi-
able income have remained relatively stable from 2004 nal DASH diet was low fat; a higher-monounsaturated-
(9.5%) to 2014 (9.7%).13 The share of foods eaten fat DASH-type diet is even more healthful and similar
away from home increased from 47.2% in 2004 to to a traditional Mediterranean dietary pattern.22,23 The
50.1% in 2014, eclipsing the share of foods eaten at Healthy Eating Index–2010, which reflects compliance
home for the first time (Chart 5-7).13 with the 2010 US Dietary Guidelines, exhibits a wide

distribution among the US population, with a 5th per- from the 1990s to the 2000s. Portion sizes for other
CLINICAL STATEMENTS
centile score of 31.7 and a 95th percentile score of foods increased, including Mexican food (from 373 to
AND GUIDELINES
70.4 based on NHANES 2003 to 2004 data (theoreti- 512 calories), cheeseburgers (from 380 to 473 calories),
cal maximum=100).24 Average diet quality is worse in soft drinks (from 121 to 155 calories), fruit drinks (from
males (score=49.8) than in females (52.7), in younger 106 to 133 calories), and salty snacks (from 124 to 165
adults (45.4) than in older adults (56.1), and in smokers calories). French fry portion sizes increased at fast food
(45.7) than in nonsmokers (53.3). locations but not stores and restaurants. Soft drink and
Between 1999 and 2010, the average Alternate pizza portion sizes increased at all food sources (stores,
Healthy Eating Index–2010 score of US adults improved restaurants, and fast foods).
from 39.9 to 46.8.25 This was related to reduced In a quantitative analysis using various US surveys
intake of trans fat (accounting for more than half of between 1977 and 2010, the relationships of national
the improvement), SSBs, and fruit juice, as well as an changes in energy density, portion sizes, and number
increased intake of whole fruit, whole grains, polyun- of daily eating/drinking occasions to changes in total
saturated fatty acids, and nuts and legumes. Adults energy intake were assessed.27,32 Changes in energy
with greater family income and education had higher density were not consistently linked to energy intake
scores, and the gap between low and high SES wid- over time, whereas increases in both portion size and
ened over time, from 3.9 points in 1999 to 2000 to 7.8
number of eating occasions were linked to greater
points in 2009 to 2010.
energy intake.
Worldwide, 2 separate, relatively uncorrelated
Among US children 2 to 18 years of age, increases
dietary patterns can be characterized, 1 by greater
in energy intake between 1977 and 2006 (179 kcal/d)
intakes of health-promoting foods (eg, fruits, vegeta-
were entirely attributable to substantial increases in
bles, nuts, fish) and 1 by lower intakes of less optimal
energy eaten away from home (255 kcal/d).33 The per-
foods (eg, processed meats, SSBs).26 In 2010, compared
with low-income nations, high-income nations had bet- centage of energy eaten away from home increased
ter diet patterns based on healthful foods but substan- from 23.4% to 33.9% during this time, with a shift
tially worse diet patterns based on unhealthful foods. toward energy from fast food as the largest contributor
Between 1990 and 2010, both types of dietary pat- to foods eaten away from home for all age groups.
terns improved in high-income Western countries but In a study using NHANES and Nielsen Homescan data
to examine disparities in calories from store-bought
worsened or did not improve in low-income countries

in Africa and Asia. Middle-income countries showed consumer packaged goods over time, beverages from
the largest improvements in dietary patterns based on stores decreased between 2003 to 2006 and 2009 to
healthful foods but the largest deteriorations in dietary 2012. However, the decline in calories from consumer
patterns based on unhealthful foods. Overall, global packaged goods was slower for NH blacks, Mexican-
consumption of healthy foods improved but was out- Americans, and lowest-income households.34
paced by increased intake of unhealthy foods in most
world regions.
Cardiovascular Health Impact
Trends in Energy Intake Cardiovascular and Metabolic Risk
Until 1980, total energy intake remained relatively
Overweight and Obesity
constant27; however, data from NHANES indicate that
average energy intake among US adults increased • For short-term (up to 1–2 years) weight loss
from 1971, peaked at 2004, and has since stabilized. among overweight and obese individuals, the
Average total energy intakes among US white adults in macronutrient composition of the diet has much
1971, 2004, and 2010 were 1992 kcal/d, 2283 kcal/d, less influence than compliance with the selected
and 2200 kcal/d, respectively. Average total energy diet.35
intakes among US black adults in 1971, 2004, and • In ad libitum (not energy-restricted) diets, a low-
2010 were 1780, 2169, and 2134 kcal/d, respectively. carbohydrate (high-fat) diet demonstrated better
This rise in energy intake was primarily attributable to weight loss and reduced fat mass than a low-fat
increased carbohydrate intake, particularly of starches, (high-carbohydrate) diet at 1 year.36
refined grains, and sugars.28–30 • In ad libitum diets, intake of dietary sugars was
In a study using 4 nationally representative US positively linked to weight gain.37 However, isoen-
Department of Agriculture surveys of food intake ergetic exchange of dietary sugars with other
among US children,31 average portion sizes among US carbohydrates had no relationship with body
children increased for many foods between 1977 and weight,37 which suggests that all refined carbo-
2006. For example, pizza portion size increased from hydrates (complex starches and simple sugars)
406 to 546 calories, much of this increase occurring might be similarly obesogenic.

• In pooled analyses across 3 prospective cohort gain include education, income, race/ethnic-
CLINICAL STATEMENTS
studies of US males and females, increased glyce- ity, and (at least cross-sectionally) neighborhood
AND GUIDELINES
mic index and glycemic load were independently availability of supermarkets.46–48
associated with greater weight gain over time.38 • Other local food-environment characteristics, such
• Across types of foods, energy density (total calo- as availability of grocery stores (ie, smaller stores
ries per gram of food) is not consistently linked than supermarkets), convenience stores, and fast-
with weight gain or obesity. For example, nuts food restaurants, are not consistently associated
have relatively high energy density and are with diet quality or adiposity and could be linked
inversely linked to weight gain, and cheese has to social determinants of health for CVD.49
high energy density and appears relatively neutral,
BP and Blood Cholesterol
whereas sugar-sweetened beverages have low
• Sodium linearly raises BP in a dose-dependent
energy density and increase obesity.38 National
fashion, with stronger effects among older
changes in energy density over time are not con-
people, hypertensive people, and blacks,50 and
sistently linked to changes in energy intake.27
induces additional BP-independent damage to
• In analyses of >120 000 US males and females in
renal and vascular tissues.51,52
3 separate US cohorts followed up for up to 20
• Compared with a usual Western diet, a DASH-
years, changes in intakes of different foods and
beverages were linked to long-term weight gain in type dietary pattern with low sodium reduced SBP
different ways.38,39 Foods and beverages linked to by 7.1 mm Hg in adults without hypertension and
increased weight gain included high-glycemic car- by 11.5 mm Hg in adults with hypertension.51
bohydrates such as potatoes, white bread, white • Compared with the low-fat DASH diet, DASH-
rice, low-fiber breakfast cereals, sweets/desserts, type diets that increased consumption of either
and SSBs, as well as red and processed meats. In protein or unsaturated fat had similar or greater
contrast, increased consumption of several other beneficial effects on CVD risk factors. Compared
foods, including nuts, whole grains, fruits, veg- with a baseline usual diet, each of the DASH-
etables, legumes, fish, and yogurt, was linked to type diets, which included various percentages
relative weight loss over time. These findings sug- (27%–37%) of total fat and focused on whole
gest that attention to food-based dietary quality, foods such as fruits, vegetables, whole grains,
not simply counting total calories, is crucial for and fish, as well as potassium and other minerals
long-term weight homeostasis.39 and low sodium, reduced SBP by 8 to 10 mm Hg,

• In both adults and children, intake of SSBs DBP by 4 to 5 mm Hg, and LDL-C by 12 to 14
has been linked to weight gain and obesity.40 mg/dL. The diets that had higher levels of pro-
Randomized trials in children demonstrate reduc- tein and unsaturated fat also lowered triglycer-
tions in obesity when SSBs are replaced with non- ide levels by 16 and 9 mg/dL, respectively.53 The
caloric beverages.40 DASH-type diet higher in unsaturated fat also
• Dietary factors that stimulate hepatic de novo improved glucose-insulin homeostasis compared
lipogenesis, such as rapidly digestible grains, with the low-fat/high-carbohydrate DASH diet.54
starches, and sugars, as well as trans fat, appear In a systematic review and meta-analysis of con-
more strongly related to weight gain.38,39,41 trolled clinical trials of dietary pattern interven-
• Diet quality might also influence energy expendi- tions, the DASH diet had the largest net effect
ture. After intentional weight loss, isocaloric diets on SBP (−7.6 mm Hg) and DBP (−4.2 mm Hg),
higher in fat and lower in rapidly digestible carbo- whereas the Mediterranean diet had an effect
hydrates produced significantly smaller declines in on DBP (−1.4 mm Hg) but not SBP.55
total energy expenditure than low-fat, high-car- • In a meta-analysis of 60 randomized controlled
bohydrate diets, with a mean difference of >300 feeding trials, consumption of 1% of calories
kcal/d.35 from saturated fat in place of carbohydrates raised
• Other possible nutritional determinants of posi- LDL-C concentrations but also raised HDL-C and
tive energy balance (more calories consumed lowered triglycerides, with no significant effects
than expended), as determined by adiposity or on apolipoprotein B concentrations.56
weight gain, include larger portion sizes, skipping • In a meta-analysis of RCTs, consumption of 1%
breakfast, consumption of fast food, and eating of calories from trans fat in place of saturated
foods prepared outside the home, although the fat, monounsaturated fat, or polyunsaturated fat,
evidence for long-term relevance of these factors respectively, increased the ratio of TC to HDL-C by
has been inconsistent.42–45 0.031, 0.054, and 0.67; increased apolipoprotein
• Societal and environmental factors independently B levels by 3, 10, and 11 mg/L; decreased apo-
associated with diet quality, adiposity, or weight lipoprotein A-1 levels by 7, 5, and 3 mg/L; and

increased lipoprotein(a) levels by 3.8, 1.4, and 1.1 lower incidence of type 2 DM (RR per 4 weekly
CLINICAL STATEMENTS
mg/L.57 1-oz servings, 0.87; 95% CI, 0.81–0.94).66

AND GUIDELINES
• In meta-analyses of RCTs, consumption of eicos- • A meta-analysis of 102 randomized controlled

apentaenoic acid and docosahexaenoic acid feeding trials that included 239 diet arms and
for 212 weeks lowered SBP by 2.1 mm Hg58 4220 adults evaluated the effects of exchang-
and lowered resting heart rate by 2.5 beats per ing different dietary fats and carbohydrates
minute.59 on markers of glucose-insulin homeostasis.67
• In a meta-analysis of 24 RCTs examining effects of Although replacing 5% energy from carbohy-
red meat intake (≥0.5 versus <0.5 servings/d) on drates with saturated fat generally had no sig-
BP or lipids, red meat intake did not significantly nificant effects, replacing carbohydrates with
affect BP, TC, LDL-C, HDL-C, or triglycerides.60 unsaturated fats lowered both HbA1c and insulin.
• In a pooled analysis of 25 randomized trials total- Replacing saturated fat with polyunsaturated fat
ing 583 males and females both with and without significantly lowered glucose, HbA1c, C-peptide,
hypercholesterolemia, nut consumption signifi- and the homeostatic model assessment of insu-
cantly improved blood lipid levels.61 For a mean lin resistance. On the basis of “gold standard”
consumption of 67 g of nuts per day, TC was acute insulin response in 10 trials, polyunsatu-
reduced by 10.9 mg/dL (5.1%), LDL-C by 10.2 mg/ rated fat also significantly improved insulin
dL (7.4%), and the ratio of TC to HDL-C by 0.24 secretion capacity (by 0.5 pmol·L−1·min−1; 95%
(5.6% change; P<0.001 for each). Triglyceride CI, 0.2–0.8 pmol·L−1·min−1) whether it replaced
levels were also reduced by 20.6 mg/dL (10.2%) carbohydrates, saturated fat, or even monoun-
in subjects with high triglycerides (>2150 mg/dL). saturated fat.
Different types of nuts had similar effects.61 • Higher consumption of dairy or milk products is
• In an RCT, compared with a low-fat diet, 2 associated with lower incidence of DM and trends
Mediterranean dietary patterns that included toward lower risk of stroke.61,68,69 The inverse
either virgin olive oil or mixed nuts lowered SBP associations with DM appear strongest for both
by 5.9 and 7.1 mm Hg, plasma glucose by 7.0 yogurt and cheese.70
and 5.4 mg/dL, fasting insulin by 16.7 and 20.4
pmol/L, the homeostasis model assessment index Cardiovascular Events
by 0.9 and 1.1, and the ratio of TC to HDL-C by

0.38 and 0.26 and raised HDL-C by 2.9 and 1.6 Fats and Carbohydrates
mg/dL, respectively. The Mediterranean dietary • In the WHI RCT (N=48 835), reduction of total
patterns also lowered levels of CRP, interleukin-6, fat consumption from 37.8% energy (baseline)
intercellular adhesion molecule-1, and vascular to 24.3% energy (at 1 year) and 28.8% energy
cell adhesion molecule-1.62 (at 6 years) had no effect on incidence of CHD
(RR, 0.98; 95% CI, 0.88–1.09), stroke (RR, 1.02;
Blood Glucose 95% CI, 0.90–1.15), or total CVD (RR, 0.98; 95%
• A review of cross-sectional and prospective CI, 0.92–1.05) over a mean of 8.1 years.71 This
cohort studies suggests that higher intake of SSBs was consistent with null results of 4 prior RCTs
is associated with greater visceral fat and higher and multiple large prospective cohort studies that
risk of type 2 DM.63 indicated little effect of total fat consumption on
• Among 24 prospective cohort studies, greater con- CVD risk.72
sumption of refined carbohydrates and sugars, as • In 3 separate meta-analyses of prospective cohort
measured by higher glycemic load, was positively studies, the largest of which included 21 stud-
associated with risk of type 2 DM: For each 100-g ies with up to 2 decades of follow-up, saturated
increment in glycemic load, 45% higher risk was fat consumption overall had no significant asso-
seen (95% CI, 1.31–1.61; P<0.001; N=24 studies, ciation with incidence of CHD, stroke, or total
7.5 million person-years of follow-up).64 CVD.3,73,74 In comparison, in a pooled individual-
• In a meta-analysis of prospective cohort studies level analysis of 11 prospective cohort studies,
that included 442 101 participants, processed the specific exchange of polyunsaturated fat
meat consumption was associated with a higher consumption in place of saturated fat was associ-
risk of DM (RR, 1.51; 95% CI, 1.25–1.83, per 50 ated with lower CHD risk, with 13% lower risk
g/d). Unprocessed red meat consumption was for each 5% energy exchange (RR, 0.87; 95% CI,
also associated with increased risk of DM (RR, 0.70–0.97).75 These findings are consistent with a
1.19; 95% CI, 1.04–1.37, per 100 g/d).65 meta-analysis of RCTs in which increased polyun-
• In one meta-analysis of observational studies and saturated fat consumption in place of saturated
trials, greater consumption of nuts was linked to fat reduced CHD events, with 10% lower risk for

each 5% energy exchange (RR, 0.90; 95% CI, 34% lower risk of incident CHD (RR, 0.66; 95%
CLINICAL STATEMENTS
0.83–0.97).76 CI, 0.58–0.75), 25% lower risk of ischemic stroke
AND GUIDELINES
• In a pooled analysis of individual-level data from (RR, 0.75; 95% CI, 0.72–0.79), and 36% lower
11 prospective cohort studies in the United States, risk of hemorrhagic stroke (RR, 0.64; 95% CI,
Europe, and Israel that included 344 696 partici- 0.56–0.74).84 In a meta-analysis of 45 prospective
pants, each 5% higher energy consumption of studies, whole grain intake was associated with
carbohydrates in place of saturated fat was asso- decreased risk of CHD (HR, 0.81; 95% CI, 0.75–
ciated with a 7% higher risk of CHD (RR, 1.07; 0.87) and CVD (HR, 0.78, 95% CI, 0.73–0.85) but
95% CI, 1.01–1.14).77 Each 5% higher energy was not significantly associated with stroke (HR,
consumption of monounsaturated fat in place 0.88; 95% CI, 0.75–1.03).85
of saturated fat was not significantly associated • In a meta-analysis of prospective cohort stud-
with CHD risk.75 A more recent meta-analysis of ies, greater whole grain food consumption (2.5
prospective cohort studies found that increased compared with 0.2 servings per day) was associ-
intake of polyunsaturated fats was associated with ated with a 21% lower risk of CVD events (RR,
lower risk of CHD, whether it replaced saturated 0.79; 95% CI, 0.73–0.85), with similar estimates
fat or carbohydrates.78 These findings suggest in males and females and for various outcomes
that reducing saturated fat without specifying the (CHD, stroke, and fatal CVD). In contrast, con-
replacement might have minimal effects on CHD sumption of refined grain food was not associ-
risk, whereas increasing polyunsaturated fats ated with lower risk of CVD (RR, 1.07; 95% CI,
from vegetable oils could reduce CHD, whether 0.94–1.22).86
replacing saturated fat or carbohydrates.23 • Fish and seafood are associated with a lower
• In a meta-analysis of prospective cohort studies, risk of fatal CHD events, attributed in part to the
each 2% of calories from trans fat was associated antiarrhythmic properties of the very long-chain
with a 23% higher risk of CHD (RR, 1.23; 95% CI, omega-3 polyunsaturated fatty acids. Intake of
1.11–1.37).79 approximately 1 serving of fatty fish per week
• In meta-analyses of prospective cohort studies, was associated with a 50% lower risk of SCD,
greater consumption of refined complex carbo- compared to intake of <1 serving per month.87–89;
hydrates, starches, and sugars, as assessed by however, fried fish is associated with a greater
risk of CVD. Among 16 479 males and females in
glycemic index or load, was associated with sig-

nificantly higher risk of CHD and DM. When the the REGARDS study, individuals who consumed
highest category was compared with the lowest ≥2 servings fried fish per week had a greater risk
category, risk of CHD was 36% greater (glycemic of CVD over 5.1 years of follow-up than those
load: RR, 1.36; 95% CI, 1.13–1.63) and risk of who consumed <1 serving per month (HR, 1.63;
DM was 40% greater (glycemic index: RR, 1.40; 95% CI, 1.11–2.40).90
95% CI, 1.23–1.59).68,69 • In a meta-analysis of 16 prospective cohort stud-
• In a prospective cohort study of urban Chinese ies that included 326 572 generally healthy indi-
females (N=64 328), high glycemic index and viduals in Europe, the United States, China, and
glycemic load were associated with increased Japan, fish consumption was associated with sig-
risk of stroke. Compared with the lowest 10th nificantly lower risk of CHD mortality.91 Compared
percentiles, risks for the 90th percentiles of gly- with no consumption, consumption of an esti-
cemic index and glycemic load were 1.19 (95% mated 250 mg of long-chain omega-3 fatty acids
CI, 1.04–1.36) and 1.27 (95% CI, 1.04–1.54), per day was associated with 35% lower risk of
respectively.80 CHD death (P<0.001).
• In a meta-analysis of prospective cohort and
Foods and Beverages case-control studies from multiple countries,
• In meta-analyses of prospective cohort studies, consumption of unprocessed red meat was not
each daily serving of fruits or vegetables was significantly associated with incidence of CHD. In
associated with a 4% lower risk of CHD (RR, 0.96; contrast, each 50-g serving per day of processed
95% CI, 0.93–0.99), a 5% lower risk of stroke meats (eg, sausage, bacon, hot dogs, deli meats)
(RR, 0.95; 95% CI, 0.92–0.97), and a 4% lower was associated with a higher incidence of CHD
risk of cardiovascular mortality (RR, 0.96; 95% CI, (RR, 1.42; 95% CI, 1.07–1.89).92
0.92–0.99).81–83 • In a meta-analysis of 6 prospective observational
• In a prospective study of 512 891 adults in China studies, nut consumption was associated with a
(only 18% consumed fresh fruit daily), individu- lower incidence of fatal CHD (RR per 4 weekly
als who ate fresh fruit daily had 40% lower risk 1-oz servings, 0.76; 95% CI, 0.69–0.84) and non-
of CVD death (RR, 0.60; 95% CI, 0.54–0.67), fatal CHD (RR, 0.78; 95% CI, 0.67–0.92).66 Nut

consumption was not significantly associated control.102 Another analysis included individuals
CLINICAL STATEMENTS
with stroke risk based on 4 studies.66 not assigned to an active sodium reduction inter-
AND GUIDELINES
• In a meta-analysis of 6 prospective observa- vention, to focus on long-term usual intake. The

tional studies, consumption of legumes (beans) sodium-potassium ratio was linearly associated
was associated with lower incidence of CHD with risk of CVD over 10 to 15 years of follow-up
(RR per 4 weekly 100-g servings, 0.86; 95% CI, (RR, 1.24 per unit; 95% CI, 1.05–1.46; P=0.01),
0.78–0.94).66 whereas both sodium and potassium intake had
• Results from a meta-analysis showed that nei- associations with risk of CVD that were of border-
ther dairy consumption or dairy fat is significantly line significance.103
associated with higher or lower risk of CHD.93,94 • In a longer-term (median 24 years) post hoc
• In a meta-analysis of 15 country-specific observa- analysis of the Trials of Hypertension Prevention
tional cohorts, which together included 636 151 (median of five 24-hour urine measurements),
unique participants, 6.5 million person-years of participants randomized to low-sodium inter-
follow-up, 28 271 total deaths, 9783 cases of ventions tended to have a lower risk of death,
incident CVD, and 23 954 cases of incident type although this finding was not statistically sig-
2 DM, consumption of butter had small or neu- nificant (HR, 0.85; 95% CI, 0.66–1.09; P=0.19).
tral overall associations with mortality, CVDs, Every 1000 mg/d increase in sodium intake was
and DM.95 For example, butter consumption was associated with a 12% higher risk of death (HR,
weakly associated with all-cause mortality (per 14 1.12; 95% CI, 1.00–1.26; P=0.05), with no evi-
g [1 tbsp] per day: RR, 1.01; 95% CI, 1.00–1.03); dence of a J-shaped or nonlinear relationship.
was not associated with CVD (RR, 1.00; 95% CI, Every 1-unit increase in sodium/potassium ratio
0.98–1.02), CHD (RR, 0.99; 95% CI, 0.96–1.03), was associated with a 13% higher risk of death
or stroke (RR, 1.01; 95% CI, 0.98–1.03); and was (HR, 1.13; 95% CI, 1.01–1.27; P=0.04).104
associated with lower risk of DM (RR, 0.96; 95%
CI, 0.93–0.99).
Dietary Supplement Trends and
Potassium and Sodium
Outcomes
Major dietary sources of potassium include vegetables,
fruits, whole grains, legumes, nuts, and dairy. In random- Use of dietary supplements is common in the United
ized trials, potassium lowers BP, with stronger effects States among both adults and children:
among hypertensive people and when dietary sodium • Approximately half of US adults in 2007 to 2010
intake is high.96 BP lowering is related to both increased used ≥1 dietary supplement, with the most com-
urinary potassium excretion and a lower urine sodium- mon supplement being multivitamin-multimineral
to-potassium ratio. Consistent with these benefits, products (32% of males and females report-
potassium-rich diets are associated with lower risk of ing such use).105 It has been shown that most
CVD, especially stroke.77 Nearly all observational studies supplements are taken daily and for ≥2 years.106
demonstrate an association between higher estimated Supplement use is associated with older age,
sodium intakes (eg, >4000 mg/d) and increased risk for higher education, greater PA, moderate alcohol
CVD events, in particular stroke.97,98 Some studies have consumption, lower BMI, abstinence from smok-
also observed higher CVD risk at estimated low intakes ing, having health insurance, and white race.105,106
(eg, <3000 g/d), which suggests a potential J-shaped Previous research also suggests that supplement
relationship with risk.77,99–101 users have higher intakes of most vitamins and
• The estimation of sodium intake through a single minerals from their food choices alone than non-
dietary recall or a single urine excretion can lead users.107,108 The primary reasons US adults in 2007
to imprecise estimates of intake and can attenu- to 2010 reported for using dietary supplements
ate the estimated effect on subsequent risk,18,21 were to “improve overall health” (45%) and to
which could explain the J shape seen in certain “maintain health” (33%).105
studies.10 • Although dietary supplement use has increased
• In well-controlled randomized feeding trials, the over time, little evidence exists to support the use
lowest tested intake for which BP reductions were of most dietary supplements in reducing risks of
clearly documented was 1500 mg/d.51 CVD or death.109
• Post hoc analyses of the Trials of Hypertension • A meta-analysis of 4 RCTs and 27 prospective
Prevention with 10 to 15 years of follow-up cohort and nested case-control studies found
found that participants randomized to sodium no significant effect of calcium supplements or
reduction had a 25% lower risk of CVD (RR, 0.75; calcium plus vitamin D supplements with CVD
95% CI, 0.57–0.99) than those randomized to events or mortality.110

• Observational studies have found that the antioxi- adherence to a plant-based diet high in less
CLINICAL STATEMENTS
dants vitamin C, beta-carotene, and vitamin E are healthy plant foods was associated with a 16%
AND GUIDELINES
associated with lower risk of CHD and mortality, (HR, 1.16; 95% CI, 1.08–1.25) increased risk of
but RCTs providing antioxidant supplementation DM.122
have demonstrated no salutary effect on CVD • In a cohort of 380 296 US males and females,
outcomes or mortality.111–116 greater versus lower adherence to a Mediterranean
• Fish oil supplementation (840 mg/d) in a random- dietary pattern, characterized by higher intakes of
ized, placebo-controlled trial of 6875 patients vegetables, legumes, nuts, fruits, whole grains,
with HF resulted in a 9% reduction in total mor- fish, and unsaturated fat and lower intakes of red
tality (RR, 0.91; 95% CI, 0.83–0.99). CVD risk and processed meat, was associated with a 22%
reduction was also shown in 2 large randomized, lower cardiovascular mortality (RR, 0.78; 95% CI,
open-label trials, one in 11 324 Italian males with 0.69–0.87).123 Similar findings have been seen for
recent MI,111 and one in 18 645 Japanese patients the Mediterranean dietary pattern and risk of inci-
with high TC.117 However, several other trials of dent CHD and stroke124 and for the DASH-type
fish oil have not shown significant effects on CVD dietary pattern.125
risk.118 A meta-analysis of all RCTs demonstrated • In a cohort of 72 113 US female nurses, a dietary
a significant reduction for cardiac mortality but no pattern characterized by higher intakes of veg-
statistically significant effects on other CVD end- etables, fruits, legumes, fish, poultry, and whole
points.119 A recent AHA scientific advisory state- grains was associated with a 28% lower cardio-
ment summarized this available evidence.120 vascular mortality (RR, 0.72; 95% CI, 0.60–0.87),
whereas a dietary pattern characterized by higher
intakes of processed meat, red meat, refined
Dietary Patterns grains, french fries, and sweets/desserts was asso-
The 2015 US Dietary Guidelines Advisory Committee ciated with a 22% higher cardiovascular mortality
recently summarized the evidence for benefits of (RR, 1.22; 95% CI, 1.01–1.48).126 Similar findings
healthful diet patterns on a range of cardiometabolic have been seen in other cohorts and for other
and other disease outcomes.21 They concluded that a outcomes, including development of DM and
healthy dietary pattern is higher in vegetables, fruits, metabolic syndrome.127–133
whole grains, low-fat or nonfat dairy, seafood, legumes,
• The observational findings for benefits of a healthy

and nuts; moderate in alcohol (among adults); lower in food–based dietary pattern have been confirmed
red and processed meat; and low in sugar-sweetened in 2 randomized clinical trials, including a small
foods and drinks and refined grains. secondary prevention trial in France among
The 2015 US Dietary Guidelines also describe a patients with recent MI134 and a large primary pre-
healthy vegetarian dietary pattern, which includes more vention trial in Spain among patients with CVD
legumes, soy products, nuts and seeds, and whole risk factors.135 The latter trial, PREDIMED, demon-
grains but does not include meats, poultry, or seafood.21 strated a 30% reduction in the risk of stroke, MI,
In a meta-analysis of 8 observational studies (3 Seventh- and death attributable to cardiovascular causes
day Adventist cohorts [N=110 723] and 5 other cohorts in those patients randomized to Mediterranean-
[N=72 598]), vegetarians had a 40% lower risk of CHD style diets rich in extra-virgin olive oil or mixed
in the Seventh-day Adventist studies (RR, 0.60; 95% nuts.
CI, 0.43–0.80) and a 16% lower risk of CHD (RR, 0.84;
95% CI, 0.74–0.96) in the other studies.121
• In a prospective study among 200 272 US males Impact on Global Mortality
and females, greater adherence to a plant-based (See Chart 5-8)
dietary pattern, defined by higher intake of plant- • A report from the GBD Study estimated the
based foods and low intake of animal based impact of 14 specific dietary factors on mortal-
foods, was associated with a 20% lower risk of ity worldwide in 2005 to 2015. In 2015, a total
DM (HR, 0.80; 95% CI, 0.74–0.87). A healthful of 6.9 million male deaths (237.4 deaths per
plant-based diet index that emphasized higher 100 000) and 5.2 million female deaths (147.0
intakes of healthy plant foods (whole grains, deaths per 100 000) worldwide were estimated to
fruits, vegetables, nuts, legumes, vegetable oils, be attributable to poor dietary habits. The popu-
tea/coffee) and lower intake of animal foods and lation attributable fraction was 22.4% for males
less healthy plant foods (fruit juices, sweetened and 20.7% for females. Although the estimated
beverages, refined grains, potatoes, sweets/des- mortality rate attributable to poor dietary factors
serts) was associated with a 34% lower risk of decreased by 15.0% in the worldwide population
DM (HR, 0.66; 95% CI, 0.61–0.72). In contrast, from 2005 to 2015, the population attributable

fraction increased by 7.9% over the same time estimate disease burden for 315 diseases and
CLINICAL STATEMENTS
period.136 injuries in 195 countries and territories. Mortality

AND GUIDELINES
• The GBD 2015 Study used statistical models rates attributable to dietary risks were highest in
and data on incidence, prevalence, case fatality, Eastern Europe, Russia, and Central Asia (Chart
excess mortality, and cause-specific mortality to 5-8).136
Table 5-1. AHA Dietary Targets and Healthy Diet Score for Defining Cardiovascular Health
Consumption Range for Alternative
AHA Target Healthy Diet Score* Alternative Scoring Range*
Primary dietary metrics†
Fruits and vegetables ≥4.5 cups/d‡ 0 to ≥4.5 cups/d‡ 0–10
Fish and shellfish 2 or more 3.5-oz servings/wk 0 to ≥7 oz/wk 0–10

(≥200 g/wk)
Sodium ≤1500 mg/d ≤1500 to >4500 mg/d 10–0
SSBs ≤36 fl oz/wk ≤36 to >210 fl oz/wk 10–0
Whole grains 3 or more 1-oz-equivalent servings/d 0 to ≥3 oz/d 0–10
Secondary dietary metrics†

Nuts, seeds, and legumes ≥4 servings/wk (nuts/seeds: 0 to ≥4 servings/d 0–10
1 oz; legumes: ½ cup)
Processed meats 2 or fewer 1.75-oz servings/wk ≤3.5 to >17.5 oz/wk 10–0
(≤100 g/wk)
Saturated fat ≤7% energy ≤7 to >15 (% energy) 10–0
AHA Diet Score (primary) Ideal: 4 or 5 dietary targets (≥80%) Sum of scores for primary metrics 0 (worst) to 100 (best)§
Intermediate: 2 or 3 dietary targets Ideal: 80–100
(40%–79%) Intermediate: 40–79
Poor: <2 dietary targets (<40%) Poor: <40
AHA Diet Score (secondary) Ideal: 4 or 5 dietary targets (≥80%) Sum of scores for primary and 0 (worst) to 100 (best)§
Intermediate: 2 or 3 dietary targets secondary metrics Ideal: 80–100
(40%–79%) Intermediate: 40–79
Poor: <2 dietary targets (<40%) Poor: <40
AHA indicates American Heart Association; and SSBs, sugar-sweetened beverages.

*Consistent with other dietary pattern scores, the highest score (10) was given for meeting or exceeding the AHA target (eg, at least 4.5 cups of fruits and
vegetables per day; no more than 1500 mg/d of sodium), and the lowest score (0) was given for zero intake (protective factors) or for very high intake (harmful
factors). The score for each metric was scaled continuously within this range. For harmful factors, the level of high intake that corresponded to a zero score was
identified as approximately the 90th percentile distribution of US population intake.
†Selected by the AHA based on evidence for likely causal effects on cardiovascular events, diabetes mellitus, or obesity; a general prioritization of food rather
than nutrient metrics; consistency with US and AHA dietary guidelines; ability to measure and track these metrics in the US population; and parsimony, that is, the
inclusion of as few components as possible that had minimal overlap with each other while at the same time having some overlap with the many other relevant
dietary factors that were not included.2 The AHA dietary metrics should be targeted in the context of a healthy diet pattern that is appropriate in energy balance and
consistent with a DASH (Dietary Approaches to Stop Hypertension)-type eating plan, including but not limited to these metrics.
‡Including up to one 8-oz serving per day of 100% fruit juice and up to 0.42 cups/d (3 cups/wk) of starchy vegetables such as potatoes or corn.
§The natural range of the primary AHA Diet Score is 0 to 50 (5 components), and the natural range of the secondary AHA Diet Score is 0 to 80 (8 components).
Both scores are then rescaled to a range of 0 to 100 for comparison purposes. The ideal range of the primary AHA Diet Score corresponds to the AHA scoring system
of meeting at least 4 of 5 binary dietary targets (≥80%), the intermediate range corresponds to meeting 2 or 3 dietary targets (40%–79%), and the poor range
corresponds to meeting <2 dietary targets (<40%). The same ranges are used for the secondary AHA Diet Score for consistency and comparison.
Sources: My Life Check - Life’s Simple 71; Lloyd-Jones et al2; Rehm et al.3

CLINICAL STATEMENTS
Primary Primary + Secondary
Primary Primary + Secondary
[p-trend<0.001] [p-trend<0.001]
AND GUIDELINES
[p-trend<0.001] [p-trend<0.001]
60 60
50.2
50 50 46.1
44.6
40.6
40 40 44.4
Diet score (0-100)
Diet score (0-100)

38.9
40.5
30 34.1 30
20 20
10 10
0 0
2003-4 2005-6 2007-8 2009-10 2011-12 2003-4 2005-6 2007-8 2009-10 2011-12
Children (age 5-19 y) Adults (age 20+ y)
Chart 5-1. Trends in mean healthy diet scores for children and adults, NHANES 2003 to 2004 through 2011 to 2012.
Primary metrics include fruits/vegetables, whole grains, fish, sugar-sweetened beverages, and sodium. Secondary metrics
include nuts, seeds, and legumes; processed meats; and saturated fats. Components of poor, intermediate, and ideal diet are
defined in Table 5-1. Mean healthy diet scores based on the alternative scoring ranges described in Table 5-1.
0.2% 0.1% 0.2% 0.2% 0.6%

100%
90%
Ideal (80%+
30.6% 33.1% adherence)
35.8%
80% 39.7% [p-trend=0.17]
44.7%
70%
% of Population
60%
Intermediate
(40-79.9%
50% adherence)
[p-trend<0.001]
40%
69.2% 66.7%
64.1%
30% 60.2% Poor (<40%
54.6%
adherence)
[p-trend<0.001]
20%
10%
0%
2003-4 2005-6 2007-8 2009-10 2011-12
Chart 5-2. Healthy diet targets in children (5–19 years old) by survey year: NHANES 2003 to 2004, 2005 to 2006,
2007 to 2008, 2009 to 2010, and 2011 to 2012.
Components of poor, intermediate, and ideal diet are defined in Table 5-1. Percentages based on the alternative scoring
ranges described in Table 5-1.

CLINICAL STATEMENTS
0.7% 0.8% 0.8% 1.5% 1.5%

100%
AND GUIDELINES
Ideal (80%+
adherence)
90% [p-trend=0.003]
80%
49.0% 51.8% 49.6%
70% 55.4% 57.5%
Intermediate
(40-79.9%
% of Population
60%
adherence)
[p-trend<0.001]
50%
40%
Poor (<40%
30% adherence)
50.3% 49.7% [p-trend<0.001]
47.4%
20% 43.2% 41.0%
10%
0%
2003-4 2005-6 2007-8 2009-10 2011-12
Chart 5-3. Healthy diet targets in adults (≥20 years of age) by survey year: NHANES 2003 to 2004, 2005 to 2006,
2007 to 2008, 2009 to 2010, and 2011 to 2012.
Components of poor, intermediate, and ideal diet are defined in Table 5-1. Percentages based on the alternative scoring
ranges described in Table 5-1.

CLINICAL STATEMENTS
AND GUIDELINES
Chart 5-4. Mean consumption of key dietary components among US adults aged ≥20 years by NHANES survey
cycle, 1999 to 2012.
AHA indicates American Heart Association; CI, confidence interval; and NHANES, National Health and Nutrition Examination Survey.
a
The majority of means were adjusted for energy to 2000 kcal/d using the residual method. The means for saturated fat were
adjusted as a percentage of total energy.

b
For the primary and secondary total diet scores only, the mean change is between 2003 to 2004 and 2011 to 2012.
c
Based on the AHA 2020 Strategic Impact Goals. Intake of each dietary component was scored from 0 to 10 (beneficial
components) and from 10 to 0 (harmful components). Components were summed to calculate the primary AHA total diet
score (range, 0–50). Components were further summed to calculate the secondary AHA total diet score (range, 0–80).
Reprinted with permission from Rehm et al.3 Copyright © 2016, American Medical Association. All rights reserved.

CLINICAL STATEMENTS
AND GUIDELINES
Chart 5-5. Mean intakes of sodium and energy, mean sodium density, and ranked percentage sodium contribu-
tion of selected food categories among people aged ≥2 years, by sex and race/ethnicity: WWEIA, NHANES, United
States, 2013 to 2014.
The percentage (%) sodium consumed is defined as the sum of the amount of sodium consumed from each specific WWEIA
food category for all participants in the designated group, divided by the sum of sodium consumed from all food categories for
all participants in the designated group multiplied by 100. All estimates use one 24-hour dietary recall, take into account the
complex sampling design, and use the 1-day diet sample weights to account for nonresponse and weekend/weekday recalls.
†All estimates use one 24-hour dietary recall, take into account the complex sampling design, and use the 1-day diet sample
weights to account for nonresponse and weekend/weekday recalls.
§Statistically significant difference (p<0.001) in mean sodium and energy intakes compared with males.
¶Statistically significant difference (p<0.001) compared with non-Hispanic whites.
**Rank based on percentage of sodium consumed for overall US population aged ≥2years. Columns of other sex and race/
ethnic groups are ordered by this ranking. WWEIA food categories available at http://www.ars.usda.gov/Services/docs.
htm?docid=23429.
††Yeast breads, rolls, buns, bagels, and English muffins.
§§Sandwiches identified by a single WWEIA food code, includes burgers, frankfurter sandwiches, chicken/turkey sandwiches,
egg/ breakfast sandwiches, and other sandwiches.
¶¶Chips, popcorn, pretzels, snack mixes, and crackers.
***Natural and processed cheese.
†††Food categories that are in the top 20 contributors to sodium within an age subgroup but not in the top 25 overall.
§§§Estimates are statistically unreliable, relative standard error >30%.
NHANES indicates National Health and Nutrition Examination Survey; and WWEIA, What We Eat In America.
Source: Centers for Disease Control and Prevention.9

CLINICAL STATEMENTS
AND GUIDELINES
Chart 5-6. Absolute and proportional cardiometabolic disease mortality associated with overall suboptimal diet in
the United States in 2012 by population subgroups.
Bars represent absolute number (left) and percentage (right) of cardiometabolic deaths jointly related to suboptimal intakes
of 10 dietary factors. The 10 factors were low intakes of fruits, vegetables, nuts/seeds, whole grains, seafood omega-3 fats,
and polyunsaturated fats (replacing saturated fats) and high intakes of sodium, unprocessed red meats, and sugar-sweetened
beverages. Error bars indicate 95% uncertainty intervals.
CHD indicates coronary heart disease; and CVD, cardiovascular disease.
Reprinted with permission from Micha et al.11 Copyright © 2017, American Medical Association. All rights reserved.

CLINICAL STATEMENTS
AND GUIDELINES
Chart 5-7. Total US food expenditures (dollars in millions) at home and away from home, 2014.
Source: US Department of Agriculture, Economic Research Service.13
Chart 5-8. Age-standardized global mortality rates attributable to dietary risks per 100 000, both sexes, 2015.
6. He FJ, Brinsden HC, MacGregor GA. Salt reduction in the United Kingdom:
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analyses. BMJ. 2013;346:f1326. use and risk of all-cause and coronary heart disease mortality in older
98. Poggio R, Gutierrez L, Matta MG, Elorriaga N, Irazola V, Rubinstein A. persons: the Established Populations for Epidemiologic Studies of the
Daily sodium consumption and CVD mortality in the general population: Elderly. Am J Clin Nutr. 1996;64:190–196.
systematic review and meta-analysis of prospective studies. Public Health 114. Stampfer MJ, Hennekens CH, Manson JE, Colditz GA, Rosner B,
Nutr. 2015;18:695–704. doi: 10.1017/S1368980014000949. Willett WC. Vitamin E consumption and the risk of coronary dis-
99. Mente A, O’Donnell M, Rangarajan S, Dagenais G, Lear S, McQueen M, ease in women. N Engl J Med. 1993;328:1444–1449. doi: 10.1056/
Diaz R, Avezum A, Lopez-Jaramillo P, Lanas F, Li W, Lu Y, Yi S, Rensheng NEJM199305203282003.
L, Iqbal R, Mony P, Yusuf R, Yusoff K, Szuba A, Oguz A, Rosengren 115. Vivekananthan DP, Penn MS, Sapp SK, Hsu A, Topol EJ. Use of antioxi-
A, Bahonar A, Yusufali A, Schutte AE, Chifamba J, Mann JF, Anand dant vitamins for the prevention of cardiovascular disease: meta-anal-
SS, Teo K, Yusuf S; PURE, EPIDREAM and ONTARGET/TRANSCEND ysis of randomised trials. Lancet. 2003;361:2017–2023. doi: 10.1016/
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100. O’Donnell M, Mente A, Rangarajan S, McQueen MJ, Wang X, Liu L, Yan 117. Yokoyama M, Origasa H, Matsuzaki M, Matsuzawa Y, Saito Y, Ishikawa
H, Lee SF, Mony P, Devanath A, Rosengren A, Lopez-Jaramillo P, Diaz R, Y, Oikawa S, Sasaki J, Hishida H, Itakura H, Kita T, Kitabatake A, Nakaya
Avezum A, Lanas F, Yusoff K, Iqbal R, Ilow R, Mohammadifard N, Gulec N, Sakata T, Shimada K, Shirato K; Japan EPA lipid intervention study
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Dunbar SB, Frohlich ED, Hall JE, Jessup M, Labarthe DR, MacGregor GA, 118. Mozaffarian D, Wu JH. Omega-3 fatty acids and cardiovascular disease:
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119. Rizos EC, Ntzani EE, Bika E, Kostapanos MS, Elisaf MS. Association be- 127. Brunner EJ, Mosdøl A, Witte DR, Martikainen P, Stafford M, Shipley MJ,
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2012;308:1024–1033. doi: 10.1001/2012.jama.11374. 128. Fitzgerald KC, Chiuve SE, Buring JE, Ridker PM, Glynn RJ. Comparison
120. Siscovick DS, Barringer TA, Fretts AM, Wu JH, Lichtenstein AH, of associations of adherence to a Dietary Approaches to Stop
Costello RB, Kris-Etherton PM, Jacobson TA, Engler MB, Alger HM, Hypertension (DASH)-style diet with risks of cardiovascular disease and
Appel LJ, Mozaffarian D; on behalf of the American Heart Association venous thromboembolism. J Thromb Haemost. 2012;10:189–198. doi:
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Cardiovascular Disease in the Young; Council on Cardiovascular and M, Pfeiffer AF, Boeing H; European Prospective Investigation into Cancer
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CIR.0000000000000482. 130. Joosten MM, Grobbee DE, van der A DL, Verschuren WM, Hendriks HF,
121. Kwok CS, Umar S, Myint PK, Mamas MA, Loke YK. Vegetarian diet, Beulens JW. Combined effect of alcohol consumption and lifestyle be-
haviors on risk of type 2 diabetes. Am J Clin Nutr. 2010;91:1777–1783.
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doi: 10.3945/ajcn.2010.29170.
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131. Lutsey PL, Steffen LM, Stevens J. Dietary intake and the development
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A, Mouw T, Hollenbeck AR, Leitzmann MF, Schatzkin A. Mediterranean
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6. OVERWEIGHT AND OBESITY Abbreviations Used in Chapter 6 Continued
CLINICAL STATEMENTS
OR odds ratio
AND GUIDELINES
PSC Prospective Studies Collaboration
Click here to return to the Table of Contents QALY quality-adjusted life-year
Overweight and obesity are major risk factors for CVD, RR relative risk
including CHD, stroke,1,2 AF,3 VTE,4,5 and CHF. The AHA
has identified BMI <85th percentile (ages 2–19 years) SD standard deviation
and <25 kg/m2 (ages ≥20 years) as 1 of the 7 compo- SES socioeconomic status
nents of ideal cardiovascular health.6 In 2013 to 2014, SOS Swedish Obese Subjects
63.1% of children and 29.6% of adults met these STEMI ST-segment–elevation myocardial infarction
criteria (Chapter 2, Cardiovascular Health). According
UI uncertainty interval
to NHANES 2013 to 2014, 37.7% of US adults were VTE venous thromboembolism
obese, and 7.7% had class III obesity.7,8 WHI Women’s Health Initiative
YRBSS Youth Risk Behavior Surveillance System
Abbreviations Used in Chapter 6
ACTION Acute Coronary Treatment and Intervention Outcomes
Network Classification of Overweight and Obesity
AF atrial fibrillation
AFFIRM Atrial Fibrillation Follow-up Investigation of Rhythm • For adults, NHLBI weight categories are as fol-
Management lows: overweight (25.0 ≤ BMI ≤29.9 kg/m2) and
AHA American Heart Association obese class I (BMI 30–35 kg/m2), class II (BMI >35
to 39.9 kg/m2), and class III (BMI ≥40 kg/m2). BMI
APCSC Asia-Pacific Cohort Studies Collaboration
ARIC Atherosclerosis Risk in Communities Study
cutoffs often misclassify obesity in those with
ARISTOTLE Apixaban for Reduction in Stroke and Other muscle mass on the upper and lower tails of the
Thromboembolic Events in Atrial Fibrillation distribution. BMI categories also vary in prognos-
BMI body mass index tic value by race/ethnicity; they appear to overesti-
BP blood pressure
mate risk in African Americans and underestimate
risk in Asians.9 For this reason, lower BMI catego-
CAC coronary artery calcification

CAD coronary artery disease ries have been recommended for Asian and South
CARDIA Coronary Artery Risk Development in Young Adults Asian populations.10
CDC Centers for Disease Control and Prevention • For children, sex-specific BMI-for-age 2000 CDC
CHD coronary heart disease growth charts for the United States are used,11
CHF congestive heart failure
overweight is defined as 85th to <95th percentile,
CI confidence interval
and obese is defined as ≥95th percentile. These
DM diabetes mellitus categories were previously called “at risk for over-
ERFC Emerging Risk Factor Collaboration weight” and “overweight.” The change in termi-
GBD Global Burden of Disease nology reflects the labels used by organizations
GWAS Genome-Wide Association Study such as the Health and Medicine Division and the
GWTG Get With the Guidelines
American Academy of Pediatrics. More informa-
HD heart disease
tion is available elsewhere.12
HF heart failure • A 2013 AHA scientific statement recommended
HR hazard ratio that the definition of severe obesity for children
HUNT 2 Nord-Trøndelag Health Study ≥2 years old and adolescents be changed to BMI
IHD ischemic heart disease ≥120% of the 95th percentile for age and sex or
an absolute BMI ≥35 kg/m, whichever is lower.13
LDL-C low-density lipoprotein cholesterol
Look AHEAD Look: Action for Health in Diabetes This definition of severe obesity among children
MESA Multi-Ethnic Study of Atherosclerosis could better identify this small but important
MHO metabolically healthy obese group compared with the other common defini-
NCDR National Cardiovascular Data Registry tion of BMI ≥99th percentile for age and sex.13
• Current obesity guidelines define waist circum-
NH non-Hispanic
ference ≥40 inches (102 cm) for males and ≥35
NHDS National Hospital Discharge Survey inches (88 cm) for females as being associated
NHIS National Health Interview Survey with increased cardiovascular risk14; however,
NHLBI National Heart, Lung, and Blood Institute lower cutoffs have been recommended for vari-
(Continued ) ous racial/ethnic groups, for example, ≥80 cm for

Asian females and ≥90 cm for Asian males.9,15 adolescents whose parents had a bachelor’s
CLINICAL STATEMENTS
Waist circumference measurement is recom- degree or higher.20

AND GUIDELINES
mended for those with BMI of 25 to 34.9 kg/m2, • According to NHANES 2011 to 2014 data, 5.8%
to provide additional information on CVD risk.16 of youth aged 2 to 19 years had extreme obesity,
defined as BMI ≥120% of the 95th percentile for
age and sex, which was similar for boys (5.7%)
Prevalence and girls (5.9%) but was higher among Hispanic
Youth and non-Hispanic black youth than among NH
(See Table 6-1 and Chart 6-1) white youth.18
• According to 2013 to 2014 data from NHANES • According to self-reported height and weight
(NCHS/CDC), the overall prevalence of over- data from the YRBSS 2015,21 13.9% of US high
weight, including obesity, in children and adoles- school students were obese and 16.0% were
cents aged 2 to 19 years was 33.4% based on a overweight. The percentages of obesity were
BMI-for-age value ≥85th percentile of the 2000 higher in boys (16.8%) than girls (10.8%) and
CDC growth charts: 16.2% were overweight, in blacks (16.8%) and Hispanics (16.4%) than in
and 17.2% were obese (≥95th percentile). By whites (12.4%). Obesity rates varied by states:
age group, the prevalence of obesity for children The highest rates of obesity in females were
aged 2 to 5 years was 9.4%; for children aged observed in Kentucky and Mississippi (16.2%),
6 to 11 years, prevalence was 17.4%; and for and in males, West Virginia (23.4%); the lowest
adolescents aged 12 to 19 years, prevalence was rates in females were observed in Nevada (6.3%),
20.6%.17 There were no significant differences whereas for males, the lowest rates were seen in
in overweight (including obesity) prevalence for Montana (13.0%).
boys and girls.18
• According to 2011 to 2014 data from NHANES Adults
(NCHS/CDC), the overall prevalence of obesity (See Table 6-1 and Charts 6-2 through 6-8)
by age group was as follows: 8.9% for children • According to NHANES 2013 to 2014, among US
aged 2 to 5 years; 17.5% for children aged 6 to adults aged ≥20 years7:
11 years; and 20.5% for adolescents aged 12 to — The age-adjusted prevalence of obesity
19 years. In this period, there were no significant was 37.7% (35.0% of males and 40.4%
differences in obesity prevalence for boys and of females), and 7.7% had class III obesity
girls.8,19 (5.5% of males and 9.9% of females).
• According to 2011 to 2014 data from NHANES — Among males, the age-adjusted prevalence
(NCHS/CDC), among children and adolescents of obesity and class III obesity was not sig-
aged 2 to 19 years, the overall prevalence of obe- nificantly different for NH blacks (38.0% and
sity (≥95th percentile of the 2000 CDC growth 7.2%), NH Asians (12.6% and data not avail-
charts) was 16.5%, but it was lower for NH Asian able for class III obesity), Hispanics (37.9%
and NH white children than for NH black and and 5.4%), and NH whites (34.7% and
Hispanic children, without significant differences 5.6%).
between NH black and Hispanic children (Chart — Among females, the age-adjusted preva-
6-1).8,19 lence of obesity and class III obesity, respec-
• According to 2013 to 2014 NHANES data, among tively, was greater in NH blacks (57.2% and
all children aged 2 to 19 years, the prevalence of 16.8%), lower in NH Asians (12.4%, data
obesity was lower for NH Asian boys (12.1%) and not available for class III obesity), and similar
girls (5.0%) than for NH white (15.9%, 14.6%), in Hispanics (46.9% and 8.7%) compared
NH black (16.8%, 20.9%), and Hispanic (20.6%, with NH whites (38.2% and 9.7%).
22.1%) boys and girls, respectively.17,18 • According to NHANES 2011 to 2014, the age-
• The prevalence of childhood obesity varies by adjusted prevalence of obesity was higher among
SES. According to 2011 to 2014 NHANES data, middle-aged (40–59 years: 40.2%) and older (≥60
for children 12 to 19 years old, the prevalence years: 37.0%) adults than younger (20–39 years:
of obesity by percentage of poverty level was 32.3%) adults. This pattern (lower prevalence of
22.4% for those below 100%, 25.7% for 100% obesity among younger adults) was similar for
to 199%, 19.7% for 200% to 399%, and 13.7% males and females, although the prevalence of
for ≥400% of poverty level.19 obesity was higher among females (Chart 6-2).8
• In addition, obesity prevalence among adoles- • Using NHANES 2011 to 2014, obesity prevalence
cents was higher for those whose parents had was higher in females than males when stratified
a high school degree or less education than for by race/ethnicity (Table 6-1 and Chart 6-3). By

sex, the only significant differences were higher 2.7), dyslipidemia (high LDL-C RR, 1.8; low
CLINICAL STATEMENTS
prevalence of obesity among NH black females HDL-C RR, 2.1; high triglycerides RR, 3.0), and
AND GUIDELINES
than among NH black males and among Hispanic carotid atherosclerosis (RR, 1.7), whereas those
females than among Hispanic males (Table 6-1 who achieved normal weight by adulthood had
and Chart 6-3).8 risks comparable to individuals who were never
• Females have had a higher prevalence of class obese.26
III obesity and a lower prevalence of overweight • The CARDIA study showed that young adults
than males in all NHANES surveys from 1999 who were overweight or obese had lower self-
through 2014 (Chart 6-4).19 reported physical health-related quality of life
• In the United States, the prevalence of obesity, as than normal-weight participants 20 years later.27
estimated from self-reported height and weight
in the BRFSS/CDC (2015),22 varies by region and Adults
state. Self-reported estimates usually underes- • Obesity is associated with increased prevalence
timate BMI and obesity. In 2015, by state, the of type 2 DM, hypertension, dyslipidemia, sleep-
prevalence of obesity was highest in Louisiana disordered breathing, subclinical atherosclerosis,
(36%) and lowest in Colorado (19.9%) (Chart CHD, stroke, VTE, AF, and dementia.28
6-5).22 When BRFSS data from 2013 to 2015 were • Analyses of continuous BMI show the risk of type
combined, the prevalence of obesity by state was 2 DM increases with increasing BMI.29
higher for Hispanic adults and substantially higher • Among 68 070 adult participants across multiple
for NH black adults than for white adults (Charts NHANES surveys, the decline in BP in recent birth
6-6 through 6-8). cohorts slowed, mediated by BMI.30
• Another systematic review and meta-analysis of
37 studies showed that high childhood BMI was
Complications associated with an increased incidence of adult
Youth DM (OR, 1.70; 95% CI, 1.30–2.22), CHD (OR,
• According to the National Longitudinal Study of 1.20; 95% CI, 1.10–1.31), and a range of can-
Adolescent Health, compared with those with cers, but not stroke or breast cancer; however,
normal weight or those who were overweight, the accuracy of childhood BMI when predicting
adolescents who were obese had a 16-fold any adult morbidity was low. Only 31% of future
increased risk of having severe obesity as adults, DM and 22% of future hypertension and CHD
and 70.5% of adolescents with severe obesity occurred in those who as youth aged ≥12 years
maintained this weight status into adulthood.23 had been classified as overweight or obese. Only
• Children and adolescents who are overweight 20% of future adult cancers occurred in children
and obese are at increased risk for future adverse classified as overweight or obese.31
health effects, including the following24: • A meta-analysis of 123 cohorts with 1.4 million
— Increased prevalence of traditional cardio- adults and 52 000 CVD events reported that asso-
vascular risk factors such as hypertension, ciations of BMI with IHD, hypertensive HD, stroke,
hyperlipidemia, and DM. Despite these risks, and DM declined with advancing age (Chart 6-9)
a recent article examined 2 decades of data but were largely similar by sex and by region. The
from 1974 to 1993 and found that although RRs for 5-kg/m2 higher BMI for ages 55 to 64
the prevalence of obesity among children years ranged from 1.44 (95% CI, 1.40–1.48) for
increased during this time period, hyperten- IHD to 2.32 (95% CI, 2.04–2.63) for DM. On the
sion did not.25 basis of their data, the authors suggested that the
— Poor school performance, tobacco use, alco- theoretical minimum-risk exposure distribution
hol use, premature sexual behavior, and poor for BMI is 21 to 23 kg/m2 ± 1.1 to 1.8 kg/m2.32
diet. • Cardiovascular risks might be even higher with
— Other associated health conditions, such class III obesity than with class I or class II obesity.33
as asthma, hepatic steatosis, sleep apnea, Among 156 775 postmenopausal females in the
stroke, some cancers (breast, colon, and kid- WHI, for severe obesity versus normal BMI, HRs
ney), renal insufficiency, musculoskeletal dis- (95% CIs) for mortality were 1.97 (1.77–2.20)
orders, and gallbladder disease. in white females, 1.55 (1.20–2.00) in African
• Data from 4 Finnish cohort studies examining American females, and 2.59 (1.55–4.31) in
childhood and adult BMI with a mean follow-up Hispanic females; for CHD, HRs were 2.05 (1.80–
of 23 years found that overweight or obese chil- 2.35), 2.24 (1.57–3.19), and 2.95 (1.60–5.41),
dren who were obese in adulthood had increased respectively; and for CHF, HRs were 5.01 (4.33–
risks of type 2 DM (RR, 5.4), hypertension (RR, 5.80), 3.60 (2.30–5.62), and 6.05 (2.49–14.69),

respectively. However, CHD risk was strongly 2.04 and 1.64 for obesity, respectively.38 The
CLINICAL STATEMENTS
related to CVD risk factors across BMI categories, inclusion of obesity in dementia forecast models
AND GUIDELINES
even in class III obesity, and CHD incidence was increased the estimated prevalence of dementia
similar by race/ethnicity with adjustment for dif- through 2050 by 9% in the United States and
ferences in BMI and CVD risk factors.33 19% in China.39
• In a meta-analysis from 58 cohorts representing • A BMI paradox is often reported, with higher-
221 934 people in 17 developed countries with BMI patients demonstrating favorable outcomes
14 297 incident CVD outcomes, BMI, waist cir- in CHF, hypertension, peripheral vascular disease,
cumference, and waist-to-hip ratio were strongly and CAD; similar findings have been seen for per-
associated with intermediate risk factors of DM, cent body fat.
higher SBP and TC, and lower HDL-C. The asso- — The ARISTOTLE trial reported that in adjusted
ciations of adiposity measures (BMI, waist circum- analyses, higher BMI was associated with
ference, waist-to-hip ratio) with CVD outcomes lower all-cause mortality (overweight HR,
were attenuated after adjustment for intermedi- 0.67 [95% CI, 0.59–0.78]; obese HR, 0.63
ate risk factors (DM, SBP, TC, and HDL-C), along [95% CI, 0.54–0.74]), similar to an earlier
with age, sex, and smoking status. Measures of study from AFFIRM.40
adiposity also did not substantively improve risk — In another study of 2625 participants with
discrimination or reclassification when data on new-onset DM pooled from 5 longitudinal
intermediate risk factors were included.34 cohort studies, rates of total, CVD, and non-
• Obesity was cross-sectionally associated with CVD mortality were higher among normal-
subclinical atherosclerosis, including CAC and weight people than among overweight/
carotid IMT, among adults in MESA, and this obese participants, with adjusted HRs of
association persisted after adjustment for CVD 2.08 (95% CI, 1.52–2.85), 1.52 (95% CI,
risk factors.35 0.89–2.58), and 2.32 (95% CI, 1.55–3.48),
• Obesity is a strong predictor of sleep-disordered respectively.41
breathing, as well as numerous cancers, non- • Recent studies have evaluated risks for MHO
alcoholic fatty liver disease, gallbladder disease, versus “metabolically unhealthy” or “metaboli-
musculoskeletal disorders, and reproductive cally abnormal” obesity. The definition of MHO
abnormalities.36 has varied across studies, but it has often com-
• A systematic review of 25 prospective studies prised 0 or 1 metabolic abnormality by metabolic

examining overweight and obesity as predictors syndrome criteria, sometimes excluding waist
of major stroke subtypes in >2 million partici- circumference.
pants with >30 000 events in ≥4 years found an — Using strict criteria of 0 metabolic syndrome
adjusted RR for ischemic stroke of 1.22 (95% CI, components and no previous CVD diagnosis,
1.05–1.41) in overweight individuals and an RR a recent report of 10 European cohort stud-
of 1.64 (95% CI, 1.36–1.99) for obese individu- ies (N=163 517 people) reported that the
als relative to normal-weight individuals. RRs for prevalence of MHO varied from 7% to 28%
hemorrhagic stroke were 1.01 (95% CI, 0.88– in females and from 2% to 19% in males.42
1.17) and 1.24 (95% CI, 0.99–1.54) for over- — MHO appears to be unstable over time, with
weight and obese individuals, respectively. These 1 study showing that 44.5% of MHO individ-
risks were graded with increasing BMI and per- uals transitioned to metabolically unhealthy
sisted after adjusting for age, lifestyle, and other obesity over 8 years of follow-up.43
cardiovascular risk factors.37 — Among younger adults in the CARDIA study,
• A recent meta-analysis of 10 case-referent studies after 20 years of follow-up, 47% of people
and 4 prospective cohort studies (including ARIC5) were defined as being metabolically healthy
reported that when individuals with BMI ≥30 kg/ overweight (presence of 0 or 1 metabolic risk
m2 were compared with those with BMI <30 kg/ factor).44
m2, obesity was associated with a significantly — A recent meta-analysis of 22 prospective
higher prevalence (OR, 2.45; 95% CI, 1.78–3.35) studies suggested that CVD risk was higher
and incidence (RR, 2.39; 95% CI, 1.79–3.17) of in MHO than metabolically healthy normal-
VTE, although there was significant heterogeneity weight participants (RR, 1.45; 95% CI, 1.20–
in the studies.4 1.70); however, the risk in MHO individuals
• A recent meta-analysis of 15 prospective studies was lower than in individuals who were met-
of midlife BMI demonstrated that the increased abolically unhealthy and normal weight (RR,
risk for Alzheimer disease or any dementia was 2.07; 95% CI, 1.62–2.65) or obese (RR, 2.31;
1.35 and 1.26 for overweight, respectively, and 95% CI, 1.99–2.69).28

— Other reports suggest that obesity, especially mortality, and no specific cause of death was
CLINICAL STATEMENTS
long-lasting or severe obesity, without meta- inversely associated with BMI. Below 22.5 to 25
AND GUIDELINES
bolic abnormalities might not increase risk kg/m2, the overall inverse association with BMI
for AMI but does increase risk for HF.45,46 was predominantly related to strong inverse asso-
ciations for smoking-related respiratory disease,
and the only clearly positive association was for
Mortality
IHD.53
• Childhood BMIs in the highest quartile were • In a meta-analysis of 1.46 million white adults,
associated with premature death as an adult in a over a mean follow-up period of 10 years, all-
cohort of 4857 American Indian children during cause mortality was lowest at BMI levels of 20.0
a median follow-up of 23.9 years (BMI for quar- to 24.9 kg/m2. Among women, compared with
tile 4 versus quartile 1: incidence rate ratio, 2.30; a BMI of 22.5 to 24.9 kg/m2, the HRs for death
95% CI, 1.46–3.62).47 were as follows: BMI 15.0 to 18.4 kg/m2, 1.47;
• According to NHIS-linked mortality data, among 18.5 to 19.9 kg/m2, 1.14; 20.0 to 22.4 kg/m2,
young adults aged 18 to 39 years, the HR for all- 1.00; 25.0 to 29.9 kg/m2, 1.13; 30.0 to 34.9 kg/
cause mortality was 1.07 (95% CI, 0.91–1.26) for m2, 1.44; 35.0 to 39.9 kg/m2, 1.88; and 40.0
self-reported overweight (not including obese), to 49.9 kg/m2, 2.51. Similar estimates were
1.41 (95% CI, 1.16–1.73) for obesity, and 2.46 observed in men.54
(95% CI, 1.91–3.16) for extreme obesity.48 • According to data from the NCDR ACTION
• On the basis of NHANES I and II data, among Registry-GWTG, among patients presenting with
adults, obesity was associated with nearly
STEMI and a BMI ≥40 kg/m2, in-hospital mortality
112 000 excess deaths (95% CI, 53 754–170 064)
rates were higher for patients with class III obesity
relative to normal weight in 2000. Class I obe-
(OR, 1.64; 95% CI, 1.32–2.03) when class I obe-
sity was associated with almost 30 000 of these
sity was used as the referent.55
excess deaths (95% CI, 8534–68 220) and class
• In a study of 22 203 females and males from
II and III obesity with >82 000 deaths (95% CI,
England and Scotland, metabolically unhealthy
44 843–119 289). Underweight was associ-
obese individuals were at an increased risk of all-
ated with nearly 34 000 excess deaths (95% CI,
cause mortality compared with MHO individuals
15 726–51 766).49 As other studies have found,50
(HR, 1.72; 95% CI, 1.23–2.41).56

being overweight but not obese was not associ-
• Relation of various anthropometric measures to
ated with excess deaths.49
• A systematic review (2.88 million people and mortality:
>270 000 deaths) showed that relative to normal — In a comparison of 5 different anthropomet-
BMI (18.5 to <25 kg/m2), all-cause mortality was ric variables (BMI, waist circumference, hip
lower for overweight individuals (BMI 18.5 to <25 circumference, waist-to-hip ratio, and waist-
kg/m2: HR, 0.94; 95% CI, 0.91–0.96) and was to-height ratio) in 62 223 individuals from
not elevated for class I obesity (HR, 0.95; 95% Norway with 12 years of follow-up from
CI, 0.88–1.01). All-cause mortality was higher for the HUNT 2 study (Nord-Trøndelag Health
obesity overall (HR, 1.18; 95% CI, 1.12–1.25) and Study), the risk of death per SD increase in
for the subset of class II and III obesity (HR, 1.29; each measure was 1.02 (95% CI, 0.99–1.06)
95% CI, 1.18–1.41).51 for BMI, 1.10 (95% CI, 1.06–1.14) for waist
• Recent meta-analysis of 3.74 million deaths circumference, 1.01 (95% CI, 0.97–1.05) for
among 30.3 million participants found that over- hip circumference, 1.15 (95% CI, 1.11–1.19)
weight and obesity were associated with higher for waist-to-hip ratio, and 1.12 (95% CI,
risk of all-cause mortality, with lowest risks at BMI 1.08–1.16) for waist-to-height ratio. For CVD
22 to 23 kg/m2 in healthy never-smokers and 20 mortality, the risk of death per SD increase
to 22 kg/m2 in never-smokers with ≥20 years of was 1.12 (95% CI, 1.06–1.20) for BMI, 1.19
follow-up.52 (95% CI, 1.12–1.26) for waist circumference,
• In a collaborative analysis of data from almost 1.06 (95% CI, 1.00–1.13) for hip circumfer-
900 000 adults in 57 prospective studies, mostly ence, 1.23 (95% CI, 1.16–1.30) for waist-to-
in western Europe and North America, overall hip ratio, and 1.24 (95% CI, 1.16–1.31) for
mortality was lowest at a BMI of ≈22.5 to 25 kg/ waist-to-height ratio.57
m2 in both sexes and at all ages, after exclusion — However, because BMI and waist circumfer-
of early follow-up and adjustment for smoking ence are strongly correlated, large samples
status. Above this range, each 5-kg/m2-higher are needed to evaluate their independent
BMI was associated with ≈30% higher all-cause contributions to risk.14,58

— A recent pooled analysis of waist circumfer- the current prevalence of adolescent overweight
CLINICAL STATEMENTS
ence and mortality in 650 386 adults fol- and obesity was estimated to be $254 billion
AND GUIDELINES
lowed up for a median of 9 years revealed ($208 billion in lost productivity secondary to pre-
that a 5-cm increment in waist circumference mature morbidity and mortality and $46 billion in
was associated with an increase in all-cause direct medical costs).65
mortality at all BMI categories examined • A recent study recommended the use of $19 000
from 20 to 50 kg/m2.59 (2012 US dollars) as the incremental lifetime med-
— Similarly, in an analysis of postmenopausal ical cost of a child with obesity relative to a nor-
females in the WHI limited to those with BMI mal-weight child who maintains normal weight
≥40 kg/m2, mortality, CHD, and CHF inci- throughout adulthood.66
dence all increased with waist circumference • According to the 2006 NHDS, the incidence
>115 and >122 cm compared with ≤108.4 of bariatric surgery was estimated at 113 000
cm.33 cases per year, with costs of nearly $1.5 billion
— Finally, among 14 941 males and females in annually.67
ARIC, the risk of SCD was associated with • A recent cost-effectiveness study of laparoscopic
higher BMI and waist circumference, with tra- adjustable gastric banding showed that after 5
ditional risk factors mediating the association years, $4970 was saved in medical expenses; if
with BMI but not with waist circumference.60 indirect costs were included (absenteeism and
presenteeism), savings increased to $6180 and
$10 960, respectively.68 However, when expressed
Cost per QALY, only $6600 was gained for laparoscopic
Obesity costs the healthcare system, healthcare payers, gastric bypass, $6200 for laparoscopic adjustable
and obese individuals themselves. gastric band, and $17 300 for open Roux-en-Y
• In the United States, the estimated annual medi- gastric bypass, none of which exceeded the stan-
cal cost of obesity in 2008 was $147 billion; the dard $50 000 per QALY gained.69 Two other recent
annual medical costs for those who were obese large studies failed to demonstrate a cost ben-
were $1429 higher than for normal-weight indi- efit for bariatric surgery versus matched patients
viduals.61 A more recent study estimated mean over 6 years of follow-up70,71; however, another 2
annual per capita healthcare expenses associated studies showed cost savings for bariatric surgery
with obesity were $1160 for males and $1525 for among patients with DM at baseline.72,73
females.62
• According to NHANES I data linked to Medicare
and mortality records, 45-year-olds who were
Secular Trends
obese had lifetime Medicare costs of $163 000 (See Charts 6-10 and 6-11)
compared with $117 000 for those who were Youth
normal weight at 65 years of age.63 • Among infants and children from birth to >2 years
• According to data from the Medicare Current old, the prevalence of high weight for recumbent
Beneficiary Survey from 1997 to 2006, in 1997, length (ie, ≥95th percentile of sex-specific CDC
expenditures for Part A and Part B services per 2000 growth charts) was 9.5% in 2003 to 2004
beneficiary were $6832 for a normal-weight and 8.1% in 2011 to 2014. The decrease of 1.4%
person, which was more than for overweight was not statistically significant.74
($5473) or obese ($5790) people; however, over • According to NCHS/CDC and NHANES surveys,
time, expenses increased more rapidly for over- the prevalence of obesity among children and
weight and obese people.64 adolescents increased substantially from 1963 to
• The costs of obesity are high: People with obesity 1965 through 2013 to 2014, but this increase has
paid on average $1429 (42%) more for health- slowed and has begun to reverse among children
care costs than normal-weight people in 2006. aged 2 to 5 years (Chart 6-10).
For beneficiaries who are obese, Medicare pays • Specifically, according to NHANES data, from
$1723 more, Medicaid pays $1021 more, and pri- 1988 to 1994, 2003 to 2006, and 2011 to 2014,
vate insurers pay $1140 more annually than for the percentage of children 12 to 19 years of
beneficiaries who are at normal weight. Similarly, age classified as obese increased from 10.5% to
people who are obese have 46% higher inpatient 17.6% to 20.5%, respectively19; however, during
costs and 27% more outpatient visits and spend the same time periods, among children aged 2
80% more on prescription drugs.61 to 5 years, the prevalence of obesity went from
• Using 4 waves of NHANES data (through 2000), 7.2% in 1988 to 1994 to 12.5% in 2003 to 2006
the total excess cost in 2007 US dollars related to to 8.9% in 2011 to 2014.18,19 Another analysis of

NHANES data showed that between 1988 to 1994 • A systematic review and meta-analysis of 15 pro-
CLINICAL STATEMENTS
and 2013 to 2014, extreme obesity increased spective cohort studies with 200 777 participants
AND GUIDELINES
among children aged 6 to 11 years (from 3.6% showed that children and adolescents who were
to 4.3%) and among adolescents aged 12 to 19 obese were ≈5 times more likely to be obese
years (from 2.6% to 9.1%). However, between in adulthood than those who were not obese.
2005 to 2006 and 2013 to 2014, no significant Approximately 55% of children who are obese
increasing trends were observed.18 go on to be obese in adolescence, 80% of obese
• According to the YRBSS, among US high school adolescents will still be obese in adulthood, and
students between 1999 and 2015, there was a 70% will be obese over age 30. However, 70%
significant linear increase in the prevalence of of obese adults were not obese in childhood or
obesity (from 10.6% to 13.9%) and in the preva- adolescence, so reducing the overall burden of
lence of overweight (from 14.1% to 16.0%). adult obesity might require interventions beyond
Between 1991 to 2015, there was a correspond- targeting obesity reduction solely at obese or
ing significant linear increase of students who overweight children.79
reported they were trying to lose weight, from • The CDC Prevention Status Reports highlight the
41.8% to 45.6%.21 status of public health policies and practices to
address public health problems, including obe-
Adults sity, by state. Reports rate the extent to which the
• In the United States, the prevalence of obesity state has implemented the policies or practices
among adults, estimated using NHANES data, identified from systemic reviews, national strate-
increased from 1999 to 2000 through 2013 to gies or action plans, or expert bodies.80 Obesity
2014 from 30.5% to 37.7%7 (Chart 6-11); how- reduction policies and programs implemented by
ever, from 2005 to 2006 through 2013 to 2014, country are also provided online.81
there was a significant linear trend for the increase
in obesity and class III obesity for females (from
35.6% to 41.1% and from 7.5% to 10.0%, Awareness
respectively) but not males (from 33.4% to 35.1% • According to NHANES 2003 to 2006 data, ≈23%
and from 7.5% to 10.0%, respectively).7 of overweight and obese adults misperceived
• From NHANES 1999 to 2002 to NHANES 2007 to themselves to be at a healthier weight status, and
2010, the prevalence of total and undiagnosed those people were less likely to have tried to lose
DM, total hypertension, total dyslipidemia, and weight in the prior year.82
smoking did not change significantly within any of • Recent studies show that parents’ perceptions of
the BMI categories, but there was a lower preva- overweight and obesity differ according to the
lence of dyslipidemia (−3.4%; 95% CI, −6.3% to child’s race and sex. Boys 6 to 15 years of age with
−0.5%) among overweight adults. However, the obesity were more likely than girls to be misper-
prevalence of untreated hypertension decreased ceived as being “about the right weight” by their
among overweight and obese adults and that of parents (OR, 1.40; 95% CI, 1.12–1.76; P=0.004).
untreated dyslipidemia decreased for all BMI cat- Obesity was significantly less likely to be misper-
egories (normal, overweight, obese, and BMI ≥35 ceived among girls 11 to 15 years of age than
kg/m2).75 among girls 6 to 10 years of age (OR, 0.46; 95%
• Another study reported that for females, but not CI, 0.29–0.74; P=0.002) and among Hispanic
males, the increase in waist circumference from males than among white males (OR, 0.58; 95%
NHANES 1999 to 2000 to NHANES 2010 to 2011 CI, 0.36–0.93; P=0.02).82 Notification of a child’s
was greater than expected based on the increase unhealthy weight by healthcare practitioners
in BMI.76 increased from 22% in 1999 to 34% in 2014.83
Prevention Treatment and Control

• In adults, 2 prevention targets are the built envi- • The randomized trial Look AHEAD showed that
ronment and the workplace. The built environ- among adults who were overweight and obese
ment plays a role in promoting healthy lifestyles and had type 2 DM, an intensive lifestyle interven-
and preventing obesity.77 Similar to schools for tion produced a greater percentage of weight loss
children, the workplace can provide an oppor- at 4 years than DM support education.84
tunity to educate adults on methods to reduce — After 8 years of intervention, the percentage
weight and can also motivate individuals to lose of weight loss ≥5% and ≥10% was greater in
weight through group participation.78 the intensive lifestyle intervention than in DM

support education groups (50.3% and 26.9% and many have not reported laboratory values or
CLINICAL STATEMENTS
versus 35.7% and 17.2%, respectively).85 medication use.89,90

AND GUIDELINES
— Look AHEAD was stopped early with a • In a large bariatric surgery cohort, the prevalence
median 9.6 years of follow-up for failure to of high 10-year predicted CVD risk was 36.5%,91
show a significant difference in CVD events but 76% of those with low 10-year risk had high
between the intensive lifestyle intervention lifetime predicted CVD risk. The correspond-
and control group.84 ing prevalence in US adults is 18% and 56%,
• Intensive lifestyle interventions produce greater respectively.92
weight loss than education alone among those • A meta-analysis of RCTs also showed substantially
with class III obesity86 and childhood obesity.87 higher weight loss and DM remission for bariat-
• Ten-year follow-up data from the nonrandom- ric surgery than for conventional medical therapy,
ized SOS bariatric intervention study (see Bariatric with follow-up of ≤2 years.93
Surgery) suggested that to maintain a favorable • According to retrospective data from the United
effect on cardiovascular risk factors, more than States, among 9949 patients who underwent
the short-term goal of 5% weight loss is needed gastric bypass surgery, after a mean of 7 years,
to overcome secular trends and aging effects.88 long-term mortality was 40% lower among the sur-
Long-term follow-up might be necessary to show gically treated patients than among obese control
reductions in CVD risk. subjects. Specifically, cancer mortality was reduced
by 60%, DM mortality by 92%, and CAD mortal-
ity by 56%. Nondisease death rates (eg, accidents,
Bariatric Surgery suicide) were 58% higher in the surgery group.94
• Lifestyle interventions often do not provide sus-
tained significant weight loss for people who are
obese. Among adults who are obese, bariatric Family History and Genetics
surgery produces greater weight loss and main- • Overweight and obesity have considerable genetic
tenance of lost weight than lifestyle interven- components, with heritability estimates ranging
tion, with some variations depending on the type from ≈40% to 75%.95
of procedure and the patient’s initial weight.29 • Monogenic or mendelian causes of obesity
Gastric bypass surgery is typically performed as a include mutations with strong effects in genes
Roux-en-Y gastric bypass, vertical sleeve gastrec- that control appetite and energy balance (eg, LEP,
tomy, adjustable gastric banding, or biliopancre- MC4R), as well as obesity that occurs in the con-
atic diversion with duodenal switch. Outcomes text of syndromes, as reviewed by Kaur et al.96
vary by bariatric surgery technique.89 A recent • However, most cases of obesity are determined by
DM consensus statement recommended bariat- the interaction of genetic and epigenetic factors
ric surgery to treat type 2 DM among adults with with an obesogenic environment, including diet,
class III obesity and recommended it be consid- PA, and the microbiome. Although BMI is most
ered to treat type 2 DM among adults with class I commonly used to define obesity at the popula-
obesity.86 tion level, measures of visceral adiposity closer
• Benefits reported for bariatric surgery include approximate the pathogenic form of excess body
substantial weight loss; remission of DM, hyper- weight.
tension, and dyslipidemia; reduced incidence of • GWAS in diverse populations have implicated
mortality; and fewer CVD events. Reported risks multiple loci for obesity, mostly defined by BMI,
with bariatric surgery include not only periopera- waist circumference, or waist-hip ratio. The FTO
tive mortality and adverse events but also weight locus is the most well-established obesity locus,
regain, DM recurrence (particularly for those first reported in 200791,97 and replicated in many
with longer DM duration before surgery), bone studies with diverse populations and age groups
loss, increases in substance use disorders, suicide, since then.98–102 The mechanisms underlying the
and nutritional deficiencies. Outcomes must be association remain incompletely elucidated but
assessed cautiously, because most bariatric sur- could be related to mitochondrial thermogen-
gery data come from nonrandomized observa- esis10 or food intake.103
tional studies, with only a few randomized clinical • Other GWAS have reported numerous addi-
trials comparing bariatric surgery to medical treat- tional loci, as reviewed by Fall and Ingelsson,104
ment for patients with DM. Furthermore, stud- with >300 putative loci, most of which explain
ies have not always reported their definition of only a small proportion of the variance in obe-
“remission” or “partial remission” for comorbidi- sity, have not been mechanistically defined, and
ties such as DM, hypertension, and dyslipidemia, have unclear clinical significance. Fine mapping

of loci, including recent efforts focused on GWAS the Federated States of Micronesia, Libya, Qatar,
CLINICAL STATEMENTS
in African ancestry,105 in addition to mechanistic Tonga, and Samoa. As of 2013, around the world,
AND GUIDELINES
studies, is required to define functionality of obe- obesity rates are higher for females than males
sity-associated loci. and in developed countries than in developing
• A large GWAS of obesity in >240 000 individuals countries. Higher obesity rates for females than
of predominately European ancestry revealed an for males occur for age ≥45 years in developed
interaction with smoking,106 which highlights the countries but at age ≥25 years in developing
need to consider gene-environment interactions countries.109
in genetic studies of obesity. • Between 1980 and 2013, the prevalence of
overweight and obesity rose by 27.5% for
adults.109 Over this same period, no declines in
Global Burden obesity prevalence were detected. In 2008, an
(See Chart 6-12) estimated 1.46 billion adults were overweight or
Maps of the prevalence of obesity worldwide are avail- obese. The prevalence of obesity was estimated
able online.107 at 205 million males and 297 million females in
• Although there is considerable variability in over- 2013. The highest prevalence of male obesity
weight and obesity data methodology and quality is in the United States, Southern and Central
worldwide, cross-country comparisons can help Latin America, Australasia, and Central and
reveal different patterns. Worldwide, from 1975 Western Europe, and the lowest prevalence is
to 2014, the prevalence of obesity increased from in South and Southeast Asia and East, Central,
3.2% in 1975 to 10.8% in 2014 in males and and West Africa. For females, the highest preva-
from 6.4% to 14.9% in females, and mean age- lence of obesity is in Southern and North Africa,
standardized BMI increased from 21.7 to 24.2 the Middle East, Central and Southern Latin
kg/m2 in males and from 22.1 to 24.4 kg/m2 in America, and the United States, and the lowest
females.108 Worldwide, between 1980 and 2013, is in South, East, and Southeast Asia, the high-
the proportion of overweight or obese adults income Asia-Pacific subregion, and East, Central,
increased from 28.8% (95% UI, 28.4%–29.3%) and West Africa.110
to 36.9% (95% UI, 36.3%–37.4%) among males • The GBD 2015 Study used statistical models and
and from 29.8% (95% UI, 29.3%–30.2%) to data on incidence, prevalence, case fatality, excess
38.0% (95% UI, 37.5%–38.5%) among females. mortality, and cause-specific mortality to estimate
Since 2006, the increase in adult obesity in disease burden for 315 diseases and injuries in
developed countries has slowed. The estimated 195 countries and territories. The Pacific Island
prevalence of adult obesity exceeded 50% of countries have the highest mortality rates attrib-
males in Tonga and females in Kuwait, Kiribati, utable to high BMI (Chart 6-12).107

Table 6-1. Overweight and Obesity

CLINICAL STATEMENTS
Prevalence of Overweight Prevalence of Overweight

AND GUIDELINES
and Obesity, 2011–2014, Prevalence of Obesity, and Obesity, 2011–2014, Prevalence of Obesity,
Age ≥20 y 2011–2014, Age ≥20 y Ages 2–19 y 2011–2014, Ages 2–19 y
n % n % n % n % Cost, 2008*
Total 157 232 115 69.4 82 241 005 36.3 24 036 573 32.1 12 339 701 16.5 $147 Billion
Males 78 854 444 72.5 37 306 309 34.3 12 326 869 32.3 6 231 683 16.3 …
Females 78 215 543 66.4 45 115 291 38.3 11 709 947 32.0 6 107 613 16.7 …
NH white
Males 53 310 267 73.0 24 537 328 33.6 5 962 553 29.3 2 848 504 14.0 …
Females 49 632 907 63.7 27 660 411 35.5 5 419 620 28.0 2 847 989 14.7 …
NH black
Males 7 968 039 69.1 4 324 189 37.5 1 734 453 32.8 924 000 17.5 …
Females 11 782 661 82.2 8 156 124 56.9 1 929 861 37.6 1 026 805 20.0 …
NH Asian
Males 2 504 566 46.6 601 956 11.2 416 430 24.9 190 805 11.4 …
Females 2 165 586 34.6 744 811 11.9 245 206 15.0 86 088 5.3 …
Hispanic
Males 13 015 852 79.6 6 377 113 39.0 3 601 223 40.4 1 939 812 21.7 …
Females 12 721 527 77.1 7 540 516 45.7 3 400 898 39.8 1 798 951 21.0 …
Overweight and obesity in adults is defined as body mass index (BMI) ≥25 kg/m . Obesity in adults is defined as BMI ≥30 kg/m . In children, overweight and obesity
2 2
are based on BMI-for-age values at or above the 85th percentile of the 2000 Centers for Disease Control and Prevention (CDC) growth charts. In children, obesity
is based on BMI-for-age values at or above the 95th percentile of the CDC growth charts. In January 2007, the American Medical Association’s Expert Task Force on
Childhood Obesity recommended new definitions for overweight and obesity in children and adolescents111; however, statistics based on this new definition are not
yet available. Estimates for the total include those of “other” racial-ethnic groups.
Ellipses (…) indicate data not available; and NH, non-Hispanic.
*Data from Finkelstein et al.112
Sources: National Health and Nutrition Examination Survey (NHANES) 2011 to 2014 (adults), unpublished CDC tabulation; NHANES 2011 to 2014 (ages 2–19
years) from Ogden et al.8 Population count extrapolations calculated using the average of the 2011 and 2013 American Community Survey Summary File data.113
Chart 6-1. US children and adolescents with obesity by race/ethnicity, 2011 to 2014.
Obesity is body mass index (BMI) at or above the sex-and age-specific 95th percentile BMI cutoff points from the 2000 CDC
growth charts.
CDC indicates Centers for Disease Control and Prevention.
Source: CDC and National Center for Health Statistics. Data derived from the National Health and Nutrition Examination
Survey, Table 59.8

CLINICAL STATEMENTS
AND GUIDELINES
Chart 6-2. Age-adjusted prevalence of obesity in adults ≥20 years of age by sex and age group (NHANES 2011–2014).
Totals were age-adjusted by the direct method to the 2000 US census population using the age groups 20 to 39, 40 to 59,
and ≥60 years old. Crude estimates are 36.5% for all, 34.5% for males, and 38.5% for females. NHANES indicates National
Health and Nutrition Examination Survey.
*Significantly different from those aged 20 to 39 years.
†Significantly different from females of the same age group.
Source: Centers for Disease Control and Prevention/National Center for Health Statistics, NHANES, 2011 to 2014.
Chart 6-3. Age-adjusted prevalence of obesity in adults ≥20 years of age by sex and race/ethnicity (NHANES
2011–2014).
*Significantly different from non-Hispanic Asian people.
†Significantly different from non-Hispanic white people.
‡Significantly different from females of the same race and Hispanic origin.
§Significantly different from non-Hispanic black people.
Source: Centers for Disease Control and Prevention/National Center for Health Statistics, NHANES, 2011 to 2014.

CLINICAL STATEMENTS
AND GUIDELINES
Chart 6-4. Trends in overweight and obesity between 1999 to 2002 and 2011 to 2014 among US adults aged ≥20
years, by sex.
Overweight but not obese (25 ≤ body mass index [BMI] <30 kg/m2); grade 1 obesity (30 ≤ BMI <35 kg/m2); grade 2 obesity (35 ≤
BMI <40 kg/m2); grade 3 obesity (BMI ≥40 kg/m2).
Source: Centers for Disease Control and Prevention/National Center for Health Statistics, Health, United States, 2015, Figure 9
and Table 58. Data from National Health and Nutrition Examination Survey.19
Chart 6-5. Prevalence† of self-reported obesity among US adults aged ≥20 years by state and territory, BRFSS, 2015.
*Sample size <50 or the relative standard error (dividing the standard error by the prevalence) ≥30%.
†Prevalence estimates reflect BRFSS methodological changes started in 2011. These estimates should not be compared to preva-
lence estimates before 2011.
Source: Centers for Disease Control and Prevention, Obesity Prevalence Map, 2013 to 2015.22

CLINICAL STATEMENTS
AND GUIDELINES
Chart 6-6. Prevalence of self-reported obesity among non-Hispanic white adults aged ≥20 years, by state and
territory, BRFSS, 2013 to 2015.
Chart 6-7. Prevalence of self-reported obesity among Hispanic adults aged ≥20 years, by state and territory, BRFSS,
2013 to 2015.

CLINICAL STATEMENTS
AND GUIDELINES
Chart 6-8. Prevalence of self-reported obesity among non-Hispanic black adults aged ≥20 years, by state and terri-
tory, BRFSS, 2013 to 2015.

CLINICAL STATEMENTS
AND GUIDELINES
Chart 6-9. Relative risks for diseases associated with body mass index by age group.
APCSC indicates Asia-Pacific Cohort Studies Collaboration; ERFC, Emerging Risk Factor Collaboration; IHD, ischemic heart
disease; and PSC, Prospective Studies Collaboration.
Reprinted from Singh et al.32 Copyright © 2013, Singh et al. This is an Open Access article distributed under the terms of the
Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, pro-
vided the original author and source are credited.
Chart 6-10. US children and adolescents with obesity, 1963 to 2014.

Obesity is body mass index (BMI) at or above the sex- and age-specific 95th percentile BMI cutoff points from the 2000 CDC
growth charts.
CDC indicates Centers for Disease Control and Prevention.
Source: CDC/National Center for Health Statistics, Health, United States, 2015, Figure 8 and Table 59. Data from the National
Health and Nutrition Examination Survey.19

CLINICAL STATEMENTS
AND GUIDELINES
Chart 6-11. Trends in obesity prevalence among adults aged ≥20 years (age adjusted) and youth aged 2 to 19
years, United States, 1999 to 2000 through 2013 to 2014.
Data from the National Center for Health Statistics.19
Chart 6-12. Age-standardized global mortality rates attributable to high body mass index per 100 000, both sexes, 2015.
7. Flegal KM, Kruszon-Moran D, Carroll MD, Fryar CD, Ogden CL. Trends
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Bonnycastle LL, Bottinger E, Braga D, Buckley BM, Buyske S, Campbell H, EC, Biryukov S, Abbafati C, Abera SF, Abraham JP, Abu-Rmeileh NM,
Chambers JC, Collins FS, Curran JE, de Borst GJ, de Craen AJM, de Geus Achoki T, AlBuhairan FS, Alemu ZA, Alfonso R, Ali MK, Ali R, Guzman
EJC, Dedoussis G, Delgado GE, den Ruijter HM, Eiriksdottir G, Eriksson NA, Ammar W, Anwari P, Banerjee A, Barquera S, Basu S, Bennett DA,
AL, Esko T, Faul JD, Ford I, Forrester T, Gertow K, Gigante B, Glorioso Bhutta Z, Blore J, Cabral N, Nonato IC, Chang JC, Chowdhury R, Courville
N, Gong J, Grallert H, Grammer TB, Grarup N, Haitjema S, Hallmans G, KJ, Criqui MH, Cundiff DK, Dabhadkar KC, Dandona L, Davis A, Dayama
Hamsten A, Hansen T, Harris TB, Hartman CA, Hassinen M, Hastie ND, A, Dharmaratne SD, Ding EL, Durrani AM, Esteghamati A, Farzadfar
Heath AC, Hernandez D, Hindorff L, Hocking LJ, Hollensted M, Holmen F, Fay DF, Feigin VL, Flaxman A, Forouzanfar MH, Goto A, Green MA,
OL, Homuth G, Jan Hottenga J, Huang J, Hung J, Hutri-Kähönen N, Gupta R, Hafezi-Nejad N, Hankey GJ, Harewood HC, Havmoeller R, Hay
Ingelsson E, James AL, Jansson JO, Jarvelin MR, Jhun MA, Jørgensen ME, S, Hernandez L, Husseini A, Idrisov BT, Ikeda N, Islami F, Jahangir E, Jassal
Juonala M, Kähönen M, Karlsson M, Koistinen HA, Kolcic I, Kolovou G, SK, Jee SH, Jeffreys M, Jonas JB, Kabagambe EK, Khalifa SE, Kengne AP,
Kooperberg C, Krämer BK, Kuusisto J, Kvaløy K, Lakka TA, Langenberg C, Khader YS, Khang YH, Kim D, Kimokoti RW, Kinge JM, Kokubo Y, Kosen
Launer LJ, Leander K, Lee NR, Lind L, Lindgren CM, Linneberg A, Lobbens S, Kwan G, Lai T, Leinsalu M, Li Y, Liang X, Liu S, Logroscino G, Lotufo
S, Loh M, Lorentzon M, Luben R, Lubke G, Ludolph-Donislawski A, Lupoli PA, Lu Y, Ma J, Mainoo NK, Mensah GA, Merriman TR, Mokdad AH,
S, Madden PAF, Männikkö R, Marques-Vidal P, Martin NG, McKenzie CA, Moschandreas J, Naghavi M, Naheed A, Nand D, Narayan KM, Nelson
McKnight B, Mellström D, Menni C, Montgomery GW, Musk AB, Narisu EL, Neuhouser ML, Nisar MI, Ohkubo T, Oti SO, Pedroza A, Prabhakaran
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7. HIGH BLOOD CHOLESTEROL AND — For NH Asians, 161.9 mg/dL for boys and
CLINICAL STATEMENTS
167.6 mg/dL for girls
OTHER LIPIDS
AND GUIDELINES
• From 1988 to 2014, mean serum TC for adoles-
See Table 7-1 and Charts 7-1 through 7-5 cents 12 to 19 years of age decreased across all
subgroups of race and sex (Chart 7-1).
Click here to return to the Table of Contents • Among adolescents 12 to 19 years of age in
NHANES 2011 to 2014, the mean TC level was
High blood cholesterol is a major risk factor for CVD.1 156.7 mg/dL. For boys, it was 152.3 mg/dL;
The AHA has identified untreated total cholesterol for girls, it was 161.3 mg/dL. The racial/ethnic
<200 mg/dL (<170 mg/dL in children 6–19 years of breakdown was as follows (unpublished NHLBI
age) as 1 of the 7 components of ideal cardiovascular tabulation):
health.2 Fifty-six million (48.6%) US adults >40 years of — For NH whites, 151.7 mg/dL for boys and
age are eligible for statin therapy on the basis of the 162.0 mg/dL for girls
new ACC/AHA guideline for the management of blood — For NH blacks, 152.3 mg/dL for boys and
cholesterol.3 Twenty-one percent of youths aged 6 to 159.5 mg/dL for girls
19 years have at least 1 abnormal cholesterol measure.4 — For Hispanics, 154.7 mg/dL for boys and
For information on dietary cholesterol, total fat, satu- 160.5 mg/dL for girls
rated fat, and other factors that affect blood choles- — For NH Asians, 158.1 mg/dL for boys and
terol levels, see Chapter 5 (Nutrition).
166.7 mg/dL for girls
• Approximately 8.2% of adolescents 12 to 19 years
Prevalence of High TC of age in NHANES 2011 to 2014 have TC levels
Youth ≥200 mg/dL (unpublished NHLBI tabulation).
(See Chart 7-1) • Twenty percent of male adolescents and 27% of
• Among children 6 to 11 years of age, the mean female adolescents have TC levels of 170 to 199
TC level is 158.9 mg/dL. For boys, it is 158.5 mg/ mg/dL.5
dL; for girls, it is 159.3 mg/dL. The racial/ethnic • Among youths aged 6 to 19 years, there was
breakdown in NHANES 2011 to 2014 is as follows a decrease in mean TC from 165 to 160 mg/dL
(unpublished NHLBI tabulation): and a decrease in the prevalence of elevated TC
— For NH whites, 156.5 mg/dL for boys and from 11.3% to 8.1% from 1988 through 1994 to
159.6 mg/dL for girls 2007 through 2010.6
— For NH blacks, 162.1 mg/dL for boys and • Mean non–HDL-C (111.7 mg/dL) and prevalence
162.2 mg/dL for girls of elevated non–HDL-C both decreased signifi-
— For Hispanics, 159.5 mg/dL for boys and cantly from the periods 1988 through 1994 to
156.9 mg/dL for girls 2007 through 2010. In 2007 to 2010, 22.0%
of youths had either a low HDL-C level or a high
non–HDL-C level, which was lower than the
ACC American College of Cardiology 27.2% in 1988 to 1994.6
• Among adolescents (aged 12–19 years) between
ASCVD atherosclerotic cardiovascular disease
BRFSS Behavioral Risk Factor Surveillance System 1988 to 1994 and 2007 to 2010, there was a
CAD coronary artery disease decrease in mean LDL-C from 95 to 90 mg/dL and
CDC Centers for Disease Control and Prevention a decrease in geometric mean triglycerides from
CHD coronary heart disease 82 to 73 mg/dL. The prevalence of elevated LDL-C
and triglycerides also decreased significantly
DALY disability-adjusted life-year
between 1988 to 1994 and 2007 to 2010.6
DM diabetes mellitus • Fewer than 1% of adolescents are potentially eli-
FH familial hypercholesterolemia gible for pharmacological treatment on the basis
GBD Global Burden of Disease of guidelines from the American Academy of
GWAS genome wide association studies Pediatrics.7,8
LDL-C low-density lipoprotein cholesterol Adults (Aged ≥20 Years)
Mex. Am. Mexican American
(See Table 7-1 and Charts 7-2 through 7-4)
NH non-Hispanic
• An estimated 28.5 million adults ≥20 years of
NHANES National Health and Nutrition Examination Survey age have serum TC levels ≥240 mg/dL (extrapo-
NHLBI National Heart, Lung, and Blood Institute lated for 2014 by use of NCHS/NHANES 2011–
TC total cholesterol 2014 data), with a prevalence of 11.9%. From
WHO World Health Organization 1988 to 2014, mean serum TC for adults ≥20

years of age decreased across all subgroups of People 2020 target is a mean total blood choles-
CLINICAL STATEMENTS
race (Chart 7-2). terol of 177.9 mg/dL for adults, which has not yet
AND GUIDELINES
• Data from BRFSS 2015 showed9 been achieved for any group.14
— 31.7% of US adults have high TC. • Overall, the decline in cholesterol levels in recent
— The percentage of adults with high TC was years appears to reflect greater uptake of choles-
highest in Alabama (36.4%) and lowest in terol-lowering medications rather than changes in
Montana (27.1%). dietary patterns.15
• During the period from 2011 to 2014 • The declining TC level appears to reflect a world-
— The percentage of adults with high TC (≥240 wide trend; a report on trends in TC in 199 coun-
mg/dL) was lower for NH black (8.6%) than tries and territories indicated that TC declined in
for NH white (12.5%) and Hispanic (13.1%) high-income regions of the world (Australasia,
adults, and the same patterns were seen in North America, and Western Europe).16 During
males and females.10 the period from 1999 to 2006, 26.0% of adults
— Overall and for males, the prevalence of high had hypercholesterolemia, 9% of adults had both
TC was lower in NH black than in NH Asian hypercholesterolemia and hypertension, 1.5% of
subgroups, but this difference was not seen adults had DM and hypercholesterolemia, and
in females (Chart 7-3).10 3% of adults had all 3 conditions.17
— NH black males ≥20 years of age had the
Screening
lowest age-adjusted prevalence of serum TC
• The percentage of adults who reported having
≥240 mg/dL (Chart 7-4).
had a cholesterol check increased from 68.6%
— Females had higher prevalence of high TC
during 1999 to 2000 to 74.8% during 2005 to
(13.0%) than males (10.6%).10
2006.18
• The prevalence of high TC has decreased over
• Nearly 70% of adults (67% of males and nearly
time, from 18.3% of adults in 1999 to 2000 to
72% of females) had been screened for choles-
11.0% of adults in 2013 to 2014.10
terol (defined as being told by a doctor their cho-
• Research suggests that long-term exposure to
lesterol was high and indicating they had their
even modestly elevated cholesterol levels can lead
blood cholesterol checked <5 years ago) accord-
to CHD later in life.11
ing to data from NHANES 2011 to 2012, which
• In NHANES 2011 to 2014, ≈5.8% of adults ≥20
was unchanged since 2009 to 2010.10

years of age had undiagnosed hypercholesterol-
— Among NH whites, 71.8% were screened
emia, defined as a TC level ≥240 mg/dL and the
(70.6% of males and 72.9% of females).
participant having responded “no” to ever having
— Among NH blacks, 71.9% were screened
been told by a doctor or other healthcare profes-
sional that the participant’s blood cholesterol level
— Among NH Asians, 70.8% were screened
was high (unpublished NHLBI tabulation). Adults
with lower education levels (<12 years of educa-
— Among Hispanic adults, 59.3% were
tion) are more likely to be undiagnosed (6.6%)
screened (54.6% of males and 64.2% of
than adults with higher education (>12 years of
females).
education; 5.8%).
— The percentage of adults screened for cho-
• The age-adjusted mean TC level for adults ≥20
lesterol in the past 5 years was lower for
years of age declined linearly from 206 mg/dL
Hispanic adults than for NH white, NH black,
(95% CI, 205–207 mg/dL) in 1988 to 1994 to
and NH Asian adults.
203 mg/dL (95% CI, 201–205 mg/dL) in 1999 to
• The Healthy People 2020 target is 82% of adults
2002 and to 196 mg/dL (95% CI, 195–198 mg/
having their blood cholesterol checked within the
dL) in 2007 to 2010 (P<0.001 for linear trend).12
past 5 years.14
• Data from NHANES 2007 to 2010 (NCHS/CDC)
showed the serum total crude mean cholesterol Awareness
level in adults to be 194 mg/dL for males and • Data from the 2015 BRFSS study of the CDC
198 mg/dL for females.12 Statistically significant showed that among adults screened for high cho-
declining trends in age-adjusted mean TC levels lesterol, the age-adjusted percentage who had
from 1988 through 2014 were observed in all reported they had high cholesterol ranged from
race/ethnicity subgroups (Chart 7-2). 27.1% in Montana to 36.4% in Alabama.9 The
• The Healthy People 2010 guideline of an age- age-adjusted US total is 31.7%.
adjusted mean TC level of ≤200 mg/dL has been • Awareness of high LDL-C increased from 48.9%
achieved in adults, in males, in females, and in all in 1999 to 2000 to 62.8% in 2003 to 2004; how-
race/ethnicity and sex subgroups.13 The Healthy ever, awareness did not increase further through

2009 to 2010 (61.5%). Treatment among those adolescents who have a family history of dyslip-
CLINICAL STATEMENTS
aware of having high LDL-C increased from idemia or premature CVD, those whose family
AND GUIDELINES
41.3% in 1999 to 2000 to 72.6% in 2007 to history is unknown, and those youths with risk
2008. In 2009 to 2010, it was 70.0%.19 factors for CVD, such as being overweight or
obese, having hypertension or DM, or being a
Treatment
smoker.7 In 2011, the NHBLI Expert Panel recom-
• In 2013, the ACC/AHA released a revised recom-
mended universal dyslipidemia screening for all
mendation for statin treatment.1 Unlike Adult
children between 9 and 11 years of age and again
Treatment Panel III and other previous recommen-
between 17 and 21 years of age.23
dations, which had LDL-C and non–HDL-C goals
• A 2015 study based on NCHS data found that 21%
based on the patient’s risk category, the 2013 ACC/
of youths aged 6 to 19 years had at least 1 abnor-
AHA guideline recommended lipid measurement
mal cholesterol measure during 2011 to 2014.4
at baseline, at 1 to 3 months after statin initiation,
and then annually to check for the expected per- Adults
centage decrease of LDL-C levels (30% to <50% • Criteria from the “2013 ACC/AHA Guideline on
with a moderate-intensity statin and ≥50% with the Treatment of Blood Cholesterol to Reduce
a high-intensity statin). They also recommended Atherosclerotic Cardiovascular Risk in Adults”1
a discussion regarding statin therapy in 4 identi- could result in >45 million middle-aged Americans
fied groups in whom it has been clearly shown to who do not have CVD being recommended for
reduce ASCVD risk. The 4 statin benefit groups are consideration of statin therapy: 33.0 million are
(1) people with clinical ASCVD, (2) those with pri- at ≥7.5% 10-year risk, and 12.8 million are at
mary elevations of LDL-C >190 mg/dL, (3) people >5.0% to 7.4% 10-year risk. This is ≈1 in every
aged 40 to 75 years who have DM with LDL-C 70 3 American adults, many of whom are already
to 189 mg/dL and without clinical ASCVD, and (4) undergoing statin treatment under the previous
those without clinical ASCVD or DM with LDL-C US guidelines.24
70 to 189 mg/dL and estimated 10-year ASCVD • From 2005 to 2010, among adults with high
risk ≥7.5%. Approximately 31.9% of the ASCVD- LDL-C, age-adjusted control of LDL-C increased
free, nonpregnant US population between 40 and from 22.3% to 29.5%.25 The prevalence of LDL-C
79 years of age has a 10-year risk of a first hard control was lowest among people who reported
CHD event of ≥10% or has DM.20 receiving medical care less than twice in the pre-
• According to a recent analysis of NHANES data vious year (11.7%), being uninsured (13.5%),
from 2005 to 2010, the number of people eligible being Mexican American (20.3%), or having
for statin therapy would rise from 43.2 million US income below the poverty level (21.9%).26
adults (37.5%) to 56.0 million (48.6%) based on
the new ACC/AHA guidelines for the management
of blood cholesterol.3 Most of the increase comes Lipid Levels
from adults 60 to 75 years old without CVD who LDL Cholesterol
have a 10-year ASCVD risk ≥7.5%; the net number
of new statin prescriptions could potentially increase Youth
by 12.8 million, including 10.4 million for primary • There are limited data available on LDL-C for chil-
prevention.3 Individuals eligible for treatment under dren 6 to 11 years of age.
Adult Treatment Panel III but not ACC/AHA guide- • Among adolescents 12 to 19 years of age in
lines had higher LDL-C levels but were otherwise NHANES 2011 to 2014, the mean LDL-C level was
at lower risk than individuals eligible under both 87.7 mg/dL (boys, 85.7 mg/dL; girls, 89.8 mg/
guidelines or only under ACC/AHA guidelines.21 dL). The racial/ethnic breakdown was as follows
• Data from NHANES 1999 to 2012 show that (unpublished NHLBI tabulation):
the use of cholesterol-lowering treatment has — For NH whites, 86.5 mg/dL for boys and 89.9
increased substantially among adults, from 8% in mg/dL for girls
1999 to 2000 to 18% in 2011 to 2012.22 During — For NH blacks, 86.6 mg/dL for boys and 90.9
this period, the use of statins increased from 7% mg/dL for girls
to 17%.22 — For Hispanic Americans, 85.9 mg/dL for boys
and 87.8 mg/dL for girls
— For NH Asians, 84.5 mg/dL for boys and 96.9
Adherence mg/dL for girls
Youth • High levels of LDL-C occurred in 5.5% of male
• The American Academy of Pediatrics recom- adolescents and 7.5% of female adolescents dur-
mends screening for dyslipidemia in children and ing 2011 to 2014 (unpublished NHLBI tabulation).

Adults in NHANES 2011 to 2014 (unpublished NHLBI

CLINICAL STATEMENTS
• The mean level of LDL-C for American adults ≥20 tabulation).

AND GUIDELINES
years of age was 113.4 mg/dL in 2011 to 2014

(unpublished NHLBI tabulation). Adults
• According to NHANES 2011 to 2014 (unpublished • According to NHANES 2011 to 2014 (unpub-
NHLBI tabulation): lished NHLBI tabulation), the mean level of
— Among NH whites, mean LDL-C levels were HDL-C for American adults ≥20 years of age is
112.1 mg/dL for males and 114.9 mg/dL for 52.9 mg/dL.
females. — Among NH whites, mean HDL-C levels were
— Among NH blacks, mean LDL-C levels were 47.6 mg/dL for males and 58.6 mg/dL for
110.4 mg/dL for males and 111.4 mg/dL for females.
females. — Among NH blacks, mean HDL-C levels were
— Among Hispanics, mean LDL-C levels were 51.3 mg/dL for males and 58.1 mg/dL for
females. — Among Hispanics, mean HDL-C levels were
— Among NH Asians, mean LDL-C levels were 45.7 mg/dL for males and 53.9 mg/dL for
females. — Among NH Asians, mean HDL-C levels were
• Mean levels of LDL-C decreased from 126.2 mg/ 47.9 mg/dL for males and 58.8 mg/dL for
dL during 1999 to 2000 to 111.3 mg/dL during females.
2013 to 2014. The age-adjusted prevalence of • The prevalence of low HDL-C (<40 mg/dL) was
high LDL-C (≥130 mg/dL) decreased from 42.9% higher (23%) in those with lower education (<12
during 1999 to 2000 to 28.5% during 2013 to years) than in those with higher education (>12
2014 (unpublished NHLBI tabulation). years; 17%). Approximately 17% of adults (just
over one quarter of males and <10% of females)
HDL Cholesterol had low HDL-C during 2011 to 2012. The per-
Youth centage of adults with low HDL-C has decreased
• Among children 6 to 11 years of age in NHANES 20% since 2009 to 2010.10
2011 to 2014, the mean HDL-C level was 54.3 — Among NH whites, 17.1% (25.4% of males
mg/dL. For boys, it was 55.6 mg/dL, and for girls, and 9.3% of females) had low HDL-C.
it was 52.9 mg/dL. The racial/ethnic breakdown — Among NH blacks, 12.7% (19.1% of males
was as follows (unpublished NHLBI tabulation): and 7.8% of females) had low HDL-C. The
— For NH whites, 55.1 mg/dL for boys and 52.8 percentage of adults with low HDL-C was
mg/dL for girls lower among NH blacks than non-Hispanic
— For NH blacks, 60.0 mg/dL for boys and 56.3 whites. These racial and ethnic differences
mg/dL for girls were also observed in males but not in
— For Hispanics, 54.3mg/dL for boys and 51.3 females.
mg/dL for girls — Among NH Asians, 14.3% (24.5% of males
— For NH Asians, 55.8 mg/dL for boys and 54.5 and 5.1% of females) had low HDL-C. The
mg/dL for girls prevalence of low HDL-C was 5 times greater
• Among adolescents 12 to 19 years of age, the among NH Asian males than females. NH
mean HDL-C level was 51.0 mg/dL. For boys, it Asian adults had consistently lower percent-
was 49.1 mg/dL, and for girls, it was 52.9 mg/ ages of low HDL-C than Hispanic adults.
dL. The racial/ethnic breakdown was as fol-
lows (NHANES 2011–2014, unpublished NHLBI Triglycerides
tabulation): Youth
— For NH whites, 48.3 mg/dL for boys and 52.0 • There are limited data available on triglycerides
mg/dL for girls for children 6 to 11 years of age.
— For NH blacks, 52.4 mg/dL for boys and 55.7 • Among adolescents 12 to 19 years of age in
mg/dL for girls NHANES 2011 to 2014, the geometric mean tri-
— For Hispanics, 48.8 mg/dL for boys and 52.8 glyceride level was 79.4 mg/dL. For boys, it was
mg/dL for girls 81.9 mg/dL, and for girls, it was 76.8 mg/dL. The
— For NH Asians, 52.0 mg/dL for boys and 57.1 racial/ethnic breakdown was as follows (unpub-
mg/dL for girls lished NHLBI tabulation):
• Low levels of HDL-C occurred in 19.2% of male — Among NH whites, 82.3 mg/dL for boys and
adolescents and 12.5% of female adolescents 77.3 mg/dL for girls

— Among NH blacks, 62.8 mg/dL for boys and • Cascade screening, which recommends choles-
CLINICAL STATEMENTS
62.7 mg/dL for girls terol testing for all first-degree relatives of an FH
AND GUIDELINES
— Among Hispanics, 89.0 mg/dL for boys and patient, can be an effective strategy to identify
85.2 mg/dL for girls affected family members who would benefit from
— Among NH Asians, 78.3 mg/dL for boys and therapeutic intervention.28
88.0 mg/dL for girls • Combined hyperlipidemia, which affects ≈1 in
• High levels of triglycerides (≥150 mg/dL) occurred 100 individuals, is characterized by elevated
in 8.7% of male adolescents and 6.3% of female LDL-C and triglycerides. Unlike FH, there is little
adolescents during 2011 to 2014 (unpublished evidence for monogenic causes of combined
NHLBI tabulation). hyperlipidemia, which indicates that most cases
of combined hyperlipidemia might be complex
Adults
and polygenic.30
• The geometric mean level of triglycerides for
• High cholesterol is heritable even in families that
American adults ≥20 years of age was 103.5 mg/
do not harbor 1 of these monogenic forms of dis-
dL in NHANES 2011 to 2014 (unpublished NHLBI
ease. Extensive efforts have focused on GWAS for
tabulation).
lipid traits in large numbers of subjects to identify
• Approximately 24.2% of adults had high triglyc-
the genetic architecture of variability in choles-
eride levels (≥150 mg/dL) in NHANES 2011 to
terol levels.
2014 (unpublished NHLBI tabulation).
• With GWAS, 95 loci were identified using
• Among males, the age-adjusted geometric mean
>100 000 subjects of European origin.31 Additional
triglyceride level was 111.6 mg/dL in NHANES
studies in even larger numbers, including indi-
2011 to 2014 (unpublished NHLBI tabulation),
viduals of diverse ancestry, and the addition of
with the following racial/ethnic breakdown:
whole-exome sequencing (which offers more
— 113.2 mg/dL for NH white males
comprehensive coverage of the coding regions of
— 86.7 mg/dL for NH black males
the genome) have brought the number of known
— 124.1 mg/dL for Hispanic males
lipid loci to >160.32–34 As expected for a causal
— 115.3 mg/dL for NH Asian males
biomarker, there is considerable overlap between
• Among females, the age-adjusted geometric
the genetics of LDL-C and the genetics of CHD.
mean triglyceride level was 96.4 mg/dL in NHANES
Furthermore, overlap between genetic loci for
2011 to 2014 (unpublished NHLBI tabulation),

triglyceride-rich lipoproteins and disease implicate
with the following racial/ethnic breakdown:
triglycerides as causal in CVD.35,36
— 99.8 mg/dL for NH white females
• Genetic studies of lipid traits have had some suc-
— 75.1 mg/dL for NH black females
cess in identifying new drug targets, particularly
— 105.3 mg/dL for Hispanic females
the genetic interrogation of extremely high and
— 91.5 mg/dL for NH Asian females
low LDL-C,37–39 which led to the development of
• The prevalence of high triglycerides (≥150 mg/dL)
PCSK9 inhibitors. Furthermore, identification of
was higher (27%) in those with lower education
variants in ANGPTL4 that associate with increased
(<12 years) than in those with higher education
triglycerides and CAD risk34,40 highlight ANGPTL4
(>12 years; 23%) (unpublished NHLBI tabulation).
inhibition as potentially therapeutic.
Family History and Genetics • As highly effective LDL-C–lowering drugs, statins
• There are several known monogenic or mendelian are widely prescribed to reduce CVD risk, but
causes of high blood cholesterol and lipids, the response to statins varies between individuals.
most common of which include FH, which affects Genetic variants that affect statin responsive-
up to ≈1 in 200 individuals.27 Patients with FH ness could predict the lipid-modulating ability
have elevated total cholesterol and LDL-C and a of statins41–43 and modulate cardioprotection.44
20-fold increased risk of CVD.28 FH has been asso- Importantly, variation in SLCO1B1 predicts risk of
ciated with mutations in LDLR, APOB, LDLRAP1, statin myopathy, a major potential adverse event,
and PCSK9, which affect uptake and clearance of which has prompted recommendations for geno-
LDL-C. type-guided dosing of simvastatin.45,46
• Individuals who are homozygous for an FH muta-
tion have severe CHD that becomes apparent in
Global Burden of Hypercholesterolemia
childhood and requires plasmapheresis; it may be
best treated using novel therapies, including gene (See Chart 7-5)
therapy.29 However, the majority of FH cases are • The GBD 2015 Study used statistical models and
heterozygous for the causal mutation, and these data on incidence, prevalence, case fatality, excess
patients remain underdiagnosed.27 mortality, and cause-specific mortality to estimate

disease burden for 315 diseases and injuries in followed by the WHO Region of the Americas
CLINICAL STATEMENTS
195 countries and territories. The highest mor- (48% for both sexes). The WHO African Region
AND GUIDELINES
tality rates attributable to high TC are in Eastern and the WHO South-East Asia Region showed
Europe and Central Asia (Chart 7-5).47 the lowest percentages (23% and 30%,
• TC went from being the 14th-leading risk factor respectively).48
in 1990 for the global burden of disease, as quan- • In low-income countries, approximately one
tified by DALYs, to the number 15 risk factor in fourth of adults had raised TC. In lower-middle-
2010.48 income countries, this rose to approximately one
• Raised TC, defined as ≥115 mg/dL or ≥3.0 mmol/L, third of the population for both sexes. In high-
is estimated to cause 4.3 million deaths.47 income countries, >50% of adults had raised TC,
• The prevalence of elevated TC was highest in the more than double the level of the low-income
WHO European Region (54% for both sexes), countries.48
Table 7-1. High TC and LDL-C and Low HDL-C

Prevalence of TC ≥200 Prevalence of TC ≥240 mg/ Prevalence of LDL-C ≥130 Prevalence of HDL-C <40
mg/dL, 2011–2014 dL, 2011–2014 mg/ dL, 2011–2014 mg/dL, 2011–2014
Population Group Age ≥20 y Age ≥20 y Age ≥20 y Age ≥20 y
Both sexes, n (%)* 94 600 000 (39.7) 28 500 000 (11.9) 71 300 000 (30.3) 44 000 000 (18.7)
Males, n (%)* 42 300 000 (37.0) 12 100 000 (10.6) 34 000 000 (30.0) 32 100 000 (27.9)
Females, n (%)* 52 300 000 (42.0) 16 400 000 (13.0) 37 300 000 (30.4) 11 900 000 (10.0)
NH white males, % 37.0 10.8 29.3 28.4
NH white females, % 43.4 13.8 32.1 10.3
NH black males, % 32.6 7.3 29.9 20.7
NH black females, % 36.1 9.6 27.9 8.0
Hispanic males, % 43.1 13.6 36.6 30.7
Hispanic females, % 41.2 12.5 28.7 11.8

NH Asian males, % 39.9 10.8 29.2 25.0
NH Asian females, % 40.5 11.2 25.0 6.7
Prevalence of TC ≥200 mg/dL includes people with TC ≥240 mg/dL. In adults, levels of 200 to 239 mg/dL are considered borderline high. Levels of ≥240 mg/dL
are considered high. HDL-C indicates high-density lipoprotein cholesterol; LDL-C, low-density lipoprotein cholesterol; NH, non-Hispanic; and TC, total cholesterol.
*Total data for TC are for Americans ≥20 years of age. Data for LDL-C, HDL-C, and all racial/ethnic groups are age adjusted for age ≥20 years.
Source for TC ≥200 mg/dL, ≥240 mg/dL, LDL-C, and HDL-C: National Health and Nutrition Examination Survey (2011–2014), National Center for Health Statistics,
and National Heart, Lung, and Blood Institute. Estimates from National Health and Nutrition Examination Survey 2011 to 2014 (National Center for Health Statistics)
were applied to 2014 population estimates.

CLINICAL STATEMENTS
175
AND GUIDELINES
170
170
166 166 166 166

165
Mean Serum Total Cholesterol
165
163
162 162
161
160 160
160 159
158
157
156
155 154
153
150
145
140
NH White Males NH White Females NH Black Males NH Black Females Mex. Am. Males* Mex. Am. Females*
1988-1994 1999-2006 2007-2014
Chart 7-1. Trends in mean serum total cholesterol among adolescents 12 to 19 years of age by race, sex, and sur-
vey year (NHANES 1988–1994, 1999–2006, and 2007–2014).
Values are in mg/dL.
Mex. Am. indicates Mexican American; NH, non-Hispanic; and NHANES, National Health and Nutrition Examination Survey.
*The category of Mexican Americans was consistently collected in all NHANES years, but the combined category of Hispanics
was only used starting in 2007. Consequently, for long-term trend data, the category Mexican American is used.
Source: National Center for Health Statistics and National Heart, Lung, and Blood Institute.
210
206
205
205 204
202
201
Mean Serum Total Cholesterol
200
196 196
195
195
190 189
185
180
1988-1994 1999-2006 2007-2014
NH White NH Black Mexican American*
Chart 7-2. Age-adjusted trends in mean serum total cholesterol among adults ≥20 years old by race and survey
year (NHANES 1988–1994, 1999–2006, and 2007–2014).
Values are in mg/dL.
NH indicates non-Hispanic; and NHANES, National Health and Nutrition Examination Survey.

CLINICAL STATEMENTS
50
46.7
AND GUIDELINES
45.1
45 44.2
40.9 41.0 41.2 41.5

40.2 39.6
40 39.2 38.6
38.4
35.9
34.7
35
31.5
29.6
30
25
20
15
10
0
Males Females Males Females Males Females Males Females
Non-Hispanic White Non-Hispanic Black Hispanic Non-Hispanic Asian
2011-2012 2013-2014
Chart 7-3. Age-adjusted trends in the prevalence of serum total cholesterol ≥200 mg/dL in adults ≥20 years of age
by race/ethnicity, sex, and survey year (NHANES 2011–2012 and 2013–2014).
16
15.2
14.2 14.1
14
13.0
12.5
12.1
12 11.6 11.5 11.4
11.2
10.9
10.1
10 9.5
7.8
8 7.4 7.2
0
2011-2012 2013-2014
Chart 7-4. Age-adjusted trends in the prevalence of serum total cholesterol ≥240 mg/dL in adults ≥20 years of age
by race/ethnicity, sex, and survey year (NHANES 2011–2012 and 2013–2014).

Chart 7-5. Age-standardized global mortality rates attributable to high total cholesterol per 100 000, both sexes, 2015.
CLINICAL STATEMENTS
AND GUIDELINES
Collaborating Group (Body Mass Index). National, regional, and global
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Kähönen M, Kaprio J, Kesäniemi A, Kivimaki M, Kooner JS, Koudstaal Johnson AD, de Craen AJ, Stott DJ, Buckley BM, Ford I, Westendorp RG,
PJ, Krauss RM, Kuh D, Kuusisto J, Kyvik KO, Laakso M, Lakka TA, Lind L, Slagboom PE, Sattar N, Munroe PB, Sever P, Poulter N, Stanton A, Shields
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Krauss RM, Wouter Jukema J, Caulfield MJ; Wellcome Trust Case Control Buckley BM, Stott DJ, Sattar N, Devlin JJ, Packard CJ, Ford I, Sacks FM,
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8. HIGH BLOOD PRESSURE Abbreviations Used in Chapter 8 Continued

CLINICAL STATEMENTS
QALY quality-adjusted life-year

ICD-9 401 to 404, ICD-10 I10 to I15. See Tables 8-1
AND GUIDELINES

and 8-2 and Charts 8-1 through 8-6 REGARDS Reasons for Geographic and Racial Differences in Stroke
Click here to return to the Table of Contents SPRINT Systolic Blood Pressure Intervention Trial
SSB sugar-sweetened beverages
HBP is a major risk factor for CVD and stroke.1 The AHA SWAN Study of Women’s Health Across the Nation
WHI Women’s Health Initiative
has identified untreated BP <90th percentile (for children)
and <120/<80 mm Hg (for adults aged ≥20 years) as 1
of the 7 components of ideal cardiovascular health.2 In Prevalence
2013 to 2014, 88.7% of children and 45.4% of adults (See Table 8-1, Chart 8-1, and Chart 8-2)
met these criteria (Chapter 2, Cardiovascular Health).
• Although surveillance definitions vary widely in
the published literature, including for the CDC
Abbreviations Used in Chapter 8 and NHBLI, the following definition of HBP has
ACEI angiotensin-converting enzyme inhibitor been proposed for surveillance3:
— SBP ≥140 mm Hg or DBP ≥90 mm Hg or self-
ARB angiotensin receptor blocker
reported antihypertensive medicine use, or
BMI body mass index — Having been told previously, at least twice,
BP blood pressure by a physician or other health professional
BRFSS Behavioral Risk Factor Surveillance System that one has HBP.
CARDIA Coronary Artery Risk Development in Young Adults • With this definition, the age-adjusted prevalence
of hypertension among US adults ≥20 years of
age was estimated to be 34.0% in NHANES in
CKD chronic kidney disease 2011 to 2014 (34.5% for males and 33.4% for
CVD cardiovascular disease females). This equates to an estimated 85.7 mil-
DALY disability-adjusted life-year lion adults ≥20 years of age who have HBP (40.8
DASH Dietary Approaches to Stop Hypertension million males and 44.9 million females), extrapo-
DBP diastolic blood pressure
lated to 2014 data (Table 8-1; unpublished NHLBI

tabulation).
ESRD end-stage renal disease • The prevalence of HBP in adults ≥20 years of age
FHS Framingham Heart Study is presented by both age and sex in Chart 8-1.
GBD Global Burden of Disease • In 2011 to 2014, the prevalence of HBP was
GWAS genome-wide association studies 11.6% among those 20 to 39 years of age,
HBP high blood pressure
37.3% among those 40 to 59 years of age, and
HCHS/SOL Hispanic Community Health Study/Study of Latinos
HCUP Healthcare Cost and Utilization Project
67.2% among those ≥60 years of age (unpub-
HD heart disease lished NHLBI tabulation).
HF heart failure • In 2011 to 2014, a higher percentage of males
HR hazard ratio than females had hypertension up to 64 years of
ICD-9 International Classification of Diseases, 9th Revision age. For those ≥65 years of age, the percentage
ICD-9-CM International Classification of Diseases, Clinical
Modification, 9th Revision
of females with hypertension was higher than for
ICD-10 International Classification of Diseases, 10th Revision males (unpublished NHLBI tabulation).
JHS Jackson Heart Study • Data from NHANES 2013 to 2014 indicate that
MEPS Medical Expenditure Panel Survey 15.9% of US adults with hypertension are not
MESA Multi-Ethnic Study of Atherosclerosis aware they have it (unpublished NHLBI tabulation).
MI myocardial infarction
• The age-adjusted prevalence of hyperten-
sion increased between 1988 to 1994, 1999 to
NH non-Hispanic 2006, and 2007 to 2014 among NH black males
NHAMCS National Hospital Ambulatory Medical Care Survey (37.5%, 39.5%, and 40.3%, respectively) and
NHANES National Health and Nutrition Examination Survey NH black females (38.2%, 41.7%, and 42.9%,
NHIS National Health Interview Survey respectively), NH white males (25.6%, 28.7%,
NHLBI National Heart, Lung, and Blood Institute
and 30.4%, respectively) and NH white females
OR odds ratio (22.9%, 27.8%, and 27.6%, respectively), and
PA physical activity Mexican American females (25.0%, 26.1%, and
PAR population attributable risk 27.2%, respectively) but not Mexican American
(Continued ) males (26.9%, 24.3%, and 26.5%, respectively).

The category of Mexican Americans was consis- • Data from NHANES 2005 to 2010 found that
CLINICAL STATEMENTS
tently collected in all NHANES years, but the com- 76.5% of US adults ≥80 years of age had hyper-
AND GUIDELINES
bined category of Hispanics was only used starting tension, which represents an increase from 69.2%
in 2007. Consequently, for long-term trend data, in 1988 to 1994.12
the category Mexican American is used (Chart • In 2005 to 2010, 30.9% of US adults ≥80 years
8-2). of age were taking ≥3 classes of antihypertensive
• Data from the 2015 BRFSS/CDC indicate that the medications. This represents an increase from
age-adjusted percentage of adults ≥18 years of 7.0% and 19.2% in 1988 to 1994 and 1999 to
age who had been told that they had HBP ranged 2004, respectively.12
from 24.2% in Minnesota to 39.9% in Mississippi. • The white coat effect (clinic minus out-of-clinic BP)
The age-adjusted percentage for the total United is larger at older ages. In the International Database
States was 29.7%.4 on Ambulatory Blood Pressure Monitoring in
• According to 2005 to 2008 NHANES data, among Relation to Cardiovascular Outcomes, a pooled
US adults with hypertension, 11.8% met the cri- analysis of 11 cohorts, the white coat effect for
teria for resistant hypertension (SBP/DBP ≥140/90 SBP was 3.8 mm Hg (95% CI, 3.1–4.6 mm Hg),
mm Hg and reported use of antihypertensive larger for each 10-year increase in age.13
medications from 3 different drug classes or drugs • In the English Longitudinal Study of Ageing, the
from ≥4 antihypertensive drug classes regardless prevalence, awareness, and treatment of hyper-
of BP). This represents an increase from 5.5% in tension increased progressively between 1998
1998 to 1994 and 8.5% in 1999 to 2004.5 and 2012 among octogenarians. Although BP
• A meta-analysis of 24 studies (N=961 035) esti- control (SBP/DBP <140/90 mm Hg) declined from
mated the prevalence of apparent treatment- 1998 to 2004 (37% to 31%), it increased to 47%
resistant hypertension to be 13.7% (95% CI, by 2012.14
11.2%–16.2%).6
Children and Adolescents
• In a cohort of patients with established kidney
• In 2011 to 2012, 11.0% (95% CI, 8.8%–13.4%)
disease, 40.4% had resistant hypertension.7
of children and adolescents aged 8 to 17 years
• SPRINT demonstrated an SBP goal of <120 mm Hg
had either HBP (SBP or DBP at the 95th percentile
resulted in fewer CVD events and a greater
or higher) or borderline HBP (SBP or DBP between
reduction in mortality than an SBP goal of <140

the 90th and 95th percentile or BP levels of
mm Hg among people with SBP ≥130 mm Hg
120/80 mm Hg or higher but <95th percentile).
and increased cardiovascular risk.8 Using NHANES
• No change occurred in the prevalence of bor-
2007 to 2012 data, it was estimated that 7.6%
derline HBP (7.6% [95% CI, 5.8%–9.8%] versus
(95% CI, 7.0%–8.3%) or 16.8 million (95% CI,
9.4% [95% CI, 7.2%–11.9%]; P=0.90) or either
15.7–17.8 million) US adults meet the SPRINT
HBP or borderline HBP (10.6% [95% CI, 8.4%–
inclusion and exclusion criteria.9
13.1%] versus 11.0% [95% CI, 8.8%–13.4%];
• Projections show that by 2030, ≈41.4% of US
P=0.26) between 1999 to 2000 and 2011 to
adults will have hypertension, an increase of
2012.15 In this age group, HBP declined from
8.4% from 2012 estimates (unpublished AHA
3.0% to 1.6% between 1999 to 2000 and 2011
computation, based on methodology described
to 2012.15
by Heidenreich et al10).
• In 2011 to 2012, HBP was more common among
• Among US adults 25 to 49 years of age, the
boys (1.8%) than girls (1.4%) and among
prevalence of ever having hypertension was
Hispanics (2.4%) than among NH blacks (1.9%),
higher in 2009 to 2012 than in 1988 to 1994
NH whites (1.1%), and NH Asians (1.7%).
(OR, 1.36; 1.08–1.70, adjusted for sociodemo-
Although having either HBP or borderline HBP
graphics and smoking). Uncontrolled hyperten-
was more common among boys than girls, NH
sion was less common in this age group in 2009
blacks were more likely to have either HBP or bor-
to 2012 than in 1988 to 1994 (OR, 0.67; 0.52–
derline HBP than Hispanic, NH white, or NH Asian
0.86, adjusted for sociodemographics, smoking,
boys or girls.15
and obesity).11
• In 2003 to 2010, for girls 8 to 11 years of age,
Older Adults 3.5%, 5.0%, and 91.5% had BP in the poor,
• In 2011 to 2014, the prevalence of hypertension intermediate, and ideal levels according to the
was 67.2% among US adults ≥60 years of age. Of AHA 2020 Strategic Impact Goals. For boys 8 to
those with hypertension, 54.0% had controlled 11 years of age, 2.8%, 4.8%, and 92.5% had BP
BP (SBP/DBP <140/90 mm Hg; unpublished NHLBI in the poor, intermediate, and ideal levels accord-
tabulation). ing to Life’s Simple 7.16

• Analysis of data for children and adolescents In 2011 to 2014, the age-adjusted prevalence of
CLINICAL STATEMENTS
aged 8 to 17 years from NHANES 1999 to 2002 hypertension was 45.0% and 46.3% among NH
AND GUIDELINES
through NHANES 2009 to 2012 found that mean black males and females; 34.5% and 32.3% among
SBP decreased from 105.6 to 104.9 mm Hg and NH white males and females; 28.8% and 25.7%
DBP decreased from 60.3 to 56.1 mm Hg.15,17 among NH Asian males and females; and 28.9%
• In NHANES 1999 to 2012, the prevalence of HBP and 30.7% among Hispanic males and females,
was 9.9% among severely obese US adolescents respectively (unpublished NHLBI tabulation).
(BMI ≥120% of 95th percentile of sex-specific BMI • From 1999 to 2000 through 2009 to 2010, the
for age or BMI ≥35 kg/m2). The OR for HBP was 5.3 prevalence of hypertension did not increase
(95% CI, 3.8%–7.3%) when comparing severely among NH black males (38.0% and 39.6% in
obese versus normal-weight adolescents.18 1999–2000 and 2009–2010, respectively) or
• Among normal-weight and overweight/obese US females (40.8% and 43.1% in 1999–2000 and
adolescents (12–19 years of age), mean SBP and 2009–2010, respectively).25
DBP did not increase between 1988 to 1994 and • In MESA and using data collected from 2000 to
2007 to 2012. The unadjusted prevalence of pre- 2002 through 2005 to 2007, the incidence of
HBP and HBP, respectively, was 11.4% and 0.9% hypertension was higher for blacks than whites
in 1988 to 1994 and 11.1% and 1.4% in 2007 through 75 years of age. For a 45-year-old with-
to 2012. Among overweight/obese adolescents, out hypertension, the 40-year cumulative inci-
the unadjusted prevalence of pre-HBP and HBP, dence of hypertension was 92.7% among blacks,
respectively, was 15.5% and 6.4% in 1988 to 92.4% among Hispanics, 86.0% among whites,
1994 and 21.4% and 3.4% in 2007 to 2012.19 and 84.1% among Asians.26
• Longitudinal BP outcomes from the National • Over 10 years of follow-up in the REGARDS study,
Childhood Blood Pressure database (ages 13–15 a higher percentage of black males and females
years) were examined after a single BP measure- (48% and 54%, respectively) developed hyper-
ment. Among those determined to have prehy- tension than white males or females (38% for
pertension, 14% of boys and 12% of girls had white males and 27% for white females 45–54
hypertension 2 years later; the overall rate of pro- years of age and 40% for white females who
gression from prehypertension to hypertension were ≥75 years old).27
was ≈7%.20 • African Americans are more likely than whites to
• The AHA has outlined conditions in which ambu- have nondipping BP (ie, BP that does not decline
latory BP monitoring may be helpful in children >10% from daytime to nighttime) and nighttime
and adolescents. These include secondary hyper- hypertension on ambulatory BP monitoring.28
tension, CKD, type 1 and type 2 DM, obesity, These phenotypes are associated with increased
sleep apnea, genetic syndromes, treated patients CVD risk, although there are few published data
with hypertension, and for research.21 In a retro- on the prognostic importance of these pheno-
spective study of 500 children screened for poten- types in African Americans.29
tial hypertension with ambulatory BP monitoring, • Among participants in SWAN who reported being
12% had white coat hypertension and 10% had diagnosed with hypertension or antihypertensive
masked hypertension.22 medication use in 1995 through 2013, 30.4%
• In a systematic review of studies evaluating secular of blacks were taking a thiazide diuretic com-
trends in BP among children and adolescents (N=18 pared with 19.2% of whites, 18.9% of Chinese,
studies with >2 million participants), BP decreased 13.4% of Japanese, and 9.0% of Hispanics.
between 1963 and 2012 in 13 studies, increased Also, 16.5% of blacks, 10.7% of whites, 4.2%
in 4 studies, and did not change in 1 study con- of Chinese, 16.1% of Japanese, and 10.5% of
ducted.23 No formal pooling of data was conducted. Hispanics were taking ≥2 classes of antihyperten-
• Among adolescents (mean age 14 years) with sive medication.30
CKD, 40% had masked hypertension (clinic SBP • At baseline in the community-based JHS (2000–
and DBP <90th percentile for age, sex, and height 2004), daytime hypertension was more common
and elevated awake or sleep BP ≥95th percentile than clinical hypertension both for participants not
or BP load ≥ 25%).24 taking (31.8% versus 14.3%) and taking (43.0%
versus 23.1%) antihypertensive medication. For
participants not taking and taking antihyperten-
Race/Ethnicity and HBP sive medication, the prevalence of masked hyper-
(See Table 8-1 and Chart 8-2) tension was 25.4% and 34.6%, respectively,
• The prevalence of hypertension in blacks in the whereas prevalence of white coat hypertension
United States is among the highest in the world. was 30.2% and 29.3%, respectively, and that of

nighttime hypertension was 49.4% and 61.7%, and more likely were unable to visit a doctor
CLINICAL STATEMENTS
respectively.31 because of the cost. NH Asians/Pacific Islanders
AND GUIDELINES
• Higher SBP explains ≈50% of the excess stroke (aggregated) were less likely than whites to have
risk among blacks compared with whites.27 these barriers.38
• Data from the 2014 NHIS showed that black • At baseline of SPRINT, a similar percentage of
adults 18 years of age were more likely (33.0%) Hispanics and non-Hispanics had controlled BP,
to have been told on ≥2 occasions that they defined as SBP/DBP <140/90 mm Hg (49.39%
had hypertension than American Indian/Alaska and 50.38%, respectively). The percentage with
Native adults (26.4%), white adults (23.5%), controlled BP was lower among Hispanic partici-
Hispanic or Latino adults (22.9%), or Asian pants from Puerto Rico than among their coun-
adults (19.5%).32 terparts living on the US mainland (43.98% and
• In HCHS/SOL, for US Hispanic or Latino males, 56.22%, respectively).39
the age-standardized prevalence of hypertension
in 2008 to 2011 ranged from a low of 19.9%
among those from South America to 32.6%
Mortality
among their counterparts from the Dominican (See Table 8-1)
Republic. For US Hispanic or Latino females, the • Using data from the National Vital Statistics
age-standardized prevalence of hypertension System, in 2015, there were 78 862 deaths pri-
was lowest for those of South American descent marily attributable to HBP. In 2015, there were
(15.9%) and highest for their counterparts from 427 631 deaths with any mention of HBP (≈16%
Puerto Rico (29.1%).33 of all deaths).40 The 2015 age-adjusted death
• Also in HCHS/SOL, there was substantial hetero- rate primarily attributable to HBP was 21.0 per
geneity in awareness, treatment, and control of 100 000. Age-adjusted death rates attributable
hypertension, with Central Americans having the to HBP (per 100 000) in 2015 were 20.2 for NH
lowest prevalence and Cubans having the highest white males, 51.8 for NH black males, 19.7 for
prevalence among males. Among females, South Hispanic males, 15.3 for NH Asian/Pacific Islander
Americans had the lowest prevalence of aware- males, 23.9 for NH American Indian/Alaska
ness and treatment, whereas hypertension con- Native males, 16.9 for NH white females, 36.4
trol was lowest among Central American females.
for NH black females, 15.3 for Hispanic females,

Only Hispanic females reporting mixed/other ori- 12.8 for NH Asian/Pacific Islander females, and
gin had a hypertension control rate that exceeded 20.7 for NH American Indian/Alaska Native
50%.34 females.41
• Among NHIS 1997 to 2005 respondents, hyper- • From 2005 to 2015, the death rate attributable
tension prevalence was higher among US-born to HBP increased 10.5%, and the actual number
adults than among foreign-born adults (adjusted of deaths attributable to HBP rose 37.5%. During
OR, 1.28; 95% CI, 1.21–1.36). Hypertension prev- this 10-year period, in NH whites, the HBP death
alence was higher among US-born NH blacks than rate increased 16.1%, whereas the actual number
among either foreign-born NH blacks (adjusted of deaths attributable to HBP increased 36.1%. In
OR, 1.24; 95% CI, 1.02–1.50) or all African-born NH blacks, the HBP death rate decreased 9.2%,
immigrants of any race/ethnicity (adjusted OR, whereas the actual number of deaths attribut-
1.45; 95% CI, 1.07–1.97).35 able to HBP increased 22.8%. In Hispanics, the
• Among adults 60 to 79 years old with hyperten- HBP death rate increased 4.8%, and the actual
sion in NHANES 2005 to 2012, blacks were more number of deaths attributable to HBP increased
likely than whites to be current smokers (18.5% 86.1% (unpublished NHLBI tabulation).
versus 11.1%) and have DM (47.0% versus • When any mention of HBP was present, the over-
27.7%). Additionally, mean 10-year predicted all age-adjusted death rate in 2015 was 113.8
ASCVD risk was higher for blacks than whites, at per 100 000 population. Death rates were 123.1
23.9% versus 21.1%, respectively.36 for NH white males, 216.3 for NH black males,
• Among adults with hypertension, blacks were 88.4 for NH Asian or Pacific Islander males,
more likely to have resistant hypertension than 146.7 for NH American Indian or Alaska Native
whites and Hispanics (19.0% versus 13.5% and males (underestimated because of underreport-
11.2%, respectively).37 ing), and 115.1 for Hispanic males. In females,
• Among US adults with hypertension, compared rates were 94.4 for NH white females, 151.9
with NH whites, NH blacks and Hispanics were for NH black females, 65.5 for NH Asian or
more likely to not have health insurance and to Pacific Islander females, 111.1 for NH American
not have a personal doctor or healthcare provider Indian or Alaska Native females (underestimated

because of underreporting), and 84.6 for commonly used risk prediction model was devel-
CLINICAL STATEMENTS
Hispanic females.40,42 oped in the FHS that includes age, sex, SBP, DBP,
AND GUIDELINES
• The proportion of all decedents aged ≥45 years BMI, smoking, and parental history of hyperten-
with any mention of hypertension on their death sion.49,50 In young adults, this model was better
certificate increased from 11.1% in 2000 to able to identify those who developed hyperten-
16.4% in 2013.43 sion over 25 years of follow-up than prehy-
• The age-adjusted hypertension-related death pertension; however, this model systematically
rate increased 23.1% from 2000 through 2013. underestimated the risk for hypertension.50
The rate for all other causes of death combined • A systematic review identified 15 different hyper-
decreased 21.0% over this time period.43 tension risk prediction models. Two models (the
• The hypertension-related death rate increased FHS and Hopkins models) have been validated
6.8% from 523.8 per 100 000 population in externally with acceptable discrimination (C sta-
2000 to 559.3 in 2005 for NH blacks, and then tistic, 0.71–0.81).51
it decreased 8.8% to 509.9 in 2013. Among • In the JHS, intermediate and ideal versus poor lev-
Hispanics, the rate increased 21.9% from 233.7 els of moderate-vigorous PA were associated with
in 2000 to 284.8 in 2013. For the NH white popu- HRs of hypertension of 0.84 (95% CI, 0.67–1.05)
lation, the rate increased 29.8% from 228.5 in and 0.76 (95% CI, 0.58–0.99), respectively.52
2000 to 296.5 in 2013.43 Also, anger, depressive symptoms, and stress
• HD, stroke, cancer, and DM accounted for 65% were associated with increased BP progression.53
of all deaths with any mention of hypertension in • In a meta-analysis of 24 trials (N=23 858 partici-
2000 and for 54% in 2013.43 pants), the DASH diet had the largest net effect
• The elimination of hypertension could reduce CVD on SBP (7.62 mm Hg; 95% CI, 5.29–9.95) and
mortality by 30.4% among males and 38.0% DBP (4.22 mm Hg; 95% CI, 2.57–5.87).54
among females.44 The elimination of hypertension
is projected to have a larger impact on CVD mor-
tality than the elimination of all other risk factors
Aftermath
among females and all except smoking among • The risk for stroke and HD mortality increased in
males.44 a log-linear fashion from SBP levels <115 mm Hg
to >180 mm Hg and from DBP levels <75 mm Hg
• Among US adults meeting the eligibility criteria

for SPRINT, SBP treatment to a treatment goal of to >105 mm Hg. Each 20-mm Hg higher SBP and
<120 mm Hg versus <140 mm Hg has been pro- 10-mm Hg higher DBP was associated with a dou-
jected to prevent ≈107 500 deaths per year (95% bling in the risk of death caused by stroke, HD, or
CI, 93 300–121 200).45 other vascular disease.55
• In a study of >1 million adults with hyperten-
sion, the lifetime risk of CVD at age 30 years was
Risk Factors 63.3% compared with 46.1% for those with nor-
• Data from the Nurses’ Health Study suggest that mal BP. Those with hypertension developed CVD
a large proportion of incident hypertension in 5.0 years earlier than their counterparts without
females can be prevented by controlling dietary hypertension.56 The largest lifetime risk differ-
and lifestyle risk factors.46 ences between people with versus without hyper-
• Among 31 146 females without hypertension at tension were for angina, MI, and stroke. At age
baseline in the WHI, randomization to a low-fat 60 years, the lifetime risk for CVD was 60.2%
diet versus usual diet resulted in a 4% lower risk for those with hypertension and 44.6% for their
for incident hypertension and 0.66 mm Hg lower counterparts without hypertension.
SBP at 1 year of follow-up.47 • Data from the FHS/NHLBI indicate that recent
• The consumption of SSBs was associated with a (within the past 10 years) and remote antecedent
risk ratio for hypertension of 1.12 (95% CI, 1.06– BP levels could be an important determinant of
1.17) in a meta-analysis of 240 508 people.48 This CVD and HF risk over and above the current BP
equated to an 8.2% increased risk for hyperten- level.57,58
sion for each additional SSB consumed per day. • Data from the FHS/NHLBI indicate that hyperten-
• Bisphenol A, a synthetic monomer used in the sion is associated with shorter overall life expec-
manufacture of polycarbonate plastics and epoxy tancy, shorter life expectancy free of CVD, and
resins, has been associated with hypertension in 3 more years lived with CVD. Total life expectancy
cross-sectional studies.49 was 5.1 years longer for normotensive males
• Risk prediction models for developing hyper- and 4.9 years longer for normotensive females
tension have been developed and validated. A than for hypertensive people of the same sex at

50 years of age. Compared with hypertensive • In an international case-control study (N=13 447
CLINICAL STATEMENTS
males at 50 years of age, males with untreated cases of stroke and N=13 472 control subjects),
AND GUIDELINES
BP <140/90 mm Hg survived on average 7.2 years a previous history of hypertension or SBP/DBP
longer without CVD and spent 2.1 fewer years of ≥140/90 mm Hg was associated with an OR for
life with CVD. Similar results were observed for stroke of 2.98 (95% CI, 2.72–3.28). The PAR
females.59 for stroke accounted for by hypertension was
• Overall, in national data, the prevalence of healthy 47.9%.67
lifestyle behaviors varies widely among those with
self-reported hypertension: 20.5% had a normal
weight, 82.3% did not smoke, 94.1% reported Hospital Discharges/Ambulatory
no or limited alcohol intake, 14.1% consumed Care Visits
the recommended amounts of fruits or vegeta- (See Table 8-1)
bles, and 46.6% engaged in the recommended
• From 2004 to 2014, the number of inpatient
amount of PA.60
discharges from short-stay hospitals with HBP
• The association of hypertension with CHD has not
as the principal diagnosis was stable at 285 000
changed from 1983 to 1990 (HR, 1.14; 95% CI,
and 292 000, respectively (HCUP, unpub-
1.11–1.16) versus 1996 to 2002 (HR, 1.13; 95%
lished NHLBI tabulation) The number of dis-
CI, 1.10–1.15). The PAR associated with hyper-
charges with any listing of HBP increased from
tension was 39.6% in the early time period and
12 461 000 to 15 638 000 (HCUP, unpublished
40.0% in the later time period.61
NHLBI tabulation).
• Among 17 312 participants with hypertension,
• In 2014, there were 90 000 principal diagno-
nondipping BP was associated with an HR for
sis discharges for essential hypertension (HCUP,
CVD of 1.40 (95% CI, 1.20–1.63).29
unpublished NHLBI tabulation).
• In the JHS, a cohort comprised exclusively of
• In 2014, there were 11 584 000 all-listed dis-
African Americans, masked hypertension was
charges for essential hypertension (HCUP, unpub-
associated with an HR of CVD of 2.49 (95% CI,
lished NHLBI tabulation).
1.26–4.93).62
• Data from the NIS from the years 2000 to 2011
• A meta-analysis (14 studies with 29 100 partici-
found the frequency of hospitalizations for malig-
pants) has shown that white coat hypertension
is associated with an increased risk for CVD and nant hypertension and hypertensive encepha-
CVD mortality (HR, 1.73 [95% CI, 1.27–2.36] lopathy increased, whereas hospitalizations for
and 2.79 [95% CI, 1.62–4.80], respectively).63 essential hospitalization decreased, which coin-
However, after multivariable adjustment, these cided with the introduction of medical sever-
associations were attenuated (HR, 1.18 [95% CI, ity diagnosis-related group billing. Overall, the
0.99–1.41] and HR, 1.39 [95% CI, 0.82–2.37], annual incidence of hypertension-related hospi-
respectively).64 talizations increased over the time period from
• Patterns of BP over time including steep increas- ≈87 000 in 2000 to ≈120 000 in 2011.68
ing, elevated stable, and elevated very high • In 2006 to 2010, 7.1% of patients with hyper-
BP, are associated with increased risk for CVD tension attending outpatient visits had treatment-
including CHD, stroke, and HF independent of resistant hypertension. The use of thiazide diuretic
contemporary BP values compared with people agents and chlorthalidone was low (56.4% and
who have low stable or low but increasing BP 1.2%, respectively).69
levels.65 • In 2014, 40 323 000 of 884 707 000 physician
• In a pooled analysis of 63 559 people without office visits had a primary diagnosis of essential
hypertension from 49 countries, sodium excretion hypertension (ICD-9-CM 401) (NCHS, NAMCS,
>7 g/d was associated with an HR for CVD of 1.23 NHLBI tabulation).70 A total of 1 107 000 of
(95% CI, 1.11–1.37), and <3 g/d was associated 141 420 000 ED visits in 2014 and 3 743 000 of
with an HR of 1.34 (95% CI, 1.23–1.47), each 125 721 000 hospital outpatient visits in 2011
compared with an HR of 4.5 g/d excretion.66 were for essential hypertension (NCHS, NHAMCS,
• Among adults with established CKD, apparent NHLBI tabulation).71,72
treatment-resistant hypertension has been associ-
ated with increased risk for CVD (HR, 1.38; 95%
Awareness, Treatment, and Control
CI, 1.22–1.56); renal outcomes (HR, 1.28; 95%
CI, 1.11–1.46); HF (HR, 1.66; 95% CI, 1.38– (See Table 8-2 and Charts 8-3 through 8-5)
2.00), and all-cause mortality (HR, 1.24; 95% CI, • Data from NHANES 2011 to 2014 showed that
1.06–1.45).7 of those with hypertension who were ≥20 years

of age, 84.1% were aware of their condition, • Among US adults with a history of stroke in 1999
CLINICAL STATEMENTS
76.0% were under current treatment, 54.4% to 2004, 72% reported a diagnosis of hyperten-
AND GUIDELINES
had their hypertension under control, and 45.6% sion, and 8% had undiagnosed hypertension.
did not have it controlled (Chart 8-3). A higher Also, 47% had uncontrolled BP.76
percentage of NH white and NH black adults • In a multinational study of 63 014 adults from
were aware of their hypertension (85.1% and high-, middle-, and low-income countries, 55.6%
85.5%, respectively) than Hispanic and NH Asian of participants were aware of their diagnosis of
adults (79.8% and 75.3%, respectively; Chart hypertension, and 44.1% and 17.1% were treated
8-3; unpublished NHLBI tabulation). Awareness and had controlled BP, respectively. Awareness
and treatment of hypertension were higher at and control were less common in upper-middle-
older ages. Hypertension control was higher in US income countries, whereas treatment was lowest
adults 40 to 59 years of age (58.3%) and those in low-income countries.77
≥60 years of age (54.0%) than in their counter- • Among US adults in NHANES 2007 to 2012,
parts 20 to 39 years of age (40.1%; Chart 8-4). 55% of those with a usual source of care com-
Overall, females were more likely than males in all pared with 14% of their counterparts without
race/ethnicity groups to be aware of their condi- a usual source of care had controlled hyper-
tion, under treatment, or in control of their hypertension (SBP/DBP <140/90 mm Hg). In addi-
tension (Chart 8-5). tion, 31% of those who reported using the
• Analysis of NHANES 1999 to 2006 and 2007 to ED as their usual source of care had controlled
2014 found the proportion of adults aware of hypertension.78
their hypertension increased within each race/ • Self-reported antihypertensive medication use
ethnicity and sex subgroup. Similarly, large increased from 2.2% in 1971 to 1975 to 7.7%
increases in hypertension treatment and con- in 2009 to 2012 among US adults 25 to 49 years
trol (≈10%) occurred in each of these groups of age.11
(Table 8-2).
• Among US adults taking prescription antihyper-
tensive medication, the age-adjusted percentage Cost
with BP control increased from 61.9% to 70.4% (See Table 8-1)
from 2003 to 2012.73
• In 2011 to 2012, medication use to lower BP • The estimated direct and indirect cost of HBP for
among those with hypertension was lowest 2013 to 2014 (annual average) was $53.2 billion
for those aged 18 to 39 years (44.5%) com- (MEPS, NHLBI tabulation).
pared with those aged 40 to 59 years (73.7%) • Controlling hypertension in all patients with CVD
and those aged ≥60 years (82.2%). NH black or stage 2 hypertension (SBP ≥160 mm Hg or
adults were more likely to take antihypertensive DBP ≥100 mm Hg) could be effective and cost-
medication than NH white, Hispanic, or Asian saving. Treating stage 1 hypertension could be
adults (77.4%, 76.7%, 73.5%, and 65.2% cost-effective for males and for females 45 to 74
respectively).74 years of age.79
• Data from NHANES 2005 to 2010 showed that • It would be cost-saving to treat US males 35 to
among those ≥80 years of age, 79.4% of those 74 years of age according to the guidelines of the
with hypertension were aware of their condi- Seventh Report of the Joint National Committee
tion, 57.4% were treated, and 39.8% had con- on Prevention, Detection, Evaluation, and
trolled their BP to targets of the Seventh Report Treatment of High Blood Pressure, with intensive
of the Joint National Committee on Prevention, treatment for high-risk individuals, or according
Detection, Evaluation, and Treatment of High to the 2014 Evidence-Based Guideline for the
Blood Pressure.12 Management of High Blood Pressure in Adults:
• Data from NHANES 1999 to 2012 show that Report From the Panel Members Appointed to
the use of various classes of antihypertensive the Eighth Joint National Committee. For females,
treatment had increased substantially among treatment according to the 2014 Evidence-
people ≥20 years of age. During this period, Based Guideline for the Management of High
the use of ACEIs increased from 6.3% of the Blood Pressure in Adults: Report From the Panel
US population to 12%, ARBs from 2.1% to Members Appointed to the Eighth Joint National
5.8%, β-blockers from 6.0% to 11%, and thi- Committee, plus intensive treatment for high-risk
azide diuretic drugs from 5.6% to 9.4%. The individuals, would be cost-effective.80
use of calcium channel blockers remained the • The median amount of US states’ costs attribut-
same, at 6%.75 able to hypertension was $1.62 billion in 2004 to

2008, with 35% of these costs borne by Medicare revealed several loci of interest that interact with
CLINICAL STATEMENTS
or Medicaid.81 smoking95,96 and with dietary intake of alcohol97
AND GUIDELINES
• Antihypertensive medication was cost-saving and and sodium.98
increased QALYs. Adjusted to 2012 US dollars, • The clinical implications and utility of hyperten-
the monetary savings and QALYs gained with life- sion genes remain unclear, although some genetic
time treatment were $7387 and 1.14 for white variants have been shown to influence response
males, $7796 and 0.89 for white females, $8400 to antihypertensive agents.99
and 1.66 for black males, and $10 249 and 1.79
for black females, respectively.82
• Projections show that by 2035, the total direct
Global Burden of Hypertension
costs of HBP could increase to an estimated (See Chart 8-6)
$220.9 billion (unpublished AHA computation, • The global mean age-adjusted SBP declined from
based on methodology described in Heidenreich 130.5 mm Hg in 1980 to 128.1 mm Hg in 2008
et al10).83 among males and from 127.2 to 124.4 mm Hg
• According to IMS Health National Prescription among females.101
Audit, the number of prescriptions for antihy- • The global age-adjusted prevalence of uncon-
pertensive medication increased from 613.7 mil- trolled hypertension decreased from 33% to 29%
lion to 653 million between 2010 and 2014. The among males and from 29% to 25% among
653 million antihypertensive prescriptions filled in females.
2014 cost $28.81 billion.84 • Because of population growth and aging, the
• Among a 5% sample of US Medicare benefi- number of people worldwide with uncontrolled
ciaries initiating antihypertensive treatment in hypertension (SBP ≥140 mm Hg or DBP ≥90
2012 (N=41 135), 21.3% discontinued treatment mm Hg) increased from 605 million to 978 million
within 1 year and an additional 31.7% had low between 1980 and 2008.101
adherence.85 • HBP went from being the fourth-leading risk fac-
tor in 1990, as quantified by DALYs, to being the
number 1 risk factor in 2010.102
Family History and Genetics • In a cross-sectional study of 628 communities
• BP is a heritable trait; family studies have yielded
(3 high-income, 10 upper-middle-income and

heritability estimates of 48% to 60% (SBP) and low-middle income countries, and 4 low-income
34% to 67% (DBP).86 countries), awareness, treatment, and con-
• Genetic studies have been conducted to identify trol of hypertension were lowest in low-income
the genetic architecture of hypertension. Several countries.103
large-scale GWAS and whole-exome studies, with • In 2010, HBP was 1 of the 5 leading risk factors in
interrogation of common and rare variants in all regions with the exception of Oceania, Eastern
>300 000 individuals, have established >100 well- sub-Saharan Africa, and Western sub-Saharan
replicated hypertension loci, with several hundred Africa.102
additional suggestive loci.87–93 • In a meta-analysis of population-studies con-
• Genetic risk scores for hypertension are also asso- ducted in Africa, the prevalence of hypertension
ciated with increased risk of CVD and MI.87 was 55.2% among adults ≥55 years of age.104
• Genes that associate with increased BP have • In a systematic review, a higher percentage
diverse functionality, including in the renal and of hypertension guidelines developed in high-
vascular system, as well as overlapping with loci income countries used high-quality systematic
for lipid traits, inflammatory diseases, DM, and reviews of relevant evidence compared with
CVD. low- and middle-income countries (63.5% ver-
• Large-scale studies have mostly included a major- sus 10%).105
ity of European ancestry individuals, but studies • On the basis of data from 135 population-
of nonwhite individuals have revealed additional based studies (N=968 419 adults from 90
loci, and the genetics of BP regulation might be countries), it was estimated that 31.1% (95%
ancestry specific.94 CI, 30.0%–32.2%) of the world adult popula-
• Given strong effects of environmental factors on tion had hypertension in 2010. The prevalence
hypertension, gene-environment interactions are was 28.5% (95% CI, 27.3%–29.7%) in high-
important in the pathophysiology of hyperten- income countries and 31.5% (95% CI, 30.2%–
sion. Large-scale gene-environment interaction 32.9%) in low-middle-income countries. It was
studies have not yet been conducted; however, also estimated that 1.39 billion adults world-
studies of several thousand people have to date wide had hypertension in 2010 (349 million in

high-income countries and 1.04 billion in low- 4-year incidence of hypertension was 5.3% for
CLINICAL STATEMENTS
and middle-income countries).106 those with baseline BP <120/80 mm Hg, 17.6%

AND GUIDELINES
• In 2015, the prevalence of SBP ≥140 mm Hg for those with SBP of 120 to 129 mm Hg or DBP
was estimated to be 20 526 per 100 000. This of 80 to 84 mm Hg, and 37.3% for those with
represents an increase from 17 307 per 100 000 SBP of 130 to 139 mm Hg or DBP of 85 to 89
in 1990.107 Also, the prevalence of SBP 110 to mm Hg. At 65 to 94 years of age, the 4-year inci-
115 mm Hg or higher increased from 73 119 per dences of hypertension were 16.0%, 25.5%, and
100 000 to 81 373 per 100 000 between 1990 49.5% for these BP categories, respectively.110
and 2015. There were 3.47 billion adults world- • Among participants with and without prehy-
wide with SBP of 110 to 115 mm Hg or higher in pertension in MESA, 23.6% and 5.3%, respec-
2015. Of this group, 847 million adults had SBP tively, developed hypertension over 4.8 years of
≥140 mm Hg.107 follow-up.111
• It has been estimated that 7.834 million deaths • Among young adults (18–30 years old at baseline)
and 143.037 million DALYs in 2015 could be with and without prehypertension in CARDIA,
attributed to SBP ≥140 mm Hg.107 In addition, 23.1% and 3.8%, respectively, developed hyper-
10.7 million deaths and 211 million DALYs in tension over 5 years of follow-up.50
2015 could be attributed to SBP of 110 to 115 • Multiple meta-analyses have demonstrated that
mm Hg or higher.107 prehypertension is associated with an increased
• Between 1990 and 2015, the number of deaths risk for CVD, ESRD, and mortality. These risks are
related to SBP ≥140 mm Hg did not increase in greater for people in the upper (130–139/85–89
high-income countries (from 2.197 to 1.956 mil- mm Hg) versus lower (120–129/80–84 mm Hg)
lion deaths) but did in high-middle-income (from range of prehypertension.112–121
1.288 to 2.176 million deaths), middle-income • Two RCTs have reported that pharmacological
(from 1.044 to 2.253 million deaths), low-middle- treatment of prehypertension is associated with a
income (from 0.512 to 1.151 million deaths), and lower incidence of hypertension.122,123
low-income (from 0.146 to 0.293 million deaths)
countries.107
Addendum Addressing the New Blood
• The GBD 2015 Study used statistical models and
Pressure Guideline
data on incidence, prevalence, case fatality, excess

mortality, and cause-specific mortality to estimate The Statistical Update was completed before publica-
disease burden for 315 diseases and injuries in tion of the 2017 ACC/AHA Guideline for the Prevention,
195 countries and territories. The highest mortal- Detection, Evaluation, and Management of High Blood
ity rates attributable to high SBP are in Eastern Pressure in Adults on November 13, 2017. This guide-
Europe and Central Asia (Chart 8-6).108 line has several recommendations that are relevant to
the Statistical Update.
The recommended definition of hypertension is an
Prehypertension SBP ≥130 mm Hg or a DBP ≥80 mm Hg. The diagnosis
• Among adults without hypertension, prehyper- of hypertension should be based on the average of BP
tension is defined by an untreated SBP of 120 measurements taken ≥2 times at ≥2 separate visits.
to 139 mm Hg or untreated DBP of 80 to 89 Antihypertensive medication is recommended for
mm Hg. adults with:
• Between 1999 to 2000 and 2011 to 2012, the • SBP ≥140 mm Hg or DBP ≥90 mm Hg
prevalence of prehypertension decreased among • SBP between 130 and 139 mm Hg or DBP
US adults from 31.2% to 28.2%.109 between 80 and 89 mm Hg with (1) a history of
• Among US adults with prehypertension, between CVD (MI, stroke or HF), (2) 10-year predicted CVD
1999 to 2000 and 2011 to 2012, there was risk ≥10%, and (3) DM or CKD
an increase in the prevalence of overweight • SBP between 130 and 139 mm Hg for adults ≥65
(33.5% to 37.3%), obesity (30.6% to 35.2%), years of age
no weekly leisure-time PA (40.0% to 43.9%), The recommended goal BP for adults taking antihy-
pre-DM (9.6% to 21.6%), and DM (6.0% to pertensive medication is SBP <130 mm Hg and DBP <80
8.5%). There was a decrease in the prevalence mm Hg, with SBP <130 mm Hg and no DBP treatment
of current smoking over the time period (25.9% goal for adults ≥65 years of age without a history of
to 23.2%).109 CVD, DM, or CKD and a 10-year predicted CVD risk
• Follow-up of 9845 males and females in the FHS/ <10%. However, only a small percentage of US adults
NHLBI who attended examinations from 1978 to ≥65 years of age meet these criteria and do not have a
1994 revealed that at 35 to 64 years of age, the DBP goal.124

The following statistics were published using the of US adults were recommended antihypertensive
CLINICAL STATEMENTS
2011 to 2014 NHANES data for US adults ≥20 years medication by the Seventh Report of the Joint National
AND GUIDELINES
of age.125 Committee on Prevention, Detection, Evaluation, and
According to the 2017 ACC/AHA guideline, Treatment of High Blood Pressure guideline. 125
45.6% of US adults have hypertension. This repre- Among US adults with SBP between 130 and 139
sents a 13.7% increase when compared to the preva- mm Hg or DBP between 80 and 89 mm Hg not taking
lence of hypertension defined using the criteria in the antihypertensive medication, 31.3% are recommended
Seventh Report of the Joint National Committee on initiation of antihypertensive medication by the 2017
Prevention, Detection, Evaluation, and Treatment of ACC/AHA guideline.125
High Blood Pressure guideline (prevalence estimate Among US adults taking antihypertensive medica-
31.9%).125 tion, 53.4% had BP above the treatment goal accord-
It is estimated that 103.3 million US adults have hyper- ing to the 2017 ACC/AHA guideline. In contrast, 39%
tension according to the 2017 ACC/AHA guideline.125 of US adults had BP above the treatment goal defined
Overall, 36.2% of US adults are recommended phar- in the Seventh Report of the Joint National Committee
macological antihypertensive medication according to on Prevention, Detection, Evaluation, and Treatment of
the 2017 ACC/AHA guideline. In comparison, 34.3% High Blood Pressure guideline.125
Table 8-1. High Blood Pressure in the United States

Prevalence, Mortality,* Hospital Discharges, Estimated Cost,
Population Group 2011–2014, Age ≥20 y 2015, All Ages 2014, All Ages 2013–2014
Both sexes 85 700 000 (34.0%) 78 862 292 000 $53.2 Billion
Males 40 800 000 (34.5%) 37 099 (47.0.%)† 142 000 …
Females 44 900 000 (33.4%) 41 763 (53.0 %)† 150 000 …
NH white males 34.5% 24 801 … …
NH white females 32.3% 29 850 … …
NH black males 45.0% 7835 … …
NH black females 46.3% 7651 … …

Hispanic males 28.9% 2874 … …
Hispanic females 30.7% 2702 … …
NH Asian males 28.8% 1057‡ … …
NH Asian females 25.7% 1176‡ … …
NH American Indian/Alaska Native 26.4%§ 485 … …
Hypertension is defined in terms of National Health and Nutrition Examination Survey blood pressure measurements and health
interviews. A subject was considered hypertensive if systolic blood pressure was ≥140 mm Hg or diastolic blood pressure was ≥90 mm Hg,
if the subject said “yes” to taking antihypertensive medication, or if the subject was told on 2 occasions that he or she had hypertension.
Prevalence in American Indians or Alaska Natives is based on self-report data from the National Health Interview Survey, with hypertension
defined as individuals having been told on ≥2 different visits that they had hypertension or high blood pressure. Ellipses (…) indicate data
not available; and NH, non-Hispanic.
*Mortality for Hispanic, American Indian or Alaska Native, and Asian and Pacific Islander people should be interpreted with caution
because of inconsistencies in reporting Hispanic origin or race on the death certificate compared with censuses, surveys, and birth
certificates. Studies have shown underreporting on death certificates of American Indian or Alaska Native, Asian, and Pacific Islander, and
Hispanic decedents, as well as undercounts of these groups in censuses.
†These percentages represent the portion of total high blood pressure mortality that is for males vs females.
‡Includes Chinese, Filipino, Hawaiian, Japanese, and other Asian or Pacific Islander.
§National Health Interview Survey (2014), National Center for Health Statistics; data are weighted percentages for Americans ≥18
years of age. Individuals had to have been told on ≥2 different visits that they had hypertension or high blood pressure to be classified as
hypertensive.31
Sources: Prevalence: National Health and Nutrition Examination Survey (2011–2014), National Center for Health Statistics, and National
Heart, Lung, and Blood Institute. Percentages for racial/ethnic groups are age adjusted for Americans ≥20 years of age. Age-specific
percentages are extrapolated to the 2014 US population estimates. Mortality: Centers for Disease Control and Prevention/National Center
for Health Statistics, 2015 Mortality Multiple Cause-of-Death–United States. These data represent underlying cause of death only. Mortality
for NH Asians includes Pacific Islanders. Hospital discharges: Healthcare Cost and Utilization Project, National (Nationwide) Inpatient
Sample, 2014. Agency for Healthcare Research and Quality.
Cost: Medical Expenditure Panel Survey data include estimated direct costs for 2013 to 2014 (annual average); indirect costs calculated
by National Heart, Lung, and Blood Institute for 2013 to 2014 (annual average).

Table 8-2. Hypertension Awareness, Treatment, and Control: NHANES 1999 to 2006 and 2007 to
CLINICAL STATEMENTS
2014, by Race/Ethnicity and Sex

AND GUIDELINES
Awareness Treatment Control

1999–2006 2007–2014 1999–2006 2007–2014 1999–2006 2007–2014
NH white males 71.8 81.3 61.8 73.0 41.9 53.9
NH white females 76.9 85.5 68.1 80.6 40.0 58.0
NH black male 70.1 79.8 59.6 68.4 34.1 41.6
NH black females 85.3 88.9 76.6 81.2 43.8 53.4
Mexican American males* 57.7 68.5 41.8 57.7 25.6 37.0
Mexican American females* 69.9 80.8 57.9 73.1 31.9 49.2
Values are percentages. Hypertension is defined in terms of NHANES blood pressure measurements and health interviews. A subject was
considered hypertensive if systolic blood pressure was ≥140 mm Hg or diastolic blood pressure was ≥90 mm Hg, or if the subject said “yes” to
taking antihypertensive medication. NH indicates non-Hispanic; and NHANES, National Health and Nutrition Examination Survey.
*The category of Mexican Americans was consistently collected in all NHANES years, but the combined category of Hispanics was only used
starting in 2007. Consequently, for long-term trend data, the category Mexican American is used.
Sources: NHANES (1999–2006, 2007–2014) and National Heart, Lung, and Blood Institute.
90
81.2
80
73.4
70 65.8
63.6
60 57.6
55.5
50
40 36.1
33.2
30
23.1 22.8
20
10.7
10 7.8
0
20-34 35-44 45-54 55-64 65-74 ≥75
Male Female
Chart 8-1. Prevalence of high blood pressure in adults ≥20 years of age by sex and age (NHANES 2011–2014).
Hypertension is defined as systolic blood pressure ≥140 mm Hg or diastolic blood pressure ≥90 mm Hg, if the subject said
“yes” to taking antihypertensive medication, or if the subject was told on 2 occasions that he or she had hypertension.

CLINICAL STATEMENTS
50
AND GUIDELINES
45 42.9
41.7
40.3
40 39.5 38.2
37.5
Percent of Population 35
30.4
30 28.7
27.827.6
26.9 26.5 27.2
25.6 26.1
24.3 25.0
25 22.9
20
15
10
0
NH White NH White NH Black NH Black Mexican Mexican
Males Females Males Females American American
Males* Females*
1988-1994 1999-2006 2007-2014
Chart 8-2. Age-adjusted prevalence trends for high blood pressure in adults ≥20 years of age by race/ethnicity,
sex, and survey year (NHANES 1988–1994, 1999–2006, and 2007–2014).
Hypertension is defined as systolic blood pressure ≥140 mm Hg or diastolic blood pressure ≥90 mm Hg, if the subject said
“yes” to taking antihypertensive medication, or if the subject was told on 2 occasions that he or she had hypertension.
90
85.5
84.1 85.1
79.8
80 77.9
75.3 76.0 75.8
69.0
Percent of Population with Hypertension
70
65.6
60 57.0
54.4
49.1 48.3
50
45.1
40
30
20
10
0
Total Pop NH White NH Black Hispanic NH Asian
Chart 8-3. Extent of awareness, treatment, and control of high blood pressure by race/ethnicity (NHANES 2011–2014).
Hypertension is defined as systolic blood pressure ≥140 mm Hg or diastolic blood pressure ≥90 mm Hg, or if the subject said
“yes” to taking antihypertensive medication.

CLINICAL STATEMENTS
100
AND GUIDELINES
90 87.5
82.6 82.9
Percent of Population with Hypertension

80
72.4
69.0
70
60 58.3
54.0
49.7
50
40.1
40
30
20
10
0
20-39 40-59 ≥60

Age (Years)
Chart 8-4. Extent of awareness, treatment, and control of high blood pressure by age (NHANES 2011–2014).
100
90.0
90 87.0
84.9
83.1 81.9
82.1 79.6 79.6
Percent of Population With Hypertension
80 76.8
73.6 74.0
70.6 70.7
70 68.0
59.1 60.3 60.0

60
54.9 54.0 54.9
49.9
50
42.7
40.9 40.0
40
30
20
10
0
Chart 8-5. Extent of awareness, treatment, and control of high blood pressure by race/ethnicity and sex (NHANES
2011–2014).

Chart 8-6. Age-standardized global mortality rates attributable to high systolic blood pressure per 100 000, both
CLINICAL STATEMENTS
sexes, 2015.
AND GUIDELINES
13. Franklin SS, Thijs L, Asayama K, Li Y, Hansen TW, Boggia J, Jacobs L,

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9. DIABETES MELLITUS Abbreviations Used in Chapter 9 Continued
CLINICAL STATEMENTS
NHIS National Health Interview Survey
ICD-9 250; ICD-10 E10 to E14. See Table 9-1 and
AND GUIDELINES
Charts 9-1 through 9-9 OR odds ratio
Click here to return to the Table of Contents PAD peripheral artery disease
REGARDS Reasons for Geographic and Racial Differences in Stroke
RR relative risk
DM is a major risk factor for CVD, such as CHD, stroke,
PAD, HF, and AF.1 The AHA has identified untreated SD standard deviation
fasting blood glucose levels of <100 mg/dL for children SEARCH Search for Diabetes in Youth Study
and adults as 1 of the 7 components of ideal cardiovas- SNP single-nucleotide polymorphism
cular health.1 SSB sugar-sweetened beverage
TODAY Treatment Options for Type 2 Diabetes in Adolescents and Youth
Abbreviations Used in Chapter 9 UI uncertainty interval
ABI ankle-brachial index USRDS US Renal Data System
ACC American College of Cardiology VTE venous thromboembolism
ADVANCE Action in Diabetes and Vascular Disease: Preterax and
Diamicron Modified Release Controlled Evaluation
Prevalence
AHA American Heart Association Youth
AP angina pectoris • Approximately 186 000 people <20 years of age
ARIC Atherosclerosis Risk in Communities have DM. During 2008 to 2009, >18 000 people
BMI body mass index
<20 years of age were diagnosed with type 1 DM
BP blood pressure
each year.2
CAC coronary artery calcification • Type 2 DM, a disease usually diagnosed in adults ≥40
CAD coronary artery disease years of age, is being diagnosed among people <20
CARDIA Coronary Artery Risk Development in Young Adults years of age. Between 2001 and 2009, the preva-
CARRS Center for Cardiometabolic Risk Reduction in South Asia lence of type 2 DM in youths increased by 30.5%.3
• Among youths with type 2 DM, 10.4% are over-
weight and 79.4% are obese.4
CKD chronic kidney disease • According to NHANES data from 1999 to 2000
CVD cardiovascular disease through 2007 to 2008, among US adolescents
DM diabetes mellitus aged 12 to 19 years, the prevalence of prediabe-
eGFR estimated glomerular filtration rate tes and type 2 DM increased from 9% to 23%.5
ESRD end-stage renal disease
• Analyses of a cohort of consecutive high school
EVEREST Efficacy of Vasopressin Antagonism in Heart Failure Outcome
Study With Tolvaptan blood donors in north Texas from September
FHS Framingham Heart Study 2011 to March 2012 comprising 14 850 adoles-
GBD Global Burden of Disease cents showed that 10.0% had HbA1c values in the
GWAS genome-wide association studies prediabetes range (HbA1c 5.7%–6.4%), and an
HbA1c hemoglobin A1c
additional 0.6% had HbA1c ≥6.5%, the threshold
HCHS/SOL Hispanic Community Health Study/Study of Latinos
endorsed to diagnose DM.6
HD heart disease
• Among US adolescents aged 12 to 19 years in
HF heart failure 2005 to 2014, the prevalence of DM was 0.8%
HR hazard ratio (95% CI, 0.6%-1.1%). Of those with DM, 28.5%
ICD-9 International Classification of Diseases, 9th Revision (95% CI, 16.4%-44.8%) were undiagnosed.7
ICD-10 International Classification of Diseases, 10th Revision • Among US adolescents aged 12 to 19 years in
JHS Jackson Heart Study
2005 to 2014, the prevalence of prediabetes was
MASALA Mediators of Atherosclerosis in South Asians Living in
17.7% (95% CI, 15.8%–19.8%).7 Males were
America more likely to have prediabetes than females
MEPS Medical Expenditure Panel Survey (22.0% [95% CI, 19.5%–24.7%] versus 13.2%
MESA Multi-Ethnic Study of Atherosclerosis [95% CI, 10.4%–16.7%]). Also, the prevalence
MET metabolic equivalent
of prediabetes was higher in NH blacks (21.0%;
95% CI, 17.7%–24.7%) and Hispanics (22.9%;
NH non-Hispanic 95% CI, 19.9%–26.3%) than in NH white partici-
NHANES National Health and Nutrition Examination Survey pants (15.1%; 95% CI, 12.3%–18.6%)
NHDS National Hospital Discharge Survey • From 2004 through 2011 in the TODAY study,
(Continued ) less than half of children (41.1% of Hispanic and

31.5% of NH black children) maintained durable people ≥20 years of age indicate that 8.0% of
CLINICAL STATEMENTS
glycemic control with monotherapy,8 a higher NH white males and 7.4% of NH white females,
AND GUIDELINES
rate of treatment failure than observed in adult 11.8% of NH Asian males and 9.1% of NH Asian
cohorts. Youths who had type 2 DM were seden- females, 12.6% of Hispanic males and 12.7% of
tary >56 minutes longer per day (via accelerom- Hispanic females, and 14.1% of NH black males
etry) than obese youths from NHANES.9 and 13.6% of NH black females had physician-
diagnosed DM (Table 9-1 and Chart 9-1; unpub-
Adults lished NCHS/NHLBI tabulation).
(See Table 9-1 and Charts 9-1 through 9-4) • On the basis of NHANES 2011 to 2014 data, the
• On the basis of data from NHANES 2011 to 2014, an age-adjusted prevalence of physician-diagnosed
estimated 23.4 million adults have diagnosed DM, DM in adults ≥20 years of age varies by race/
7.6 million adults have undiagnosed DM, and 81.6 ethnicity and years of education. NH white adults
million adults (33.9%) have prediabetes (eg, fasting with more than a high school education had the
blood glucose of 100 to <126 mg/dL). The preva- lowest prevalence (6.6%), and NH black adults
lence of prediabetes and DM differs by sex and race/ with less than a high school education had the
ethnicity (Table 9-1; unpublished NHLBI tabulation). highest prevalence (16.0%; Chart 9-2; unpub-
• The age-adjusted prevalence of diagnosed DM lished NCHS/NHLBI tabulation).
and undiagnosed DM increased from 4.96% and • The prevalence of physician-diagnosed DM in
3.45%, respectively, in 1999 to 2000 to 7.78% adults was higher for both males and females
and 4.36%, respectively, in 2009 to 2010.10 The in the 2011 to 2014 NHANES data than in the
prevalence of diagnosed DM increased among 1988 to 1994 NHANES data. Prevalence of undi-
NH whites and blacks over this time period, but agnosed DM differed only slightly for both males
the prevalence of undiagnosed DM did not expe- and females between studies (Chart 9-3; unpub-
rience a statistically significant increase. lished NCHS/NHLBI tabulation). In 1997, the
• Type 2 DM accounts for 90% to 95% of all diag- threshold definition for physician-diagnosed DM
nosed cases of DM in adults.2 was lowered from ≥140 mg/dL to ≥126 mg/dL.16
• Minority groups remain disproportionately affected • The prevalence of physician-diagnosed DM in
by DM.11 The prevalence of DM (diagnosed DM or adults was higher for NH black, NH white, and
HbA1c ≥6.5%) in NH blacks was almost twice as high Hispanic adults in NHANES 1988 to 2010 than
as in whites (15.4% versus 8.6%), and Mexican in NHANES 1988 to 1994. Prevalence of undi-
Americans have a 35% higher prevalence of DM agnosed DM increased slightly between studies
than whites (11.6% versus 8.6%, respectively).11 (Chart 9-4; unpublished NCHS/NHLBI tabulation).
• The prevalence of DM was 25% in a study of • In the prospective, multicenter, population-based
American Indian adults living in Oklahoma.12 HCHS/SOL, 16 415 adults of Hispanic/Latino
• The prevalence of concurrent DM, hyperten- descent aged 18 to 74 years were enrolled from
sion, and hypercholesterolemia among US adults 4 US metropolitan areas from 2008 to 2011. The
increased between 1999 to 2000 and 2011 to prevalence of DM was considerably diverse across
2012 from 3% to 6.3%.13 adults with different Hispanic backgrounds.
• Across counties in the United States, the preva- DM prevalence ranged from 10.2% in South
lence of diagnosed DM was estimated to range Americans to 13.4% in Cubans, 17.7% in Central
from 5.6% to 20.4%, the prevalence of undiag- Americans, 18.0% in Dominicans and Puerto
nosed DM ranged from 3.2% to 6.8%, and the Ricans, and 18.3% in Mexicans.17
prevalence of total DM ranged from 8.8% to • On the basis of 2015 BRFSS (CDC) data, the
26.4%.14 The prevalence of diagnosed DM was age-adjusted prevalence of adults in the United
highest in the deep South, near the Texas-Mexico States who reported ever having been told by a
border, and in counties with Native American res- physician that they had DM ranged from 6.4%
ervations and was lowest in counties in the upper in Colorado to 13.6% in Mississippi. The mean
Midwest and parts of Alaska and New England. percentage among all states was 9.5%.18
• Among foreign-born participants of the US • Using data from the REGARDS study, the median
NHANES 1999 to 2012, the prevalence of DM (range) predicted prevalence of DM was 14%
increased with duration of time spent in the (10%–20%) among whites and 31% (28%–41%)
United States and was 6.1%, 9.3%, 11.1%, and among blacks.19 DM was most prevalent in the west
20.0% among those in the United States for <1, and central Southeast among whites (Louisiana,
1 to 9, 10 to 19, and ≥20 years, respectively.15 Arkansas, Mississippi, Alabama, Tennessee, and
• After adjustment for population age differences, south Kentucky, as well as parts of North Carolina
2011 to 2014 NHANES national survey data for and South Carolina).

Incidence females, 32.8 for NH black females, 21.4 for
CLINICAL STATEMENTS
Hispanic females, 13.8 for NH Asian/Pacific
Youth
AND GUIDELINES
Islander females, and 40.2 for NH American
• During 2008 to 2009, an estimated 18 436 people
Indian/Alaska Native females.24
<20 years of age in the United States were newly
• According to data from the CDC, the National
diagnosed with type 1 DM, and 5089 individuals
Diabetes Information Clearinghouse, the National
<20 years old were newly diagnosed with type 2
Institute of Diabetes and Digestive and Kidney
DM annually.2
Diseases, and the National Institutes of Health23:
• In the SEARCH study, the incidence rate of type
— At least 68% of people >65 years of age
1 DM increased by 1.4% annually (from 19.5 to
with DM die of some form of HD; 16% die
21.7 cases per 100 000 youths per year in 2003 to
of stroke.
2012).20 The increase was larger for boys than for
— HD death rates among adults with DM are
girls and for Hispanics and Asian or Pacific Islanders
2 to 4 times higher than the rates for adults
than for other ethnic groups. Also, the incidence of
without DM.
type 2 DM increased by 7.1% annually (from 9.0 to
• In the Swedish National Diabetes Register, the
12.5 cases per 100 000 youths per year from 2003
absolute change in all-cause mortality among
to 2012). The annual increase was larger among
patients with type 1 DM from 1998 to 2014 was
girls than boys and among NH blacks, Hispanics,
−31.4 deaths (95% CI,−56.1 to −6.7) per 10 000
Asian or Pacific Islanders, and Native Americans
person-years. Among patients with type 2 DM, all-
compared with NH whites.
cause mortality declined by −69.6 deaths (95% CI,
• Projecting disease burden for the US population
−95.9 to −43.2) per 10 000 person years. These
<20 years of age by 2050, the number of youths
reductions were larger than the declines in mortal-
with type 1 DM is expected to increase from
ity for the control population without type 1 DM.25
166 018 to 203 382, and the number with type 2
• In the Swedish National Diabetes Registry, the
DM will increase from 20 203 to 30 111. Less con-
adjusted HRs for mortality comparing patients
servative modeling projects the number of youths
with type 1 DM achieving all and no risk factor
with type 1 DM at 587 488 and those with type 2
targets compared with control subjects without
DM at 84 131 by 2050.21
DM were 1.31 (95% CI, 0.93–1.85) and 7.33
Adults (95% CI, 5.08–10.57), respectively.26
(See Table 9-1) • In a collaborative meta-analysis of 820 900 indi-

• A total of 1.7 million new cases of DM (type 1 or viduals from 97 prospective studies, DM was asso-
type 2) were diagnosed in US adults ≥20 years of ciated with the following risks: all-cause mortality
age in 20122 (Table 9-1). (HR, 1.80; 95% CI, 1.71–1.90), cancer death (HR,
• According to data from NHANES and BRFSS, up 1.25; 95% CI, 1.19–1.31), and vascular death
to 48.7% of individuals with self-reported DM did (HR, 2.32; 95% CI, 2.11–2.56). In particular, DM
not meet glycemic, BP, and lipid targets, and only was associated with death attributable to the fol-
14.3% met all 3 targets and did not smoke.22 lowing cancers: liver, pancreatic, ovarian, colorec-
• Gestational DM complicates 2% to 10% of preg- tal, lung, bladder, and breast. A 50-year-old with
nancies and increases the risk of developing type DM died on average 6 years earlier than an indi-
2 DM by 35% to 60%.23 vidual without DM.27
Mortality Awareness
(See Table 9-1) (See Chart 9-5)
• DM was listed as the underlying cause of mortal- • On the basis of NHANES 2011 to 2014 data for
ity for 79 535 people (43 123 males and 36 412 adults with DM, 20.8% had their DM treated and
females) in the United States in 2015 (Table 9-1). controlled, 46.4% had their DM treated but uncon-
• There were 252 806 deaths with DM as the under- trolled, 9.9% were aware they had DM but were
lying cause in 2015.24 not treated, and 22.9% were undiagnosed and not
• The 2015 overall underlying-cause age-adjusted treated (Chart 9-5; unpublished NHLBI tabulations).
death rate attributable to DM was 21.3 per • Although the prevalence of diagnosed DM has
100 000. Death rates per 100 000 population increased over the past decade, the numbers of
were 23.8 for NH white males, 45.1 for NH black adults with undiagnosed DM and impaired fast-
males, 29.8 for Hispanic males, 18.5 for NH Asian/ ing glucose has remained relatively stable. Of the
Pacific Islander males, 50.6 for NH American estimated 21 million adults with DM, 84.8% were
Indian/Alaska Native males, 14. 9 for NH white told they had DM or were undergoing treatment,

and 11% (2.3 million) of those with confirmed risk of incident aortic valve calcium (adjusted OR,
CLINICAL STATEMENTS
DM (calibrated HbA1c level ≥6.5% and fasting 2.1; 95% CI, 1.4–3.1).
AND GUIDELINES
plasma glucose level ≥126 mg/dL) were unaware • In a nationwide Danish registry, the adjusted inci-
of their diagnosis.11 At baseline (2008–2011) in dence rate ratios (95% CIs) for AF comparing
the HCHS/SOL population-based study of adults people with and without DM were 2.34 (1.52–
of Hispanic/Latino descent, only 58.7% of partici- 3.60), 1.52 (1.47–1.56), 1.20 (1.18–1.23), and
pants with DM were aware of their diagnosis.17 0.99 (0.97–1.01) for adults 18 to 39, 40 to 64, 65
to 74, and 75 to 100 years of age, respectively.35
• In an analysis of NHANES 2001 to 2010 partici-
Aftermath pants with CHD, the prevalence of AP was similar
(See Chart 9-6) for adults with and without DM (49% and 46%,
• In NHANES 2009 to 2010, 19.8% of adults with respectively).36
DM had chronic lower back pain compared with • According to NHANES 2007 to 2012, 17% of US
12.9% of those without DM. After multivariable adults with DM met the criteria for major depres-
adjustment, the OR for chronic lower back pain sion or subsyndromal symptomatic depression.
comparing adults with and without DM was 1.39 This represents 3.7 million US adults with these
(95% CI, 1.02–1.92).28 conditions.37
• Among adults with DM in NHANES 2007 to 2012, • The prevalence of any diabetic kidney disease,
the overall age-adjusted prevalence of CKD was defined as persistent albuminuria, persistent
40.2% in 2007 to 2008, 36.9% in 2009 to 2010, reduced eGFR, or both, did not significantly change
and 37.6% in 2011 to 2012.29 The prevalence from the period 1988 to 1994 (28.4%; 95% CI,
of CKD was 58.7% in US adults with DM aged 23.8%–32.9%) to 2009 to 2014 (26.2%; 95% CI,
≥65 years, 25.7% in those <65 years, 43.5% in 22.6%–29.9%). However, the prevalence of albu-
African-Americans and Mexican-Americans, and minuria decreased from 20.8% (95% CI, 16.3%–
38.7% in NH whites. 25.3%) to 15.9% (95% CI, 12.7%–19.0%) and
• Among NHIS participants enrolled in 2000 to the prevalence of reduced eGFR increased from
2009 and followed up through 2011, males and 9.2% (95% CI, 6.2%–12.2%) to 14.1% (95% CI,
females with diagnosed DM had 1.56 and 1.69 11.3%–17.0%) over this time period.38
• In a study of NHIS 1997 to 2009 participants fol-
times higher risk of death of all causes, respec-

tively (HR, 1.56 [95% CI, 1.49–1.64] and 1.69 lowed up through 2011, DM was the underly-
[95% CI, 1.61–1.78]). DM was associated with ing cause for 3.3% of deaths and a contributing
increased risk for HD, cerebrovascular disease, cause for 10.8% of deaths, and the population
and CVD mortality among males and females.30 attributable fraction for death associated with
• In a meta-analysis of 19 studies, DM was not DM was 11.5%. Although DM was more often
associated with an increased risk for VTE (pooled cited as an underlying and contributing cause of
RRs: 1.10; 95% CI, 0.94–1.29).31 death for NH blacks and Hispanics compared with
• Among participants in the ARIC study without a NH whites, the population attributable fraction
prior diagnosis of DM, hospitalization rates were was similar in each racial/ethnic group.39
163 (95% CI, 158–169), 217 (95% CI, 206–228), • DM increases the risk of HF and adversely affects
and 254 (95% CI, 226–281) per 1000 person- outcomes among patients with HF.
years with HbA1c <5.7%, 5.7% to <6.5%, and — DM alone qualifies for the most recent ACC/
≥6.5% respectively.32 Among those with diag- AHA diagnostic criteria for stages A and B HF,
nosed DM, the incidence rates were 340 (95% CI, a classification of patients without HF but at
297–384) and 504 (95% CI, 462–547) for partici- notably high risk for its development.40
pants with HbA1c <7.0% and ≥7.0%, respectively. — DM should be treated similarly for patients
• Compared with those with normal glucose, with HF as for the general population.40
carotid-femoral pulse-wave velocity was 1107, — In a meta-analysis of 10 prospective cohort
1140, and 1239 cm/s higher for participants with studies, the HR for HF per 1-mmol/L (≈18 mg/
normal glucose, prediabetes, and DM.33 A simi- dL) increase in fasting plasma glucose level was
lar pattern was present for brachial-ankle pulse- 1.11 (95% CI, 1.04–1.17), which suggests an
wave velocity. independent and continuous positive associa-
• In MESA, 63% of participants with DM had a tion between fasting plasma glucose and HF.41
CAC >0 compared with 48% of those without — Post hoc analysis of data from the EVEREST
DM.34 DM was also associated with an increased randomized trial of patients hospitalized
prevalence of aortic valve calcium (RR 2.1 for DM with decompensated systolic HF stratified by
in females and 1.7 for males) and an increased DM status, which evaluated cardiovascular

outcomes over a follow-up period of 9.9 SSBs. A recent meta-analysis showed that each
CLINICAL STATEMENTS
months, demonstrated an increased adjusted 1 serving/day higher consumption of SSBs was
AND GUIDELINES
HR for the composite of cardiovascular mor- associated with an 18% increased risk for DM.49
tality and HF rehospitalization associated • Reduced insulin sensitivity is found during pro-
with DM (HR, 1.17; 95% CI, 1.04–1.31).42 longed sedentary behavior that can be mitigated
• DM increases the risk of AF. On the basis of a meta- with short bouts of PA. Prospective evidence is
analysis of published observational data comprising accumulating that sedentary behavior could be a
11 studies and >1.6 million participants, DM was risk factor for CVD and DM morbidity and mortal-
associated with a 39% increased risk for AF (RR, ity and for all-cause mortality.50
1.39; 95% CI, 1.10–1.75), with the association • In a meta-analysis, each 1-SD higher BMI in child-
remaining statistically significant after multivariable hood was associated with an increased risk for
adjustment (adjusted RR, 1.24; 95% CI, 1.06–1.44), developing DM as an adult (pooled OR, 1.23 [95%
yielding an estimate of the population attributable CI, 1.10–1.37] for children ≤6 years of age; 1.78
fraction of AF attributable to DM of 2.5%.43 [95% CI, 1.51–2.10] for age 7 to 11 years; and 1.70
• On the basis of analyses of data from the NHIS, [95% CI, 1.30 – 2.22] for those 12 to 18 years).51
the NHDS, the USRDS, and the US National Vital • In a meta-analysis, 600 to 3999, 4000 to 7999,
Statistics System, between 1990 and 2010, the and ≥8000 MET min/week versus <600 MET min/
rate of incident MI among patients with DM week each were associated with an RR (UI) for
declined 67.8%. (Chart 9-6)44 developing DM of 0.86 (0.82–0.90), 0.75 (0.701–
• On the basis of analyses of data from the NHIS, the 0.799), and 0.72 (0.68–0.77), respectively.52
NHDS, the USRDS, and the US National Vital Statistics • In MESA, the incidence rate of DM per 1000 per-
System, between 1990 and 2010 (Chart 9-6): son-years associated with having 0, 1, 2, 3, 4, and
— The age-standardized rate of incident stroke 5 to 6 ideal cardiovascular health factors was 21.8,
among patients with DM declined 52.7%.44 18.6, 13.0, 11.2, 4.7, and 3.6, respectively.53 Lower
— The age-standardized rate of incident ESRD DM risk with more ideal cardiovascular health fac-
among patients with DM declined 28.3%.44 tors was present for NH whites, Chinese Americans,
— The relative decline in the age-standardized African Americans, and Hispanic Americans. Ideal
rate was 51.4% for amputation and 64.4% cardiovascular health factors included TC, BP,
dietary intake, tobacco use, PA, and BMI.
for death attributable to hyperglycemic crisis.44

• DM accounted for 44% of the new cases of ESRD • In the ARIC study, participants with an ABI ≤0.9
in 2011.45 were more likely to develop DM than their coun-
• In 2012, the incidence rate of ESRD attributed to DM terparts with an ABI of 1.11 to 1.20 (age-, sex-,
in adults ≥20 years in the Veterans Affairs health sys- race-, and multivariable-adjusted HR, 1.41 [95%
tem increased with age, from 4.44 per 100 000 in CI, 1.17–1.68] and 1.18 [95% CI, 0.98–1.41],
those aged 20 to 29 years to 110.35 per 100 000 respectively).54
in those ≥70 years old, compared with rates of 2.40 • A systematic review by Biswas et al55 identified
and 81.88, respectively, in those without DM.46 5 studies (4 were prospective) that assessed the
• The HRs of CHD events comparing participants with association between sedentary time and type 2
DM only, DM and prevalent CHD, and neither DM DM and found that even after adjustment for
nor prevalent CHD with those with prevalent CHD PA, higher sedentary time was associated with
were 0.65 (95% CI, 0.54–0.77), 1.54 (95% CI, elevated risk of type 2 DM (RR, 1.91; 95% CI,
1.30–1.83), and 0.41 (95% CI, 0.35–0.47), respec- 1.64–2.22). These findings suggest prolonged
tively, after adjustment for demographics and risk sedentary time might have deleterious metabolic
factors.47 Compared with participants who had prev- effects independent of PA.56
alent CHD, the HR of CHD events for participants • In the CARDIA study, higher fitness was associated
with severe DM was 0.88 (95% CI, 0.72–1.09). with lower risk for developing incident prediabetes/
• The association between glycemia and outcomes DM (difference of 1 MET: HR, 0.99898; 95% CI,
has been mixed in patients with HF, and there is 0.99861–0.99940; P<0.01), which persisted (dif-
insufficient evidence to recommend specific glucose ference of 1 MET: HR, 0.99872; 95% CI, 0.99840–
treatment goals in patients hospitalized with HF.48 0.99904; P<0.01) after adjustment for covariates.57
• A recent study, which used mediation analysis
methodologies, found that the effects of low
Risk Factors for Developing DM birth weight on type 2 DM risk appear to be medi-
• Of the 20.9 million new cases of DM predicted ated mainly by insulin resistance, which is further
to occur over 10 years in the United States, 1.8 explained by circulating levels of sex hormone–
million could be attributable to consumption of binding globulin and E-selectin, as well as SBP.58

Treatment of CVD Among Patients With DM that it might be a marker for susceptibility. In
CLINICAL STATEMENTS
the ADVANCE trial, risk factors for hypoglycemia

• In a pooled analysis of ARIC, MESA, and JHS,
AND GUIDELINES
included older age, DM duration, worse renal

41.8%, 32.1%, and 41.9% of participants were
function, lower BMI, lower cognitive function, use
at target levels for BP, LDL-C, and HbA1c, respec-
of multiple glucose-lowering medications, and ran-
tively; 41.1%, 26.5%, and 7.2% were at target
domization to the intensive glucose control arm.65
levels for any 1, 2, or all 3 factors, respectively.
• According to data from the 2004 to 2008
Having 1, 2, and 3 factors at goal was associated
MarketScan database, which included 536 581
with 36%, 52%, and 62%, respectively, lower
individuals with type 2 DM, the incidence rate of
risk of CVD events compared with participants
hypoglycemia was 153.8 per 10 000 person-years
with no risk factors at goal.59
and was highest in adults aged 18 to 34 years
• Among HCHS/SOL study participants with DM,
(218.8 per 10 000 person-years).66
those in the lowest versus highest tertile of seden-
tary time were more likely to have controlled their
HbA1c to <7% (OR, 1.76; 95% CI, 1.10–2.82) and Cost
their triglycerides to <150 mg/dL (OR, 2.16; 95% (See Table 9-1)
CI, 1.36–3.46).60
• In 2012, the cost of DM was estimated at $245
• Treatment of hypercholesterolemia is recom-
billion (Table 9-1), up from $174 billion in 2007,
mended for adults with DM, with the cornerstone
accounting for 1 in 5 healthcare dollars.67,68 Of these
of treatment being statin therapy, which is recom-
costs, $176 billion were direct medical costs and $69
mended for all patients with DM >40 years of age
billion resulted from reduced productivity. Inpatient
independent of baseline cholesterol, with at least
care accounted for 43% of these costs, 18% were
a moderate dose of statin therapy.61
attributable to prescription costs to treat DM com-
• Findings from a recent genetic study on type 2
plications, and 12% were related to anti-DM agents
DM and CVD found that these 2 diseases share
and supplies.67,68 After adjustment for age and sex,
several common biological pathways and key reg-
medical costs for patients with DM were 2.3 times
ulatory genes, which has profound implications
higher than for people without DM.23
for the design of future interventions and thera-
• According to the insurance claims and MarketScan
pies targeting both diseases simultaneously.62
data from 7556 youth <19 years of age with insu-

• In MEPS, 70% (95% CI, 68%–71%), 67% (95% lin-treated DM, costs for youths with hypoglycemia
CI, 66%–69%), and 68% (95% CI, 66%–71%) of were $12 850 compared with $8970 for youths
US adults received appropriate DM care (HbA1c mea- without hypoglycemia. For diabetic ketoacidosis,
surement, foot examination, and an eye examina- costs were $14 236 for youths with versus $8398
tion) in 2002, 2007, and 2013, respectively.63 for youths without diabetic ketoacidosis.69
Hospitalizations Type 1 DM
(See Table 9-1) • Type 1 DM constitutes 5% to 10% of DM in the
Adults United States.70
• Among Medicare beneficiaries with type 2 DM • Between 1996 and 2010, the number of youths
hospitalized between 2012 and 2014, 17.1% with type 1 DM increased by 5.7% per year.71
were readmitted within 30 days.64 • Among youths with type 1 DM, the prevalence of
• According to the HCUP, there were a total of overweight is 22.1% and the prevalence of obe-
551 000 discharges with DM listed as primary sity is 12.6%.4
diagnosis in 2014, of which 301 000 were males • According to 30-year mortality data from Allegheny
and 250 000 were females (NHLBI tabulation). County, PA, those with type 1 DM have a mortality
rate 5.6 times higher than the general population.72
• The leading cause of death among patients with
Hypoglycemia type 1 DM is CVD, which accounted for 22% of
• Severe hypoglycemia was associated with an deaths among those in the Allegheny County, PA,
increased risk of major macrovascular events (HR, type 1 DM registry, followed by renal (20%) and
2.88; 95% CI, 2.01–4.12), cardiovascular death infectious (18%) causes.73
(HR, 2.68; 95% CI, 1.72–4.19), and all-cause • Among 3987 older patients (>60 years of age)
death (HR, 2.69; 95% CI, 1.97–3.67), including with type 1 DM, the risk of severe hypoglycemia
nonvascular outcomes. The lack of specificity of was twice as high as for those <60 years of age
hypoglycemia with vascular outcomes suggests (40.1 versus 24.3 per 100 patient-years).74

Family History and Genetics antigen region, estimated to contribute to ≈50%
CLINICAL STATEMENTS
of the genetic risk.88
Genetics
AND GUIDELINES
• A genotype risk score composed of 9 type 1
• DM is heritable; twin or family studies have dem-
onstrated a range of heritability estimates from DM–associated risk variants has been shown to
30% to 70%75,76 depending on age of onset. In discriminate type 1 DM from type 2 DM (area
the FHS, having a parent or sibling with DM con- under the curve=0.87), which could be clinically
ferred a 3.4 times increased risk of DM, increasing useful given the increasing prevalence of obesity
to 6.1 if both parents were affected.77 in young adults.89
• There are parents-of-origin effects in DM, whereby • The risk of complications from DM is also heri-
effects of genetic variants depend on the parent table. For example, diabetic kidney disease
from whom they are inherited.78 shows familial clustering, with diabetic siblings
• There are monogenic forms of DM such as MODY of patients with diabetic kidney disease having a
(maturity-onset diabetes of the young) that are 2-fold increased risk of also developing diabetic
caused by genetic mutations in the glucokinase kidney disease.90 Genetic variants have also been
(GCK) and 28 other genes,79 but these affect <5% identified that appear to increase the risk of CAD
of patients with DM.80 The majority of DM is a in patients with DM.91
complex disease characterized by multiple genetic
variants with gene-gene and gene-environment Global Burden of DM
interactions. Genome-wide genetic studies of
(See Charts 9-7 to 9-9)
common DM conducted in large sample sizes
via meta-analyses have identified >100 genetic • The prevalence of DM increased from 4.7% to
variants associated with DM, with the most con- 8.5% between 1980 and 2014. Overall, it is esti-
sistent being a common intronic variant in the mated that the number of adults worldwide with
transcription factor 7–like 2 (TCF7L2) gene.81,82 DM increased from 108 million to 422 million
• Other risk loci for DM identified from GWAS over this time period.92 It is estimated that there
include variants in the genes SLC30A8 and HHEX will be 642 million people with DM in 2040.93
(related to β-cell development or function), and in • According to international survey and epidemio-
the N-acetyltransferase 2 (NAT1) gene associated logical data from 2.7 million participants, the
with insulin sensitivity.81,83 prevalence of DM in adults increased from 8.3%

• GWAS in non-European ethnicities have also in males and 7.5% in females in 1980 to 9.8% in
identified significant risk loci for DM, including males and 9.2% in females in 2008. The number
variants in the gene KCNQ1 (identified from a of individuals affected with DM increased from
GWAS in Japanese individuals and replicated in 153 million in 1980 to 347 million in 2008.94
other ethnicities).84,85 Transethnic analyses have • The prevalence of prediabetes is high among Indians
also identified genetic variants that are spe- living in the United States and might be higher than
cific to certain ethnicities, for example, within the prevalence of prediabetes among Indians liv-
the PEPD gene (specific to East Asian ances- ing in India. In a comparison of the MASALA and
try) and the KLF14 gene (specific to European CARRS studies, the prevalence of prediabetes was
ancestry).82 33% in the US sample and 24% in the Chennai,
• Some studies have suggested that genetic vari- India, sample.95 A low amount of exercise was most
ants could predict response to DM therapies. strongly associated with prediabetes in MASALA.96
For example, the response to metformin is heri- • In 2015, an estimated 5.2 million deaths were
table, and an SNP in the ataxia telangiectasia attributed to DM globally. This represents a mor-
mutated (ATM) gene has been associated with tality rate of 82.4 per 100 000.97
this response.86 • The GBD 2015 Study used statistical models and
• Recent genetic technological advances, including data on incidence, prevalence, case fatality, excess
whole-genome sequencing, have enabled identi- mortality, and cause-specific mortality to estimate
fication of novel genes that harbor rare variants disease burden for 315 diseases and injuries in
associated with common DM, with the strongest 195 countries and territories.97
being a variant in the gene CCND2 (encoding a — Mortality rates attributable to high fasting
protein that helps regulate the cell cycle), which plasma glucose were highest in the Pacific
reduces the risk of DM by half.87 Island countries (Chart 9-7).
• Type 1 DM is also heritable. Early genetic studies — Mortality attributable to DM is highest in the
identified the role of the major histocompatibil- Pacific Island countries (Chart 9-8).
ity complex (MHC) gene in this disease, with the — The prevalence of DM is highest in the Pacific
greatest contributor being the human leukocyte Island countries (Chart 9-9).

Table 9-1. Diabetes Mellitus

CLINICAL STATEMENTS
Prevalence of Prevalence of
AND GUIDELINES
Physician-Diagnosed Undiagnosed DM, Prevalence of Incidence of Hospital

DM, 2011–2014: Age 2011–2014: Age Prediabetes, 2011– Diagnosed DM: Mortality, Discharges, Cost,
Population Group ≥20 y ≥20 y 2014: Age ≥20 y Age ≥20 y* 2015: All Ages† 2014: All Ages 2012‡
Both sexes 23 400 000 (9.1%) 7 600 000 (3.1%) 81 600 000 (33.9%) 1 700 000 79 535 551 000 $245 Billion
Males 11 400 000 (9.4%) 4 500 000 (3.8%) 46 200 000 (40.2%) … 43 123 (54.2%)§ 301 000 …
Females 12 000 000 (8.9%) 3 100 000 (2.3%) 35 400 000 (27.8%) … 36 412 (45.8%)§ 250 000 …
NH white males 8.0% 3.6% 39.6% … 29 813 … …
NH white females 7.4% 1.5% 29.2% … 23 777 … …
NH black males 14.1% 2.8% 32.8% … 6806 … …
NH black females 13.6% 3.5% 24.1% … 6887 … …
Hispanic males 12.6% 6.3% 45.9% … 4426 … …
Hispanic females 12.7% 4.4% 25.0% … 3852 … …
NH Asian males 11.8% 5.7% 42.0% … 1322 … …
NH Asian females 9.1% 4.3% 25.5% … 1277 … …
NH American Indian … … … … 1034 … …
or Alaska Native
Undiagnosed DM is defined as those whose fasting glucose is ≥126 mg/dL but who did not report being told by a healthcare provider that they had DM.
Prediabetes is a fasting blood glucose of 100 to <126 mg/dL (impaired fasting glucose); prediabetes includes impaired glucose tolerance. DM indicates diabetes
mellitus; ellipses (…), data not available; and NH, non-Hispanic.
*Centers for Disease Control and Prevention, National Diabetes Statistics Report, 2014.2
†Mortality for Hispanic, American Indian or Alaska Native, and Asian and Pacific Islander people should be interpreted with caution because of inconsistencies
in reporting Hispanic origin or race on the death certificate compared with censuses, surveys, and birth certificates. Studies have shown underreporting on death
certificates of American Indian or Alaska Native, Asian and Pacific Islander, and Hispanic decedents, as well as undercounts of these groups in censuses.
‡American Diabetes Association.68
§These percentages represent the portion of total DM mortality that is for males vs females.
Sources: Prevalence: Prevalence of diagnosed and undiagnosed DM: National Health and Nutrition Examination Survey 2011 to 2014, National Center for Health
Statistics (NCHS), and National Heart, Lung, and Blood Institute. Percentages for racial/ethnic groups are age adjusted for Americans ≥20 years of age. Age-specific
percentages are extrapolations to the 2014 US population estimates. Mortality: Centers for Disease Control and Prevention/NCHS, 2015 Mortality Multiple Cause-of-
Death–US. These data represent underlying cause of death only. Mortality for NH Asians includes Pacific Islanders. Hospital discharges: Healthcare Cost and Utilization
Project, Hospital Discharges, 2014.
16
14.1
14 13.6
12.6 12.7
11.8
12
10
9.1
8.0
8 7.4
0
Male Female
NH White NH Black Hispanic NH Asian
Chart 9-1. Age-adjusted prevalence of physician-diagnosed diabetes mellitus in adults ≥20 years of age by race/
ethnicity and sex (NHANES 2011–2014).

CLINICAL STATEMENTS
18
AND GUIDELINES
16.0
16
14.2 14.3
14
12.9 12.7
12.0
10.4
10.0 9.8
10 9.5
8.9
8
6.6
6
0
NH White NH Black Hispanic NH Asian
Less than high school High school More than high school
Chart 9-2. Age-adjusted prevalence of physician-diagnosed diabetes mellitus in adults ≥20 years of age by race/
ethnicity and years of education (NHANES 2011–2014).
10
9.4
8.9
9
7
6
5.4 5.4
4 3.8
3.4
3
2.5
2.3
2
0
Physician Diagnosed Physician Diagnosed Undiagnosed 1988-94 Undiagnosed 2011-14
1988-94 2011-14
Male Female
Chart 9-3. Trends in diabetes mellitus prevalence in adults ≥20 years of age by sex (NHANES 1988–1994 and
2011–2014).
The definition of diabetes changed in 1997 (from glucose ≥140 mg/dL to ≥126 mg/dL).

CLINICAL STATEMENTS
AND GUIDELINES
Chart 9-4. Trends in the

prevalence of diagnosed and
undiagnosed diabetes mellitus
(calibrated hemoglobin A1c
levels >6.5%), by racial/ethnic
group.
Data from US adults aged 20 years
in NHANES 1988 to 1994, 1999 to
2004, and 2005 to 2010.
NHANES indicates National Health
and Nutrition Examination Survey.
Reprinted from Selvin et al11
with the permission of American
College of Physicians, Inc.
Copyright © 2014, American
College of Physicians. All Rights
Reserved.
Treated and Controlled

20.8%
22.9% Treated and Uncontrolled
Not Treated, but Aware
Chart 9-5. Diabetes mellitus

awareness, treatment, and con-
trol in adults ≥20 years of age
(NHANES 2011–2014).
NHANES indicates National Health
9.9% and Nutrition Examination Survey.
Source: National Heart, Lung, and
Blood Institute.
46.4%

CLINICAL STATEMENTS
AND GUIDELINES
Chart 9-6. Trends in age-standardized rates of diabetes mellitus–related complications among US adults with and
without diagnosed diabetes.
ESRD indicates end-stage renal disease.
Reprinted from Gregg et al44 with permission from Massachusetts Medical Society. Copyright © 2014, Massachusetts Medical
Society.

Chart 9-7. Age-standardized global mortality rates attributable to high fasting plasma glucose per 100 000, both
CLINICAL STATEMENTS
sexes, 2015.
AND GUIDELINES
Chart 9-8. Age-standardized global mortality rates of diabetes mellitus per 100 000, both sexes, 2015.
Chart 9-9. Age-standardized global prevalence rates of diabetes mellitus per 100 000, both sexes, 2015.
13. Song Y, Liu X, Zhu X, Zhao B, Hu B, Sheng X, Chen L, Yu M, Yang T, Zhao

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C, Luan J, Lindgren CM, Müller-Nurasyid M, Pechlivanis S, Rayner NW, Hawley SA, Donnelly LA, Schofield C, Groves CJ, Burch L, Carr F, Strange
Scott LJ, Wiltshire S, Yengo L, Kinnunen L, Rossin EJ, Raychaudhuri S, A, Freeman C, Blackwell JM, Bramon E, Brown MA, Casas JP, Corvin A,
Johnson AD, Dimas AS, Loos RJ, Vedantam S, Chen H, Florez JC, Fox C, Craddock N, Deloukas P, Dronov S, Duncanson A, Edkins S, Gray E, Hunt
Liu CT, Rybin D, Couper DJ, Kao WH, Li M, Cornelis MC, Kraft P, Sun Q, S, Jankowski J, Langford C, Markus HS, Mathew CG, Plomin R, Rautanen
van Dam RM, Stringham HM, Chines PS, Fischer K, Fontanillas P, Holmen A, Sawcer SJ, Samani NJ, Trembath R, Viswanathan AC, Wood NW;
OL, Hunt SE, Jackson AU, Kong A, Lawrence R, Meyer J, Perry JR, Platou MAGIC investigators, Harries LW, Hattersley AT, Doney AS, Colhoun H,
CG, Potter S, Rehnberg E, Robertson N, Sivapalaratnam S, Stančáková Morris AD, Sutherland C, Hardie DG, Peltonen L, McCarthy MI, Holman
A, Stirrups K, Thorleifsson G, Tikkanen E, Wood AR, Almgren P, Atalay RR, Palmer CN, Donnelly P, Pearson ER. Common variants near ATM are
M, Benediktsson R, Bonnycastle LL, Burtt N, Carey J, Charpentier G, associated with glycemic response to metformin in type 2 diabetes. Nat
Crenshaw AT, Doney AS, Dorkhan M, Edkins S, Emilsson V, Eury E, Forsen Genet. 2011;43:117–120. doi: 10.1038/ng.735.
T, Gertow K, Gigante B, Grant GB, Groves CJ, Guiducci C, Herder C, 87. Steinthorsdottir V, Thorleifsson G, Sulem P, Helgason H, Grarup N,
Hreidarsson AB, Hui J, James A, Jonsson A, Rathmann W, Klopp N, Kravic Sigurdsson A, Helgadottir HT, Johannsdottir H, Magnusson OT, Gudjonsson
J, Krjutškov K, Langford C, Leander K, Lindholm E, Lobbens S, Männistö S, SA, Justesen JM, Harder MN, Jørgensen ME, Christensen C, Brandslund
Mirza G, Mühleisen TW, Musk B, Parkin M, Rallidis L, Saramies J, Sennblad I, Sandbæk A, Lauritzen T, Vestergaard H, Linneberg A, Jørgensen T,
B, Shah S, Sigurðsson G, Silveira A, Steinbach G, Thorand B, Trakalo J, Hansen T, Daneshpour MS, Fallah MS, Hreidarsson AB, Sigurdsson G,
Veglia F, Wennauer R, Winckler W, Zabaneh D, Campbell H, van Duijn C, Azizi F, Benediktsson R, Masson G, Helgason A, Kong A, Gudbjartsson
Uitterlinden AG, Hofman A, Sijbrands E, Abecasis GR, Owen KR, Zeggini DF, Pedersen O, Thorsteinsdottir U, Stefansson K. Identification of low-
E, Trip MD, Forouhi NG, Syvänen AC, Eriksson JG, Peltonen L, Nöthen frequency and rare sequence variants associated with elevated or reduced
MM, Balkau B, Palmer CN, Lyssenko V, Tuomi T, Isomaa B, Hunter DJ, Qi risk of type 2 diabetes. Nat Genet. 2014;46:294–298. doi: 10.1038/
L, Shuldiner AR, Roden M, Barroso I, Wilsgaard T, Beilby J, Hovingh K, ng.2882.
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FS, Mohlke KL, Bergman RN, Tuomilehto J, Boehm BO, Gieger C, Hveem AT, Weedon MN. A type 1 diabetes genetic risk score can aid discrimina-
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TM, Hattersley AT, Boerwinkle E, Melander O, Kathiresan S, Nilsson PM, BI. Heritability of GFR and albuminuria in Caucasians with type 2 diabetes
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10. METABOLIC SYNDROME Abbreviations Used in Chapter 10 Continued

CLINICAL STATEMENTS
MORGAM MONICA [Monitoring Trends and Determinants in

See Charts 10-1 through 10-10
AND GUIDELINES
Cardiovascular Disease], Risk, Genetics, Archiving and

Monograph Project
Click here to return to the Table of Contents MRI magnetic resonance imaging
NCDS National Child Development Study
• Metabolic syndrome is a multicomponent risk
factor for CVD and type 2 DM that reflects the NIPPON DATA National Integrated Project for Prospective Observation of
clustering of individual cardiometabolic risk Noncommunicable Disease and Its Trends in Aged
factors related to abdominal obesity and insu- NL The Netherlands
lin resistance. Clinically, metabolic syndrome is OR odds ratio
Abbreviations Used in Chapter 10 PAR population attributable risk
AF atrial fibrillation PREVEND Prevention of Renal and Vascular End-Stage Disease
AHA American Heart Association RCT randomized controlled trial
ARIC Atherosclerosis Risk in Communities RR relative risk
ATP III Adult Treatment Panel III RV right ventricular
BIOSHARE-EU Biobank Standardization and Harmonization for Research SBP systolic blood pressure
Excellence in the European Union SES socioeconomic status
BMI body mass index SSB sugar-sweetened beverage
BP blood pressure TG triglycerides
CAC coronary artery calcification VTE venous thromboembolism
CAD coronary artery disease Waist waist circumference
Carbs carbohydrates circumf.
CARRS Center for Cardiometabolic Risk Reduction in South Asia WC waist circumference
CDC Centers for Disease Control and Prevention WHO World Health Organization
CHRIS Collaborative Health Research in South Tyrol Study
a useful entity for communicating the nature
COURAGE Clinical Outcomes Utilizing Revascularization and of lifestyle-related cardiometabolic risk to both
Aggressive Drug Evaluation patients and clinicians. Although several differ-
CRP C-reactive protein ent clinical definitions for metabolic syndrome

CT computed tomography
have been proposed, the International Diabetes
DBP diastolic blood pressure
Federation, NHLBI, AHA, and others proposed a
DESIR Data From an Epidemiological Study on the Insulin harmonized definition for metabolic syndrome.1
Resistance Syndrome By this definition, metabolic syndrome is diag-
DILGOM Dietary, Lifestyle, and Genetics Determinants of Obesity nosed when any 3 of the following 5 risk factors
and Metabolic Syndrome
are present:
EGCUT Estonian Genome Center of the University of Tartu — Fasting plasma glucose ≥100 mg/dL or under-
GFR glomerular filtration rate going drug treatment for elevated glucose.
HCHS/SOL Hispanic Community Health Study/Study of Latinos — HDL-C <40 mg/dL in males or <50 mg/dL in
HDL high-density lipoprotein females or undergoing drug treatment for
reduced HDL-C.
HF heart failure
HIV human immunodeficiency virus
— Triglycerides ≥150 mg/dL or undergoing drug
HR hazard ratio treatment for elevated triglycerides.
HUNT2 Nord-Trøndelag Health Study — Waist circumference >102 cm in males or
IMT intima-media thickness >88 cm in females for people of most ances-
JHS Jackson Heart Study tries living in the United States. Ethnicity and
KNHANES Korean National Health and Nutrition Examination Survey
country-specific thresholds can be used for
KORA Cooperative Health Research in the Region of Augsburg
diagnosis in other groups, particularly Asians
LV left ventricular and individuals of non-European ancestry
MASALA Mediators of Atherosclerosis in South Asians Living in who have predominantly resided outside the
America United States.
MESA Multi-Ethnic Study of Atherosclerosis
— SBP ≥130 mm Hg or DBP ≥85 mm Hg or
MetS metabolic syndrome
Mex.-Am. Mexican American
undergoing drug treatment for hyperten-
MHO metabolically healthy obesity sion, or antihypertensive drug treatment in a
MI myocardial infarction patient with a history of hypertension.
MICROS Microisolates in South Tyrol Study • The new harmonized metabolic syndrome defi-
(Continued ) nition identifies a comparable risk group and

predicts CVD risk similarly to the prior metabolic analysis strongly suggests the existence of a single
CLINICAL STATEMENTS
syndrome definitions.2 grouping of cardiometabolic risk factors shared
AND GUIDELINES
• There are many adverse health conditions that are commonly across the spectrum from children to
related to metabolic syndrome but are not part of adults.9
its clinical definition. These include nonalcoholic • Additional evidence of the instability of the diag-
fatty liver disease, sexual/reproductive dysfunc- nosis of metabolic syndrome in children exists.
tion (erectile dysfunction in males and polycystic In children 6 to 17 years of age participating in
ovarian syndrome in females), obstructive sleep research studies in a single clinical research hos-
apnea, certain forms of cancer, and possibly pital, the diagnosis of metabolic syndrome was
osteoarthritis, as well as a general proinflamma- unstable in 46% of cases after a mean of 5.6
tory and prothrombotic state.3 years of follow-up.10
• Those with a fasting glucose level ≥126 mg/dL • Uncertainty remains concerning the definition of
or a casual glucose value ≥200 mg/dL or taking the obesity component of metabolic syndrome
hypoglycemic medication will normally be classi- in the pediatric population because it is age
fied separately as having DM; many of these peo- dependent. Therefore, use of BMI percentiles11
ple will also have metabolic syndrome because and waist-height ratio12 has been recommended.
of the presence of ≥2 of the additional risk fac- Using standard CDC and FitnessGram standards
tors noted above. For treatment purposes, many for pediatric obesity, the prevalence of metabolic
researchers will prefer to separate those with DM syndrome in obese youth ranges from 19% to
into a separate group. 35%.11
• Identification and treatment of metabolic syn- • Data from NHANES 2009 to 2010 and 2011 to
drome fits closely with the current AHA 2020 2012 suggest that the prevalence of metabolic
Impact Goals, including emphasis on PA, healthy syndrome is decreasing in 12- to 19-year-olds.
diet, and healthy weight for attainment of ideal This appears to be correlated with decreases in
BP, serum cholesterol, and fasting blood glu- low HDL-C and decreases in triglycerides despite a
cose. Metabolic syndrome should be considered persistently increasing level of obesity. The lifestyle
largely a disease of unhealthy lifestyle. Prevalence factors that correlate with decreasing metabolic
of metabolic syndrome is a secondary metric in syndrome are decreasing carbohydrate intake and
the 2020 Impact Goals. Identification of meta- increasing unsaturated fat intake (Chart 10-2).13
bolic syndrome represents a call to action for the
healthcare provider and patient to address the Adults
underlying lifestyle-related risk factors. A multidis- (See Charts 10-3 through 10-8)
ciplinary team of healthcare professionals is desir- The following estimates include many who also have
able to adequately address these multiple issues DM, in addition to those with metabolic syndrome
in patients with metabolic syndrome.4 without DM:
• Despite its high prevalence (see Prevalence), the • Prevalence of metabolic syndrome varies by the
public’s recognition of metabolic syndrome is definition used, with definitions such as that from
limited.5 A diagnosis of metabolic syndrome may the International Diabetes Federation and the
increase risk perception and motivation toward a harmonized definition suggesting lower thresh-
healthier behavior.6 olds for defining central obesity in European
whites, Asians (in particular, South Asians), Middle
Easterners, sub-Saharan Africans, and Hispanics,
Prevalence which results in higher prevalence estimates.14
Youth • The phenotypic expression of metabolic syndrome
(See Charts 10-1 and 10-2) also varies by race/ethnicity15 and is likely influ-
• According to the 2009 AHA scientific statement enced by genetic factors. For example, in commu-
about metabolic syndrome in children and adoles- nity-based US data from the 2000 to 2002 MESA
cents, metabolic syndrome should be diagnosed study participants, nonalcoholic fatty liver disease
with caution in this age group, because metabolic was present in 17% of African Americans with
syndrome categorization in adolescents is not sta- metabolic syndrome but was present in 39% of
ble.7 Approximately half of the 1098 adolescent Hispanics with metabolic syndrome.16 The pheno-
participants in the Princeton School District Study typic expression of metabolic syndrome also varies
diagnosed with pediatric Adult Treatment Panel by country and culture, particularly in Europe.17
III metabolic syndrome lost the diagnosis over • On the basis of data from NHANES 2003 to 2012,
3 years of follow-up.8 Despite this, mathemati- the age-adjusted prevalence of metabolic syn-
cal research in the form of confirmatory factor drome in the United States peaked in the 2007

to 2008 cycle and declined in the 2009 to 2010 • The prevalence of prediabetes is high among
CLINICAL STATEMENTS
NHANES cycle (Chart 10-3).18 Indians living in the United States and might be
AND GUIDELINES
• Prevalence of metabolic syndrome was lower in higher than the prevalence of prediabetes among
NH black males than white males and Mexican- Indians living in India. In a comparison of the
American males in the NHANES cycle 1999 to MASALA and CARRS studies, the prevalence of
2010 (Chart 10-4). prediabetes was 33% in the US sample and 24%
• Prevalence of metabolic syndrome was higher in the Chennai, India, sample.22 A low amount of
in Mexican-American females than white and exercise was most strongly associated with pre-
black females in the NHANES cycle 1999 to 2010 diabetes in MASALA.23 The overall prevalence of
(Chart 10-5). metabolic syndrome in the MASALA study was
• The changing trends in age-adjusted meta- 34.5% (Alka Kanaya, MD, unpublished data,
bolic syndrome prevalence are attributable 2015). Similarly, Filipinos in the United States are
to changes in the prevalence of its individual at high risk for metabolic syndrome at lower BMI
components. From NHANES data cycles 1999 levels.24
through 2010, hypertriglyceridemia and ele- • The prevalence of metabolic syndrome has
vated BP were lower in the total population, been noted to be high among select special
whereas hyperglycemia and elevated waist cir- populations, including those with schizophrenia
cumference were higher in the total population; spectrum disorders,25 those taking atypical anti-
however, these trends varied significantly by sex psychotic drugs,26 those receiving prior organ
and race/ethnicity (Chart 10-6). Differences in transplants,27 HIV-infected individuals,28 those
the prevalence statistics are the result of differ- previously treated for blood cancers,29 those with
ent handling of age adjustment as the preva- systemic inflammatory disorders such as pso-
lence of metabolic syndrome increases with age riasis,30 individuals with well-controlled type 1
and handling of medication therapy for its com- DM,31 those with hypopituitarism,32 those with
ponent conditions. prior gestational DM,33 and individuals in select
• Additionally, on the basis of NHANES 2001 to professions, including law enforcement34 and
2012, the prevalence of metabolic syndrome firefighters.35
was higher among females (34.4%) than males • There is a bidirectional relationship between met-
(29%). The prevalence of metabolic syndrome abolic syndrome and depression. In prospective
increased with age, from 17% among people studies, the presence of depression increases the
<40 years old to 29.7% for people 40 to 49 years risk of metabolic syndrome (OR, 1.49; 95% CI,
old, 37.5% among people 50 to 59 years old, and 1.19–1.87), while metabolic syndrome increases
>44% among people ≥60 years of age.19 the risk of depression (OR, 1.52; 95% CI,
• The prevalence of metabolic syndrome is high 1.20–1.91).36
among Hispanics/Latinos of diverse backgrounds • Perhaps most important with respect to meet-
living in the United States. Using data from the ing the 2020 goals, the prevalence of metabolic
population-representative HCHS/SOL study 2008 syndrome increases with greater cumulative life-
to 2011, the overall prevalence of metabolic syn- course exposure to sedentary behavior and physi-
drome among Hispanics/Latinos was 34% among cal inactivity37; screen time, including television
males and 36% among females (Chart 10-7); it viewing38; fast food intake39; short sleep dura-
increased with age, with the highest prevalence tion40; and intake of SSBs.41,42 Each of these risk
in females 70 to 74 years of age (Chart 10-8). factors is reversible with lifestyle change.
In males and females, the lowest prevalence of
metabolic syndrome was observed among South
Americans (27%). In males, the highest preva-
Global Burden of Metabolic Syndrome
lence was observed in Cubans (35%), and in (See Chart 10-9)
females, the highest prevalence was observed • Metabolic syndrome is becoming hyperendemic
among Puerto Ricans (41%). Some differences in around the world. Recent evidence has described
individual components exist by specific Hispanic/ the prevalence of metabolic syndrome in Canada,43
Latino background (Chart 10-7).20 Latin America,44 India,45,46 Bangladesh,47 Iran,48
• The prevalence of metabolic syndrome is similarly Nigeria,49 South Africa,50 and Vietnam,51 as well as
high in the African American population from many other countries. On the basis of data from
Mississippi. Using data from the JHS, the overall NIPPON DATA (1990–2005), the age-adjusted
prevalence of metabolic syndrome was 34%, and prevalence of metabolic syndrome in a Japanese
it was higher in females than in males (40% ver- population was 19.3%.52 In a partially representa-
sus 27%, respectively).21 tive Chinese population, the 2009 age-adjusted

prevalence of metabolic syndrome in China was American males than in white males at all time
CLINICAL STATEMENTS
21.3%,53 whereas in northwest China, the preva- points and for all ages across the study. African
AND GUIDELINES
lence for 2010 was 15.1%.54 American females had higher prevalence of met-
• In a report from BIOSHARE-EU, which harmonizes abolic syndrome than white females at baseline
modern data from 10 different population-based and subsequent steps for all ages except for those
cohorts in 7 European countries, the age-adjusted >60 years of age (Chart 10-10).60
prevalence of metabolic syndrome in obese sub- • Isolated metabolic syndrome, which could be con-
jects ranged from 24% to 65% in females and sidered an earlier form of metabolic syndrome,
from ≈43% to ≈78% in males. In the obese pop- has been defined as those with ≥3 metabolic
ulation, the prevalence of metabolic syndrome far syndrome components but without overt hyper-
exceeded the prevalence of MHO, which had a tension and DM. In a population-based random
prevalence of 7% to 28% in females and 2% to sample of 2042 residents of Olmsted County, MN,
19% in males. The prevalence of metabolic syn- those with isolated metabolic syndrome were
drome varied considerably by European country in found to be at increased risk of incident hyper-
the BIOSHARE-EU consortium (Chart 10-9).55 tension, DM, diastolic dysfunction, and reduced
• The prevalence of metabolic syndrome has been renal function (GFR <60 mL/min) compared with
reported to be low (14.6%) in a population-rep- healthy control subjects (P<0.05). However, iso-
resentative study in France (the French Nutrition lated metabolic syndrome was not significantly
and Health Survey, 2006–2007) compared with associated with higher rates of mortality (P=0.12)
other industrialized countries.56 or development of HF (P=0.64) over the 8-year
• In a recent systematic review of 10 Brazilian stud- follow-up.61
ies, the weighted mean prevalence of metabolic
syndrome in Brazil was 29.6%.57
• In a report from a representative survey of the Risk
northern state of Nuevo León, Mexico, the prev- Youth
alence of metabolic syndrome in adults (≥16 • Few prospective pediatric studies have examined
years old) for 2011 to 2012 was 54.8%. In obese the future risk for CVD or DM according to baseline
adults, the prevalence reached 73.8%. The prev- metabolic syndrome status. Data from 771 partici-
alence in adult North Mexican females (60.4%) pants 6 to 19 years of age from the NHLBI’s Lipid
was higher than in adult North Mexican males Research Clinics Princeton Prevalence Study and
(48.9%).58 the Princeton Follow-up Study showed that the risk
• Metabolic syndrome is highly prevalent in mod- of developing CVD was substantially higher among
ern indigenous populations, notably in Brazil and those with metabolic syndrome than among those
Australia. The prevalence of metabolic syndrome without this syndrome (OR, 14.6; 95% CI, 4.8–
was estimated to be 41.5% in indigenous groups 45.3) who were followed up for 25 years.62
in Brazil,57 33.0% in Australian Aborigines, and • In a study of 6328 subjects from 4 prospective
50.3% in Torres Strait Islanders.59 studies, compared with people with normal BMI
as children and as adults, those with consistently
Natural History and Progression of high adiposity from childhood to adulthood had
an increased risk of the following metabolic syn-
Metabolic Syndrome drome components: hypertension (RR, 2.7; 95%
(See Chart 10-10) CI, 2.2–3.3), low HDL-C (RR, 2.1; 95% CI, 1.8–
• Preclinical forms of metabolic syndrome are com- 2.5), elevated triglycerides (RR, 3.0; 95% CI, 2.4–
monly progressive and precede the development 3.8), type 2 DM (RR, 5.4; 95% CI, 3.4–8.5), and
of overt metabolic syndrome. In the ARIC study, a increased carotid IMT (RR, 1.7; 95% CI, 1.4–2.2).
sex and race/ethnicity-specific metabolic syndrome Those people who were overweight or obese dur-
severity score increased in 76% of participants, ing childhood but were not obese as adults had
with faster progression observed in younger par- no increased risk compared with those with con-
ticipants and in females. The metabolic syndrome sistently normal BMI.63
severity score predicted time to development of • Among 1757 youths from the Bogalusa Heart
incident metabolic syndrome over mean 10-year Study and the Cardiovascular Risk in Young Finns
follow-up (1987–1989 to 1996–1998). In ARIC, Study, those with metabolic syndrome in youth
prevalence of metabolic syndrome increased from and adulthood were at 3.4 times increased risk
33% to 50% over the mean 10-year follow-up, of high carotid IMT and 12.2 times increased
with differences by age and sex. The prevalence risk of type 2 DM in adulthood as those without
of metabolic syndrome was lower in African metabolic syndrome at either time. Adults whose

metabolic syndrome had resolved after their and 3.99 (95% CI, 1.89–8.41) for males with ≥3
CLINICAL STATEMENTS
youth were at no increased risk of having high components.73 Among females, the HRs were 3.39
AND GUIDELINES
IMT or type 2 DM.64 (95% CI, 1.31–8.81) for 1 or 2 components and

• In the Princeton Lipid Research Cohort Study, meta- 5.95 (95% CI, 2.20–16.11) for ≥3 components.
bolic syndrome severity scores during childhood Compared with males without a metabolic abnor-
were lowest among those who never developed mality in the British Regional Heart Study, the HRs
CVD and were proportionally higher progressing were 1.74 (95% CI, 1.22–2.39) for 1 component,
from those who developed early CVD (mean 38 2.34 (95% CI, 1.65–3.32) for 2 components, 2.88
years old) to those who developed CVD later in life (95% CI, 2.02–4.11) for 3 components, and 3.44
(mean 50 years old).65 Metabolic syndrome severity (95% CI, 2.35–5.03) for 4 or 5 components.73
score was also strongly associated with early onset • The cardiovascular risk associated with metabolic
of DM.66 Similarly, metabolic syndrome score, based syndrome varies on the basis of the combination
on the number of components of metabolic syn- of metabolic syndrome components present. Of
drome, was associated with biomarkers of inflam- all possible ways to have 3 metabolic syndrome
mation, endothelial damage, and CVD risk in a components, the combination of central obesity,
separate cohort of 677 prepubertal children.67 elevated BP, and hyperglycemia conferred the
greatest risk for CVD (HR, 2.36; 95% CI, 1.54–
Adults
3.61) and mortality (HR, 3.09; 95% CI, 1.93–
Clinical CVD 4.94) in the Framingham Offspring Study.74
• Consistent with 2 previous meta-analyses, a • Data from the Aerobics Center Longitudinal Study
recent meta-analysis of prospective studies con- indicate that risk for CVD mortality is increased in
cluded that metabolic syndrome increased the males without DM who have metabolic syndrome
risk of developing CVD (summary RR, 1.78; 95% (HR, 1.8; 95% CI, 1.5–2.0); however, among
CI, 1.58–2.00).68 The RR of CVD tended to be those with metabolic syndrome, the presence of
higher in females (summary RR, 2.63) than in DM is associated with even greater risk for CVD
males (summary RR, 1.98; P=0.09). On the basis mortality (HR, 2.1; 95% CI, 1.7–2.6).75
of results from 3 studies, metabolic syndrome was • Among patients with stable CAD in the COURAGE
associated with an increased risk of cardiovascular trial, the presence of metabolic syndrome was
events after adjustment for the individual compo- associated with an increased risk of death or
nents of the syndrome (summary RR, 1.54; 95% MI (unadjusted HR, 1.41; 95% CI, 1.15–1.73;
CI, 1.32–1.79). Metabolic syndrome is also associ- P=0.001); however, after adjustment for its indi-
ated with incident CVD independent of the base- vidual components, metabolic syndrome was no
line subclinical CVD.69 A more recent meta-analysis longer significantly associated with outcome (HR,
among 87 studies comprising 951 083 subjects 1.15; 95% CI, 0.79–1.68; P=0.46).76
showed an even higher risk of CVD associated • In the INTERHEART case-control study of 26 903
with metabolic syndrome (summary RR, 2.35; subjects from 52 countries, metabolic syndrome
95% CI, 2.02–2.73), with significant increased was associated with an increased risk of MI, both
risks (RRs ranging from 1.6 to 2.9) for all-cause according to the WHO (OR, 2.69; 95% CI, 2.45–
mortality, CVD mortality, MI, and stroke, as well as 2.95) and the International Diabetes Federation
for those with metabolic syndrome without DM.70 (OR, 2.20; 95% CI, 2.03–2.38) definitions, with a
• In one of the earlier studies among US adults, mor- PAR of 14.5% (95% CI, 12.7%–16.3%) and 16.8%
tality follow-up of the second NHANES showed a (95% CI, 14.8%–18.8%), respectively, and associa-
stepwise increase in risk of CHD, CVD, and total tions that were similar across all regions and ethnic
mortality across the spectrum of no disease, met- groups. In addition, the presence of ≥3 risk fac-
abolic syndrome (without DM), DM, prior CVD, tors with subthreshold values was associated with
and those with CVD and DM, with an HR for CHD increased risk of MI (OR, 1.50; 95% CI, 1.24–1.81)
mortality of 2.02 (95% CI, 1.42–2.89) associated compared with having “normal” values. Similar
with metabolic syndrome. Increased risk was seen results were observed when the International
with increased numbers of metabolic syndrome Diabetes Federation definition was used.77
risk factors.71 • In the Three-City Study, among 7612 participants
• Estimates of RR for CVD generally increase as aged ≥65 years who were followed up for 5.2
the number of components of metabolic syn- years, metabolic syndrome was associated with
drome increases.72 Compared with males with- increased total CHD (HR, 1.78; 95% CI, 1.39–2.28)
out an abnormal component in the Framingham and fatal CHD (HR, 2.40; 95% CI, 1.41–4.09);
Offspring Study, the HRs for CVD were 1.48 (95% however, metabolic syndrome was not associated
CI, 0.69–3.16) for males with 1 or 2 components with CHD beyond its individual risk components.78

• The United States has a higher prevalence of meta- • Individuals with metabolic syndrome have a higher
CLINICAL STATEMENTS
bolic syndrome and a higher CVD mortality rate degree of endothelial dysfunction than individuals
AND GUIDELINES
than Japan. It is estimated that 13.3% to 44% with a similar burden of traditional cardiovascular
of the excess CVD mortality in the United States risk factors.98 Furthermore, individuals with both
is explained by metabolic syndrome or metabolic metabolic syndrome and DM have demonstrated
syndrome–related existing CVD.52 increased microvascular and macrovascular dys-
• In addition to CVD, metabolic syndrome has been function.99 Metabolic syndrome is associated with
associated with incident AF,79 recurrent AF after abla- increased thrombosis, including increased resis-
tion,80 HF,81 PAD,82 erectile dysfunction,83 and cogni- tance to aspirin100 and clopidogrel loading.101
tive decline.84 Data from case-control studies, but • In modern imaging studies using echocardiogra-
not prospective studies, support an association with phy, MRI, cardiac CT, and positron emission tomog-
VTE.85 There may be an association with increased raphy, metabolic syndrome has been shown to be
incident asthma.86 In MESA, the prevalence of erec- closely related to increased epicardial adipose tis-
tile dysfunction among participants aged 55 to 65 sues,102 regional neck fat distribution,103 increased
years with metabolic syndrome was 16% compared visceral fat in other locations,104 high-risk coronary
with 10% without metabolic syndrome (P<0.001). plaque features including increased necrotic core,105
• Using the 36 cohorts represented in the MORGAM impaired coronary flow reserve,106 abnormal indices
Project, the prognosis associated with metabolic of LV strain,107 LV diastolic dysfunction,108 LV dysyn-
syndrome has been shown to vary substantially by chrony,109 and subclinical RV dysfunction.110
age and sex.87 • Metabolic syndrome is associated with increased
healthcare use and healthcare-related costs
Subclinical CVD among individuals with and without DM. Overall,
• In MESA, among 6603 people aged 45 to 84 healthcare costs increase by ≈24% for each addi-
years (1686 [25%] with metabolic syndrome tional metabolic syndrome component present.111
without DM and 881 [13%] with DM), subclini-
cal atherosclerosis assessed by CAC was more
severe in people with metabolic syndrome and Risk Factors
DM than in those without these conditions, and • Investigation of genetic factors related to metabolic
the extent of CAC was a strong predictor of CHD syndrome had shed some light on the underlying
and CVD events in these groups.88 There appears pathways and mediators. A recent genetic study
to be a synergistic relationship between meta- of metabolic syndrome components in African
bolic syndrome, nonalcoholic fatty liver disease, Americans identified several pleiotropic variants
and prevalence of CAC,89,90 as well as a synergis- (TCF7L2, LPL, APOA5, CETP, and APOC1/APOE/
tic relationship with smoking.91 Furthermore, the TOMM40), which may explain some of the corre-
progression of CAC was greater in people with lated architecture of metabolic syndrome traits.112
metabolic syndrome and DM than in those with- • Risk of metabolic syndrome probably begins before
out, and progression of CAC predicted future birth. The Prediction of Metabolic Syndrome in
CVD event risk both in those with metabolic syn- Adolescence Study showed that the coexistence
drome and in those with DM.92,93 In MESA, the of low birth weight, small head circumference, and
prevalence of thoracic calcification was 33% for parental history of overweight or obesity places chil-
people with metabolic syndrome compared with dren at the highest risk for metabolic syndrome in
38% for those with DM (with and without meta- adolescence. Other risk factors identified included
bolic syndrome) and 24% of those with neither parental history of DM, gestational hypertension in
DM nor metabolic syndrome.94 the mother, and lack of breastfeeding.113 However,
• In the DESIR cohort, metabolic syndrome was a recent RCT that tested a breastfeeding promotion
associated with an unfavorable hemodynamic intervention did not lead to reduced childhood met-
profile, including increased brachial central pulse abolic syndrome among healthy term infants.114
pressure and increased pulse pressure amplifi- • In NHANES, adolescents 12 to 19 years old were
cation, compared with similar individuals with at greater risk of metabolic syndrome if they had
isolated hypertension but without metabolic syn- concurrent exposure to secondhand smoke and
drome.95 In MESA, metabolic syndrome was asso- low exposure to certain nutrients (vitamin E and
ciated with major and minor electrocardiographic omega-3 polyunsaturated fatty acids)115 and if
abnormalities, although this varied by sex.96 they consumed more sugar in their diet.116
Metabolic syndrome is associated with reduced • In prospective or retrospective cohort stud-
heart rate variability and altered cardiac auto- ies, the following factors have been reported as
nomic modulation in adolescents.97 being directly associated with incident metabolic

syndrome, defined by 1 of the major definitions: muscular strength,170 increased PA or physical fit-
CLINICAL STATEMENTS
age,117 low educational attainment,118,119 low ness,124,171 aerobic training,172 moderate alcohol
AND GUIDELINES
SES,120 not being able to understand or read food intake,73,88 fiber intake,173 fruits and vegetables,174
labels,121 urbanization,122 smoking,119,120,123,124 white fish intake,175 Mediterranean diet,176 dairy
parental smoking,125 low levels of PA,119,120,123,124 consumption130 (particularly yogurt and low-fat
low levels of physical fitness,126–128 intake of soft dairy products177), consumption of fermented milk
drinks,129 intake of diet soda,130 fructose intake,131 with Lactobacillus plantarum,178 animal or fat pro-
magnesium intake,132,133 energy intake,134 car- tein,179 hot tea consumption (but not sugar-sweet-
bohydrate intake,118,124,135 total fat intake,136,137 ened iced tea),180 coffee consumption,181 vitamin
meat intake (red but not white meat138), intake D intake,182,183 intake of tree nuts,184 avocado
of fried foods,130 skipping breakfast,139 heavy intake,185 intake of long-chain omega-3 polyun-
alcohol consumption,140 abstention from alcohol saturated fatty acid,186 potassium intake,187 ability
use,118 parental history of DM,136 long-term stress to interpret nutrition labels,121 insulin sensitivity,148
at work,141 pediatric metabolic syndrome,136 obe- ratio of aspartate aminotransferase to alanine
sity or BMI,64,75,88,137,142 childhood obesity,143 intra- transaminase,154 total testosterone,144,148,188 serum
abdominal fat,144 gain in weight or BMI,125,137 25-hydroxyvitamin D,189 sex hormone–binding
weight fluctuation,145 heart rate,146 homeosta- globulin,144,148,188 and Δ5-desaturase activity.190
sis model assessment,147,148 fasting insulin,148 In cross-sectional studies, increased standing,191
2-hour insulin,148 proinsulin,148 oxidized LDL-C,147 a vegetarian diet,192 subclinical hypothyroidism
lipoprotein-associated phospholipase A2,149 uric in males,193 and marijuana use194 were inversely
acid,150,151 γ-glutamyltransferase,150,152,153 alanine associated with metabolic syndrome.
transaminase,150,152,154,155 plasminogen activator • In >6 years of follow-up in the ARIC study, 1970
inhibitor-1,156 aldosterone,156 leptin,157 ferritin,158 individuals (25%) developed metabolic syn-
CRP,159,160 adipocyte–fatty acid binding protein,161 drome, and compared with the normal-weight
testosterone and sex hormone–binding globu- group (BMI <25 kg/m2), the ORs of developing
lin,162,163 matrix metalloproteinase 9,164 active metabolic syndrome were 2.81 (95% CI, 2.50–
periodontitis,165 and urinary bisphenol A levels.166 3.17) and 5.24 (95% CI, 4.50–6.12) for the
In cross-sectional studies, a high-salt diet,167 overweight (BMI 25–30 kg/m2) and obese (BMI
stress,168 and obstructive sleep apnea169 were sig- ≥30 kg/m2) groups, respectively. Compared with
nificant predictors of metabolic syndrome. the lowest quartile of leisure-time PA, the ORs of
• The following factors have been reported as developing metabolic syndrome were 0.80 (95%
being inversely associated with incident metabolic CI, 0.71–0.91) and 0.92 (95% CI, 0.81–1.04)
syndrome, defined by 1 of the major definitions, for people in the highest and middle quartiles,
in prospective or retrospective cohort studies: respectively.195
Chart 10-1. Secular trend of metabolic syndrome components in youth in the NHANES and KNHANES cohorts.
BP indicates blood pressure; HDL, high-density lipoprotein cholesterol; KNHANES, Korean National Health and Nutrition
Examination Survey; NHANES, National Health and Nutrition Examination Survey; TG, triglycerides; and WC, waist circumference.
*Significant difference between NHANES 2003 to 2006 and NHANES III.
†Significant difference between NHANES 2003 to 2006 and NHANES 1999 to 2002.
‡Significant difference between KNHANES 2007 and KNHANES 1998.
§Significant difference between KNHANES 2007 and KNHANES 2001.
Reproduced with permission from Lim et al.196 Copyright © 2013, by the American Academy of Pediatrics.

CLINICAL STATEMENTS
AND GUIDELINES
Chart 10-2. Prevalence of metabolic syndrome in youth.

ATP indicates Adult Treatment Panel; BMI, body mass index; Carbs, carbohydrates; HDL, high-density lipoprotein; and MetS,
metabolic syndrome.
Reproduced with permission from Lee et al.13 Copyright © 2016 by the American Academy of Pediatrics.
30
27.5 27.4 27.5
27.0 26.2 26.5
25.5 25.8
25.3 24.9
24.6
25 23.7
23.3 23.2 23.5
22.9
22.1 21.8
20
15
10
0
1999-2000 2001-2002 2003-2004 2005-2006 2007-2008 2009-2010
Total Men Women
Chart 10-3. Age-adjusted prevalence of metabolic syndrome in the United States, NHANES 1999 to 2010.
Data derived from Beltrán-Sánchez et al.117

CLINICAL STATEMENTS
40
AND GUIDELINES
34.8
35 33.7
31.1
30
28.1
26.8 26.5 27.2 27.2
26.2
25.2
25 23.9
22.9
19.9
20 19.0
17.4 17.5 17.3
16.3
15
10
0
1999-2000 2001-2002 2003-2004 2005-2006 2007-2008 2009-2010
Whites Blacks Mexican-Americans
Chart 10-4. Age-adjusted prevalence of metabolic syndrome among adult males by race, NHANES 1999 to 2010.
40
37.6 37.5
35
33.4 32.4
30 28.5
27.1 27.6 26.9 26.8
25.7 25.8 25.9
24.5
25 23.2 22.8 22.3
21.7
20.3
20
15
10
0
1999-2000 2001-2002 2003-2004 2005-2006 2007-2008 2009-2010
Whites Blacks Mexican-Americans
Chart 10-5. Age-adjusted prevalence of metabolic syndrome among adult females by race, NHANES 1999 to 2010.

CLINICAL STATEMENTS
AND GUIDELINES
Chart 10-6. Prevalence and trends of the 5 components of metabolic syndrome in the adult US population (≥20
years old), 1999 to 2010, by sex (first column), race/ethnicity (second column), and race/ethnicity and sex (third
and fourth columns).
Shaded areas represent 95% confidence intervals.
HDL-C indicates high-density lipoprotein cholesterol; Mex-Am, Mexican American; and Waist circumf., waist circumference.
Reprinted from Beltrán-Sánchez et al117 with permission from the American College of Cardiology Foundation. Copyright ©
2013, by the American College of Cardiology Foundation.

CLINICAL STATEMENTS
AND GUIDELINES
Chart 10-7. Age-standardized prevalence of metabolic syndrome by sex and Hispanic/Latino background, 2008 to 2011.
Values were weighted for survey design and nonresponse and were age standardized to the population described by the 2010
US census.
Source: Hispanic Community Health Study/Study of Latinos.20
Chart 10-8. Age-standardized prevalence of metabolic syndrome by age and sex in Hispanics/Latinos, 2008 to 2011.
Values were weighted for survey design and nonresponse and were age standardized to the population described by the
2010 US census.
Source: Hispanic Community Health Study/Study of Latinos.20

CLINICAL STATEMENTS
AND GUIDELINES
Chart 10-9. Age-standardized prevalence of MetS and MHO among obese (body mass index ≥30 kg/m2) males (A)
and females (B) in different cohorts.
CHRIS indicates Collaborative Health Research in South Tyrol Study; DILGOM, Dietary, Lifestyle, and Genetics Determinants
of Obesity and Metabolic Syndrome; EGCUT, Estonian Genome Center of the University of Tartu; HUNT2, Nord-Trøndelag
Health Study; KORA, Cooperative Health Research in the Region of Augsburg; MetS, metabolic syndrome; MHO, metabolically
healthy obesity; MICROS, Microisolates in South Tyrol Study; NCDS, National Child Development Study; NL, the Netherlands;
and PREVEND, Prevention of Renal and Vascular End-Stage Disease.
Reprinted from van Vliet-Ostaptchouketet al.55 Copyright © 2014, van Vliet-Ostaptchouk et al.; licensee BioMed Central Ltd.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecom-
mons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original
work is properly credited.

CLINICAL STATEMENTS
AND GUIDELINES
Chart 10-10. Ten-year progression of metabolic syndrome in the ARIC study, stratified by age, sex, and race/ethnicity.
ARIC indicates Atherosclerosis Risk in Communities.
Adapted from Vishnu et al60 with permission from Elsevier. Copyright © 2015, Elsevier Ireland Ltd.
6. Jumean MF, Korenfeld Y, Somers VK, Vickers KS, Thomas RJ, Lopez-
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resistance in men. Diabetes Care. 2010;33:1618–1624. doi: 10.2337/ 770. doi: 10.3945/ajcn.114.104026.
dc09-1788. 180. Vernarelli JA, Lambert JD. Tea consumption is inversely associated with
164. Yadav SS, Mandal RK, Singh MK, Verma A, Dwivedi P, Sethi R, Usman K, weight status and other markers for metabolic syndrome in US adults.
Khattri S. High serum level of matrix metalloproteinase 9 and promoter Eur J Nutr. 2013;52:1039–1048. doi: 10.1007/s00394-012-0410-9.

181. Shang F, Li X, Jiang X. Coffee consumption and risk of the metabolic syn- 189. Chacko SA, Song Y, Manson JE, Van Horn L, Eaton C, Martin LW,
CLINICAL STATEMENTS
drome: a meta-analysis. Diabetes Metab. 2016;42:80–87. doi: 10.1016/j. McTiernan A, Curb JD, Wylie-Rosett J, Phillips LS, Plodkowski RA,
AND GUIDELINES
diabet.2015.09.001. Liu S. Serum 25-hydroxyvitamin D concentrations in relation to

182. Liu S, Song Y, Ford ES, Manson JE, Buring JE, Ridker PM. Dietary calcium, cardiometabolic risk factors and metabolic syndrome in postmeno-
vitamin D, and the prevalence of metabolic syndrome in middle-aged pausal women. Am J Clin Nutr. 2011;94:209–217. doi: 10.3945/
and older U.S. women. Diabetes Care. 2005;28:2926–2932. ajcn.110.010272.
183. Maki KC, Fulgoni VL 3rd, Keast DR, Rains TM, Park KM, Rubin MR. 190. Warensjö E, Risérus U, Vessby B. Fatty acid composition of serum lip-
Vitamin D intake and status are associated with lower prevalence of met- ids predicts the development of the metabolic syndrome in men.
abolic syndrome in U.S. adults: National Health and Nutrition Examination Diabetologia. 2005;48:1999–2005. doi: 10.1007/s00125-005-1897-x.
Surveys 2003-2006. Metab Syndr Relat Disord. 2012;10:363–372. doi: 191. Shuval K, Barlow CE, Finley CE, Gabriel KP, Schmidt MD, DeFina LF.
10.1089/met.2012.0020. Standing, obesity, and metabolic syndrome: findings from the Cooper
184. O’Neil CE, Keast DR, Nicklas TA, Fulgoni VL 3rd. Nut consumption is as- Center Longitudinal Study. Mayo Clin Proc. 2015;90:1524–1532. doi:
sociated with decreased health risk factors for cardiovascular disease and 10.1016/j.mayocp.2015.07.022.
metabolic syndrome in U.S. adults: NHANES 1999-2004. J Am Coll Nutr. 192. Sabaté J, Wien M. A perspective on vegetarian dietary patterns and risk
2011;30:502–510. of metabolic syndrome. Br J Nutr. 2015;113 Suppl 2:S136–S143. doi:
185. Fulgoni VL 3rd, Dreher M, Davenport AJ. Avocado consumption is as- 10.1017/S0007114514004139.
sociated with better diet quality and nutrient intake, and lower meta- 193. Benseñor IM, Goulart AC, Molina Mdel C, de Miranda ÉJ, Santos IS,
bolic syndrome risk in US adults: results from the National Health and Lotufo PA. Thyrotropin levels, insulin resistance, and metabolic syndrome: a
Nutrition Examination Survey (NHANES) 2001-2008. Nutr J. 2013;12:1. cross-sectional analysis in the Brazilian Longitudinal Study of Adult Health
doi: 10.1186/1475-2891-12-1. (ELSA-Brasil). Metab Syndr Relat Disord. 2015;13:362–369. doi: 10.1089/
186. Kim YS, Xun P, He K. Fish consumption, long-chain omega-3 polyunsatu- met.2015.0045.
rated fatty acid intake and risk of metabolic syndrome: a meta-analysis. 194. Vidot DC, Prado G, Hlaing WM, Florez HJ, Arheart KL, Messiah SE.
Nutrients. 2015;7:2085–2100. doi: 10.3390/nu7042085. Metabolic syndrome among marijuana users in the United States: an
187. Shin D, Joh HK, Kim KH, Park SM. Benefits of potassium intake on analysis of National Health and Nutrition Examination Survey Data. Am J
metabolic syndrome: the fourth Korean National Health and Nutrition Med. 2016;129:173–179. doi: 10.1016/j.amjmed.2015.10.019.
Examination Survey (KNHANES IV). Atherosclerosis. 2013;230:80–85. 195. Cheriyath P, Duan Y, Qian Z, Nambiar L, Liao D. Obesity, physical activity
doi: 10.1016/j.atherosclerosis.2013.06.025. and the development of metabolic syndrome: the Atherosclerosis Risk
188. Liu S, Sun Q. Sex differences, endogenous sex-hormone hormones, sex- in Communities study. Eur J Cardiovasc Prev Rehabil. 2010;17:309–313.
hormone binding globulin, and exogenous disruptors in diabetes and doi: 10.1097/HJR.0b013e32833189b8.
related metabolic outcomes [published ahead of print December 19, 196. Lim S, Jang HC, Park KS, Cho SI, Lee MG, Joung H, Mozumdar A,
2016]. J Diabetes. 2016. doi: 10.1111/1753-0407. http://onlinelibrary. Liguori G. Changes in metabolic syndrome in American and Korean
wiley.com/doi/10.1111/1753-0407.12517/abstract;jsessionid=983EBEBF youth, 1997-2008. Pediatrics. 2013;131:e214–e222. doi: 10.1542/
90B64E1FE584D45B14BF424E.f02t03. peds.2012-0761.

11. KIDNEY DISEASE mg/gCr), or both, is a serious health condition and a
CLINICAL STATEMENTS
worldwide public health problem that is associated
ICD-10 N18.0. See Charts 11-1 through 11-15
AND GUIDELINES
with poor outcomes and a high cost to the US health-
care system.1
• GFR is usually estimated from the serum creati-
nine level using equations that account for age,
Definition sex, and race. The CKD-EPI equation more accu-
CKD, defined as reduced GFR (<60 mL·min−1·1.73 rately estimates GFR from serum creatinine than
m−2), excess urinary albumin excretion (≥30 mg/d or the previously established MDRD Study equation.2
• The spot urine ACR is recommended as a measure
Abbreviations Used in Chapter 11 of urine albumin excretion.
ACC American College of Cardiology
• CKD has been staged as 1 (eGFR ≥90
ACR albumin-to-creatinine ratio mL·min−1·1.73−2 with albuminuria), 2 (eGFR 60–89
AF atrial fibrillation mL·min−1·1.73−2 with albuminuria), 3 (eGFR 30–59
AFIB atrial fibrillation mL·min−1·1.73−2), 4 (eGFR 15–29 mL·min−1·1.73−2),
AHA American Heart Association and 5 (eGFR <15 mL·min−1·1.73−2) mainly based
on eGFR, but the KDIGO CKD 2012 guideline rec-
ASHD atherosclerotic heart disease
ommends characterizing CKD according to both
BMI body mass index eGFR and albuminuria stages, as well as cause of
CABG coronary artery bypass graft surgery CKD.
CAD coronary artery disease • ESRD is defined as severe CKD requiring chronic
CHD coronary heart disease renal replacement treatment such as hemodialy-
CHF congestive heart failure
sis, peritoneal dialysis, or kidney transplantation.1
CKD chronic kidney disease ESRD is an extremely high-risk population for car-
CKD-EPI Chronic Kidney Disease Epidemiology Collaboration diovascular morbidity and mortality.
CRIC Chronic Renal Insufficiency Cohort
CVA/TIA cerebrovascular accident/transient ischemic attack
CVD cardiovascular disease Prevalence
DBP diastolic blood pressure (See Charts 11-1 through 11-4)
eGFR estimated glomerular filtration rate • According to the USRDS, the overall prevalence
ESRD end-stage renal disease of CKD in the United States among NHANES par-
GBD Global Burden of Disease ticipants aged ≥20 years was 14.8% (95% CI,
GFR glomerular filtration rate 13.6%–16.0%) in 2011 to 2014.1 The prevalence
GWAS Genome-Wide Association Study
of CKD by eGFR and albuminuria categories is
HF heart failure
shown in Chart 11-1.
HR hazard ratio • The prevalence of CKD increases substantially
HTN hypertension with age, as follows1:
ICD-10 International Classification of Diseases, 10th Revision — 6.6% for those 20 to 39 years of age
— 10.6% for those 40 to 59 years of age
KDIGO Kidney Disease: Improving Global Outcomes
MDRD Modification of Diet in Renal Disease
— 32.6% for those ≥60 years of age
MI myocardial infarction • From 1999 to 2014, the prevalence of ACR ≥30
NH non-Hispanic mg/g was higher but the prevalence of eGFR <60
NHANES National Health and Nutrition Examination Survey mL·min−1·1.73−2 was lower among NH blacks than
OR odds ratio among NH whites.1
• At the end of 2014, the unadjusted prevalence
PCI percutaneous coronary intervention
RR relative risk
of ESRD estimated from cases reported to the
SBP systolic blood pressure Centers for Medicare & Medicaid Services in the
SCA/VA sudden cardiac arrest and ventricular arrhythmias United States was 2067 per million (0.2%; Chart
SCD sudden cardiac death 11-2). Of the 678 383 total patients receiving
SNP single-nucleotide polymorphism treatment for ESRD in the United States, 70%
SR self-report
were receiving renal replacement therapy and
STS Society of Thoracic Surgeons
TAVR transcatheter aortic valve replacement
30% had received a transplant.1
USRDS US Renal Data System • The prevalence of ESRD varies regionally across
VHD valvular heart disease the United States (Chart 11-3), mirroring the
VTE venous thromboembolism prevalence of traditional risk factors such as DM
VTE/PE venous thromboembolism and pulmonary embolism or hypertension.1

• ESRD prevalence is higher in blacks compared to $3870), $1700 (95% CI, $530–$2840), $3500
CLINICAL STATEMENTS
with other races and in those of Hispanic com- (95% CI, $1780–$4620), and $12 700 (95% CI,
AND GUIDELINES
pared with NH ethnicity (Chart 11-4).1 $6000–$49 650).8

• The total annual cost of treating ESRD in the
United States was $32.8 billion in 2014, which
Incidence represents >7% of total Medicare claims paid.1
(See Chart 11-5) Total spending per patient per year is now
• For US adults aged 30 to 49, 50 to 64, and ≥65 $87 638.1
years without CKD, the residual lifetime incidences
of CKD are projected to be 54%, 52%, and 42%,
respectively, in the CKD Health Policy Model simu-
Risk Factors
lation based on 1999 to 2010 NHANES data.3 (See Charts 11-6 and 11-7)
• The incidence of ESRD is higher among blacks than • Many traditional CVD risk factors are also risk
whites (Chart 11-5), which could be explained in factors for CKD, including older age, male sex,
part by the higher prevalence of albuminuria in hypertension, DM, smoking, and family history
this population4; however, even after controlling of CVD (Chart 11-6). Among those with CKD
for major ESRD risk factors, blacks have a higher in NHANES (2011–2014), ≈30% have HBP and
risk of ESRD than whites.5 ≈40% have DM. Nearly 18% are obese (BMI >30
kg/m2). Adjusted (age, sex, race) ORs for CKD are
4.1 for HBP, 3.1 for DM, and 1.4 for obesity.1
Secular Trends • Prehypertension (SBP of 120–139 mm Hg and/or
(See Charts 11-2 and 11-5) DBP of 80–89 mm Hg) was associated with incident
• The prevalence of CKD (eGFR 15–59 mL·min−1·1.73 decreased eGFR (<60 mL·min−1·1.73 m−2) in a meta-
m−2) in the United States increased slowly over analysis of observational cohorts (RR, 1.19 [95% CI,
time until 2004 because of an aging population 1.07–1.33] over a mean follow-up of 6.5 years).9
and higher prevalence of risk factors, but the • SBP maintains a strong and graded association
prevalence plateaued from 2004 to 2011.6 with kidney disease progression and risk of ESRD
• The prevalence of ESRD is increasing more rapidly among individuals with CKD10 (Chart 11-7).
primarily because of improved survival, because • Although obesity is a risk factor for kidney dis-
the incidence rate appears to be stabilizing or ease, the association between BMI and ESRD is
decreasing slightly (Chart 11-2).1 modified by metabolic risk factors, and the strong
• The prevalence of CKD in adults ≥30 years of age association between metabolic syndrome and
is projected to increase to 14.4% in 2020 and ESRD risk is independent of BMI.11
16.7% in 2030.3 • Obstructive sleep apnea is associated with CKD
• The incidence of ESRD adjusted for age, sex, race, and CKD progression independent of BMI and
and ethnicity has been stable for >15 years (Chart other traditional risk factors.12
11-2). Despite improvements in incidence rate • Zip code–level poverty is associated with ≈25%
among blacks and Native Americans, substantial higher ESRD incidence after accounting for
disparities persist (Chart 11-5). age, sex, and race/ethnicity, and this association
• Among the very old (>80 years), the prevalence of appears to be getting stronger over time (2005–
an eGFR <60 mL·min−1·1.73 m−2 increased from 2010 versus 1995–2004).13
40.5% in 1988 to 1994 to 49.9% and 51.2% • Importantly, cardiovascular fitness and healthy
in 1999 to 2004 and 2005 to 2010, respectively. lifestyles are associated with decreased risk of
The prevalence of albuminuria (ACR ≥30 mg/g) CKD and CKD progression.14,15
was 30.9%, 33.0%, and 30.6% in 1988 to 1994,
1999 to 2004, and 2005 to 2010, respectively.7
Awareness
• Awareness of CKD status in NHANES is particu-
Costs larly low, ranging from 3% to 5% for early-stage
• In 2014, Medicare spent more than $50 billion CKD to 44% for more advanced CKD (eGFR <30
caring for people >65 years of age with CKD. mL·min−1·1.73 m−2).1
Over 70% of this spending was attributable to • The prevalence of “recognized” CKD, meaning
patients who had comorbid DM or CHF.1 that a provider or billing coder recognized the
• Yearly per person costs attributable specifically prevalence of CKD, is also low in the Medicare
to stage 1, 2, 3, and 4 CKD, respectively, com- 5% sample but is increasing over time, from
pared with no CKD were $1600 (95% CI, −$900 5.9% in 2006 to 11.0% in 2014.1

Global Burden of Kidney Disease and kidney injury and diabetic kidney disease,20–28
CLINICAL STATEMENTS
(See Charts 11-8 through 11-11) although the clinical implications and utility of
AND GUIDELINES
these genetic variants are not yet clear.20–28
• The GBD 2015 Study used statistical models and • Variation in UMOD has been shown to be asso-
data on incidence, prevalence, case fatality, excess ciated with kidney disease, through modulation
mortality, and cause-specific mortality to estimate of the translation and folding of uromodulin, an
disease burden for 315 diseases and injuries in important renal protein. In addition to autosomal
195 countries and territories.16 dominant renal disease associated with rare cod-
• According to GBD, the prevalence of CKD is rising mutations in UMOD,29,30 common variation in
ing in almost every country of the world, primarily UMOD has been found to associate with kidney
because of aging populations (Chart 11-8).16 function in GWAS.22,31
• In 2015, the total estimated prevalence was 323 • Race differences in CKD prevalence might be attrib-
million people (95% CI, 313–330 million), a 27% utable to differences in genetic risk. The APOL1
increase since 2005.16 Notably, there was a down- gene has been well studied as a kidney disease locus
ward revision of estimated CKD prevalence and in individuals of African ancestry.32 SNPs in APOL1,
disability in GBD 2015 compared with prior GBD esti- which are present in individuals of African ancestry
mates caused by a refinement of modeling methods. but absent in other racial groups, might have been
The prevalence of CKD is highest in South Asia, sub- subject to positive selection, conferring protec-
Saharan Africa, and Latin America (Chart 11-9).16 tion against trypanosome infection but leading to
• GBD 2015 has also estimated the global preva- increased risk of renal disease, potentially through
lence of CKD by cause and the percentage change
disruption of mitochondrial function.33
from 2005 to 201517:
— The prevalence of CKD attributable to DM
rose 27% during this time period to 101 mil- CVD in People With Kidney Disease
lion (95% CI, 87–116 million), but age-stan- Prevalence of CVD Among People With CKD
dardized prevalence only increased 2.1%. (See Charts 11-12 and 11-13)
— CKD attributable to HBP rose 26% to 79 mil- • People with CKD, as well as those with ESRD,
lion (95% CI, 68–91 million), but age-stan- have an extremely high prevalence of comorbid
dardized prevalence only increased 0.2%.
CVDs ranging from IHD and HF to arrhythmias

— CKD attributable to glomerulonephritis rose and VTE (Charts 11-12 and 11-13).1
29% to 67 million (95% CI, 58–77 mil- • More than two thirds of CKD patients >66 years
lion), but age-standardized prevalence only old have CVD, compared with one third of
increased 1.1%. patients without CKD in this age group.1
— CKD attributable to other causes rose 26% • The prevalence of CVD in ESRD patients differs by
to 95 million (95% CI, 81–109 million), but treatment modality. Approximately 74% of ESRD
age-standardized prevalence only increased patients on hemodialysis have any CVD, whereas
by 0.1%. only 55% of transplant patients have any CVD
• Globally, the burden of years lived with disability (Chart 11-13).
attributable to CKD is generally heaviest in high- • The association of CKD with an increased preva-
income countries (Chart 11-10). Total years lived lence and incidence of CVD has been consistently
with disability attributable to CKD were 8.2 mil- reported across age, race, and sex subgroups,34
lion (95% CI, 6.1–10.2 million) in 2015.17 although some minor differences in outcomes
• CKD rose from the 25th leading cause of death might exist.
in 1990 to the 17th leading cause of death in
2015.18 Incidence of CVD Events Among People With CKD
• The Pacific Island countries had the highest mor- • CKD is a risk factor for incident and recurrent
tality rates attributable to CKD in 2015 (Chart CHD events,35 stroke,36 HF,37 and AF.38
11-11).16 • In a study of 1.3 million people, the risk of MI
was 18.5 per 1000 person-years for those with a
history of MI, 6.9 per 1000 person-years for those
Family History and Genetics with CKD but no history of MI or DM, and 5.4
• There is evidence of moderate heritability for cre- per 1000 person-years among those without MI
atinine and GFR, which supports a genetic com- or CKD but with DM.39
ponent of CKD.19 • Both eGFR and albuminuria appear to more
• GWAS have revealed several candidate loci for strongly predict HF events than CHD or stroke
CKD phenotypes, including GFR, albuminuria, events.37

• GFR predicts stroke risk but is not as strongly • Mortality risk depends not only on eGFR but also
CLINICAL STATEMENTS
associated as albuminuria. In 4 community-based on category of albuminuria (Chart 11-15). The

AND GUIDELINES
cohorts, lower eGFR (45 versus 95 mL·min−1·1.73 adjusted RR of all-cause mortality and cardiovas-
m−2) was associated with an increased risk for isch- cular mortality is highest in those with eGFR 15 to
emic stroke (HR, 1.30; 95% CI, 1.01–1.68) but 30 mL·min−1·1.73 m−2 and those with ACR >300
not hemorrhagic stroke (HR, 0.92; 95% CI, 0.47– mg/g.
1.81). Albuminuria (ACR of 300 versus 5 mg/g) • Elevated levels of the alternative glomerular filtra-
was associated with both ischemic and hemor- tion marker cystatin C have been associated with
rhagic stroke (HR, 1.62 [95% CI, 1.27–2.07] and increased risk for all-cause mortality in studies
2.57 [95% CI, 1.37–4.83], respectively).40 In a from a broad range of cohorts.
meta-analysis of 83 studies of >30 000 strokes, — The addition of cystatin C to the combination
there were linear relationships of both eGFR and of creatinine and ACR significantly improves
albuminuria with stroke regardless of stroke sub- the prediction of all-cause mortality, cardio-
type.36 Among people with CKD, proteinuria but vascular death, and development of ESRD.47
not eGFR independently predicted stroke risk.41 — This strengthened associations with out-
• In one study of people with CKD aged 50 to 79 comes might be explained in part by non-
years, the ACC/AHA pooled cohort risk equations GFR determinants of cystatin C such as
appear to be well calibrated (Hosmer-Lemeshow chronic inflammation.48
χ2=2.7, P=0.45), with moderately good discrimi- Costs of CVD in People With CKD
nation (C index, 0.71; 95% CI, 0.65–0.77) for • In the Study of Heart and Renal Protection
ASCVD events.42 of patients in Europe, North America, and
• The addition of eGFR or albuminuria improves Australasia, nonfatal major cardiovascular events
CVD prediction beyond traditional risk factors were associated with £6133 (95% CI, £5608–
used in risk equations.37 £6658) higher costs for ESRD patients on dialy-
• Higher dietary sodium intake appears to be asso- sis and £4350 (95% CI, £3819–£4880) for other
ciated with elevated risk of events among people CKD patients in the year of the event (compared
with CKD (adjusted HR for highest versus lowest with years before the event).49
quartile of urinary sodium: 1.36 for composite • Worse preoperative creatinine clearance was
CVD events, 1.34 for HF, and 1.81 for stroke).43 associated with higher total costs of CABG from
• Females with CKD appear to have a higher risk of 2000 to 2012 in the STS database ($1250 per
incident PAD than males, particularly at younger 10-mL/min lower clearance).50
ages.44
• A patient-level pooled analysis of randomized Prevention and Treatment of CVD in People
trials explored the effect of CKD on progno- With CKD
sis for females who undergo PCI.45 Creatinine • One potential explanation for the higher CVD
clearance <45 mL/min was an independent risk event rate in people with CKD is the low uptake
factor for 3-year major adverse cardiovascular of standard therapies. Furthermore, people with
events (adjusted HR, 1.56) and all-cause mortality advanced CKD and ESRD are often excluded from
(adjusted HR, 2.67). clinical trials of cardiovascular drugs and devices,51
• Despite higher overall event rates than NH whites, although recent observational data from large
NH blacks with CKD have similar (or possibly registries can provide insight into the risks and
lower) rates of ASCVD events, HF events, and benefits in this population.50
death after adjustment for demographic factors, • In a nationwide US cohort that included 4726
baseline kidney function, and cardiovascular risk participants with CKD, only 2366 (50%) were tak-
factors.46 ing statins, whereas 1984 participants (42%) met
recommendations for statin treatment according
Mortality Attributable to CVD Among to the ACC/AHA guidelines but were not using
People With CKD statins.42
(See Charts 11-14 and 11-15) • For CKD and ESRD patients with multivessel CAD,
• CVD is the leading cause of death among those CABG could be associated with improved out-
with kidney disease. For those with ESRD, CVD comes compared with PCI.52 Similar findings were
accounts for more than half of deaths with known seen in a Northern California Kaiser Permanente
causes, with arrhythmias and SCD accounting for cohort.53
nearly 40% (Chart 11-14).1 • People with CKD are at higher risk of complica-
• For people with CKD, death of CVD is more com- tions after PCI, and accurate estimation of kid-
mon than progression to ESRD.1 ney function is required to dose antiplatelet and

antithrombotic medications. Compared with with a defibrillator than patients with higher
CLINICAL STATEMENTS
older equations (Cockcroft-Gault), the CKD-EPI eGFR58; however, in a smaller propensity-matched
AND GUIDELINES
eGFR equation more accurately predicted kidney cohort study, primary prevention implantation of
outcomes and appropriate drug dosing in a large an implantable cardioverter-defibrillator was not
sample of nearly 130 000 patients undergoing PCI associated with improved 3-year mortality among
in Michigan.54 ESRD patients with systolic HF.59
• In 4880 veterans with CKD who had PCI, dual- • For patients undergoing TAVR in the United
antiplatelet therapy use beyond 12 months Kingdom, eGFR <45 mL·min−1·1.73 m−2 was asso-
decreased the risk of death or MI for those receiv- ciated with higher odds of in-hospital mortality
ing first-generation drug-eluting stents.55 (adjusted OR, 1.45; 95% CI, 1.03–2.05) and lon-
• In a study of >12 000 people undergoing hemo- ger-term mortality (median, 543 days; adjusted
dialysis in the USRDS who had AF, only 15% initi- OR, 1.36; 95% CI, 1.17–1.58) than higher eGFR.60
ated warfarin therapy within 30 days, and 70% Global Burden of CVD Among People With CKD
discontinued use within 1 year.56 Warfarin was • In low- and middle-income countries, the bur-
marginally associated with reductions in ischemic den of CKD is high (see Global Burden of Kidney
stroke and mortality. In a large meta-analysis of Disease), but data on the magnitude of the asso-
observational studies of people with AF, warfa- ciation between CKD and various cardiovascular
rin use was associated with reductions in throm- outcomes are lacking. These data are necessary
boembolic events (HR, 0.70) and mortality (HR, to properly model the public health and economic
0.65) among those with less severe CKD but was burden of CKD in these countries.
not associated with benefit (HR, 0.96 for mortal-
ity) in those with ESRD.57
• Patients with eGFR <60 mL·min−1·1.73 m−2 and FOOTNOTE
left bundle-branch block (but not other morpholo- Disclosure: A portion of the data reported has been supplied by the USRDS.1
The interpretation and reporting of these data are the responsibility of the
gies) appear to derive greater absolute reductions authors and in no way should be seen as an official policy or interpretation of
in death and HF from cardiac resynchronization the US government.
Chart 11-1. Percentage of NHANES participants within KDIGO GFR and albuminuria categories, 2011 to 2014 (2016
USRDS Annual Report, volume 1, Table 1.1).1
GFR indicates glomerular filtration rate; KDIGO, Kidney Disease: Improving Global Outcomes; NHANES, National Health and
Nutrition Examination Survey; and USRDS, US Renal Data System.
The data reported here have been supplied by the USRDS.1 The interpretation and reporting of these data are the responsibility
of the author(s) and in no way should be seen as an official policy or interpretation of the US government.

CLINICAL STATEMENTS
AND GUIDELINES
Chart 11-2. Trends in unadjusted and adjusted* end-stage renal disease prevalence (A) and incidence rates (B)
from 1996 to 2014 in the United States (2016 USRDS Annual Data Report, volume 2, Figures 1.10 and i.2).1
USRDS indicates US Renal Data System.
*Adjusted for age, sex, race, and ethnicity. The standard population was the US population in 2011.
Source: Reference Table A.2(2) and special analyses, USRDS end-stage renal disease database.
Chart 11-3. Map of the adjusted* prevalence (per million/year) of end-stage renal disease by health service area in
the US population, 2014 (2016 USRDS Annual Data Report, volume 2, Figure 1.12).1
*Adjusted for age, sex, and race. The standard population was the US population in 2011.
Source: Special analyses, USRDS end-stage renal disease database.

CLINICAL STATEMENTS
AND GUIDELINES
Chart 11-4. Trends in adjusted* prevalence (per million) of end-stage renal disease, by race (A) and ethnicity (B) in
the US population, 1996 to 2014 (2016 USRDS Annual Data Report, volume 1.14, Figure 1.15).1
*Year-end point prevalence adjusted for age and sex; the ethnicity analysis (B) is further adjusted for race. The standard popu-
lation was the US population in 2011.
Source: Tables B.1, B.2(2) and special analyses, USRDS end-stage renal disease database.
Chart 11-5. Trends in adjusted* end-stage renal disease incidence rate (per million/year), by race, in the US popula-
tion, 1996 to 2014 (2016 USRDS Annual Data Report, volume 2, Figure 1.5).1
*Year-end point prevalence adjusted for age and sex. The standard population was the US population in 2011.
Source: Tables A.2.2 and special analyses, USRDS end-stage renal disease database.

CLINICAL STATEMENTS
AND GUIDELINES
Chart 11-6. Adjusted odds ratios of chronic kidney disease (CKD) in NHANES participants by risk factor, 1999 to
2014 (2016 USRDS Annual Data Report, volume 1, Figure 1.9).1
CKD defined as presence of estimated glomerular filtration rate (eGFR) <60 mL·min−1·1.73 m−2, urine albumin-to-creatinine
ratio (ACR) ≥30 mg/g, and either eGFR <60 mL·min−1·1.73 m−2 or ACR ≥30 mg/g for each of the comorbid conditions.
Adjusted for age, sex, and race; single-sample estimates of eGFR and ACR; eGFR calculated with the Chronic Kidney Disease
Epidemiology Collaboration equation. Whisker lines indicate 95% confidence intervals.
BMI indicates body mass index; CVD, cardiovascular disease; DM, diabetes mellitus; HTN, hypertension; NHANES, National
Health and Nutrition Examination Survey; SR, self-report; and USRDS, US Renal Data System.
Source: NHANES 1999 to 2002, 2003 to 2006, 2007 to 2010, and 2011 to 2014.
Chart 11-7. Estimated cumulative incidence of ESRD across categories of time-updated SBP among participants in
the CRIC Study.
CRIC indicates Chronic Renal Insufficiency Cohort; ESRD, end-stage renal disease; and SBP, systolic blood pressure.
Reprinted from Anderson et al.10 Copyright © 2015, American College of Physicians. All Rights Reserved. Reprinted with the
permission of American College of Physicians, Inc.

Chart 11-8. Annual percentage change in the prevalence of chronic kidney disease per 100 000 population, all ages,
CLINICAL STATEMENTS
both sexes, 1990 to 2015.
AND GUIDELINES
Chart 11-9. Age-standardized global prevalence rates of chronic kidney disease per 100 000, both sexes, 2015.
Chart 11-10. Years of life lived with disability (per 100 000) because of chronic kidney disease, both sexes, all ages, 2015.
Chart 11-11. Age-standardized global mortality rates of chronic kidney disease per 100 000, both sexes, 2015.
Chart 11-12. Prevalence of CVD in patients with or without CKD, 2014 (2016 USRDS Annual Data Report, volume 1,
Figure 4.1).1
AFIB indicates atrial fibrillation; AMI, acute myocardial infarction; ASHD, atherosclerotic heart disease; CHF, congestive heart
failure; CKD, chronic kidney disease; CVA/TIA, cerebrovascular accident/transient ischemic attack; CVD, cardiovascular disease;
PAD, peripheral artery disease; SCA/VA, sudden cardiac arrest and ventricular arrhythmias; USRDS, US Renal Data System;
VHD, valvular heart disease; and VTE/PE, venous thromboembolism and pulmonary embolism.
Source: Special analyses, Medicare 5% sample.

CLINICAL STATEMENTS
AND GUIDELINES
Chart 11-13. Prevalence of CVD in patients with end-stage renal disease (ESRD) by treatment modality, 2014 (2016
USRDS Annual Data Report, volume 2, Figure 9.2).1
Point prevalent hemodialysis, peritoneal dialysis, and transplant patients aged ≥22 years with Medicare as primary payer on
January 1, 2014, who were continuously enrolled in Medicare Parts A and B from January, 1, 2013, to December 31, 2013,
and whose ESRD service date was at least 90 days before January 1, 2014.
AFIB indicates atrial fibrillation; AMI, acute myocardial infarction; ASHD, atherosclerotic heart disease; CHF, congestive heart
failure; CVA/TIA, cerebrovascular accident/transient ischemic attack; CVD, cardiovascular disease; PAD, peripheral artery disease;
SCA/VA, sudden cardiac arrest and ventricular arrhythmias; USRDS, US Renal Data System; VHD, valvular heart disease; and
VTE/PE, venous thromboembolism and pulmonary embolism.
Source: Special analyses, USRDS ESRD database.
Chart 11-14. Causes of death in end-stage renal disease patients among those with a known cause of death, 2012
to 2014 (2016 USRDS Annual Data Report, volume 2, Figure 9.1.a).1
ASHD indicates atherosclerotic heart disease; AMI, acute myocardial infarction; CHF, congestive heart failure; CVA, cerebrovascular
accident; and USRDS, US Renal Data System.
Source: Special analysis using Reference Table H12, USRDS end-stage renal disease database.

CLINICAL STATEMENTS
A B
AND GUIDELINES
Chart 11-15. Adjusted relative risk of (A) all-cause mortality and (B) cardiovascular mortality in the general popula-
tion categorized by KDIGO 2012 categories of chronic kidney disease.
Data are derived from categorical meta-analysis of population cohorts. Pooled relative risks are expressed relative to the refer-
ence (Ref) cell. Colors represent the ranking of the adjusted relative risks (green=low risk; yellow=moderate risk; orange=high
risk; red=very high risk).
ACR indicates urine albumin-to-creatinine ratio; eGFR, estimated glomerular filtration rate; and KDIGO, Kidney Disease:
Improving Global Outcomes.
Modified from Levey et al61 with permission from International Society of Nephrology. Copyright © 2011, International Society
of Nephrology.
9. Garofalo C, Borrelli S, Pacilio M, Minutolo R, Chiodini P, De Nicola L,

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Molina AJ, Langefeld CD, Murea M, Parks JS, Freedman BI. APOL1 doi: 10.1053/j.ajkd.2016.03.429.
renal-risk variants induce mitochondrial dysfunction. J Am Soc Nephrol. 47. Shlipak MG, Matsushita K, Ärnlöv J, Inker LA, Katz R, Polkinghorne KR,
2017;28:1093–1105. doi: 10.1681/ASN.2016050567. Rothenbacher D, Sarnak MJ, Astor BC, Coresh J, Levey AS, Gansevoort
34. Hui X, Matsushita K, Sang Y, Ballew SH, Fülöp T, Coresh J. CKD and cardio- RT; CKD Prognosis Consortium. Cystatin C versus creatinine in determin-
vascular disease in the Atherosclerosis Risk in Communities (ARIC) study: ing risk based on kidney function. N Engl J Med. 2013;369:932–943. doi:
interactions with age, sex, and race. Am J Kidney Dis. 2013;62:691–702. 10.1056/NEJMoa1214234.
doi: 10.1053/j.ajkd.2013.04.010. 48. Schei J, Stefansson VT, Mathisen UD, Eriksen BO, Solbu MD, Jenssen
35. Baber U, Gutierrez OM, Levitan EB, Warnock DG, Farkouh ME, Tonelli M, TG, Melsom T. Residual associations of inflammatory markers with eGFR
Safford MM, Muntner P. Risk for recurrent coronary heart disease and all- after accounting for measured GFR in a community-based cohort with-
cause mortality among individuals with chronic kidney disease compared out CKD. Clin J Am Soc Nephrol. 2016;11:280–286. doi: 10.2215/CJN.
with diabetes mellitus, metabolic syndrome, and cigarette smokers. Am 07360715.
Heart J. 2013;166:373–380.e2. doi: 10.1016/j.ahj.2013.05.008. 49. Kent S, Schlackow I, Lozano-Kühne J, Reith C, Emberson J, Haynes R, Gray
36. Masson P, Webster AC, Hong M, Turner R, Lindley RI, Craig JC. Chronic kid- A, Cass A, Baigent C, Landray MJ, Herrington W, Mihaylova B; SHARP
ney disease and the risk of stroke: a systematic review and meta-analysis. Collaborative Group. What is the impact of chronic kidney disease stage
Nephrol Dial Transplant. 2015;30:1162–1169. doi: 10.1093/ndt/gfv009. and cardiovascular disease on the annual cost of hospital care in moder-
37. Matsushita K, Coresh J, Sang Y, Chalmers J, Fox C, Guallar E, Jafar T, ate-to-severe kidney disease? BMC Nephrol. 2015;16:65. doi: 10.1186/
Jassal SK, Landman GW, Muntner P, Roderick P, Sairenchi T, Schöttker s12882-015-0054-0.
B, Shankar A, Shlipak M, Tonelli M, Townend J, van Zuilen A, Yamagishi 50. LaPar DJ, Rich JB, Isbell JM, Brooks CH, Crosby IK, Yarboro LT, Ghanta
K, Yamashita K, Gansevoort R, Sarnak M, Warnock DG, Woodward M, RK, Kern JA, Brown M, Quader MA, Speir AM, Ailawadi G. Preoperative
Ärnlöv J; CKD Prognosis Consortium. Estimated glomerular filtration rate renal function predicts hospital costs and length of stay in coronary artery
and albuminuria for prediction of cardiovascular outcomes: a collaborative bypass grafting. Ann Thorac Surg. 2016;101:606–612. doi: 10.1016/j.
meta-analysis of individual participant data. Lancet Diabetes Endocrinol. athoracsur.2015.07.079.
2015;3:514–525. doi: 10.1016/S2213-8587(15)00040-6. 51. Konstantinidis I, Nadkarni GN, Yacoub R, Saha A, Simoes P, Parikh CR,
38. Alonso A, Lopez FL, Matsushita K, Loehr LR, Agarwal SK, Chen LY, Soliman Coca SG. Representation of patients with kidney disease in trials of cardio-
EZ, Astor BC, Coresh J. Chronic kidney disease is associated with the inci- vascular interventions: an updated systematic review. JAMA Intern Med.
dence of atrial fibrillation: the Atherosclerosis Risk in Communities (ARIC) 2016;176:121–124. doi: 10.1001/jamainternmed.2015.6102.
study. Circulation. 2011;123:2946–2953. doi: 10.1161/CIRCULATIONAHA. 52. Bangalore S, Guo Y, Samadashvili Z, Blecker S, Xu J, Hannan EL.
111.020982. Revascularization in patients with multivessel coronary artery disease
39. Tonelli M, Muntner P, Lloyd A, Manns BJ, Klarenbach S, Pannu N, James and chronic kidney disease: everolimus-eluting stents versus coronary
MT, Hemmelgarn BR; Alberta Kidney Disease Network. Risk of coronary artery bypass graft surgery. J Am Coll Cardiol. 2015;66:1209–1220. doi:
events in people with chronic kidney disease compared with those with 10.1016/j.jacc.2015.06.1334.
diabetes: a population-level cohort study. Lancet. 2012;380:807–814. 53. Krishnaswami A, McCulloch CE, Tawadrous M, Jang JJ, Lee H, Melikian V,
doi: 10.1016/S0140-6736(12)60572-8. Yee G, Leong TK, Go AS. Coronary artery bypass grafting and percutane-
40. Mahmoodi BK, Yatsuya H, Matsushita K, Sang Y, Gottesman RF, Astor ous coronary intervention in patients with end-stage renal disease. Eur J
BC, Woodward M, Longstreth WT Jr, Psaty BM, Shlipak MG, Folsom AR, Cardiothorac Surg. 2015;47:e193–e198. doi: 10.1093/ejcts/ezv104.
Gansevoort RT, Coresh J. Association of kidney disease measures with 54. Parsh J, Seth M, Aronow H, Dixon S, Heung M, Mehran R, Gurm HS.
ischemic versus hemorrhagic strokes: pooled analyses of 4 prospective Choice of estimated glomerular filtration rate equation impacts drug-
community-based cohorts. Stroke. 2014;45:1925–1931. doi: 10.1161/ dosing recommendations and risk stratification in patients with chronic
STROKEAHA.114.004900. kidney disease undergoing percutaneous coronary interventions. J Am
41. Sandsmark DK, Messé SR, Zhang X, Roy J, Nessel L, Lee Hamm L, He Coll Cardiol. 2015;65:2714–2723. doi: 10.1016/j.jacc.2015.04.037.
J, Horwitz EJ, Jaar BG, Kallem RR, Kusek JW, Mohler ER 3rd, Porter A, 55. Siddiqi OK, Smoot KJ, Dufour AB, Cho K, Young M, Gagnon DR, Ly S,
Seliger SL, Sozio SM, Townsend RR, Feldman HI, Kasner SE; CRIC Study Temiyasathit S, Faxon DP, Gaziano JM, Kinlay S. Outcomes with prolonged

clopidogrel therapy after coronary stenting in patients with chronic 59. Pun PH, Hellkamp AS, Sanders GD, Middleton JP, Hammill SC, Al-Khalidi
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kidney disease. Heart. 2015;101:1569–1576. doi: 10.1136/heartjnl- HR, Curtis LH, Fonarow GC, Al-Khatib SM. Primary prevention implantable
AND GUIDELINES
2014-307168. cardioverter defibrillators in end-stage kidney disease patients on dialysis:

56. Shen JI, Montez-Rath ME, Lenihan CR, Turakhia MP, Chang TI, a matched cohort study. Nephrol Dial Transplant. 2015;30:829–835. doi:
Winkelmayer WC. Outcomes after warfarin initiation in a cohort of hemo- 10.1093/ndt/gfu274.
dialysis patients with newly diagnosed atrial fibrillation. Am J Kidney Dis. 60. Ferro CJ, Chue CD, de Belder MA, Moat N, Wendler O, Trivedi U,
2015;66:677–688. doi: 10.1053/j.ajkd.2015.05.019. Ludman P, Townend JN; UK TAVI Steering Group; National Institute
57. Dahal K, Kunwar S, Rijal J, Schulman P, Lee J. Stroke, major bleeding, for Cardiovascular Outcomes Research. Impact of renal function on
and mortality outcomes in warfarin users with atrial fibrillation and survival after transcatheter aortic valve implantation (TAVI): an analy-
chronic kidney disease: a meta-analysis of observational studies. Chest. sis of the UK TAVI registry. Heart. 2015;101:546–552. doi: 10.1136/
2016;149:951–959. doi: 10.1378/chest.15-1719. heartjnl-2014-307041.
58. Daimee UA, Moss AJ, Biton Y, Solomon SD, Klein HU, McNitt S, Polonsky 61. Levey AS, de Jong PE, Coresh J, El Nahas M, Astor BC, Matsushita K,
B, Zareba W, Goldenberg I, Kutyifa V. Long-term outcomes with cardiac Gansevoort RT, Kasiske BL, Eckardt KU. The definition, classification, and
resynchronization therapy in patients with mild heart failure with mod- prognosis of chronic kidney disease: a KDIGO Controversies Conference
erate renal dysfunction. Circ Heart Fail. 2015;8:725–732. doi: 10.1161/ report [published correction appears in Kidney Int. 2011;80:1000]. Kidney
CIRCHEARTFAILURE.115.002082. Int. 2011;80:17–28.

12. TOTAL CARDIOVASCULAR while reducing deaths attributable to CVDs and
CLINICAL STATEMENTS
stroke by 20%.2
DISEASES
AND GUIDELINES
ICD-9 390 to 459, ICD-10 I00 to I99. See Tables
12-1 through 12-4 and Charts 12-1 through 12-22 Mortality
(See Tables 12-1 through 12-3 and Charts
12-2 through 12-17)
Prevalence ICD-10 I00 to I99 for CVD; C00 to C97 for
(See Table 12-1 and Chart 12-1) cancer; C33 to C34 for lung cancer; C50
On the basis of NHANES data (Table 12-1), 11.5% of for breast cancer; J40 to J47 for CLRD;
American adults (27.6 million) have been diagnosed G30 for Alzheimer disease; E10 to E14 for
with HD.1 DM; and V01 to X59 and Y85 to Y86 for
• The prevalence of CVD (comprising CHD, HF, accidents.
stroke, and hypertension) in adults ≥20 years of
age increases with age in both males and females • Deaths attributable to diseases of the heart and
(Chart 12-1). CVD in the United States increased steadily dur-
• The AHA’s 2020 Impact Goals are to improve the ing the 1900s to the 1980s and declined into the
cardiovascular health of all Americans by 20% 2010s (Charts 12-2 and 12-3).
• CHD (43.8%) is the leading cause of deaths attrib-
utable to CVD in the United States, followed by
Abbreviations Used in Chapter 12 stroke (16.8%), HBP (9.4%), HF (9.0%), diseases
AF atrial fibrillation of the arteries (3.1%), and other CVDs (17.9%)
(Chart 12-4).
ARIC Atherosclerosis Risk in Communities
BMI body mass index
• On the basis of 2015 mortality data3:
BP blood pressure — CVD currently claims more lives each year
CDC Centers for Disease Control and Prevention than cancer and CLRD combined (Charts
CHA Chicago Heart Association 12-5 through 12-15). More than 360 000
CHD coronary heart disease people died in 2015 of CHD, the most com-
mon type of HD.
CLRD chronic lower respiratory disease
CVD cardiovascular disease — The mortality trends for males and females in
DM diabetes mellitus the United States have declined from 1979
ED emergency department to 2015 (Chart 12-16).
FHS Framingham Heart Study — In 2015, 2 712
630 resident deaths were
GBD Global Burden of Disease
registered in the United States. Ten leading
causes accounted for 74.2% of all regis-
HD heart disease tered deaths. The 10 leading causes of death
HDL high-density lipoprotein in 2015 were the same as in 2014; these
HF heart failure include diseases of the heart (No. 1), cancer
ICD-9 International Classification of Diseases, 9th Revision (No. 2), CLRD (No. 3), unintentional injuries
ICD-10 International Classification of Diseases, 10th Revision
(No. 4), stroke (No.5), Alzheimer disease
LDL-C low-density lipoprotein cholesterol (No.6), DM (No. 7), influenza and pneumo-
MEPS Medical Expenditure Panel Survey nia (No.8), kidney disease (No.9), and suicide
MESA Multi-Ethnic Study of Atherosclerosis (No.10). Eight of the 10 leading causes of
MI myocardial infarction death had an increase in age-adjusted death
rate. The age-adjusted death rate increased
NH non-Hispanic
by 0.9% for HD but decreased by 1.7% for
NHAMCS National Hospital Ambulatory Medical Care Survey cancer, whereas CLRD, unintentional inju-
NHANES National Health and Nutrition Examination Survey ries, stroke, Alzheimer disease, DM, kidney
NHDS National Hospital Discharge Survey disease, and suicide deaths increased by
2.7%, 6.7%, 3.0%, 15.7%, 1.9%, 1.5%,
OR odds ratio
and 2.3% respectively.4
RR relative risk — The age-adjusted death rates per 100 000
SBP systolic blood pressure population for CVD, CHD, and stroke differ
SES socioeconomic status by US state (Chart 12-17; Table 12-2) and
TC total cholesterol globally (Table 12-3).

— The age-adjusted death rate increased by • From 1993 to 2014, the number of hospital dis-
CLINICAL STATEMENTS
1.2% from 724.6 per 100 000 population in charges for CVD in the United States increased in
AND GUIDELINES
2014 to 733.1 in 2015. In the same period, the first decade and then began to decline in the
the age-adjusted death rate increased from second decade (Chart 12-18).
1060.3 to 1070.1 (0.9%) for NH black males, • In 2014, cardiovascular causes were the leading
from 872.3 to 881.3 (1.0%) for NH white diagnostic group of hospital discharges in the
males, and from 633.8 to 644.1 (1.6%) United States (Chart 12-19).
for NH white females. The rates among NH • In 2014, there were 82 724 000 physician office
black females, Hispanic males, and Hispanic visits with a primary diagnosis of CVD (NCHS,
females did not change significantly during NAMCS, NHLBI tabulation) In 2014, there were
the same period.4 4 749 000 ED visits with a primary diagnosis
— The age-adjusted death rate attributable of CVD (unpublished NCHS, NHAMCS, NHLBI
to CVD decreased from 286.6 per 100 000 tabulation).
population in 2005 to 222.7 per 100 000 in
2015, which amounts to a 22.3% decrease.
Operations and Procedures
In the same period, the actual number of
CVD deaths per year declined by 2.8%. (See Chapter 24 for detailed
— HD accounted for 633 813 of all 836 546 information.)
CVD deaths. The number of CVD deaths was
• In 2014, an estimated 7 440 000 inpatient cardio-
422 355 for males and 414 191 for females.
vascular operations and procedures were per-
The number was 329 397 for NH white
formed in the United States (unpublished NHLBI
males, 51 053 for NH black males, 26 739
tabulation of NHDS, NCHS).
for Hispanic males, 327 279 for NH white
females, 50 231 for NH black females, and
23 350 for Hispanic females. Among other Cost
causes of death, cancer caused 595 919
(See Chapter 25 for detailed
deaths; CLRD, 155 037; accidents, 146 553;
and Alzheimer disease, 110 561. information.)
• The life expectancy at birth for the total US popu- • In the United States, 22.2% of adults (53 316 677
lation was 78.8 years in 2015, which is 0.1 year people) report any disability.5 In 2006, 26.7%
less than the 2014 estimate of 78.9 years. The life of resident adult healthcare expenditures were
expectancy for males decreased from 76.5 years associated with disability care and totaled $397.8
in 2015 to 76.3 years in 2014, and for females it billion.6 For people with disabilities in the United
decreased from 81.3 years in 2014 to 81.2 years States, HD, stroke, and hypertension were among
in 2015.4 Approximately 159 032 Americans who the 15 leading conditions that caused those dis-
were <65 years of age died of CVD, and 36% of abilities. Disabilities were defined as difficulty with
deaths attributed to CVD occurred before the age activities of daily living or instrumental activities of
of 75 years, which is well below the average life daily living, specific functional limitations (except
expectancy of 78.8 years. vision, hearing, or speech), and limitation in abil-
ity to do housework or work at a job or business.7
The estimated direct and indirect cost of CVD for
Hospital Discharges, Ambulatory Care 2013 to 2014 was $329.7 billion (MEPS, NHLBI
Visits, Home Healthcare Patients, Nursing tabulation).
Home Residents, and Hospice Care • In 2016, the AHA estimated that by 2035, 45.1%
Discharges of the US population would have some form of
(See Table 12-1 and Charts 12-18 CVD. Total costs of CVD are expected to reach
$1.1 trillion in 2035, with direct medical cost pro-
and 12-19) jected to reach $748.7 billion and indirect costs
• From 2004 to 2014, the number of inpatient dis- estimated to reach $368 billion.8
charges from short-stay hospitals with CVD as
the principal diagnosis decreased from 5 797 000
to 4 791 000 (HCUP, hospital discharges 2014; Risk Factors
NHDS, NCHS, and NHLBI; Table 12-1). The CVD • In a study reported by the US Burden of Disease
principal diagnosis discharges in 2014 comprised Collaborators, the 10 leading risk factors related
2 571 000 males and 2 220 000 females (unpub- to deaths were dietary risks (No. 1), tobacco
lished NHDS, NCHS, and NHLBI tabulation). smoking (No. 2), HBP (No. 3), high BMI (No. 4),

physical inactivity and low PA (No. 5), high fasting • Data from the Cardiovascular Lifetime Risk Pooling
CLINICAL STATEMENTS
plasma glucose (No. 6), high TC (No. 7), ambient Project, which involved 18 cohort studies and
AND GUIDELINES
particulate matter pollution (No. 8), alcohol use combined data on 257 384 people (both black
(No. 9), and drug use (No. 10).9 and white males and females), indicate that at 45
• It is estimated that 47% of all Americans have years of age, participants with optimal risk factor
at least 1 of the 3 well-established key risk fac- profiles had a substantially lower lifetime risk of
tors for CVD, which are HBP, high cholesterol, and CVD events than those with 1 major risk factor
smoking.10 (1.4% versus 39.6% among males; 4.1% versus
• In 2005, HBP was the single largest risk factor for 20.2% among females). Having ≥2 major risk
cardiovascular mortality in the United States and factors further increased lifetime risk to 49.5% in
was responsible for an estimated 395 000 (95% males and 30.7% in females.15
CI, 372 000–414 000) cardiovascular deaths • In another study, FHS investigators conducted
(45% of all cardiovascular deaths). Additional follow-up of 2531 males and females who
risk factors for cardiovascular mortality were were examined between the ages of 40 and 50
overweight/obesity, physical inactivity, high years and observed their overall rates of survival
LDL-C, smoking, high dietary salt, high dietary and survival free of CVD to 85 years of age and
trans fatty acids, and low dietary omega-3 fatty beyond. Low levels of the major risk factors in
acids.11 middle age were associated with overall survival
• Neighborhood-level socioeconomic deprivation and morbidity-free survival to ≥85 years of age.16
was associated with greater risk of CVD mortality • Data from the CHA Detection Project in Industry
in older males in Britain, independent of individual (1967–1973, with an average follow-up of 31
social class or risk factors.12 In the United States, years) showed the following:
there are significant state-level variations in poor — In younger females (18–39 years of age) with
cardiovascular health explained by individual and favorable levels for all 5 major risk factors (BP,
state-level factors such as policies, food, and PA serum cholesterol, BMI, DM, and smoking),
environments.13 future incidence of CHD and CVD is rare, and
long-term and all-cause mortality are much
lower than for those who have unfavor-
Impact of Healthy Lifestyle and Low Risk able or elevated risk factor levels at young
Factor Levels ages. Similar findings applied to males in this

(See Chapter 2 for more detailed study.17
statistics regarding healthy lifestyles and — Participants (18–64 years of age at baseline)
without a history of MI were investigated to
low risk factor levels.)
determine whether traditional CVD risk fac-
A number of studies suggest that prevention of risk tors were similarly associated with CVD mor-
factor development at younger ages could be the key tality in black and white males and females.
to “successful aging,” and they highlight the need for In general, the magnitude and direction of
evaluation of the potential benefits of intensive pre- associations were similar by race. Most tradi-
vention efforts at younger and middle ages once risk tional risk factors demonstrated similar asso-
factors develop to increase the likelihood of healthy ciations with mortality in black and white
longevity. adults of the same sex. Small differences
• A study of the decrease in US deaths attributable were primarily in the strength and not the
to CHD from 1980 to 2000 suggests that ≈47% direction of the association.18
of the decrease was attributable to increased use • Data from NHANES 2005 to 2010 showed that
of evidence-based medical therapies for second- only 8.8% of adults complied with ≥6 heart-
ary prevention and 44% to changes in risk fac- healthy behaviors. Of the 7 factors studied,
tors in the population attributable to lifestyle and healthy diet was the least likely to be achieved
environmental changes.7 (only 22% of adults with a healthy diet).14
• Approximately 80% of CVDs can be prevented • In the United States, higher whole grain con-
through not smoking, eating a healthy diet, sumption was associated with lower CVD mor-
engaging in PA, maintaining a healthy weight, tality, independent of other dietary and lifestyle
and controlling HBP, DM, and elevated lipid lev- factors. Every serving (28 g/d) of whole grain
els. The presence of a greater number of optimal consumption was associated with a 9% (95% CI,
cardiovascular health metrics is associated with a 4%–13%) lower CVD mortality.19
graded and significantly lower risk of total and • Seventeen-year mortality data from the NHANES
CVD mortality.14 II Mortality Follow-Up Study indicated that the

RR for fatal CHD was 51% lower for males and incomes below the poverty level were more than
CLINICAL STATEMENTS
71% lower for females with none of the 3 major twice as likely as adults in the highest family
AND GUIDELINES
risk factors (hypertension, current smoking, and income group to be current smokers (29.2% ver-
elevated TC [≥240 mg/dL]) than for those with sus 13.9%, respectively; NCHS/CDC, 2013).25
≥1 risk factor. If all 3 major risk factors had not • A study of nearly 1500 participants in MESA
occurred, it is hypothesized that 64% of all CHD found that Hispanics with hypertension, hyper-
deaths among females and 45% of CHD deaths cholesterolemia, or DM who spoke Spanish at
in males could have been avoided.20 home (as a proxy of lower levels of acculturation)
or had spent less than half a year in the United
States had higher SBP, LDL-C, and fasting blood
Disparities in CVD Risk Factors glucose, respectively, than Hispanics who were
(See Chart 12-20) preferential English speakers and who had lived a
• Although traditional cardiovascular risk factors longer period of time in the United States.26
are generally similar for males and females, there • Findings from >15 000 Hispanics of diverse back-
are several female-specific risk factors, such as grounds demonstrated that a sizeable proportion
disorders of pregnancy, adverse pregnancy out- of both males and females had major CVD risk
comes, and menopause.21 factors, with higher prevalence among Puerto
• Analysis of >14 000 middle-aged participants in Rican subgroups and those with lower SES and a
the ARIC study sponsored by the NHLBI showed higher level of acculturation.27
that ≈90% of CVD events in black participants,
compared with ≈65% in white participants,
Family History of CVD
appeared to be explained by elevated or border-
line risk factors. Furthermore, the prevalence of (See Table 12-4)
participants with elevated risk factors was higher • A family history of CVD increases risk of CVD,
in black participants; after accounting for educa- with the largest increase in risk if the family mem-
tion and known CVD risk factors, the incidence of ber’s CVD was premature (Table 12-4).28
CVD was identical in black and white participants. • A reported family history of premature parental
Although organizational and social barriers to pri- CHD is associated with incident MI or CHD in
mary prevention do exist, the primary prevention offspring. In FHS, the occurrence of a validated
of elevated risk factors might substantially impact premature atherosclerotic CVD event in either a
the future incidence of CVD, and these benefi- parent29 or a sibling30 was associated with an ≈2-
cial effects would likely be applicable not only for fold elevated risk for CVD, independent of other
white but also for black participants.22 traditional risk factors. Addition of a family history
• Mortality data from the National Vital Statistics of premature CVD to a model that contained tra-
System from 2001 to 2010 show that the avoid- ditional risk factors provided improved prognostic
able death rate among blacks was nearly twice value in FHS.29
that of whites.23 • Parental history of premature CHD is associated
• Data from the MEPS 2004 full-year data file with increased burden of subclinical atheroscle-
showed that nearly 26 million US adults ≥18 years rosis in the coronary arteries and the abdominal
of age were told by a doctor that they had HD, aorta.31,32
stroke, or any other heart-related disease24: • The association of a family history of CVD with
— Among those told that they had HD, 33.9% increased risk of CVD appears to be present across
self-reported that they had a healthy weight ethnic subgroups.33,34
compared with 39.3% who had never been • Family history is also associated with subtypes of
told they had HD. CVD, including HF,35 stroke, AF,36 and thoracic
— Among those ever told that they had indica- aortic disease.37
tors of HD, 18.3% continued to smoke. • Estimates of familial clustering of CVD are likely
— More than 93% engaged in at least 1 rec- underestimated by self-report; in the multigener-
ommended behavior for prevention of HD ational FHS, only 75% of participants with a doc-
(not smoking, engaging in physical exercise umented parental history of a heart attack before
regularly, and maintaining healthy weight): age 55 years reported that history when asked.38
75.5% engaged in 1 or 2; 18% engaged in • Despite the importance of family history, several
all 3; and 6.5% did not engage in any of the barriers impede first-degree relatives of people
recommended behaviors. with CVD from engaging in risk-reducing behav-
• Data from the CDC’s Vital and Health Statistics iors, such as few being aware of the specific
2008 to 2010 showed that smokers with family health information from relatives necessary to

develop a family history; in addition, there is an • The GBD 2015 Study used statistical models and
CLINICAL STATEMENTS
inappropriate risk perception or an underestima- data on incidence, prevalence, case fatality, excess
AND GUIDELINES
tion of one’s own vulnerability.39 mortality, and cause-specific mortality to estimate
• A comprehensive scientific statement on the role disease burden for 315 diseases and injuries in
of genetics and genomics for the prevention and 195 countries and territories.42
treatment of CVD is available elsewhere.40 — The highest mortality rates attributable to
CVD were in Eastern Europe and Central Asia
(Chart 12-21).
Awareness of Warning Signs and Risk — CVD prevalence was high in sub-Saharan
Factors for CVD Africa, Eastern Europe, and Central Asia
Surveys conducted every 3 years since 1997 by the AHA (Chart 12-22).
to evaluate trends in females’ awareness, knowledge, • CVD is the leading global cause of death and is
and perceptions related to CVD found most recently (in expected to account for >23.6 million deaths by
2012) that awareness of HD as the leading cause of 2030.43 Deaths attributable to IHD increased by
death among females was 56%, compared with 30% an estimated 41.7% from 1990 to 2013.44
in 1997 (P<0.05). Awareness among black and Hispanic • In 2013, CVD deaths represented 31% of all
females in 2012 was similar to that of white females in global deaths.45
1997; however, awareness rates in 2012 among black • In 2011, data from the World Economic Forum
and Hispanic females remained below that of white found that CVD represented 50% of noncom-
females. Awareness of heart attack signs remained low municable disease deaths.44 CVD represents 37%
for all racial/ethnic and age groups surveyed during the of deaths of individuals under the age of 70
same time.41 years that are attributable to noncommunicable
diseases.46
• In 2013, ≈70% of CVD deaths occurred in
Global Burden of CVD
low- to middle-income countries.47 CVD deaths
(See Table 12-3 and Charts 12-21 occur substantially in males and females.37 In
and 12-22) 2015, the total numbers of global CVD deaths
• In 2015, ≈17.9 million (95% CI, 17.6–18.3 in males and females were 9.4 million (95% CI,
million) deaths were attributed to CVD glob- 9.2–9.6 million) and 8.5 million (95% CI, 8.3–
ally, which amounted to an increase of 12.5% 8.7 million), respectively.42 The corresponding
(95% CI, 10.6%–14.4%) from 2005.42 The age- age-adjusted death rates per 100 000 popula-
adjusted death rate per 100 000 population was tion for both sexes were 334.6 (95% CI, 327.3–
285.5 (95% CI, 280.2–291.2), which represents a 342.2) and 242.0 (95% CI, 236.4–248.3).42 In
decrease of 15.5% (95% CI, −16.9% to −14.2%) May 2012, during the World Health Assembly,
from 2005. Overall, the crude prevalence of CVD ministers of health agreed to adopt a global
was 422.7 million (95% CI, 415.5–427.9 mil- target to reduce premature (age 30–70 years)
lion) in 2015, an increase of 24.8% (95% CI, noncommunicable disease mortality by 25% by
24.0%–25.6%) compared with 2005; however, 2025.48 Targets for 6 risk factors (tobacco and
the age-adjusted prevalence was 6304.0 (95% alcohol use, salt intake, obesity, and raised BP
CI, 6196.1–6382.8), a decrease of 1.8% (95% and glucose) were also agreed on to address
CI, −2.5% to −1.2%) from 2005.42 this goal. It is projected that if the targets are
• The death rates for all causes and CVD in selected met, premature deaths attributable to CVDs in
countries are presented in Table 12-3. In these 2025 will be reduced by 34%, with 11.4 million
data, Ukraine and Belarus ranked first and sec- and 15.9 million deaths delayed or prevented
ond, respectively, for the highest CVD death rate, in those aged 30 to 69 years and ≥70 years,
whereas Israel had the lowest. respectively.49

Table 12-1. Cardiovascular Diseases

CLINICAL STATEMENTS
Prevalence, 2011–2014: Mortality, 2015: Hospital Discharge,

AND GUIDELINES
Population Group Age ≥20 y All Ages* 2014: All Ages Cost, 2013–2014
Both sexes 92 100 000 (36.6%) 836 546 4 791 000 $329.7 Billion
Males 44 300 000 (37.4%) 422 355 (50.5%)† 2 571 000 $206.7 Billion
Females 47 800 000 (35.9%) 414 191 (49.5%)† 2 220 000 $123.0 Billion
NH white males 37.7% 329 397 … …
NH white females 35.1% 327 279 … …
NH black males 46.0% 51 053 … …
NH black females 47.7% 50 231 … …
Hispanic males 31.3% 26 739 … …
Hispanic females 33.3% 23 350 … …
NH Asian males 31.0% 10 584‡ … …
NH Asian females 27.0% 9969‡ … …
NH American Indian/ … 4300 … …
Alaska Native

*Mortality for Hispanic, American Indian or Alaska Native, and Asian and Pacific Islander people should be interpreted with
caution because of inconsistencies in reporting Hispanic origin or race on the death certificate compared with censuses, surveys,
and birth certificates. Studies have shown underreporting on death certificates of American Indian or Alaska Native, Asian and
Pacific Islander, and Hispanic decedents, as well as undercounts of these groups in censuses.
†These percentages represent the portion of total cardiovascular disease mortality that is attributable to males vs females.
‡Includes Chinese, Filipino, Hawaiian, Japanese, and other Asian or Pacific Islander.
Sources: Prevalence: National Health and Nutrition Examination Survey 2011 to 2014, National Center for Health Statistics
(NCHS) and National Heart, Lung, and Blood Institute (NHLBI). Percentages for racial/ethnic groups are age adjusted for Americans
≥20 years of age. Age-specific percentages are extrapolated to the 2014 US population estimates. Mortality: Centers for Disease
Control and Prevention/NCHS, 2014 Mortality Multiple Cause-of-Death–United States. These data represent underlying cause of
death only for International Classification of Diseases, 10th Revision codes I00 to I99 (diseases of the circulatory system). Mortality
for NH Asians includes Pacific Islanders. Hospital discharges: Healthcare Cost and Utilization Project, National (Nationwide) Inpatient
Sample, 2014. Agency for Healthcare Research and Quality. Cost: Medical Expenditure Panel Survey, average annual 2013 to
2014 (direct costs) and mortality data from NCHS and present value of lifetime earnings from the Institute for Health and Aging,
University of California, San Francisco (indirect costs).
Table 12-2. Age-Adjusted Death Rates per 100 000 Population for CVD, CHD, and Stroke by State, 2013 to 20153
CVD CHD Stroke
% Change, % Change, % Change,
2003–2005 to 2003–2005 to 2003–2005 to
State Rank Death Rate 2013–2015 Rank Death Rate 2013–2015 Rank Death Rate 2013–2015
Alabama 51 296.9 −19.8 23 92.9 −31.5 51 49.5 −24.1
Alaska 12 196.4 −20.6 10 79.0 −22.8 27 36.5 −35.4
Arizona 6 186.3 −27.6 21 91.6 −37.0 6 29.3 −33.2
Arkansas 49 282.1 −17.7 50 130.1 −26.7 50 46.6 −29.2
California 16 200.3 −30.5 25 94.0 −40.3 22 35.0 −35.0
Colorado 3 176.9 −27.5 6 70.7 −37.1 14 33.4 −27.7
Connecticut 9 189.9 −24.2 8 77.5 −39.1 3 27.7 −30.3
Delaware 29 218.8 −28.3 37 105.6 −38.0 36 38.4 −15.2
District of Columbia 44 256.9 −25.8 47 121.4 −37.7 18 34.0 −19.2
Florida 14 199.0 −26.6 29 96.4 −38.5 15 33.6 −20.9
Georgia 37 242.4 −27.0 11 79.6 −39.4 43 43.2 −28.7
Hawaii 5 184.8 −23.4 3 68.6 −26.7 24 35.8 −30.3
Idaho 22 203.3 −23.6 12 82.8 −34.2 26 36.2 −36.0
Illinois 34 224.5 −25.5 24 93.9 −39.4 32 37.5 −27.7
Indiana 38 242.6 −23.3 36 104.6 −32.3 39 40.5 −26.7
Iowa 27 213.5 −22.4 41 109.7 −29.2 17 33.7 −34.4
(Continued )

CLINICAL STATEMENTS
CVD CHD Stroke
AND GUIDELINES
% Change, % Change, % Change,
2003–2005 to 2003–2005 to 2003–2005 to
State Rank Death Rate 2013–2015 Rank Death Rate 2013–2015 Rank Death Rate 2013–2015
Kansas 30 221.2 −21.4 18 87.7 −31.6 37 38.6 −27.7
Kentucky 46 259.1 −24.5 40 109.7 −35.2 41 41.4 −27.6
Louisiana 48 275.8 −20.8 39 106.8 −34.3 47 45.2 −24.3
Maine 13 198.8 −24.0 16 85.9 −33.7 11 33.0 −32.8
Maryland 32 222.5 −25.1 32 101.0 −37.2 29 37.3 −27.7
Massachusetts 4 181.4 −27.8 9 78.0 −35.4 5 28.3 −34.8
Michigan 43 255.3 −20.8 48 124.8 −28.4 30 37.3 −27.9
Minnesota 2 165.8 −23.5 1 61.8 −33.4 12 33.2 −28.1
Mississippi 52 308.0 −21.7 43 110.9 −34.8 52 49.6 −18.0
Missouri 42 252.0 −23.0 45 114.9 −32.8 40 40.8 −26.5
Montana 20 202.4 −18.9 14 84.5 −21.8 25 35.9 −28.6
Nebraska 21 202.8 −22.9 7 77.2 −29.1 21 34.8 −31.1
Nevada 41 247.9 −23.1 35 103.3 −21.9 20 34.8 −34.9
New Hampshire 8 189.6 −28.8 17 86.1 −41.4 4 27.8 −33.9
New Jersey 28 213.7 −25.4 33 101.1 −38.2 8 31.6 −22.5
New Mexico 11 191.2 −23.0 28 95.5 −26.3 10 32.4 −22.7
New York 33 224.2 −27.8 49 126.7 −38.3 1 26.1 −22.6
North Carolina 31 221.8 −27.4 26 94.6 −35.8 45 43.4 −30.3
North Dakota 15 200.0 −23.1 22 91.6 −35.7 16 33.7 −34.8
Ohio 40 247.5 −22.1 44 111.6 −33.8 38 40.2 −24.4
Oklahoma 50 292.0 −22.2 52 145.5 −31.2 46 43.5 −31.3

Oregon 10 190.2 −27.1 5 68.9 −38.4 31 37.4 −38.8
Pennsylvania 36 229.9 −25.1 34 102.5 −35.7 33 37.6 −25.0
Puerto Rico 1 158.3 −31.3 2 68.0 −41.4 7 29.4 −33.3
Rhode Island 19 202.2 −29.4 42 110.7 −42.0 2 26.8 −34.3
South Carolina 39 242.6 −24.0 27 95.2 −32.5 49 46.1 −30.0
South Dakota 23 204.2 −23.0 38 106.4 −28.4 28 36.6 −27.7
Tennessee 47 269.0 −24.0 51 133.6 −30.5 48 45.4 −30.7
Texas 35 227.5 −25.8 30 98.9 −37.7 42 41.5 −26.7
Utah 18 201.9 −18.1 4 68.8 −26.2 35 38.1 −24.0
Vermont 17 201.2 −20.7 31 100.7 −25.4 13 33.3 −22.7
Virginia 26 208.5 −28.1 15 84.5 −35.7 34 37.8 −33.5
Washington 7 188.5 −28.0 13 82.9 −37.8 19 34.7 −37.0
West Virginia 45 258.8 −26.6 46 120.8 −34.7 44 43.3 −23.3
Wisconsin 25 208.0 −22.5 20 91.3 −29.5 23 35.4 −29.4
Wyoming 24 204.9 −21.5 19 88.5 −28.1 9 32.2 −32.4
Total United States 221.9 −25.5 99.6 −36.0 36.8 −28.2
Rates are most current data available as of May 2017. Rates are per 100 000 people. International Classification of Diseases, 10th Revision codes used were I00 to
I99 for CVD, I20 to I25 for CHD, and I60 to I69 for stroke. CHD indicates coronary heart disease; and CVD, cardiovascular disease.
Sources: National Center for Health Statistics and National Heart, Lung, and Blood Institute.

Table 12-3. Death Rates for CVDs and All Causes in Selected Countries
CLINICAL STATEMENTS
Sorted Alphabetically Sorted by Descending

AND GUIDELINES
by Country CVD CHD Stroke Total CVD Death Rate CVD CHD Stroke Total
Males aged 35–74 y
Australia (14) 115.6 68.5 16.5 515.2 Ukraine (14) 1041.2 709.2 204.3 2002.1
Austria (14) 169.4 98.6 23.1 671.6 Belarus (14) 979.5 710.6 175.9 1884.6
Belarus (14) 979.5 710.6 175.9 1884.6 Romania (15) 518.8 213.8 132.8 1286.6
Belgium (14) 134.5 58.0 23.6 669.2 Hungary (15) 488.7 262.3 93.1 1352.4
Croatia (15) 364.5 183.2 94.8 1062.3 Serbia (15) 466.0 131.9 101.4 1241.6
Czech Republic (15) 327.0 173.9 48.3 949.1 Slovakia (14) 400.6 222.5 89.0 1173.6
Denmark (14) 126.1 51.4 26.2 665.4 Croatia (15) 364.5 183.2 94.8 1062.3
Finland (14) 217.6 124.7 35.4 698.1 Czech Republic (15) 327.0 173.9 48.3 949.1
France (13) 111.1 43.4 20.9 686.0 United States (15) 233.8 123.5 27.2 816.9
Germany (14) 187.7 90.9 25.0 713.2 Finland (14) 217.6 124.7 35.4 698.1
Hungary (15) 488.7 262.3 93.1 1352.4 Germany (14) 187.7 90.9 25.0 713.2
Ireland (13) 175.3 109.4 23.1 599.1 Ireland (13) 175.3 109.4 23.1 599.1
Israel (14) 96.0 44.7 20.1 529.1 Austria (14) 169.4 98.6 23.1 671.6
Italy (12) 141.8 64.9 25.5 579.1 Taiwan (15) 168.1 51.0 50.1 826.2
Japan (14) 129.4 42.8 41.9 547.6 United Kingdom (13) 166.5 103.3 24.3 620.3
Korea, South (13) 112.4 32.4 48.7 672.4 New Zealand (12) 163.1 104.9 23.0 566.0
Netherlands (15) 119.1 42.2 21.1 553.0 Sweden (15) 147.2 82.4 20.8 514.1
New Zealand (12) 163.1 104.9 23.0 566.0 Italy (12) 141.8 64.9 25.5 579.1
Norway (14) 116.2 61.0 17.9 522.4 Portugal (13) 141.5 52.4 48.9 764.5
Portugal (13) 141.5 52.4 48.9 764.5 Belgium (14) 134.5 58.0 23.6 669.2
Romania (15) 518.8 213.8 132.8 1286.6 Spain (14) 130.5 61.0 23.1 595.6
Serbia (15) 466.0 131.9 101.4 1241.6 Japan (14) 129.4 42.8 41.9 547.6
Slovakia (14) 400.6 222.5 89.0 1173.6 Denmark (14) 126.1 51.4 26.2 665.4
Spain (14) 130.5 61.0 23.1 595.6 Netherlands (15) 119.1 42.2 21.1 553.0
Sweden (15) 147.2 82.4 20.8 514.1 Norway (14) 116.2 61.0 17.9 522.4
Switzerland (13) 112.1 54.3 13.8 506.0 Australia (14) 115.6 68.5 16.5 515.2
Taiwan (15) 168.1 51.0 50.1 826.2 Korea, South (13) 112.4 32.4 48.7 672.4
Ukraine (14) 1041.2 709.2 204.3 2002.1 Switzerland (13) 112.1 54.3 13.8 506.0
United Kingdom (13) 166.5 103.3 24.3 620.3 France (13) 111.1 43.4 20.9 686.0
United States (15) 233.8 123.5 27.2 816.9 Israel (14) 96.0 44.7 20.1 529.1
Females aged 35–74 y
Australia (14) 48.6 18.3 12.7 311.9 Ukraine (14) 432.6 286.4 105.7 790.0
Austria (14) 66.8 28.9 14.5 359.3 Belarus (14) 348.3 228.0 88.6 662.2
Belarus (14) 348.3 228.0 88.6 662.2 Serbia (15) 234.1 49.9 63.4 663.6
Belgium (14) 62.1 17.2 16.1 382.6 Romania (15) 230.9 79.8 71.4 572.9
Croatia (15) 147.3 61.9 46.1 481.5 Hungary (15) 202.1 96.0 44.8 643.0
Czech Republic (15) 123.2 53.8 24.2 451.4 Slovakia (14) 154.6 77.9 40.0 505.1
Denmark (14) 55.0 14.6 17.4 421.6 Croatia (15) 147.3 61.9 46.1 481.5
Finland (14) 68.5 26.8 20.0 336.6 Czech Republic (15) 123.2 53.8 24.2 451.4
France (13) 39.8 9.4 11.6 320.6 United States (15) 116.9 48.2 20.4 516.0
Germany (14) 77.0 25.9 15.5 382.8 Germany (14) 77.0 25.9 15.5 382.8
Hungary (15) 202.1 96.0 44.8 643.0 New Zealand (12) 72.8 32.0 19.1 378.0
Ireland (13) 65.7 29.2 15.1 372.1 United Kingdom (13) 72.3 31.2 17.9 404.6
Israel (14) 40.1 12.2 10.7 311.1 Finland (14) 68.5 26.8 20.0 336.6
(Continued )

CLINICAL STATEMENTS
Sorted Alphabetically Sorted by Descending
AND GUIDELINES
by Country CVD CHD Stroke Total CVD Death Rate CVD CHD Stroke Total
Italy (12) 59.4 18.2 16.4 313.8 Austria (14) 66.8 28.9 14.5 359.3
Japan (14) 46.5 11.1 17.8 252.7 Ireland (13) 65.7 29.2 15.1 372.1
Korea, South (13) 47.7 10.1 24.1 269.4 Taiwan (15) 62.4 15.3 19.7 375.9
Netherlands (15) 56.2 13.7 16.0 387.7 Belgium (14) 62.1 17.2 16.1 382.6
New Zealand (12) 72.8 32.0 19.1 378.0 Sweden (15) 61.2 24.5 14.1 336.1
Norway (14) 47.1 17.0 14.1 333.8 Portugal (13) 60.0 14.4 24.7 329.0
Portugal (13) 60.0 14.4 24.7 329.0 Italy (12) 59.4 18.2 16.4 313.8
Romania (15) 230.9 79.8 71.4 572.9 Netherlands (15) 56.2 13.7 16.0 387.7
Serbia (15) 234.1 49.9 63.4 663.6 Denmark (14) 55.0 14.6 17.4 421.6
Slovakia (14) 154.6 77.9 40.0 505.1 Australia (14) 48.6 18.3 12.7 311.9
Spain (14) 47.0 13.3 12.5 267.6 Korea, South (13) 47.7 10.1 24.1 269.4
Sweden (15) 61.2 24.5 14.1 336.1 Norway (14) 47.1 17.0 14.1 333.8
Switzerland (13) 44.7 14.2 10.7 295.0 Spain (14) 47.0 13.3 12.5 267.6
Taiwan (15) 62.4 15.3 19.7 375.9 Japan (14) 46.5 11.1 17.8 252.7
Ukraine (14) 432.6 286.4 105.7 790.0 Switzerland (13) 44.7 14.2 10.7 295.0
United Kingdom (13) 72.3 31.2 17.9 404.6 Israel (14) 40.1 12.2 10.7 311.1
United States (15) 116.9 48.2 20.4 516.0 France (13) 39.8 9.4 11.6 320.6
Rates are for the most recent year available (shown in parentheses as last 2 digits of year); most current data available as of May 2017. Rates are per 100 000
people, adjusted to the European Standard population. International Classification of Diseases, 10th Revision codes used were I00 to I99 for cardiovascular disease,
I20 to I25 for coronary heart disease, and I60 to I69 for stroke. CHD indicates coronary heart disease; and CVD, cardiovascular disease.
Sources: The World Health Organization, National Center for Health Statistics, and National Heart, Lung, and Blood Institute.
Table 12-4. OR for Combinations of Parental Heart

Attack History
OR (95% CI)
No family history 1.00
One parent with heart attack ≥50 y of age 1.67 (1.55–1.81)
One parent with heart attack <50 y of age 2.36 (1.89–2.95)
Both parents with heart attack ≥50 y of age 2.90 (2.30–3.66)
Both parents with heart attack, one <50 y of age 3.26 (1.72–6.18)
Both parents with heart attack, both <50 y of age 6.56 (1.39–30.95)
CI indicates confidence interval; and OR, odds ratio.

Data derived from Chow et al.28

CLINICAL STATEMENTS
100
AND GUIDELINES
90 86.5
84.4
80
69.6 68.6
70
60
50
41.4
39.4
40
30
20
13.5
11.5
10
0
20-39 40-59 60-79 80+
Age (Years)
Males Females
Chart 12-1. Prevalence of cardiovascular disease in adults ≥20 years of age, by age and sex (NHANES 2011–2014).
These data include coronary heart disease, heart failure, stroke, and hypertension.
1,000
800
Deaths in Thousands
600
400
200
0
1900 1910 1920 1930 1940 1950 1960 1970 1980 1990 2000 2010 2015
Year
Chart 12-2. Deaths attributable to diseases of the heart (United States: 1900–2015).
See Glossary (Chapter 27) for an explanation of “diseases of the heart.” In the years 1900 to 1920, the International
Classification of Diseases codes were 77 to 80; for 1925, 87 to 90; for 1930 to 1945, 90 to 95; for 1950 to 1960, 402 to 404
and 410 to 443; for 1965, 402 to 404 and 410 to 443; for 1970 to 1975, 390 to 398 and 404 to 429; for 1980 to 1995,
390 to 398, 402, and 404 to 429; for 2000 to 2014, I00 to I09, I11, I13, and I20 to I51. Before 1933, data are for a death
registration area and not the entire United States. In 1900, only 10 states were included in the death registration area, and this
increased over the years, so part of the increase in numbers of deaths is attributable to an increase in the number of states.
Source: National Heart, Lung, and Blood Institute.

CLINICAL STATEMENTS
1,200
AND GUIDELINES
1,000
800
Deaths in Thousands
600
400
200
0
1910 1920 1930 1940 1950 1960 1970 1980 1990 2000 2005 2014 2015
Year
Chart 12-3. Deaths attributable to cardiovascular disease (United States: 1910–2015).

Cardiovascular disease (International Classification of Diseases, 10th Revision codes I00–I99) does not include congenital heart
disease. Before 1933, data are for a death registration area and not the entire United States.
Chart 12-4. Percentage breakdown of deaths attributable to cardiovascular disease (United States: 2015).
Total may not add to 100 because of rounding. Coronary heart disease includes International Classification of Diseases, 10th
Revision (ICD-10) codes I20 to I25; stroke, I60 to I69; heart failure, I50; high blood pressure, I10 to I15; diseases of the arteries,
I70 to I78; and other, all remaining ICD-I0 I categories.
Source: National Heart, Lung, and Blood Institute from National Center for Health Statistics reports and data sets.

CLINICAL STATEMENTS
AND GUIDELINES
Chart 12-5. CVD deaths vs cancer deaths by age (United States: 2015).
CVD includes International Classification of Diseases, 10th Revision codes I00 to I99; cancer, C00 to C97.
CVD indicates cardiovascular disease.
Source: National Center for Health Statistics.
900,000
800,000
Accidents
700,000
Alzheimer's Disease
600,000
CLRD
Deaths
500,000 Cancer
400,000 Other CVD
300,000 Stroke
Heart Disease
200,000
100,000
0
All Ages <85 ≥85
Chart 12-6. CVD and other major causes of death: all ages, <85 years of age, and ≥85 years of age.
Deaths among both sexes, United States, 2015. Heart disease includes International Classification of Diseases, 10th Revision
codes I00 to I09, I11, I13, and I20 to I51; stroke, I60 to I69; all other CVD, I10, I12, I15, and I70 to I99; cancer, C00 to C97;
CLRD, J40 to J47; Alzheimer disease, G30; and accidents, V01 to X59 and Y85 and Y86.
CLRD indicates chronic lower respiratory disease; and CVD, cardiovascular disease.

CLINICAL STATEMENTS
450,000
AND GUIDELINES
400,000
350,000 Accidents
Alzheimer's Disease
300,000 CLRD
Cancer
Deaths
250,000
Other CVD
Stroke
200,000
Heart Disease
150,000
100,000
50,000
0
All Ages <85 ≥85
Chart 12-7. CVD and other major causes of death in males: all ages, <85 years of age, and ≥85 years of age.
Deaths among males, United States, 2015. Heart disease includes International Classification of Diseases, 10th Revision codes
I00 to I09, I11, I13, and I20 to I51; stroke, I60 to I69; all other CVD, I10, I12, I15, and I70 to I99; cancer, C00 to C97; CLRD,
J40 to J47; and accidents, V01 to X59 and Y85 and Y86.
450,000
400,000
350,000 Accidents
Alzheimer's Disease
300,000
CLRD
Cancer
250,000
Deaths
Other CVD
Stroke
200,000
Heart Disease
150,000
100,000
50,000
0
All Ages <85 ≥85
Chart 12-8. CVD and other major causes of death in females: all ages, <85 years of age, and ≥85 years of age.
Deaths among females, United States, 2015. Heart disease includes International Classification of Diseases, 10th Revision
codes I00 to I09, I11, I13, and I20 to I51; stroke, I60 to I69; all other CVD, I10, I12, I15, and I70 to I99; cancer, C00 to C97;
CLRD, J40 to J47; and Alzheimer disease, G30.

CLINICAL STATEMENTS
AND GUIDELINES
Chart 12-9. CVD and other major causes of death for all males and females (United States: 2015).
Diseases included: CVD (International Classification of Diseases, 10th Revision codes I00–I99); cancer (C00–C97); accidents
(V01–X59 andY85–Y86); CLRD (J40–J47); diabetes mellitus (E10–E14); and Alzheimer disease (G30).
Chart 12-10. CVD and other major causes of death for NH white males and females (United States: 2015).
(V01–X59 andY85–Y86); CLRD (J40–J47); diabetes mellitus (E10–E14); and Alzheimer disease (G30).
CLRD indicates chronic lower respiratory disease; CVD, cardiovascular disease; and NH, non-Hispanic.

CLINICAL STATEMENTS
AND GUIDELINES
Chart 12-11. CVD and other major causes of death for NH black males and females (United States: 2015).
(V01–X59 andY85–Y86); CLRD (J40–J47); diabetes mellitus (E10–E14); and nephritis (N00-N07, N17-N19, N25-N27)
Chart 12-12. CVD and other major causes of death for Hispanic or Latino males and females (United States: 2015).
Number of deaths shown may be lower than actual because of underreporting in this population. Diseases included: CVD
(International Classification of Diseases, 10th Revision codes I00–I99); cancer (C00–C97); accidents (V01–X59 andY85–Y86);
CLRD (J40–J47); diabetes mellitus (E10–E14); and Alzheimer disease (G30).

CLINICAL STATEMENTS
AND GUIDELINES
Chart 12-13. CVD and other major causes of death for NH Asian or Pacific Islander males and females (United
States: 2015).
“Asian or Pacific Islander” is a heterogeneous category that includes people at high CVD risk (eg, South Asian) and people
at low CVD risk (eg, Japanese). More specific data on these groups are not available. Number of deaths shown may be lower
than actual because of underreporting in this population. Diseases included: CVD (International Classification of Diseases, 10th
Revision codes I00–I99); cancer (C00–C97); accidents (V01–X59 andY85–Y86); influenza and pneumonia (J09-J18); diabetes
mellitus (E10–E14); and Alzheimer disease (G30).
CVD indicates cardiovascular disease; and NH, non-Hispanic.

CLINICAL STATEMENTS
AND GUIDELINES
Chart 12-14. CVD and other major causes of death for NH American Indian or Alaska Native males and females
(United States: 2015).
Number of deaths shown may be lower than actual because of underreporting in this population. Diseases included: CVD
(International Classification of Diseases, 10th Revision codes I00–I99); cancer (C00–C97); accidents (V01–X59 andY85–Y86);
chronic liver disease (K70, K73-K74); diabetes mellitus (E10–E14); and Alzheimer disease (G30).

CLINICAL STATEMENTS
AND GUIDELINES
Chart 12-15. Age-adjusted death rates for CHD, stroke, and lung and breast cancer for NH white and black females
(United States: 2015).
CHD includes International Classification of Diseases, 10th Revision codes I20 to I25; stroke, I60 to I69; lung cancer, C33 to
C34; and breast cancer, C50.
CHD indicates coronary heart disease; and NH, non-Hispanic.
550
530
510
490
Deaths in Thousands
470
450
430
410
390
370
350
1979 1980 1985 1990 1995 2000 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015
Year
Males Females
Chart 12-16. Cardiovascular disease (CVD) mortality trends for males and females (United States: 1979–2015).
CVD excludes congenital cardiovascular defects (International Classification of Diseases, 10th Revision [ICD-10] codes I00–I99).
The overall comparability for cardiovascular disease between the International Classification of Diseases, 9th Revision (1979–
1998) and ICD-10 (1999–2015) is 0.9962. No comparability ratios were applied.

CLINICAL STATEMENTS
AND GUIDELINES
Chart 12-17. US maps corresponding to the state age-adjusted death rates per 100 000 population for cardiovascular
disease, coronary heart disease, and stroke (including the District of Columbia), 2015.
Source: National Center for Health Statistics and National Heart, Lung, and Blood Institute.3

CLINICAL STATEMENTS
AND GUIDELINES
Chart 12-18. Hospital discharges for cardiovascular disease (United States: 1993–2014).
Hospital discharges include people discharged alive, dead, and “status unknown.
”Source: Healthcare Cost and Utilization Project, Agency for Healthcare Research and Quality and National Heart, Lung, and
Blood Institute.
Chart 12-19. Hospital discharges (International Classification of Diseases, 9th Revision) for the 10 leading diagnostic
groups (United States: 2014).
Source: Healthcare Cost and Utilization Project, Agency for Healthcare Research and Quality and National Heart, Lung, and
Blood Institute.

CLINICAL STATEMENTS
AND GUIDELINES
Chart 12-20. Estimated average 10-year cardiovascular disease risk in adults 50 to 54 years of age according to
levels of various risk factors (FHS).
BP indicates blood pressure; FHS, Framingham Heart Study; and HDL, high-density lipoprotein.
Data derived from D’Agostino et al.50
Chart 12-21. Age-standardized global mortality rates of cardiovascular diseases per 100 000, both sexes, 2015.
Chart 12-22. Age-standardized global prevalence rates of cardiovascular diseases per 100 000, both sexes, 2015.
7. Centers for Disease Control and Prevention. Prevalence and most com-
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47. Roth GA, Huffman MD, Moran AE, Feigin V, Mensah GA, Naghavi M, 49. Kontis V, Mathers CD, Rehm J, Stevens GA, Shield KD, Bonita R, Riley
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Murray CJ. Global and regional patterns in cardiovascular mortality LM, Poznyak V, Beaglehole R, Ezzati M. Contribution of six risk factors
AND GUIDELINES
from 1990 to 2013. Circulation. 2015;132:1667–1678. doi: 10.1161/ to achieving the 25×25 non-communicable disease mortality reduction
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disease and stroke). Circulation. 2012;126:2769–2775. doi: 10.1161/ Framingham Heart Study. Circulation. 2008;117:743–753. doi: 10.1161/
CIR.0b013e318267e99f. CIRCULATIONAHA.107.699579.

13. STROKE (CEREBROVASCULAR Abbreviations Used in Chapter 13 Continued

CLINICAL STATEMENTS
DISEASE) GFR glomerular filtration rate

AND GUIDELINES
GWAS genome wide association study

ICD-9 430 to 438; ICD-10 I60 to I69. See Table 13-1 GWTG Get With The Guidelines
and Charts 13-1 through 13-16 HBP high blood pressure
HD heart disease
HF heart failure
Stroke Prevalence HR hazard ratio
(See Table 13-1 and Chart 13-1) ICD-9

ICD-9-CM
International Classification of Diseases, 9th Revision
International Classification of Diseases, 9th Revision, Clinical
• Stroke prevalence estimates may differ slightly Modification
between studies because each study selects and ICD-10 International Classification of Diseases, 10th Revision
ICH intracerebral hemorrhage
recruits a sample of participants to represent the tar-
get study population (eg, state, region, or country). IQ intelligence quotient
• An estimated 7.2 million Americans ≥20 years of IVT intravenous thrombolysis
age self-report having had a stroke (extrapolated LDLC low-density lipoprotein cholesterol
to 2014 by use of NHANES 2011–2014 data). MEPS Medical Expenditure Panel Survey
Overall stroke prevalence during this period was MESA Multi-Ethnic Study of Atherosclerosis
MIDAS Myocardial Infarction Data Acquisition System
Abbreviations Used in Chapter 13 MONICA Monitoring Trends and Determinants of Cardiovascular Disease
MR CLEAN Multicenter Randomized Clinical Trial of Endovascular
ABCD2 age, blood pressure, clinical features, duration, diabetes
Treatment for Acute Ischemic Stroke in the Netherlands
ACCORD Action to Control Cardiovascular Risk in Diabetes
MRI magnetic resonance imaging
ACR albumin-creatinine ratio
NH non-Hispanic
AHI apnea-hypopnea index
ARIC Atherosclerosis Risk in Communities study
ASPECTS Alberta Stroke Program Early CT Score
ATRIA Anticoagulation and Risk Factors in Atrial Fibrillation
NIHSS National Institutes of Health Stroke Scale

BASIC Brain Attack Surveillance in Corpus Christi
NINDS National Institutes of Neurological Disorders and Stroke
BNP B-type natriuretic peptide
BP blood pressure
NOMAS Northern Manhattan Study
ONTARGET Ongoing Telmisartan Alone and in Combination With
CAD coronary artery disease
Ramipril Global Endpoint Trial
OR odds ratio
CHS Cardiovascular Health Study
PAR population attributable risk
PISTE Pragmatic Ischaemic Stroke Thrombectomy Evaluation
CKD chronic kidney disease
PREVEND Prevention of Renal and Vascular End-Stage Disease
CREST Carotid Revascularization Endarterectomy Versus Stenting Trial
REVASCAT Revascularization With Solitaire FR Device Versus Best
CVD cardiovascular disease Medical Therapy in the Treatment of Acute Stroke Due
DALY disability-adjusted life-year to Anterior Circulation Large Vessel Occlusion Presenting
DASH Dietary Approaches to Stop Hypertension Within Eight Hours of Symptom Onset
DBP diastolic blood pressure RR relative risk
DM diabetes mellitus SAH subarachnoid hemorrhage
ED emergency department SBP systolic blood pressure
eGFR estimated glomerular filtration rate SD standard deviation
EPIC European Prospective Investigation Into Cancer and Nutrition SES socioeconomic status
ESCAPE Endovascular Treatment for Small Core and Anterior SHS Strong Heart Study
Circulation Proximal Occlusion With Emphasis on SPRINT Systolic Blood Pressure Intervention Trial
Minimizing CT to Recanalization Times SPS3 Secondary Prevention of Small Subcortical Strokes
EXTEND-IA Extending the Time for Thrombolysis in Emergency STOP Stroke Prevention Trial in Sickle Cell Anemia
Neurological Deficits–Intra-Arterial
SWIFT Solitaire With the Intention for Thrombectomy as Primary
FHS Framingham Heart Study PRIME Endovascular Treatment
FUTURE Follow-up of TIA and Stroke Patients and Unelucidated Risk TC total cholesterol
Factor Evaluation
THRACE Trial and Cost-effectiveness Evaluation of Intra-arterial
GBD Global Burden of Disease Thrombectomy in Acute Ischemic Stroke
GCNKSS Greater Cincinnati/Northern Kentucky Stroke Study TIA transient ischemic attack
(Continued ) tPA tissue-type plasminogen activator

an estimated 2.7% (NHANES, NHLBI tabulation; • With the increase in the aging population, preva-
CLINICAL STATEMENTS
Table 13-1). lence of stroke survivors is projected to increase,
AND GUIDELINES
• Prevalence of stroke in the United States increases especially among elderly females.5
with advancing age in both males and females
(Chart 13-1).
• According to data from the 2015 BRFSS (CDC)1: Stroke Incidence
— 2.7% of males and 2.7% of females ≥18 (See Table 13-1 and Chart 13-2)
years of age had a history of stroke; 2.6% • Each year, ≈795 000 people experience a new
of NH whites, 4.1% of NH blacks, 1.5% of or recurrent stroke (Table 13-1). Approximately
Asian/Pacific Islanders, 2.3% of Hispanics (of 610 000 of these are first attacks, and 185 000 are
any race), 5.2% of American Indian/Alaska recurrent attacks (GCNKSS, NINDS, and NHLBI;
Natives, and 4.7% of other races or multira- GCNKSS and NINDS data for 1999 provided July
cial people had a history of stroke. 9, 2008; estimates compiled by NHLBI).
— Stroke prevalence in adults is 2.7% in the • Of all strokes, 87% are ischemic and 10% are ICH
United States, with the lowest prevalence in strokes, whereas 3% are SAH strokes (GCNKSS,
Minnesota (1.9%) and highest prevalence in NINDS, 1999).
Alabama (4.3%). • On average, every 40 seconds, someone in the
• Over the time period 2006 to 2010, data from United States has a stroke (AHA computation
BRFSS show that the overall self-reported stroke based on the latest available data).
prevalence did not change. Older adults, blacks,
people with lower levels of education, and peo- Temporal Trends
ple living in the southeastern United States had • In the multicenter ARIC study of black and white
higher stroke prevalence.2 adults, stroke incidence rates decreased from
• Analysis of temporal trends in age-, sex- and race/ 1987 to 2011. The decreases varied across age
ethnicity-specific stroke prevalence rates from groups but were similar across sex and race.6
2006 to 2010, according to BRFSS, revealed that • Data from the BASIC Project for the time period
stroke prevalence remained stable in individu- 2000 through 2010 demonstrated that ischemic
als aged 18 to 44 and 45 to 64 years but had stroke rates declined significantly in people aged
a declining trend among individuals ≥65 years ≥60 years but remained largely unchanged over
old across the study period (−1.2%, P=0.09). time in those aged 45 to 59 years.
From 2006 to 2010, stroke prevalence declined — Rates of stroke decline did not differ signifi-
in males (−3.6%, P<0.01) while remaining stable cantly for NH whites and Mexican Americans
in females across the study period, such that in overall in any age group. However, ethnic
more recent years, stroke prevalence was similar disparities in stroke rates persist between
in both males and females. From 2006 to 2010, Mexican Americans and NH whites in the 45-
there were no statistically significant temporal to 59-year-old and 60- to 74-year-old age
trends in stroke prevalence by race/ethnicity.2 groups.7
• The prevalence of stroke-related symptoms was — Data from the BASIC Project showed that the
found to be relatively high in a general population age-, sex-, and ethnicity-adjusted incidence
free of a prior diagnosis of stroke or TIA. On the of ICH decreased from 2000 to 2010 from
basis of data from 18 462 participants enrolled an annual incidence rate of 5.21 per 10 000
in a national cohort study, 17.8% of the popula- (95% CI, 4.36–6.24) to 4.30 per 10 000
tion >45 years of age reported at least 1 symp- (95% CI, 3.21–5.76).8
tom. Stroke symptoms were more likely among • GCNKSS data show that compared with the
blacks than whites, among those with lower 1990s, when incidence rates of stroke became
income and lower educational attainment, and stable, stroke incidence in 2005 had decreased
among those with fair to poor perceived health for whites. A similar decline was not seen in
status. Symptoms also were more likely in partici- blacks. These changes for whites were driven
pants with higher Framingham stroke risk scores by a decline in ischemic strokes. There were no
(REGARDS, NINDS).3 changes in incidence of ischemic stroke for blacks
• Projections show that by 2030, an additional 3.4 or of hemorrhagic strokes in blacks or whites.9
million US adults aged ≥18 years, representing • Analysis of data from the FHS suggests that stroke
3.88% of the adult population, will have had incidence is declining over time in this largely white
a stroke, a 20.5% increase in prevalence from cohort. Data from 1950 to 1977, 1978 to 1989,
2012. The highest increase (29%) is projected to and 1990 to 2004 showed that the age-adjusted
be in white Hispanic males.4 incidence of first stroke per 1000 person-years in

each of the 3 periods was 7.6, 6.2, and 5.3 in through 2004 was 6.79 per 100 person-years,
CLINICAL STATEMENTS
males and 6.2, 5.8, and 5.1 in females, respec- with 86% of incident strokes being ischemic.16
AND GUIDELINES
tively. Lifetime risk for incident stroke at 65 years • In the REGARDS study, the increased risk of ICH
of age decreased significantly in the latest data with age differed between blacks and whites:
period compared with the first, from 19.5% to there was a 2.25-fold (95% CI, 1.63–3.12)
14.5% in males and from 18.0% to 16.1% in increase per decade older age in whites but no
females.10 Data from the Tromsø Study found that age association with ICH risk in blacks (HR, 1.09;
changes in cardiovascular risk factors accounted 95% CI, 0.70–1.68 per decade older age).17
for 57% of the decrease in ischemic stroke inci-
Sex
dence for the time period from 1995 to 2012.11
• Each year, ≈55 000 more females than males have
Race/Ethnicity a stroke (GCNKSS, NINDS).9
• Annual age-adjusted incidence for first-ever stroke • Females have a higher lifetime risk of stroke than
was higher in black individuals than white indi- males. In the FHS, lifetime risk of stroke among
viduals in data collected in 1993 to 1994, 1999, those 55 to 75 years of age was 1 in 5 for females
and 2005 for each of the following stroke types: (95% CI, 20%–21%) and ≈1 in 6 for males (95%
ischemic stroke, ICH, and SAH (Chart 13-2). CI, 14%–17%).18
• In the national REGARDS cohort, in 27 744 par- • Age-specific incidence rates are substantially
ticipants followed up for 4.4 years (2003–2007), lower in females than males in younger and mid-
the overall age- and sex-adjusted black/white inci- dle-age groups, but these differences narrow so
dence rate ratio was 1.51, but for ages 45 to 54 that in the oldest age groups, incidence rates in
years, it was 4.02, whereas for those ≥85 years of females are approximately equal to or even higher
age, it was 0.86.12 Similar trends for decreasing than in males.5,19–23
black/white incidence rate ratio with older age
were seen in the GCNKSS.13
• The BASIC Project (NINDS) demonstrated an TIA: Prevalence, Incidence, and Prognosis
increased incidence of stroke among Mexican • In a nationwide survey of US adults, the estimated
Americans compared with NH whites in a com- prevalence of self-reported physician-diagnosed
munity in southeast Texas. The crude 3-year TIA increased with advancing age and was 2.3%
cumulative incidence (2000–2002) was 16.8 per overall, which translates to ≈5 million people.
1000 in Mexican Americans and 13.6 per 1000 The true prevalence of TIA is likely to be greater,
in NH whites. Specifically, Mexican Americans had because many patients who experience neurolog-
a higher cumulative incidence of ischemic stroke ical symptoms consistent with a TIA fail to report
than NH whites at younger ages (45–59 years of them to their healthcare provider.24
age: RR, 2.04 [95% CI, 1.55–2.69]; 60–74 years • In the GCNKSS, according to data from 1993 and
of age: RR, 1.58 [95% CI, 1.31–1.91]) but not at 1994, the age-, sex-, and race-adjusted incidence
older ages (≥75 years of age: RR, 1.12; 95% CI, rate for TIA was 0.83 per 10 000.25 In a more
0.94–1.32). Mexican Americans also had a higher recent Italian community-based registry con-
incidence of ICH and SAH than NH whites after ducted in 2007 to 2009, the crude TIA incidence
adjustment for age.14 rate was 0.52 per 1000.26
• The age-adjusted incidence of first ischemic • Incidence of TIA increases with age and varies by
stroke per 1000 was 0.88 in whites, 1.91 in sex and race/ethnicity. Males, blacks, and Mexican
blacks, and 1.49 in Hispanics according to data Americans have higher rates of TIA than their
from NOMAS (NINDS) for 1993 to 1997. Among female and NH white counterparts.14,25
blacks, compared with whites, the RR of intracra- • Approximately 12% of all strokes are heralded by
nial atherosclerotic stroke was 5.85; of extracra- a TIA.27
nial atherosclerotic stroke, 3.18; of lacunar stroke, • TIAs confer a substantial short-term risk of stroke,
3.09; and of cardioembolic stroke, 1.58. Among hospitalization for CVD events, and death. Of
Hispanics (primarily Cuban and Puerto Rican), 1707 TIA patients evaluated in the ED of Kaiser
compared with whites, the relative rate of intra- Permanente Northern California, 180 (11%)
cranial atherosclerotic stroke was 5.00; of extra- experienced a stroke within 90 days, and 91 (5%)
cranial atherosclerotic stroke, 1.71; of lacunar had a stroke within 2 days. Predictors of stroke
stroke, 2.32; and of cardioembolic stroke, 1.42.15 included age >60 years, DM, focal symptoms of
• Among 4507 American Indian participants with- weakness or speech impairment, and symptoms
out a prior stroke in the SHS from 1989 to 1992, that lasted >10 minutes.28 In a more recent pro-
the age- and sex-adjusted incidence of stroke spective European cohort, stroke risk after TIA

was 1.5% at 2 days, 3.7% at 90 days, and 5.1% TIA, 19.4% (95% CI, 14.6%–24.3%) after isch-
CLINICAL STATEMENTS
at 1 year.29 Higher recurrence rates were associ- emic stroke, and 9.8% (95% CI, 1.0%–18.7%)
AND GUIDELINES
ated with higher ABCD2 scores (a score based after ICH.39
on age, BP, clinical features, duration, and DM), • Among 1867 stroke patients aged 18 to 45 years
large-artery atherosclerosis, and the presence of in the Italian Project on Stroke in Young Adults,
multiple infarctions. the 10-year cumulative risk of brain ischemia was
• Meta-analyses of cohorts of patients with TIA 14.0% (95% CI, 11.4%–17.1%).40
have shown the short-term risk of stroke after TIA • In North Dublin Population Stroke Study, the
to be ≈3% to 10% at 2 days and 9% to 17% at cumulative 2-year stroke recurrence rate was
90 days.30,31 10.8%, and case fatality was 38.6%.41
• Individuals who have a TIA and survive the ini- • Children with arterial ischemic stroke, particularly
tial high-risk period have a 10-year stroke risk of those with arteriopathy, remain at high risk for
roughly 19% and a combined 10-year stroke, MI, recurrent arterial ischemic stroke despite increased
or vascular death risk of 43% (4% per year).32 use of antithrombotic agents. The cumulative
• In the GCNKSS, the 1-year mortality rate after a stroke recurrence rate was 6.8% (95% CI, 4.6%–
TIA was 12%.25 10%) at 1 month and 12% (95% CI, 8.5%–15%)
• In the community-based Oxford Vascular Study, at 1 year. The 1-year recurrence rate was 32%
among patients with TIA, disability levels increased (95% CI, 18%–51%) for moyamoya, 25% (95%
from 14% (modified Rankin scale >2) before the CI, 12%–48%) for transient cerebral arteriopa-
TIA to 23% at 5 years after the TIA (P=0.002). In thy, and 19% (95% CI, 8.5%–40%) for arterial
this same study, the 5-year risk of institutionaliza- dissection.42
tion after TIA was 11%.33 • Annual recurrent stroke rates in control arms of
• In a meta-analysis of 47 studies,34 it was estimated stroke prevention trials fell from 8.71% in trials
that approximately one third of TIA patients have launched in the 1960s to 6.10% in the 1970s,
an acute lesion present on diffusion-weighted 5.41% in the 1980s, 4.04% in the 1990s, and
MRI and thus would be classified as having had 4.98% in the 2000s. If one assumes a continued
a stroke under a tissue-based case definition35,36; linear decline, the annual recurrent stroke rate in
however, substantial between-study heterogene- trial control arms in the coming decade is pro-
jected to be 2.25%.43
ity was noted.

• A meta-analysis of 13 studies derived from hos-
pital-based or community-based stroke registries
Recurrent Stroke found a pooled cumulative stroke recurrence
• Among 600 Scandinavian stroke patients <70 risk of 3.1% (95% CI, 1.7%–4.4%) at 30 days,
years of age followed up for 2 years, 55 (9.2%) 11.1% (95% CI, 9.0%–13.3%) at 1 year, 26.4%
had a recurrent stroke, 15 (2.5%) had a TIA, 4 (95% CI, 20.1%–32.8%) at 5 years, and 39.2%
(0.7%) had a coronary event, and 24 (4.0%) (95% CI, 27.2%–51.2%) at 10 years.44 There was
had died. Recurrent stroke occurred in 19.2% of a temporal reduction in the 5-year risk of stroke
patients with index stroke caused by large-artery recurrence from 32% to 16.2%, but substantial
disease, 4.9% with small-vessel disease, 8.2% differences across studies in terms of case mix and
with cardioembolic cause, 5.6% with cryptogenic definition of stroke recurrence were reported.
cause, and 12.8% with other and undetermined • Among 6700 patients with first-ever ischemic
causes combined.37 stroke or ICH who survived the first 28 days in the
• During a median 5.3 years of follow-up among Northern Sweden MONICA stroke registry from
987 ARIC participants with first-ever strokes, 1995 to 2008, the cumulative risk of recurrence
there were 183 recurrent strokes among 147 par- was 6% at 1 year, 16% at 5 years, and 25% at
ticipants. Approximately 70% of recurrent strokes 10 years.45 The risk of stroke recurrence decreased
were of the same subtype; however, 28% were 36% between 1995 to 1998 and 2004 to 2008.
the same when the index stroke was lacunar. Approximately 62% of all recurrent strokes after
One-year stroke recurrence rates by index subtype ICH (63 of 101) were ischemic.
were 7.9% for thrombotic, 6.5% for cardioem- • Approximately 10% of participants with a prior
bolic, and 6.5% for lacunar events.38 stroke in the REGARDS study had a recurrent
• In a long-term follow-up study of recurrent vas- stroke during a mean follow-up of 6.8 years.46
cular events among 724 first-ever TIA, ischemic Although black participants aged 45 to 75 years
stroke, or ICH patients aged 18 to 50 years in the had an increased risk of incident stroke compared
Netherlands, cumulative 20-year risk of recurrent with white participants, there were no significant
stroke was 17.3% (95% CI, 9.5%–25.1%) after black-white differences in risk of recurrent stroke.

Stroke Mortality 44 years (−15.4%; 5.2 to 4.4 per 100 000),

CLINICAL STATEMENTS
(See Table 13-1 and Charts 13-3 45 to 54 years (−18.0%; 15.0 to 12.3 per
AND GUIDELINES
100 000), and 55 to 64 years (−9.5%; 32.7

through 13-6)
and 29.6 per 100 000). Despite the improve-
See “Factors Influencing the Decline in Stroke Mortality: ments noted since 2005, there has been a
a Statement From the American Heart Association/ recent flattening or increase in death rates
American Stroke Association”47 for more in-depth cov- among all age groups (Charts 13-4 and
erage of factors contributing to the decline in stroke 13-5).
mortality over the past several decades. — Age-adjusted stroke death rates declined
• In 201548,49: by ≈16% or more among all racial/ethnic
— On average, every 3 minutes 45 seconds, groups; however, in 2015, rates remained
someone died of a stroke. higher among NH blacks (52.2 per 100 000;
— Stroke accounted for ≈1 of every 19 deaths change since 2005: −23.5%) than among
in the United States. NH whites (36.4 per 100 000; −21.2%), NH
— When considered separately from other Asians/Pacific Islanders (30.0 per 100 000;
CVDs, stroke ranks No. 5 among all causes −26.8%), NH American Indians/Alaska
of death, behind diseases of the heart, Natives (32.0 per 100 000; −29.8%), and
cancer, CLRD, and unintentional injuries/ Hispanics (32.3 per 100 000; −16.3%).
accidents. • There are substantial geographic disparities in
— The number of deaths with stroke as an stroke mortality, with higher rates in the south-
underlying cause was 140 323 (Table 13-1); eastern United States, known as the “stroke
the age-adjusted death rate for stroke as belt” (Chart 13-6). This area is usually defined to
an underlying cause of death was 37.6 per include the 8 southern states of North Carolina,
100 000, whereas the age-adjusted rate for South Carolina, Georgia, Tennessee, Mississippi,
any-mention of stroke as a cause of death Alabama, Louisiana, and Arkansas. These geo-
was 63.0 per 100 000. graphic differences have existed since at least
— Approximately 62% of stroke deaths 1940,50 and despite some minor shifts,51 they per-
occurred outside of an acute care hospital. sist.52–54 Within the stroke belt, a “buckle” region
— In 2015, NH black males and females had along the coastal plain of North Carolina, South
higher age-adjusted death rates for stroke Carolina, and Georgia has been identified with an
than NH white, NH Asian, NH Indian or Alaska even higher stroke mortality rate than the remain-
Native, and Hispanic males and females in der of the stroke belt. Historically, the overall aver-
the United States (Chart 13-3). age stroke mortality has been ≈30% higher in
— More females than males die of stroke each the stroke belt than in the rest of the nation and
year because of a larger number of elderly ≈40% higher in the stroke buckle.55 Additional
females than males. Females accounted for clusters of counties with high stroke mortality
58% of US stroke deaths in 2015. have been identified outside of the stroke belt.56
• Conclusions about changes in stroke death rates Counties with high stroke mortality were reported
from 2005 to 2015 are as follows48: to have lower SES, a greater proportion of black
— The age-adjusted stroke death rate decreased residents, and higher rates of chronic disease and
21.7% (from 48.0 per 100 000 to 37.6 per healthcare utilization.
100 000), and the actual number of stroke • In examining trends in stroke mortality by US cen-
deaths declined 2.3% (from 143 579 deaths sus divisions from 1999 to 2007 for people ≥45
to 140 323 deaths). years of age, the rate of decline varied by geo-
— The decline in age-adjusted stroke death graphic region and racial/ethnic group. Among
rates for males and females was similar black and white females and white males, rates
(−21.9% and −21.5%, respectively). declined by ≥2% annually in every census divi-
— Crude stroke death rates declined most sion, but among black males, rates declined little
among people aged 65 to 74 years (−24.3%; in the East and West South Central divisions.57
from 99.8 to 75.5 per 100 000), 75 to 84 • On the basis of national death statistics for the
years (−23.8%; from 358.4 to 273.0 per time period 1990 to 2009, stroke mortality rates
100 000), and ≥85 years (−21.3%; from among American Indian and Alaska Native people
1239.7 to 975.8 per 100 000). By compari- were higher than among whites for both males
son, crude stroke death rates declined more and females in contract health services deliv-
modestly among those aged 25 to 34 years ery area counties in the United States and were
(−7.1%; from 1.4 to 1.3 per 100 000), 35 to highest in the youngest age groups (35–44 years

old). Stroke mortality rates and the rate ratios for High BP
CLINICAL STATEMENTS
American Indians/Alaska Natives to whites var- (See Chapter 8 for more information.)
AND GUIDELINES
ied by region, with the lowest in the Southwest • BP is a powerful determinant of risk for both isch-
and the highest in Alaska. Starting in 2001, rates emic stroke and intracranial hemorrhage.
among American Indian/Alaska Native people • From a recent meta-analysis, 9 trials showed high-
decreased in all regions.58 strength evidence that BP control to <150/90
• Data from the ARIC study (1987–2011; 4 US cit- mm Hg reduces stroke (RR, 0.74; 95% CI, 0.65–
ies) showed that the cumulative all-cause mor- 0.84), and 6 trials yielded low- to moderate-
tality rate after a stroke was 10.5% at 30 days, strength evidence that lower targets (≤140/85
21.2% at 1 year, 39.8% at 5 years, and 58.4% at mm Hg) are associated with significant decreases
the end of 24 years of follow-up. Mortality rates in stroke (RR, 0.79; 95% CI, 0.59–0.99).61
were higher after an incident hemorrhagic stroke • There was agreement across meta-analyses that
(67.9%) than after ischemic stroke (57.4%). intensive BP lowering appears to be most benefi-
Age-adjusted mortality after an incident stroke cial for the reduction in risk of stroke.62–64
decreased over time (absolute decrease of 8.1 • Median SBP declined 16 mm Hg between 1959
deaths per 100 strokes after 10 years), which and 2010 for different age groups in association
was mainly attributed to the decrease in mortality with large accelerated reductions in stroke mortal-
among those aged ≤65 years (absolute decrease ity.47 In a meta-analysis of clinical trials, antihyper-
of 14.2 deaths per 100 strokes after 10 years).6 tensive therapy was associated with an average
• Data from the BASIC Project showed there was no decline of 41% (95% CI, 33%–48%) in stroke
change in ICH case fatality or long-term mortality incidence with SBP reductions of 10 mm Hg or
from 2000 to 2010 in a South Texas community. DBP reductions of 5 mm Hg.65
Yearly age-, sex-, and ethnicity-adjusted 30-day • Risk prediction models identify elevated BP as a
case fatality ranged from a low of 28.3% (95% key parameter in the assessment of cardiovascular
CI, 19.9%–40.3%) in 2006 to 46.5% (95% CI, and stroke risk.66
35.5%–60.8%) in 2008.8 — Diabetic subjects with BP <120/80 mm Hg
• A report released by the CDC in collaboration with have approximately half the lifetime risk of
the Centers for Medicare & Medicaid Services, the stroke of subjects with hypertension. The
treatment and lowering of BP among dia-
“Atlas of Stroke Hospitalizations Among Medicare

Beneficiaries,” found that in Medicare beneficia- betic hypertensive individuals was associated
ries over the time period 1995 to 2002, the 30-day with a significant reduction in stroke risk.67,68
mortality rate varied by age: 9.0% in patients 65 to — A review identified the benefit of intense BP
74 years of age, 13.1% in those 74 to 84 years of reduction and reduced stroke outcome risks
age, and 23.0% in those ≥85 years of age.59 in recent clinical trials.69 Combined results
• Projections of stroke mortality from 2012 to 2030 from SPRINT and ACCORD demonstrated
differ based on what factors are included in the that intensive BP control (<120 mm Hg)
forecasting.60 Conventional projections that only compared with standard treatment (<140
incorporate expected population growth and mm Hg) resulted in a significantly lower risk
aging reveal that the number of stroke deaths of stroke (RR, 0.75; 95% CI, 0.58–0.97).68
in 2030 may increase by ≈50% compared with • Cross-sectional baseline data from the SPS3 trial
the number of stroke deaths in 2012. However, if showed that more than half of all patients with
previous stroke mortality trends are also incorpo- symptomatic lacunar stroke had uncontrolled
rated into the forecasting, the number of stroke hypertension at 2.5 months after stroke.70
deaths among the entire population is projected • A meta-analysis of 19 prospective cohort studies
to remain stable through 2030, with potential (including 762 393 participants) found that prehy-
increases among the population aged ≥65 years. pertension is associated with incident stroke. The
Moreover, the trend-based projection method risk is particularly noted in those with BP values in
reveals that the disparity in stroke deaths among the higher prehypertension range.71
NH blacks compared with NH whites could • Several studies have shown significantly lower
increase from an RR of 1.10 (95% CI, 1.08–1.13) rates of recurrent stroke with lower BPs. Most
in 2012 to 1.30 (95% CI, 0.45–2.44) in 2030.60 recently, the BP-reduction component of the SPS3
trial showed that targeting an SBP <130 mm Hg
(versus a higher group at 130–149 mm Hg) was
Stroke Risk Factors likely to reduce recurrent stroke by ≈20% (HR,
For prevalence and other information on any of these spe- 0.81; 95% CI, 0.64–1.03; P=0.08) and signifi-
cific risk factors, refer to the specific risk factor chapters. cantly reduced ICH by two thirds (HR, 0.37; 95%

CI, 0.14–0.89; P=0.03) compared with an SBP and impaired glucose tolerance, may be associ-
CLINICAL STATEMENTS
goal of 130 to 149 mm Hg.72 ated with a higher future risk of stroke, but the
AND GUIDELINES
• Results from the SPS3 study showed the lowest RRs are modest. A meta-analysis of 15 prospec-
risk of events was observed at an SBP of 120 to tive cohort studies including 760 925 participants
128 mm Hg and a DBP of 65 to 70 mm Hg.73 revealed that when prediabetes was defined as
• In the Ethnic/Racial Variations of Intracerebral fasting glucose of 110 to 125 mg/dL (5 studies),
Hemorrhage study, both treated and untreated the adjusted RR for stroke was 1.21 (95% CI,
hypertension conferred a greater risk of ICH 1.02–1.44; P=0.03).78
among blacks (treated: OR, 3.02 [95% CI, 2.16– • DM is an independent risk factor for stroke
4.22]; untreated: OR, 12.46 [95% CI, 8.08–19.20]) recurrence; a meta-analysis of 18 studies
and Hispanics (treated: OR, 2.50 [95% CI, 1.73– involving 43 899 participants with prior stroke
3.62]; untreated: OR, 10.95 [95% CI, 6.58–18.23]) revealed higher stroke recurrence in patients
compared with whites (treated: OR, 1.57 [95% CI, with DM than in those without (HR, 1.45; 95%
1.24–1.98]; untreated: OR, 8.79 [95% CI, 5.66– CI, 1.32–1.59).79
13.66]), as well as among blacks compared with • A Swedish population-based stroke registry of
whites and Hispanics (P for interaction <0.0001).74 12 375 first-ever stroke patients 25 to 74 years
• In cross-sectional analysis from the REGARDS old who were followed up to 23 years found
study (NINDS), blacks with hypertension were that patients with DM at stroke onset (21%)
more likely to be aware of their HBP and more had a higher risk of death than patients without
frequently received treatment for it than whites DM (adjusted HR, 1.67; 95% CI, 1.58–1.76).79a
but were less likely than whites to have their BP The reduced survival of stroke patients with DM
controlled.75 In the SPS3 trial, black participants was more pronounced in females (P=0.02) and
were more likely to have SBP ≥150 mm Hg at younger individuals (P<0).
both study entry (40%) and end-study visit (17%; • In a meta-analysis of 11 RCTs that included 56 161
mean follow-up, 3.7 years) than whites (9%) and patients with type 2 DM and 1835 stroke cases,
Hispanics (11%) at end-study visit.75a it was revealed that those who were random-
• The higher stroke risk for the stroke belt compared ized to intensive glucose control did not have a
with other regions does not appear to be attrib- reduction in stroke risk compared with those with
conventional glucose control (RR, 0.94; 95% CI,
utable to hypertension management, because

treatment and control rates were similar for the 2 0.84–1.06; P=0.33; I2 P=0.20); however, there
geographic areas.75 was a 10% reduction in all MI (RR, 0.90; 95% CI,
0.82–0.98; P=0.02; I2 P=0.20).80
Diabetes Mellitus • A retrospective analysis of 220 patients with DM
(See Chapter 9 for more information.) with acute ischemic stroke revealed that those
• DM increases ischemic stroke incidence at all who had been taking and continued taking sulfo-
ages, but this risk is most prominent (risk ratio for nylureas were less likely to experience symptom-
ischemic stroke conferred by DM >5) before 65 atic hemorrhagic transformation than those who
years of age in both blacks and whites. Overall, did not take sulfonylureas (P=0.02).81
ischemic stroke patients with DM are younger, • A meta-analysis of 40 RCTs of BP lowering among
more likely to be black, and more likely to have 100 354 participants with DM revealed a lower
HBP, MI, and high cholesterol than nondiabetic risk of stroke (combined RR, 0.73 [95% CI, 0.64–
patients.76 0.83]; absolute risk reduction, 4.06 [95% CI,
• The association between DM and stroke risk dif- 2.53–5.40]).82
fers between sexes. A systematic review of 64 • A subsequent meta-analysis of 28 RCTs involv-
cohort studies representing 775 385 individuals ing 96 765 participants with DM revealed that
and 12 539 strokes revealed that the pooled fully a decrease in SBP by 10 mm Hg was associ-
adjusted RR of stroke associated with DM was ated with a lower risk of stroke (21 studies’ RR,
2.28 (95% CI, 1.93–2.69) in females and 1.83 0.74; 95% CI, 0.66–0.83). Significant interac-
(95% CI, 1.60–2.08) in males. Compared with tions were observed, with lower RRs (RR, 0.71;
males with DM, females with DM had a 27% 95% CI, 0.63–0.80) observed among trials with
greater RR for stroke when baseline differences in mean baseline SBP ≥140 mm Hg and no signifi-
other major cardiovascular risk factors were taken cant associations among trials with baseline SBP
into account (pooled ratio of RR, 1.27; 95% CI, <140 mm Hg (RR, 0.90; 95% CI, 0.69–1.17). The
1.10–1.46; I2=0%).77 associations between BP lowering and stroke risk
• Prediabetes, defined as impaired glucose toler- reduction were present for both the achieved SBP
ance or a combination of impaired fasting glucose of <130 mm Hg and the ≥130 mm Hg stratum.83

• The ACCORD study showed that in patients with authors estimated that subclinical atrial tachyar-
CLINICAL STATEMENTS
type 2 DM, targeting SBP to <120 mm Hg did not rhythmias were associated with a 13% PAR for
AND GUIDELINES
reduce the rate of cardiovascular events com- stroke or systemic embolism.96
pared with subjects in whom the SBP target was • An analysis of patients from the Veterans
<140 mm Hg, except for the end point of stroke, Administration showed that among patients with
for which intensive therapy reduced the risk of device-documented AF, the presence of relatively
any stroke (HR, 0.59; 95% CI, 0.39–0.89) and brief amounts of AF raised the short-term risk of
nonfatal stroke (HR, 0.63; 95% CI, 0.41–0.96).67 stroke 4- to 5-fold. This risk was highest in the
• ONTARGET revealed that in both patients with initial 5 to 10 days after the episode of AF and
and without DM, the adjusted risk of stroke con- declined rapidly after longer periods.97
tinued to decrease down to achieved SBP values • Important risk factors for stroke in the setting of
of 115 mm Hg, whereas there was no benefit for AF include advancing age, hypertension, HF, DM,
other fatal or nonfatal cardiovascular outcomes previous stroke or TIA, vascular disease, renal
below an SBP of 130 mm Hg.84 dysfunction, and female sex.82,98–101 Additional
• The ATRIA Study demonstrated that the duration biomarkers, including high levels of troponin
of DM is a stronger predictor of ischemic stroke and BNP, are associated with an increased risk of
than glycemic control for patients with DM and stroke in the setting of AF in models adjusted for
AF.85 Duration of DM ≥3 years was associated well-established clinical characteristics.102
with an increased rate of ischemic stroke (HR, • In patients with AF on anticoagulation, presence
1.74; 95% CI, 1.10–2.76) compared with a dura- of persistent AF versus paroxysmal AF is associ-
tion of <3 years. ated with higher risk of stroke.103,104
• A significant obesity paradox has been noted for
Disorders of Heart Rhythm
stroke risk among AF patients in a meta-analysis
(See Chapter 15 for more information.)
of RCTs with newer oral anticoagulant trials such
• AF is a powerful risk factor for stroke, indepen-
that overweight to obese participants had lower
dently increasing risk ≈5-fold throughout all ages.
risk of stroke and systemic embolism.105 However,
The percentage of strokes attributable to AF
this relationship is not observed in the observa-
increases steeply from 1.5% at 50 to 59 years of
tional studies.106
age to 23.5% at 80 to 89 years of age.86,87
• Left atrial enlargement is associated with AF, caus-

• A recent analysis from the FHS demonstrated that
ing the 2 conditions to often coexist. A system-
the risk of stroke associated with AF has declined
atic review of 9 cohort studies including 67 875
by 73% in the past 50 years from 1958 to 2007.88
participants revealed that those with left atrial
However, analysis from the Olmsted County, MN,
enlargement in the setting of sinus rhythm had
database suggests that AF-associated stroke risk
stroke rates ranging from 0.64 to 2.06 per 100
has not changed over the past decade (from 2000
person-years. Two studies found potential indica-
to 2010).89
tions of modification by sex, with only positive
• Because AF is often asymptomatic90,91 and likely
associations observed in females.107
frequently undetected clinically,92 the stroke risk
attributed to AF could be substantially underesti- High Blood Cholesterol and Other Lipids
mated.93 Screening for AF in patients with crypto- (See Chapter 7 for more information.)
genic stroke or TIA by use of outpatient telemetry • Overall, the association of each cholesterol sub-
for 21 to 30 days has resulted in an AF detection fraction with total stroke has shown inconsistent
rate of 12% to 23%.92–94 results, and the data are limited on associations
• In an RCT among patients with cryptogenic stroke, with specific ischemic stroke subtypes. Further
the cumulative incidence of AF detected with an research is needed to identify the association
implantable cardiac monitor was 30% by 3 years. of cholesterol with ischemic stroke subtypes,
Approximately 80% of the first AF episodes were as well as the association of lobar versus deep
asymptomatic.95 ICH.29,107–111 For clarity, results for different types
• Among 2580 participants ≥65 years of age with of cholesterol (TC, subfractions) are described in
hypertension in whom a cardiac rhythm device this section.
that included an atrial lead was implanted, 35% • An association between TC and ischemic stroke has
developed subclinical tachyarrhythmias (defined been found in some prospective studies113–115 but
as an atrial rate ≥190 beats per minute that lasted not others.29,108,109 In the Women’s Pooling Project,
≥6 minutes). These subclinical events were inde- including those <55 years of age without CVD, TC
pendently associated with a 2.5-fold increased was associated with an increased risk of stroke at
risk of ischemic stroke or systemic embolism. The the highest quintile (mean cholesterol 7.6 mmol/L)

in black (RR, 2.58; 95% CI, 1.05–6.32) but not stroke,113 and LDL-C may have a stronger asso-
CLINICAL STATEMENTS
white (RR, 1.47; 95% CI, 0.57–3.76) females.110 ciation for large-artery atherosclerotic subtype.123
AND GUIDELINES
An association of elevated TC with risk of stroke In a pooled analysis of CHS and ARIC, low LDL C
was noted to be present in those 40 to 49 years (<158.8 mg/dL) was associated with an increased
old and 50 to 59 years old but not in other age risk of ICH.124
groups in the Prospective Studies Collaboration.111 • Among 13 951 patients in the Copenhagen
In a recent meta-analysis of data from 61 cohorts, Heart Study followed up for 33 years for ischemic
TC was only weakly associated with risk of stroke, stroke, increasing stepwise levels of nonfasting
with no significant difference between males and triglycerides were associated with increased risk
females (HR [95% CI] for ischemic stroke per 1 of ischemic stroke in both males and females,125
mmol/L higher TC: 1.01 [0.98–1.05] in females although in ARIC, the Physician’s Health Study,
and 1.03 [1.00–1.05] in males).116 and the SHS, there was no association.120,126,127 In
• Elevated TC is inversely associated in multiple the Rotterdam study (N=9068), increasing quar-
studies with hemorrhagic stroke. In a meta-anal- tiles of serum triglycerides were associated with a
ysis of 23 prospective cohort studies, 1 mmol reduced risk of ICH.128
higher TC was associated with a 15% lower
risk of hemorrhagic stroke (HR, 0.85; 95% CI, Smoking/Tobacco Use
0.80–0.91).112 (See Chapter 3 for more information.)
• Data from the Honolulu Heart Program/NHLBI • Current smokers have a 2 to 4 times increased risk
found that in Japanese males 71 to 93 years of of stroke compared with nonsmokers or those
age, low concentrations of HDL-C were more who have quit for >10 years.129,130
likely to be associated with a future risk of throm- • Cigarette smoking is a risk factor for ischemic
boembolic stroke than were high concentra- stroke and SAH.129–131
tions.117 However, a meta-analysis of 23 studies • Smoking is perhaps the most important modifi-
performed in the Asia-Pacific region showed no able risk factor in preventing SAH, with the high-
significant association between low HDL-C and est PAR (38%–43%) of any SAH risk factor.132
stroke risk,118 although another meta-analysis • In a large Danish cohort study, among people
without geographic restriction demonstrated a with AF, smoking was associated with a higher
protective association of HDL-C with stroke.29 A risk of ischemic stroke/arterial thromboembolism
Finnish study of 27 703 males and 30 532 females or death, even after adjustment for other tradi-
followed up for >20 years for ischemic stroke tional risk factors.133
found an independent inverse association of • Data support a dose-response relationship
HDL-C with the risks of total and ischemic stroke between smoking and risk of stroke across old
in females.109 In the CHS, higher HDL-C was and young age groups.131,134
associated with a lower risk of ischemic stroke in • A meta-analysis that compared pooled data of
males but not in females.119 In the SHS, a possible almost 4 million smokers and nonsmokers found
interaction was noted between DM status and a similar risk of stroke associated with current
HDL-C for risk of stroke such that higher HDL-C smoking in females and males.135
was protective against stroke risk in patients with • Discontinuation of smoking has been shown
DM (HR per 1-SD higher HDL-C, 0.72; 95% CI, to reduce stroke risk across sex, race, and age
0.53–0.97) but not in those without DM (HR per groups.134,135
1-SD higher HDL-C, 0.93; 95% CI, 0.69–1.26).120 • Smoking may impact the effect of other stroke
In a recent meta-analysis, no significant associa- risk factors on stroke risk. For example, a synergis-
tion was observed between HDL-C levels and risk tic effect appears to exist between SBP136 and oral
of hemorrhagic stroke.112 contraceptives137,138 and the risk of stroke.
• Data from the Dallas Heart Study suggest that • Exposure to secondhand smoke, also termed pas-
higher HDL-C efflux capacity is strongly associ- sive smoking or secondhand tobacco smoke, is a
ated with lower risk of stroke.121 risk factor for stroke.
• In an analysis by the Emerging Risk Factors — Meta-analyses have estimated a pooled RR
Collaboration of individual records on 302 430 of 1.25 for exposure to spousal smoking
people without initial vascular disease from 68 (or nearest equivalent) and risk of stroke. A
long-term prospective studies, HR for ischemic dose-response relationship between expo-
stroke was 1.12 (95% CI, 1.04–1.20), with non– sure to secondhand smoke and stroke risk
HDL-C in analyses using the lowest quantile as was also reported.139,140
the referent group. In the Women’s Health Study, — Data from REGARDS found that after adjust-
LDL-C was associated with an increased risk of ment for other stroke risk factors, the risk of

overall stroke was 30% higher among nonexercise treadmill testing was inversely associ-
CLINICAL STATEMENTS
smokers who had secondhand smoke expo- ated with risk of stroke in older age, including in
AND GUIDELINES
sure during adulthood (95% CI, 2%–67%).141 models that were adjusted for the interim devel-
— Data from another large-scale prospective opment of stroke risk factors such as DM, hyper-
cohort study of females in Japan showed tension, and AF.148
that secondhand tobacco smoke exposure • Similarly, a prospective study of young Swedish
at home during adulthood was associated males demonstrated that the highest compared
with an increased risk of stroke mortality in with the lowest tertile of fitness (HR, 1.70; 95%
those aged ≥80 years (HR, 1.24; 95% CI, CI, 1.50–1.93) and lower muscle strength (HR,
1.05–1.46). Overall, the increased risk was 1.39; 95% CI, 1.27–1.53) were associated with
most evident for SAH (HR, 1.66; 95% CI, higher risk of stroke over 42 years of follow-up.149
1.02–2.70) in all age groups.142 • Several recent prospective studies found associa-
— A study using NHANES data found that indi- tions of PA and stroke risk in females.
viduals with a prior stroke have a greater — In the Million Women Study, a prospective
odds of having been exposed to secondhand cohort study among females in England and
smoke (OR, 1.46; 95% CI, 1.05–2.03), and Scotland, over an average follow-up of 9
secondhand smoke exposure was associated years, self-report of any PA at baseline was
with a 2-fold increase in mortality among associated with reduced risk of any stroke,
stroke survivors compared with stroke sur- as well as stroke subtypes; however, more
vivors without the exposure (age-adjusted frequent or strenuous activity was not asso-
mortality rate: 96.4±20.8 versus 56.7±4.8 ciated with increased protection against
per 100 person-years; P=0.026).143 stroke.150
• The FINRISK study found a strong association — Similarly, a low level of leisure-time PA was
between current smoking and SAH compared associated with a 1.5 times higher risk of
with nonsmokers (HR, 2.77; 95% CI, 2.22–3.46) stroke and a 2.4 times higher risk of fatal
and reported a dose-dependent and cumulative stroke compared with intermediate to high
association with SAH risk that was highest in levels of activity in a cohort of ≈1500 Swedish
females who were heavy smokers.144 females followed up for up to 32 years.151
— The EPIC-Heidelberg cohort included 25 000

Physical Inactivity males and females and identified stroke out-
(See Chapter 4 for more information.) comes over a mean of 13 years of follow-up.
• Over a mean follow-up of 17 years, the ARIC Among females, participation in any level of
study found a significant trend among African- PA was associated with a nearly 50% reduc-
Americans toward reduced incidence of stroke
tion in stroke risk compared with inactivity;
with increasing level of PA; a similar trend was
no similar pattern was seen for males.152
observed for whites in the study, although it was
• A dose-response effect was seen for total number
not statistically significant. Data from this study
of hours spent walking per week, and increased
showed that although the highest levels of activ-
walking time was associated with reduced risk of
ity were most protective, even modest levels of PA
incident stroke among 4000 males in the British
appeared to be beneficial.145
Regional Heart Study. Those reporting ≥22 hours of
• Among individuals >80 years of age in NOMAS,
walking per week had one third the risk of incident
physical inactivity was associated with higher risk
stroke as those who walked <4 hours per week.
of stroke (physical inactivity versus PA: HR, 1.60;
No clear association between stroke and walking
95% CI, 1.05–2.42).146
speed or distance walked was seen in this study.153
• In the CHS, a greater amount of leisure-time PA
• Recent studies have also demonstrated a signifi-
(across quintiles, Ptrend=0.001), as well as exer-
cant association between sedentary time duration
cise intensity (categories: high, moderate, low
and risk of CVD including stroke, independent of
versus none, Ptrend<0.001), were both associated
PA levels.154,155 In the REGARDS study, screen time
with lower risk of stroke among individuals >65
>4 h/d was associated with 37% higher risk (HR,
years of age. The relation between greater PA and
1.37; 95% CI, 1.10–1.71) of stroke over a 7-year
lower risk of stroke was even observed in indi-
follow-up.156
viduals ≥75 years of age.
• In the Cooper Center Longitudinal Study of partic- Nutrition
ipants who underwent evaluation at the Cooper (See Chapter 5 for more information.)
Clinic in Dallas, TX, investigators found that car- • Adherence to a Mediterranean-style diet that was
diorespiratory fitness in mid-life as measured by higher in nuts and olive oil was associated with a

reduced risk of stroke (diet with nuts: HR, 0.54; RR estimate for stroke (0.91 [95% CI, 0.83–0.99]
CLINICAL STATEMENTS
95% CI, 0.35–0.84; diet with olive oil: HR, 0.67; and 0.69 [95% CI, 0.60–0.81], respectively).165
AND GUIDELINES
95% CI, 0.46–0.98; Mediterranean diets com- • A meta-analysis of 20 prospective cohort studies
bined versus control: HR, 0.61; 95% CI, 0.44– of the association between nut consumption and
0.86) in an RCT conducted in Spain.156 cardiovascular outcomes (N=467 389) revealed no
• In the Nurses Health and Health Professionals association between nut consumption and stroke
Follow-up Studies, each 1-serving increase in (2 studies; RR, 1.05 [95% CI, 0.69–1.61]) but did
sugar-sweetened soda beverage was associated find an association with stroke mortality (3 stud-
with a 13% increased risk of ischemic stroke, and ies; RR, 0.83 [95% CI, 0.69–1.00]).166
each 1-serving increase in low-calorie or diet soda • A meta-analysis of 8 prospective studies
was associated with a 7% increased risk of isch- (N=410 921) revealed no significant association
emic stroke and a 27% increased risk of hemor- between consumption of refined grains and risk
rhagic stroke.158 of stroke.167 A second meta-analysis of 8 prospec-
• A meta-analysis of >94 000 people with 34 817 tive studies (N=468 887) revealed that a diet that
stroke events demonstrated that eating ≥5 serv- contained greater amounts of legumes was not
ings of fish per week versus eating <1 serving per associated with a lower risk of stroke; however,
week was associated with a 12% reduction in a diet with greater amounts of nuts was associ-
stroke risk; however, these results were not con- ated with lower risk of stroke (summary RR, 0.90;
sistent across all cohort studies.159 95% CI, 0.81–0.99). Sex significantly modified
• According to registry data from Sweden, people the effects of nut consumption on stroke risk, and
eating ≥7 servings of fruits and vegetables per high nut intake was associated with reduced risk
day had a 19% reduced risk of stroke com- of stroke in females (summary RR, 0.85; 95% CI,
pared with those eating only 1 serving per day 0.75–0.97) but not in males (summary RR, 0.95;
among people who did not have hyperten- 95% CI, 0.82–1.11).168
sion.160 Results from 2 prospective cohorts from • A meta-analysis of 21 studies (N=13 033) evaluat-
Sweden, comprising 74 404 males and females ing the effect of vitamin D on cardiovascular out-
45 to 83 years of age free of stroke at base- comes revealed that vitamin D supplementation
line, found that high adherence to the modified was not associated with a lower risk of stroke (HR,
DASH diet is associated with a reduced risk of 1.07; 95% CI, 0.91–1.29).169
ischemic stroke (RR, 0.86; 95% CI, 0.78–0.94 • A meta-analysis of 14 cohorts (N=333 250)
for the highest versus lowest quartile of diet revealed that potassium intake is associated with
adherence).161 A Nordic diet, including fish, lower risk of stroke (RR, 0.80; 95% CI, 0.72–0.90).
apples and pears, cabbages, root vegetables, In addition, the dose-response analysis showed
rye bread, and oatmeal, was associated with a that for every 1 g/d (25.6 mmol/d) increase in
decreased risk of stroke among 55 338 males vitamin K intake, there was a 10% reduction in
and females (HR, 0.86; 95% CI, 0.76–0.98 for stroke risk (RR, 0.90; 95% CI, 0.84–0.96).170
high versus low diet adherence).162 • A meta-analysis of 8 studies (N=280 174) indi-
• A meta-analysis of case-control, prospective cated an inverse association between flavonol
cohort studies and an RCT investigating the asso- intake and stroke (summary RR, 0.86; 95% CI,
ciation between olive oil consumption and the 0.75–0.99). An increase in flavonol intake of
risk of stroke (N=38 673 participants) revealed 20 mg/d was associated with a 14% decrease
a reduction in stroke risk (RR, 0.74; 95% CI, in the risk for developing stroke (summary RR,
0.60–0.92).163 0.86; 95% CI, 0.77–0.96). Subgroup analy-
• A meta-analysis of 10 prospective cohort stud- ses suggested an inverse association between
ies including 314 511 nonoverlapping individu- highest flavonol intake and stroke risk among
als revealed that higher monounsaturated fatty males (summary RR, 0.74; 95% CI, 0.56–0.97)
acid intake was not associated with risk of but not females (summary RR, 0.99; 95% CI,
overall stroke (RR, 0 .86; 95% CI, 0.74–1.00) 0.85–1.16).171
or risk of ischemic stroke (RR, 0.92; 95% CI, • In a population of Chinese adults, folate therapy
0.79–1.08) but was associated with a reduced combined with enalapril was associated with a
risk of hemorrhagic stroke (RR, 0.68; 95% CI, significant reduction in ischemic stroke risk (HR,
0.49–0.96).164 0.76; 95% CI, 0.64–0.91). Although the US pop-
• A meta-analysis of prospective cohort studies ulation is not as likely to be at risk of folate defi-
evaluating the impact of dairy intake on CVD ciency because of folate fortification of grains,
noted that total dairy intake and calcium from this study demonstrates the importance of ade-
dairy were associated with an inverse summary quate folate levels for stroke prevention.172

• A study using Framingham data found that recent elasticum, and mitochondrial myopathy,
CLINICAL STATEMENTS
consumption and an increased cumulative intake encephalopathy, lactic acidosis, and stroke
AND GUIDELINES
of artificially sweetened soft drinks was associ- (MELAS).177
ated with a higher risk of stroke, with the stron- • ICH also appears to have a genetic compo-
gest association observed for ischemic stroke; no nent, with heritability estimates of 34% to 74%
association was observed for sugary beverages or depending on the subtype.183 A GWAS of ICH
sugar-sweetened soft drinks.173 suggests that 15% of this heritability is attrib-
utable to genetic variants in the apolipoprotein
Family History and Genetics
E (APOE) gene and 29% is attributable to non-
• Ischemic stroke is a heritable disease; family his-
APOE genetic variants.183
tory of stroke is associated with increased risk
• Genetic variants that predispose to hypertension
of ischemic stroke, stroke subtypes, and carotid
also have been associated with ICH risk.184 The
atherosclerosis.174
other strongest genes associated with ICH are
• In the Family Heart Study, the adjusted ORs of
PMF1 and SLC25A44, which have been linked
stroke for a positive paternal and maternal his-
to ICH with small-vessel disease.185,186 Additional,
tory of stroke were 2.0 and 1.4, respectively, with
larger GWAS are necessary to understand the full
similar patterns seen in African Americans and
genetic architecture of ICH risk.
European Americans.175
• Genetic factors appear to be more important in Kidney Disease
large-artery and small-vessel stroke than in cryp- (See Chapter 11 for more information.)
togenic or cardioembolic stroke.176 • A meta-analysis of 21 studies including >280 000
• Genetic studies have identified genetic variants patients showed a 43% (RR, 1.43; 95% CI,
associated with risk of ischemic stroke, with dis- 1.31–1.57) increased incident stroke risk among
tinct genetic associations177 for different stroke patients with a GFR <60 mL·min−1·1.73 m−2.187
subtypes. • A meta-analysis showed that a higher albumin-
— For example, variants in the paired-like home- uria level confers greater stroke risk, providing evi-
odomain transcription factor 2 (PITX2) gene dence that albuminuria is strongly linked to stroke
discovered through an unbiased genome- risk, and suggested that people with elevated
wide approach for AF have been shown to levels of urinary albumin excretion could benefit
be associated with cardioembolic stroke.178 from more intensive vascular risk reduction.188
— Variants in the chromosome 9p21 locus iden- • A meta-analysis showed stroke risk increases lin-
tified through a genome-wide approach for early and additively with declining GFR (RR per 10
CAD have been shown to be associated with mL·min−1·1.73 m−2 decrease in GFR, 1.07; 95%
large-artery stroke. CI, 1.04–1.09) and increasing albuminuria (RR
• GWAS have identified a small number of addi- per 25 mg/mmol increase in ACR, 1.10; 95% CI,
tional new genes associated with stroke, including 1.01–1.20), which indicates that CKD staging
histone deacetylase (HDAC9), which is associated might also be a useful clinical tool to identify peo-
with large-artery stroke,179 and a region on chro- ple who might benefit most from interventions to
mosome 12q24 associated with all types of isch- reduce stroke risk.189
emic stroke that has also been associated with • A pooled analysis of 4 prospective community-
other cardiovascular risk factors.180 based cohorts (ARIC, MESA, CHS, and PREVEND)
• Monogenic forms of ischemic stroke have much including 29 595 participants showed that low
higher risk associated with the underlying genetic eGFR (45 mL·min−1·1.73 m−2) was significantly
variant but are rare.181 associated with increased risk of ischemic stroke
— For example, cerebral autosomal dominant (HR, 1.30; 95% CI, 1.01–1.68) but not hemor-
arteriopathy with subcortical infarcts and leu- rhagic stroke (HR, 0.92; 95% CI, 0.47–1.81) com-
koencephalopathy (CADASIL), an autosomal pared with normal GFR (95 mL·min−1·1.73 m−2). A
dominant disease presenting with stroke, high ACR of 300 mg/g was associated with both
progressive cognitive impairment, and char- ischemic stroke (HR, 1.62; 95% CI, 1.27–2.07)
acteristic bilateral involvement of the anterior and hemorrhagic stroke (HR, 2.57; 95% CI, 1.37–
temporal white matter and external capsule, 4.83) compared with 5 mg/g.190
is caused by mutations in NOTCH3.182 • Among patients registered in the Scottish Stroke
— Other monogenic causes of stroke include Care Audit, 32% of the 2520 stroke patients
Fabry disease, sickle cell disease, homocys- admitted to 2 teaching hospitals over 3 years had
tinuria, Marfan syndrome, vascular Ehlers- renal dysfunction (eGFR <45 mL·min−1·1.73 m−2).
Danlos syndrome (type IV), pseudoxanthoma Stroke patients admitted with renal dysfunction

were more likely to die in the hospital (OR, 1.59; the combined pregnancy/postpregnancy period
CLINICAL STATEMENTS
95% CI, 1.26–2.00).191 was 8.1 per 100 000 pregnancies.212

AND GUIDELINES
• Proteinuria and albuminuria are better predictors • Analyses of the US NIS from 1994 to 1995 and
of stroke risks than eGFR in patients with kidney from 2006 to 2007 showed a temporal increase
disease.192 in the proportion of pregnancy hospitalizations
that were associated with a stroke, with a 47%
increase for antenatal hospitalizations and an
Risk Factor Issues Specific to Females 83% increase for postpartum hospitalizations.
See the “Guidelines for the Prevention of Stroke in Increases in the prevalence of HD and hyper-
Women: a Statement for Healthcare Professionals tensive disorders accounted for almost all the
From the American Heart Association/American Stroke increase in postpartum stroke hospitalizations but
Association” for more in-depth coverage of stroke risk not the antenatal stroke hospitalizations.113
factors unique to females.193 • Preeclampsia is a risk factor for ischemic stroke
• On average, females are ≈4 years older at stroke remote from pregnancy.168 The increase in stroke
onset than males (≈75 years compared with 71 risk related to preeclampsia could be mediated by
years).194 later risk of hypertension and DM.213 A case-con-
• In the setting of AF, females have a significantly trol study of females aged 12 to 55 years admit-
higher risk of stroke than males.195–199 ted to New York State hospitals found several
• Analysis of data from the FHS found that females factors increased the risk of pregnancy-associated
with natural menopause before 42 years of age stroke in females with preeclampsia, including
had twice the ischemic stroke risk of females with infections present on admission (OR, 3.0; 95% CI,
natural menopause after 42 years of age; how- 1.6–5.8), prothrombotic states (OR, 3.5; 95% CI,
ever, no association was found between age at 1.3–9.2), coagulopathies (OR, 3.1; 95% CI, 1.3–
natural menopause and risk of ischemic or hem- 7.1), and chronic hypertension (OR, 3.2; 95% CI,
orrhagic stroke in the Nurses’ Health Study.200 1.8–5.5).214
• Overall, randomized clinical trial data indicate
that the use of estrogen plus progestin, as well
as estrogen alone, increases stroke risk in post- Sleep-Disordered Breathing and Sleep
menopausal, generally healthy females and pro- Duration
vides no protection for postmenopausal females • In the Wisconsin Sleep Cohort Study, for the time
with established CHD201–204 and recent stroke period 2001 to 2010, the prevalence of sleep-
or TIA.205 disordered breathing, defined as an AHI ≥5, was
• In a nested case-control study of the United estimated to be 34% for males and 17% for
Kingdom’s General Practice Research Database, females aged 30 to 70 years.215
stroke risk was not increased for users of low- • In the MESA Sleep Cohort, the prevalence of mild
dose (≤50 µg) estrogen patches (RR, 0.81; 95% (AHI 5–14), moderate (AHI 15–29), and severe (AHI
CI, 0.62–1.05) but was increased for users of ≥30) sleep-disordered breathing was estimated to
high-dose (>50 µg) patches (RR, 1.89; 95% CI, be 32.6%, 17.9%, and 12.4% in whites; 31.1%,
1.15–3.11) compared with nonusers.206 17.5%, and 14.9% in blacks; 33.3%, 20.5%,
• Low-estrogen-dose oral contraceptives are associ- and 17.7% in Hispanics; and 27.0%, 21.6%, and
ated with a 93% increased risk of ischemic stroke, 17.8% in Chinese. After accounting for sex, age,
but the absolute increased risk is small (4.1 isch- and study site, blacks had greater odds of sleep
emic strokes per 100 000 nonsmoking, normo- apnea syndrome (AHI ≥5 and Epworth Sleepiness
tensive females).207–209 Scale score >10) than whites, and Hispanics had
• Migraine with aura is associated with ischemic greater odds of mild, moderate, and severe sleep-
stroke in younger females, particularly if they disordered breathing than whites.216
smoke or use oral contraceptives. The combi- • Obstructive sleep apnea is common after stroke,
nation of all 3 factors increases the risk ≈9-fold with prevalence >50%.217–219
compared with females without any of these • In the BASIC Project, Mexican Americans had a
factors.210,211 higher prevalence of poststroke sleep-disordered
• In the Baltimore-Washington Cooperative Young breathing, defined as an AHI ≥10, than NH whites
Stroke Study, the risk of ischemic stroke or ICH after adjustment for confounders (prevalence
during pregnancy and the first 6 weeks after giv- ratio, 1.21; 95% CI, 1.01–1.46).219
ing birth was 2.4 times greater than for nonpreg- • In the BASIC Project, acute infarction involving
nant females of similar age and race. The excess the brainstem (versus no brainstem involvement)
risk of stroke (all types except SAH) attributable to was associated with the odds of sleep-disordered

breathing, defined as an AHI ≥10, with an OR of subsequent stroke after adjustment for potential
CLINICAL STATEMENTS
3.76 (95% CI, 1.44–9.81) after adjustment for confounding factors (pooled RR, 1.34; 95% CI,
AND GUIDELINES
demographics, risk factors, and stroke severity.219a 1.17–1.54); however, substantial between-study
In this same study, ischemic stroke subtype was heterogeneity was noted. Associations were simi-
not found to be associated with the presence or lar for males and females.231
severity of sleep-disordered breathing.220 • A meta-analysis of 28 prospective cohort studies
• Obstructive sleep apnea is associated with higher comprising 317 540 participants with a follow-
poststroke mortality221–223 and worse functional up period that ranged from 2 to 29 years found
outcome.224 that depression was associated with an increased
• In a meta-analysis of 11 studies, long sleep, mostly risk of total stroke (pooled HR, 1.45; 95% CI,
defined as self-reported sleep of ≥8 to 9 hours per 1.29–1.63), fatal stroke (pooled HR, 1.55; 95%
night, was associated with incident stroke, with CI, 1.25–1.93), and ischemic stroke (pooled HR,
an HR of 1.45 (95% CI, 1.30–1.62) after adjust- 1.25; 95% CI, 1.11–1.40).232
ment for demographics, vascular risk factors, and • Several meta-analyses have revealed that ≈1
comorbidities.225 In this same meta-analysis, short of every 3 stroke survivors develops poststroke
sleep, defined as sleep ≤5 to 6 hours per night, depression. The most recent meta-analysis involv-
was also associated with incident stroke (HR, ing 61 studies (N=25 488) revealed similar results,
1.15; 95% CI, 1.07–1.24) after adjustment for with depression being present in 33% (95% CI,
similar factors. 26%–39%) of patients at 1 year after stroke,
• In a recent meta-analysis of 10 studies, a J-shaped with a decline beyond 1 year to 25% (95% CI,
relationship was reported between sleep duration 16%–33%) up to 5 years and 23% (95% CI,
and stroke risk, with the lowest risk among those 14%–31%) at 5 years.233
with a sleep duration of 6 to 7 h/d.226 • Poststroke depression is associated with higher
mortality. A meta-analysis of 13 studies involv-
ing 59 598 individuals revealed a pooled OR
Psychosocial Factors for mortality at follow-up of 1.22 (95% CI,
• Approximately one third of stroke survivors 1.02–1.47).234
develop poststroke depression, and the frequency • Twelve RCTs (N=1121 subjects) suggested that
is highest in the first year after a stroke.227 antidepressant medications might be effective in
• Among 6019 adults followed up for a mean of treating poststroke depression, with a beneficial
16.3 years from the first NHANES, higher levels of effect of antidepressants on remission (pooled OR
anxiety symptoms were associated with increased for meeting criteria for depression: 0.47; 95% CI,
risk of incident stroke after adjustment for demo- 0.22–0.98) and response, measured as a >50%
graphic, cardiovascular, and behavioral risk factors reduction in mood scores (pooled OR, 0.22; 95%
(HR, 1.14; 95% CI, 1.03–1.25). This association CI, 0.09–0.52).235
remained significant with further adjustment for • Seven trials (N=775 subjects) suggested that
depressive symptoms.228 brief psychosocial interventions could be use-
• In the Chicago Health and Aging Project, higher ful and effective in treatment of poststroke
psychological distress was associated with higher depression.235–239
stroke mortality (HR, 1.29; 95% CI, 1.10–1.52) • A meta-analysis of 8 RCTs assessing the efficacy of
and incident hemorrhagic strokes (HR, 1.70; preventive pharmacological interventions among
95% CI, 1.28–2.25) among 4120 adults after 776 initially nondepressed stroke patients revealed
risk adjustment for age, sex, race, and stroke risk that the likelihood of developing poststroke
factors.229 depression was reduced among subjects receiving
• Depression was associated with a nearly 2-fold active pharmacological treatment (OR, 0.34; 95%
increased odds of stroke after adjustment for CI, 0.22–0.53), especially after a 1-year treatment
age, SES, lifestyle, and physiological risk factors (OR, 0.31; 95% CI, 0.18–0.56) and with the use
(OR, 1.94; 95% CI, 1.37–2.74) in a cohort of of a selective serotonin reuptake inhibitor (OR,
10 547 females aged 47 to 52 years who were 0.37; 95% CI, 0.22–0.61). All studies excluded
followed up for 12 years as part of the Australian those with aphasia or significant cognitive impair-
Longitudinal Study on Women’s Health.230 ment, which limits their generalizability.240
• In a meta-analysis of 17 community-based or • Five RCTs (N=1078 subjects) suggested that
population-based prospective studies published psychosocial therapies could prevent the devel-
between 1994 and 2010 involving 206 641 partic- opment of poststroke depression; however,
ipants, people with a history of depression expe- the studies were limited by heterogeneity in
rienced a 34% higher risk for the development of design, analysis, inclusion and exclusion criteria,

inadequate concealment of randomization, and knowledge for both sexes, whereas age <35 years
CLINICAL STATEMENTS
high numbers of dropouts.235,241 versus 35 to 54 years and Hispanic ethnicity were

AND GUIDELINES
• A meta-analysis of 14 studies revealed a 33% associated with poor stroke knowledge only for
(95% CI, 17%–50%) increased risk of total stroke females. Sudden confusion or difficulty speak-
for those with general or work stress and those ing and sudden numbness or weakness of the
who experienced stressful life events, although face, arm, or leg were the most commonly cor-
there was significant statistical heterogeneity rectly identified stroke symptoms, whereas sud-
between studies.242 Among 10 studies reporting den headache was the least; 60% of females and
sex-specific analyses, 6 of 7 showed a positive 58% of males incorrectly identified sudden chest
association, with a pooled HR of 1.24 (95% CI, pain as a stroke symptom.
1.12–1.36 for males); 3 studies reporting results • In a study of patients with AF, there was a lack
for females only showed a pooled HR of 1.90 of knowledge about stroke subtypes, com-
(95% CI, 1.40–2.56), and 1 case-control study mon symptoms of stroke, and the increased risk
showed no difference by sex. of stroke associated with AF.249 Only 68% of
patients without a prior stroke history were able
to identify the most common symptoms of stroke.
Awareness of Stroke Warning Signs Approximately half of patients were satisfied with
and Risk Factors the information provided by their physician about
• Several studies have demonstrated low knowl- AF, and there was a disconnect between patient
edge regarding risk factors for stroke in blacks, and physician perspectives related to conversa-
particularly in relation to hypertension, whereas tions about AF and stroke and patient willingness
stress is often identified as a major risk factor to comply with treatment recommendations.
for stroke instead.243,244 Although data are more • Among 2975 stroke/TIA cases in the GCNKSS,
limited, knowledge on stroke risk factors and symptoms of weakness, decreased level of con-
symptoms is also limited in children, with stroke sciousness, speech/language abnormalities, and
knowledge lowest for those living in communi- dizziness increased the odds that 9-1-1 was called
ties with greater economic need and sociodemo- for emergency transport to the hospital, indepen-
graphic distress and lower school performance.245 dent of age, prior stroke, location of patients,
stroke subtype, stroke severity, and prestroke dis-
• A study of CVD awareness performed by the

AHA among females in the United States who ability. Numbness and vision disturbances were
were >75 years old (N=1205) showed that low associated with decreased odds of calling 9-1-1;
proportions of females identified severe head- headache was not associated with 9-1-1 use.250
ache (23%), unexplained dizziness (20%), and • A systematic review of 18 studies from 8 coun-
vision loss/changes (18%) as stroke warning tries concluded that general stroke knowledge
symptoms.246 and awareness of stroke symptoms were limited
• Further research is required to identify interven- for many stroke survivors.251 Room for improve-
tions aimed at improving stroke literacy, as well as ment in the knowledge of stroke risk factors was
whether these interventions translate to improved also noted, with 1 study finding no difference
risk factor control and earlier arrival to the hospi- in knowledge when comparing those with and
tal for acute stroke care. without a prior stroke/TIA.
• In a single-center study of 144 stroke survivors,
Hispanics scored lower on a test of stroke symp-
Complications and Recovery
toms and the appropriate response to those
symptoms than NH whites (72.5% versus 79.1% (See Charts 13-7 through 13-9)
of responses correct) and were less often aware • Stroke is a leading cause of serious long-term
of tPA as a treatment for stroke (91.5% versus disability in the United States (Survey of Income
79.2%).247 and Program Participation, a survey of the US
• In the 2009 BRFSS (N=132 604), 25% of males Census Bureau).252 About 3% of males and 2% of
versus 21% of females had low stroke symptom females reported that they were disabled because
knowledge scores (correct response to 0–4 of of stroke.
the 7 survey questions).248 After adjustment for • On the basis of pooled data from several large
sociodemographic factors and having a primary studies, the probability of death within 1 year or 5
care physician, males were 36% more likely to years after a stroke was highest in individuals 75
have low scores than females (OR, 1.36; 95% CI, years of age or older (Charts 13-7 and 13-8). The
1.28–1.45). Age >75 years, nonwhite race, and probability of death within 1 year of a stroke was
lower income were associated with poor stroke lowest in black males aged 45 to 64 years (Chart

13-7). The probability of death within 5 years of a controlling for stroke severity and comparable
CLINICAL STATEMENTS
stroke was lowest for white males aged 45 to 64 rehabilitation use.259
AND GUIDELINES
years (Chart 13-9). • In a study of 90-day poststroke outcomes among
• On the basis of pooled data from several large ischemic stroke patients in the BASIC Project,
studies, the probability of death with recurrent Mexican Americans scored worse on neurologi-
stroke in 5 years after a stroke was lowest for cal, functional, and cognitive outcomes than NH
black males 45 to 64 years of age and highest whites after multivariable adjustment.260
for black females 65 to 74 years of age (Chart
13-9).
• Stroke was among the top 18 diseases contribut- Stroke in Children
ing to years lived with disability in 2010; of these • On the basis of pathogenic differences, pediat-
18 causes, only the age-standardized rates for ric strokes are typically classified as either peri-
stroke increased significantly between 1990 and natal (occurring at ≤28 days of life and including
2010 (P<0.05).253 in utero strokes) or (later) childhood. Presumed
• In data from 2011, 19% of Medicare patients perinatal strokes are children with no symptoms
were discharged to inpatient rehabilitation facili- in the newborn period presenting with hemi-
ties, 25% were discharged to skilled nursing facil- paresis or other neurological symptoms later in
ities, and 12% received home health care.253a infancy.
• The 30-day readmission rate for Medicare fee-for- • The prevalence of perinatal strokes is 29 per
service beneficiaries with ischemic stroke in 2006 100 000 live births, or 1 per 3500 live births in
was 14.4%.254 the 1997 to 2003 Kaiser Permanente of Northern
• The 30-day hospital readmission rate after dis- California population.261
charge from postacute rehabilitation for stroke • A history of infertility, preeclampsia, prolonged
was 12.7% among fee-for-service Medicare rupture of membranes, and chorioamnionitis
patients. The mean rehabilitation length of stay are independent maternal risk factors for peri-
for stroke was 14.6 days.255 natal arterial ischemic stroke.262 However, mater-
• After stroke, females often have greater disability nal health and pregnancies are normal in most
than males. For example, an analysis of commu- cases.263
nity-living adults (>65 years of age) found that • Diagnostic delays are more common in isch-
females were half as likely to be independent in emic than hemorrhagic stroke in children, with a
activities of daily living after stroke, even after median time from symptom onset to diagnostic
controlling for age, race, education, and marital neuroimaging of 3 hours for hemorrhagic and 24
status.256 hours for ischemic stroke in a population-based
• A meta-analysis of >25 studies examining sex dif- study from the south of England.264
ferences in long-term outcomes among stroke • The most common cause of arterial ischemic
survivors found that females tended to have stroke in children is a cerebral arteriopathy, found
worse functional recovery and hence greater in more than half of all cases.265,266 Childhood
long-term disability and handicap. However, con- arteriopathies are heterogeneous and can be dif-
fidence in these conclusions was limited by the ficult to distinguish from a partially thrombosed
quality of the studies and variability in the statisti- artery in the setting of a cardioembolic stroke;
cal approach to confounding.257 incorporation of clinical data and serial vascular
• A national study of inpatient rehabilitation after imaging is important for diagnosis.267
first stroke found that blacks were younger, had • In a retrospective population-based study in
a higher proportion of hemorrhagic stroke, and northern California, 7% of childhood ischemic
were more disabled on admission. Compared strokes and 2% of childhood hemorrhagic strokes
with NH whites, blacks and Hispanics also had were attributable to congenital heart defects.
a poorer functional status at discharge but were Congenital heart defects increased a child’s risk
more likely to be discharged to home rather than of stroke 19-fold (OR, 19; 95% CI, 4.2–83). The
to another institution, even after adjustment for majority of children with stroke related to congen-
age and stroke subtype. After adjustment for ital heart defects were outpatients at the time of
the same covariates, compared with NH whites, the stroke.268 In a single-center Australian study,
blacks also had less improvement in functional infants with cyanotic congenital heart defects
status per inpatient day.258 undergoing palliative surgery were the highest-
• Blacks were less likely to report independence in risk group to be affected by arterial ischemic
activities of daily living and instrumental activities stroke during the periprocedural period; stroke
of daily living than whites 1 year after stroke after occurred in 22 per 2256 cardiac surgeries (1%).269

• In another study of the same northern Californian diminished since 1998 when the STOP trial was
CLINICAL STATEMENTS
population, adolescents with migraine had a published, which established a method for pri-
AND GUIDELINES
3-fold increased odds of ischemic stroke com- mary stroke prevention in children with sickle cell
pared with those without migraine (OR, 3.4; 95% disease.280
CI, 1.2–9.5); younger children with migraine had • Among young adult survivors of childhood stroke,
no significant difference in stroke risk.270 37% had a normal modified Rankin score, 42%
• In a post hoc analysis, head or neck trauma in the had mild deficits, 8% had moderate deficits, and
prior week was a strong risk factor for childhood 15% had severe deficits.281 Concomitant involve-
arterial ischemic stroke (adjusted OR, 36; 95% CI, ment of the basal ganglia, cerebral cortex, and
5–281), present in 10% of cases.271 posterior limb of the internal capsule predicts a
• Exposure to minor infection in the prior month persistent hemiparesis.282
was also associated with stroke and was present • Survivors of childhood arterial ischemic stroke
in one third of cases (adjusted OR, 3.9; 95% CI, have, on average, low-normal cognitive per-
2.0–7.4).271 The effect of infection on pediatric formance,283,284 with poorest performance in
stroke risk is short-lived, lasting for days; 80% of visual-constructive skills, short-term memory, and
infections preceding childhood stroke are respira- processing speed. Younger age at stroke and
tory.272 A prospective study of 355 children with seizures, but not laterality of stroke (left versus
acute stroke serological evidence of acute herpes right), predict worse cognitive outcome.284
virus infection doubled the odds of childhood • Compared with referent children with asthma,
acute ischemic stroke, even after adjusting for childhood stroke survivors have greater impair-
age, race, and SES (OR, 2.2; 95% CI, 1.2–4.0; ments in adaptive behaviors, social adjustment,
P=0.007).273 Among 187 cases with acute and and social participation, even if their IQ is nor-
convalescent blood samples, 85 (45%) showed mal.285 Severity of disability after perinatal stroke
evidence of acute herpes virus infection; herpes correlates with maternal psychosocial outcomes
simplex virus 1 was found most often. Most infec- such as depression and quality of life.286
tions were asymptomatic. • Despite current treatment, at least 1 of 10 chil-
• Thrombophilias (genetic and acquired) are risk dren with ischemic or hemorrhagic stroke will
factors for childhood stroke, with summary ORs have a recurrence within 5 years.287,288 Of 355
ranging from 1.6 to 8.8 in a meta-analysis.274 In children with stroke followed up prospectively as
contrast, a population-based, controlled study part of a multicenter study with a median follow-
suggests minimal association between perinatal up of 2 years, the cumulative stroke recurrence
stroke and thrombophilia,275 and therefore, rou- rate was 6.8% (95% CI, 4.6%–10%) at 1 month
tine testing is not recommended in very young and 12% (CI, 8.5%–15%) at 1 year.42 The sole
children. predictor of recurrence was the presence of an
• In a prospective Swiss registry,276 atherosclerotic arteriopathy, which increased the risk of recur-
risk factors were less common in children with rence 5-fold compared with an idiopathic acute
arterial ischemic stroke than in young adults; the ischemic stroke (HR, 5.0; 95% CI, 1.8–14). In a
most common of these factors in children was retrospective cohort, with a cerebral arteriopathy,
hyperlipidemia (15%). However, an analysis of the 5-year recurrence risk was as high as 60%
the NIS suggests a low but rising prevalence of among children with abnormal arteries on vascu-
these factors among US adolescents and young lar imaging.289 The recurrence risk after perinatal
adults hospitalized for ischemic stroke (1995 ver- stroke, however, was negligible.289
sus 2008).277 • Among 59 long-term survivors of pediatric
• Compared with girls, US boys have a 25% brain aneurysms, 41% developed new or recur-
increased risk of ischemic stroke and a 34% rent aneurysm during a median follow-up of 34
increased risk of ICH, whereas a study in the years; of those, one third developed multiple
United Kingdom found no sex difference in aneurysms.290
childhood ischemic stroke.278 Compared with • More than 25% of survivors of perinatal ischemic
white children, black children in both the United strokes develop delayed seizures within 3 years;
States and United Kingdom have a >2-fold risk babies with larger strokes are at higher risk.291
of stroke.279 The increased risk among blacks is The cumulative risk of delayed seizures after later
not fully explained by the presence of sickle cell childhood stroke is 13% at 5 years and 30% at
disease, nor is the excess risk among boys fully 10 years.292 Children with acute seizures (within
explained by trauma.279 7 days of their stroke) have the highest risk for
• The excess ischemic stroke mortality in US black delayed seizures, >70% by 5 years after the
children compared with white children has stroke.293 In survivors of ICH in childhood, 13%

developed delayed seizures and epilepsy with 2 person-years in the period 1995 to 1999 to 23.6
CLINICAL STATEMENTS
years.294 Elevated intracranial pressure requiring strokes per 100 000 person-years from 2010
AND GUIDELINES
acute intervention at the time of acute ICH is a to 2014 (rate ratio, 2.47; 95% CI, 2.07–2.96;
risk factor for delayed seizures and epilepsy. P<0.0001).302 Rates of stroke in those aged 40 to
• Pediatric stroke teams and stroke centers295 are 44, 45 to 49, and 50 to 54 years also increased
developing worldwide. In a study of 124 children significantly. Strokes rates in those >55 years of
presenting to a children’s hospital ED with stroke age decreased during these time periods.
symptoms where a “stroke alert” was paged, • Vascular risk factors are common among stroke
24% had a final diagnosis of stroke, 2% were patients aged 20 to 54 years. During 2005, in
TIAs, and 14% were other neurological emer- the biracial GCNKSS, hypertension prevalence
gencies, which underscores the need for prompt was estimated at 52%, hyperlipidemia at 18%,
evaluation of children with “brain attacks.”296 DM at 20%, CHD at 12%, and current smoking
Implementation of a pediatric stroke clinical path- at 46% among stroke patients 20 to 54 years of
way improved time to MRI from 17 hours to 4 age.194
hours at 1 center.297 • In the FUTURE study, the 30-day case fatality
• In a study of 111 pediatric stroke cases admit- rate among stroke patients 18 to 50 years of age
ted to a single US children’s hospital, the median was 4.5%. One-year mortality among 30-day
1-year direct cost of a childhood stroke (inpatient survivors was 1.2% (95% CI, 0.0%–2.5%) for
and outpatient) was ≈$50 000, with a maximum TIA, 2.4% (95% CI, 1.2%–3.7%) for ischemic
approaching $1 000 000. More severe neurologi- stroke, and 2.9% (95% CI, 0.0%–6.8%) for
cal impairment after a childhood stroke correlated ICH.303
with higher direct costs of a stroke at 1 year and • In the FUTURE study, after a mean follow-up of
poorer quality of life in all domains.298 13.9 years, 44.7% of young stroke patients had
• A prospective study at 4 centers in the United poor functional outcome, defined as a modified
States and Canada found that the median Rankin score >2. The strongest baseline predictors
1-year out-of-pocket cost incurred by the fam- of poor outcome were female sex (OR, 2.7; 95%
ily of a child with a stroke was $4354 (maximum CI, 1.5–5.0) and baseline NIHSS (OR, 1.1; 95% CI,
$38 666), which exceeded the median American 1.1–1.2 per point increase).304
household cash savings of $3650 at the time of

the study and represented 6.8% of the family’s
annual income.299
Stroke in the Very Elderly
• Stroke patients >85 years of age make up 17% of
all stroke patients, and in this age group, stroke is
Stroke in the Young more prevalent in females than in males.305,306
• In the NIS, hospitalizations for ischemic stroke • Very elderly patients have a higher risk-adjusted
increased among adolescents and young adults mortality,307 have greater disability,307 have longer
(aged 5–44 years) between 1995 and 2010, hospitalizations,308 receive less evidence-based
whereas SAH hospitalizations decreased during care,248,249 and are less likely to be discharged to
that same period.277,300 their original place of residence.308,309
• Approximately 10% of all strokes occur in indi- • According to analyses from the US NIS, over
viduals 18 to 50 years of age.301 the past decade, in-hospital mortality rates after
• In the 2005 GCNKSS study period, the sex- stroke have declined for every age/sex group
adjusted incidence rate of first-ever stroke was except males aged >84 years.310
48 per 100 000 (95% CI, 42–53) among whites • Over the next 40 years (2010–2050), the num-
aged 20 to 54 years compared with 128 per ber of incident strokes is expected to more
100 000 (95% CI, 106–149) among blacks of the than double, with the majority of the increase
same age. Both races had a significant increase among the elderly (aged ≥75 years) and minor-
in the incidence rate from 1993/1994.194 Similarly, ity groups.311
other studies suggest an increase in the incidence • A Danish stroke registry reported on 39 cen-
of stroke in young adults. According to MIDAS tenarians (87% females; age range 100–107
29, an administrative database containing hospi- years) hospitalized with acute stroke. Although
tal records of all patients discharged from non- they had more favorable risk profiles than other
federal hospitals in New Jersey with a diagnosis age groups (lower prevalence of previous MI,
of CVD or an invasive cardiovascular procedure, stroke, and DM), their strokes were more severe
the rate of stroke more than doubled in patients and were associated with high 1-month mortal-
aged 35 to 39 years, from 9.5 strokes per 100 000 ity (38.5%).312

Organization of Stroke Care 0.31–0.77) but had lower mortality rates (OR,
CLINICAL STATEMENTS
0.66; 95% CI, 0.47–0.92).

• Among 30 947 patients hospitalized with acute
AND GUIDELINES
• Implementation of Target Stroke, a national qual-

ischemic stroke in the state of New York between
ity improvement initiative to improve the timeli-
2005 and 2006, admission to a designated stroke
ness of tPA administration, found that among
center (49.4% of patients) was associated with
71 169 patients with acute ischemic stroke treated
lower 30-day mortality (10.1% versus 12.5%;
with tPA at 1030 GWTG-Stroke participating hos-
adjusted mortality difference, −2.5%; 95% CI,
pitals, participation in the program was associated
−3.6% to −1.4%) and greater use of thrombo-
with a decreased door-to-needle time, lower in-
lytic therapy (4.8% versus 1.7%; adjusted differ-
hospital mortality (OR, 0.89; 95% CI, 0.83–0.94)
ence, 2.2%; 95% CI, 1.6%–2.8%), but there was
no difference in 30-day all-cause readmission or and intracranial hemorrhage (OR, 0.83; 95% CI,
discharge to a skilled nursing facility.313 0.76–0.91), and an increase in the percentage
• A 2006 study using Medicare data found that of patients discharged home (OR, 1.14; 95% CI,
among 6197 SAH and 31 272 ICH stroke dis- 1.09–1.19).318
charges, patients treated at Joint Commission– • Approximately 70% of Medicare beneficia-
certified primary stroke centers had lower 30-day ries who are discharged with acute stroke use
risk-adjusted mortality than patients treated at Medicare-covered postacute care,319 with most
noncertified centers (SAH OR, 0.66 [95% CI, receiving care from >1 type of setting.320,321 The
0.58–0.76] and ICH OR, 0.86 [95% CI, 0.80– majority of stroke patients receive rehabilitation
0.92]), but no difference was seen for 30-day all- care in a skilled nursing facility after discharge
cause risk-adjusted readmission.314 (32%), followed by an inpatient rehabilita-
• A study of 36 981 patients admitted with a pri- tion facility (22%), and then home health care
mary diagnosis of ICH or SAH in New Jersey (15%).319
between 1996 and 2012 found that patients • The proportion of stroke patients not referred
admitted to a comprehensive stroke center were to any postacute care has increased in recent
more likely to have neurosurgical or endovascular years,319 with an analysis of 2006 Medicare data
treatments and had lower 90-day mortality (OR, finding that proportion to be as high as 42%.322
0.93; 95% CI, 0.89–0.97) than patients admitted
to other hospitals.315 Hospital Discharges and Ambulatory

• A Cochrane review of 28 trials involving 5855 Care Visits
participants concluded that stroke patients who
receive organized inpatient care in a stroke unit
(See Table 13-1)
had better outcomes, including decreased odds • From 2004 to 2014, the number of inpatient
of mortality (median of 1 year; OR, 0.81; 95% CI, discharges from short-stay hospitals with stroke
0.69–0.94), death or institutionalized care (0.78; as the principal diagnosis remained stable, with
95% CI, 0.68–0.89), and death or dependency 897 000 and 888 000 (Table 13-1), respectively
(OR, 0.79; 95% CI, 0.68–0.90) than patients (HCUP, NHLBI tabulation).
treated in an alternative form of inpatient care. • In 2014, the average length of stay for discharges
The findings were adjusted for patient age, sex, with stroke as the principal diagnosis was 4.7
initial stroke severity, or stroke type.316 days (HCUP, NHLBI tabulation).
• A GWTG-Stroke study found differences in • In 2014, there were 596 000 ED visits with stroke
the quality measures and in-hospital outcomes as the principal diagnosis, and in 2011, there were
among hospitals that received primary stroke 209 000 outpatient visits with stroke as the first-
center certification, depending on the differ- listed diagnosis (NHAMCS, unpublished NHLBI
ent certification bodies (Joint Commission, tabulation). In 2014, physician office visits for a
Healthcare Facilities Accreditation Program, Det first-listed diagnosis of stroke totaled 1 950 000
Norske Veritas, or state-based agencies).317 State (NAMCS, unpublished NHLBI tabulation).
agency–certified hospitals had lower intravenous • In 2014, males and females accounted for
tPA utilization rates (OR, 0.76; 95% CI, 0.68– roughly the same number of inpatient hospital
0.86) and higher risk-adjusted in-hospital mor- stays for stroke in the 18- to 44-year-old and 65-
tality rates (OR, 1.23; 95% CI, 1.07–1.41) than to 84-year-old age groups. Among people 45 to
Joint Commission–certified centers; Healthcare 64 years of age, 55.6% of stroke patients were
Facilities Accreditation Program–accredited hos- males. Among those ≥85 years of age, females
pitals were less likely to achieve door-to-needle constituted 66.0% of all stroke patients (HCUP,
times within 60 minutes (OR, 0.49; 95% CI, NHLBI tabulation).

• Age-specific acute ischemic stroke hospitalization • In the Medicare population, 30-day readmission
CLINICAL STATEMENTS
rates from 2000 to 2010 decreased for individu- rates and long-term risk of adverse clinical out-
AND GUIDELINES
als aged 65 to 84 years (−28.5%) and ≥85 years comes associated with carotid artery stenting
(−22.1%) but increased for individuals aged 25 to were similar to those for carotid endarterectomy
44 years (43.8%) and 45 to 64 years (4.7%). Age- after adjustment for patient- and provider-level
adjusted acute ischemic stroke hospitalization factors.324,325,327,328
rates were lower in females, and females had a • Evidence on comparative costs of carotid endar-
greater rate of decrease from 2000 to 2010 than terectomy and stenting are mixed; whereas some
males (−22% versus −17.8%, respectively).300 studies found carotid stenting to be associated
• A first-ever county-level Atlas of Stroke with significantly higher costs than carotid end-
Hospitalizations Among Medicare Beneficiaries arterectomy,329 particularly among asymptomatic
was released in 2008 by the CDC in collabora- patients330 and that they might be less cost-effec-
tion with the Centers for Medicare & Medicaid tive in general,331 CREST found that the overall
Services. It found that the stroke hospitaliza- cost of carotid stenting was not different from
tion rate for blacks between 1995 and 2002 that of carotid endarterectomy (US $15 055 ver-
was 27% higher than for the US population in sus US $14 816).332
general, 30% higher than for whites, and 36% • The percentage of patients undergoing carotid
higher than for Hispanics. In contrast to whites endarterectomy within 2 weeks of the onset of
and Hispanics, the highest percentage of strokes stroke increased from 13% in 2007 to 47% in
in blacks (42.3%) occurred in the youngest 2010.333
Medicare age group (65–74 years of age).59 The • Meta-analyses of 5 trials that investigated the effi-
NIS (2010) estimated that age-adjusted acute cacy of modern endovascular therapies for stroke
ischemic stroke hospitalization rates between (MR CLEAN, ESCAPE, SWIFT PRIME, EXTEND-IA
2000 and 2010 decreased for both Hispanics and REVASCAT) have provided strong evidence to
(−21.7%) and whites (−12.4%) but increased support the use of thrombectomy initiated within
for blacks (13.7%), driven by a sharp rise in rates 6 hours of stroke onset, irrespective of patient
in the second half of the decade (11.16% per age, NIHSS score, or receipt of IVT.334 Retrospective
year from 2006 and 2010).300 analyses of patient databases have found similar
• An analysis of the 2011 to 2012 NIS for acute isch- results.335
emic stroke found that after risk adjustment, all • Since the meta-analysis, results from the recent
racial/ethnic minorities except Native Americans THRACE trial of >400 patients in France found
had a significantly higher likelihood of length of that the primary outcome of functional indepen-
stay ≥4 days than whites.323 dence at 3 months was significantly higher in
those given IVT plus mechanical thrombectomy
than in those given IVT only; however, there
Operations and Procedures were no significant differences in mortality at
(See Chart 13-10) 3 months or symptomatic intracranial hemor-
• In 2014, an estimated 86 000 inpatient endarter- rhage at 24 hours.336 Results from the PISTE trial
ectomy procedures were performed in the United in the United Kingdom found insignificant dif-
States. Carotid endarterectomy is the most fre- ferences in the primary outcome of functional
quently performed surgical procedure to prevent independence at day 90 between IVT alone and
stroke (HCUP, NHLBI tabulation). adjunctive mechanical thrombectomy, as well as
• Although rates of carotid endarterectomy insignificant differences in mortality. However,
decreased between 1997 and 2014 (Chart 13-10), secondary analyses found that patients treated
the use of carotid stenting increased dramatically with adjunctive mechanical thrombectomy dis-
from 2004 to 2014 (HCUP, NHLBI tabulation). played a significantly greater likelihood of full
• In-hospital mortality for carotid endarterectomy neurological recovery (modified Rankin score
has decreased steadily from 1993 to 2014 (HCUP, 0–1) at day 90.337
NHLBI tabulation). • Meta-analyses of 7 trials (ESCAPE, EXTEND-IA,
• In the Medicare population, in-hospital stroke MR CLEAN, PISTE, REVASCAT, SWIFT PRIME,
rate and mortality are similar for carotid endarter- and THRACE) suggest that pretreatment with
ectomy and carotid stenting.324,325 IVT before initiation of endovascular therapy
• Similarly, a recent study from the NIS database in patients with emergent large-vessel occlu-
demonstrated significant improvement in the in- sion might be associated with lower rates of
hospital outcomes associated with carotid artery death or severe dependency at 3 months. These
stenting over the past decade.326 findings contradict the recent observational

single-center studies that reported potential • In a recent meta-analysis of 8 RCTs, compared

CLINICAL STATEMENTS
equality between endovascular therapy and with fibrinolysis only, endovascular therapy with
AND GUIDELINES
bridging therapy (combined IVT and endovas- or without fibrinolysis was associated with sig-
cular therapy) in patients with emergent large- nificantly higher rates of functional independence
vessel occlusion.338 at 90 days, with no difference in risk of all-cause
• Endovascular therapy with standard care was mortality or intracranial hemorrhage.344
found to be cost-effective compared with stan-
dard care in most subgroups. In patients with
ASPECTS ≤5 or with M2 occlusions, cost-effec- Cost
tiveness remains uncertain based on current (See Table 13-1)
data.339 • In 2013 to 2014 (average annual):
• Several recent clinical trials reported improved — The direct and indirect cost of stroke was
functional outcome at 90 days among patients $40.1 billion (MEPS, NHLBI tabulation; Table
receiving endovascular treatment in conjunction 13-1).
with intravenous tPA for acute ischemic stroke — The estimated direct medical cost of stroke
caused by occlusions in the proximal anterior
was $23.6 billion. This includes hospital
intracranial circulation versus tPA alone. In the
outpatient or office-based provider visits,
SWIFT PRIME trial, thrombectomy with a stent
hospital inpatient stays, ED visits, prescribed
retriever plus intravenous tPA reduced disability
medicines, and home health care.344a
at 90 days over the entire range of scores on
— The mean expense per patient for direct care
the modified Rankin scale (P<0.001). The rate of
for any type of service (including hospital
functional independence (modified Rankin scale
inpatient stays, outpatient and office-based
score 0–2) was higher in the intervention group
visits, ED visits, prescribed medicines, and
than in the control group (60% versus 35%,
home health care) in the United States was
P<0.001).340
estimated at $6574.345
• In patients with ischemic stroke with a proximal
• Between 2015 and 2035, total direct medical
cerebral arterial occlusion and salvageable tissue
stroke-related costs are projected to more than
on CT perfusion imaging in the EXTEND-IA trial,
double, from $36.7 billion to $94.3 billion, with
early thrombectomy with the Solitaire FR stent
much of the projected increase in costs arising

retriever, compared with alteplase alone, improved
from those ≥80 years of age.346
reperfusion, early neurological recovery, and func-
• The total cost of stroke in 2035 (in 2015 dollars)
tional outcome. Endovascular therapy, initiated
is projected to be $81.1 billion for NH whites,
at a median of 210 minutes after the onset of
$32.2 billion for NH blacks, and $16.0 billion for
stroke, increased early neurological improve-
Hispanics.346
ment at 3 days (80% versus 37%, P=0.002) and
• During 2001 to 2005, the average cost for out-
improved functional outcome at 90 days, with
patient stroke rehabilitation services and medica-
more patients achieving functional independence
tions the first year after inpatient rehabilitation
(score of 0–2 on the modified Rankin scale, 71%
discharge was $11 145. The corresponding aver-
versus 40%; P=0.01).341
age yearly cost of medication was $3376, whereas
• Among patients with acute ischemic stroke with
the average cost of yearly rehabilitation service
a proximal vessel occlusion in the ESCAPE trial,
rapid endovascular treatment improved func- utilization was $7318.347
tional outcomes and reduced mortality. The rate • In adjusted models that controlled for relevant
of functional independence (90-day modified covariates, the attributable 1-year cost of post-
Rankin score of 0–2) was increased with the stroke aphasia was estimated at $1703 in 2004
intervention (53.0% versus 29.3% in the control dollars.348
group, P<0.001).342
• Among patients with anterior circulation stroke
Global Burden of Stroke
in the REVASCAT trial, stent retriever thrombec-
tomy reduced the severity of disability over the (See Charts 13-11 to 13-16)
range of the modified Rankin scale (adjusted Although global age-adjusted mortality rates for isch-
OR for improvement of 1 point, 1.7; 95% emic and hemorrhagic stroke decreased between 1990
CI, 1.05–2.8) and led to higher rates of func- and 2015, the absolute number of people who have
tional independence (a score of 0–2) at 90 days strokes annually, as well as related deaths and DALYs
(43.7% versus 28.2%; adjusted OR, 2.1; 95% lost, increased. The majority of global stroke burden is
CI, 1.1–4.0).343 in low-income and middle-income countries.349,350

Prevalence Mortality
CLINICAL STATEMENTS
• In 2015, prevalence of cerebrovascular disease • In 2015351:
AND GUIDELINES
was 42.4 million people.351 — There were 6.3 million cerebrovascular disease
• Ischemic stroke was 24.9 million, and hemor- deaths worldwide, making stroke the second-
rhagic stroke was 18.7 million.352 leading global cause of death behind IHD.
• 5.2 million first strokes (31%) were in those <65 — Stroke deaths accounted for 11.8% of total
years of age.350 deaths worldwide.350
• There was a 5.2% decline in ischemic stroke prev- — The absolute number of cerebrovascular dis-
alence from 2005 to 2015 and an 11.6% decline ease deaths increased 36.4% between 1990
from 1990 to 2015.351 and 2015; however, the age-standardized
• There was a 3.3% decline in hemorrhagic stroke death rate decreased 30.0%.
prevalence from 1990 to 2015 and a 7.4% decline — The absolute number of cerebrovascular dis-
from 1990 to 2015.351 ease deaths increased 5.0% between 2005
• The GBD 2015 Study used statistical models and and 2015; however, the age-standardized
data on incidence, prevalence, case fatality, excess death rate for the 10-year period decreased
mortality, and cause-specific mortality to estimate 21.1%.
disease burden for 315 diseases and injuries in — A total of 3.0 million individuals died of isch-
195 countries and territories.351 emic stroke, and 3.3 million died of hemor-
— Age-standardized prevalence rates of cere- rhagic stroke.
brovascular disease were higher in Eastern • The GBD 2015 Study used statistical models and
Europe, Central Asia, and Eastern sub-Saha- data on incidence, prevalence, case fatality, excess
ran Africa (Chart 13-11). mortality, and cause-specific mortality to estimate
— The prevalence of hemorrhagic stroke is high disease burden for 315 diseases and injuries in
in Central and East Asia and sub-Saharan 195 countries and territories.351
Africa (Chart 13-12). — Eastern Europe, East Asia, Central Asia, and
— Countries in Eastern Europe, Central Asia, sub-Saharan Africa have higher rates of cere-
and East Asia have the highest prevalence brovascular disease mortality than the rest of
rates of ischemic stroke (Chart 13-13). the world (Chart 13-14).
— Hemorrhagic stroke mortality is highest in
Incidence Mongolia (Chart 13-15).

• In 2010, there were an estimated 11.6 million — Afghanistan and Russia have the highest
events of incident ischemic stroke and 5.3 million mortality rates of ischemic stroke (Chart
events of incident hemorrhagic stroke, 63% and 13-16).
80%, respectively, in low- and middle-income • In 2010, 39.4 million DALYs were lost because of
countries.353 ischemic stroke and 62.8 million because of hem-
• Between 1990 and 2010353: orrhagic stroke (64% and 86%, respectively, in
— Incidence of ischemic stroke was signifi- low- and middle-income countries).353
cantly reduced by 13% (95% CI, 6%–18%) • In 2010, the mean age of stroke-related death
in high-income countries. No significant in high-income countries was 80.4 years com-
change was seen in low- or middle-income pared with 72.1 years in low- and middle-income
countries. countries.354
— Incidence of hemorrhagic stroke decreased • Between 1990 and 2010, ischemic stroke mor-
by 19% (95% CI, 1%–15%) in high-income tality decreased 37% in high-income countries
countries. Rates increased by 22% (95% CI, and 14% in low- and middle-income countries.
5%–30%) in low- and middle-income coun- Hemorrhagic stroke mortality decreased 38% in
tries, with a 19% increase in those aged high-income countries and 23% in low- and mid-
<75 years. dle-income countries.353

Table 13-1. Stroke
CLINICAL STATEMENTS
Prevalence, 2014: New and Recurrent Mortality, 2015: Hospital Discharges, Cost,
AND GUIDELINES
Population Group Age ≥20 y Attacks, All Ages All Ages* 2014: All Ages 2013–2014
Both sexes 7 200 000 (2.7%) 795 000 140 323 888 000 $40.1 Billion
Males 3 100 000 (2.4%) 370 000 (46.5%)† 58 288 (41.7%)† 434 000 …
Females 4 100 000 (2.9%) 425 000 (53.5%)† 82 035 (58.3%)† 454 000 …
NH white males 2.2% 325 000‡ 43 100 … …
NH white females 2.8% 365 000‡ 63 730 … …
NH black males 3.9% 45 000‡ 7962 … …
NH black females 4.0% 60 000‡ 9798 … …
Hispanic males 2.0% … 4544 … …
Hispanic females 2.6% … 5251 … …
NH Asian males 1.0% … 2153§ … …
NH Asian females 2.5% … 2645§ … …
NH American Indian or
3.0%‖¶ … 646 … …
Alaska Native

*Mortality for Hispanic, American Indian or Alaska Native, and Asian and Pacific Islander people should be interpreted with caution because of
inconsistencies in reporting Hispanic origin or race on the death certificate compared with censuses, surveys, and birth certificates. Studies have shown
underreporting on death certificates of American Indian or Alaska Native, Asian and Pacific Islander, and Hispanic decedents, as well as undercounts of
these groups in censuses.
†These percentages represent the portion of total stroke incidence or mortality that applies to males vs females.
‡Estimates include Hispanics and non-Hispanics. Estimates for whites include other nonblack races.
§Includes Chinese, Filipino, Hawaiian, Japanese, and other Asian or Pacific Islander.
‖National Health Interview Survey (2014), National Center for Health Statistics (NCHS); data are weighted percentages for Americans ≥18 years
of age.355
¶Estimate considered unreliable or does not meet standards of reliability or precision.
Sources: Prevalence: National Health and Nutrition Examination Survey 2011 to 2014, NCHS and National Heart, Lung, and Blood Institute (NHLBI).
Percentages for racial/ethnic groups are age adjusted for Americans ≥20 years of age. Age-specific percentages are extrapolated to the 2014 US
population. Incidence: Greater Cincinnati/Northern Kentucky Stroke Study/National Institutes of Neurological Disorders and Stroke data for 1999
provided on August 1, 2007. US estimates compiled by NHLBI. See also Kissela et al.356 Data include children. Mortality: Centers for Disease Control
and Prevention/NCHS, 2015 Mortality Multiple Cause-of-Death–United States. These data represent underlying cause of death only. Mortality for
NH Asians includes Pacific Islanders. Hospital discharges: Healthcare Cost and Utilization Project, Agency for Healthcare Research and Quality. Data
include those inpatients discharged alive, dead, or status unknown. Cost: NHLBI. Data include estimated direct and indirect costs for 2013 to 2014
(average annual).
18
16
14.9
13.8
14
12
10
8
6.5
6.1
6
4
2.4
2 1.6
0.3 0.6
0
20-39 40-59 60-79 80+
Age (Years)
Male Female
Chart 13-1. Prevalence of stroke by age and sex (NHANES: 2011–2014).


CLINICAL STATEMENTS
350
AND GUIDELINES
303
294
291
300
250 241
Incidence per 100,000
206
200
179
150
100
54 59 56
50
32 30
25
15 15 20
9 9 8
0
White Ischemic Black Ischemic White ICH Black ICH White SAH Black SAH
1993-94 1999 2005
Chart 13-2. Annual age-adjusted incidence of first-ever stroke by race.

Hospital plus out-of-hospital ascertainment, 1993 to 1994, 1999, and 2005. ICH indicates intracerebral hemorrhage; and SAH,
subarachnoid hemorrhage.
Data derived from Kleindorfer et al.9
Chart 13-3. Age-adjusted death rates for stroke by sex and race/ethnicity, 2015.
Death rates for the American Indian or Alaska Native and Asian or Pacific Islander populations are known to be underestimated.
Stroke includes International Classification of Diseases, 10th Revision codes I60 through I69 (cerebrovascular disease). Mortality
for NH Asians includes Pacific Islanders.

CLINICAL STATEMENTS
25-34 years 35-44 years 45-54 years 55-64 years

AND GUIDELINES
60
32.7 32.9
31.7
30.6
29.7
50 29.3 29.4 29.6
28.7 28.9 29.3
Rate per 100,000 population
40
30
15.0 14.6 14.5

13.7 13.7 13.1
20 12.8 12.8 12.4 12.3 12.3
10
5.2 5.1 5.0 4.8 4.6 4.6 4.2 4.3 4.2 4.3 4.4
1.4 1.3 1.3 1.3 1.3 1.3 1.3 1.3 1.2 1.3 1.3
0
2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015
Chart 13-4. Crude stroke mortality rates among young US adults (aged 25–64 years), 2005 to 2015.
65-74 years 75-84 years 85+ years

1800
1239.7
1131.7
1600 1110.7
1071.0
992.2 993.8
1400 975.8
943.7
931.2 929.7
906.0
1200
Rate per 100,000 population
1000
800
600
358.4
333.9 320.8 313.3 294.9 288.3 285.4 272.2 273.0
400 268.9 265.7
200
99.8 94.9 91.4 87.3 82.8 81.7 78.2 75.7 74.2 74.5 75.5
0
2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015
Chart 13-5. Crude stroke mortality rates among older US adults (aged ≥65 years), 2005 to 2015.

CLINICAL STATEMENTS
AND GUIDELINES
Chart 13-6. Stroke death rates, 2013 through 2015, all ages, by count.
Rates are spatially smoothed to enhance the stability of rates in counties with small populations. International Classification of
Diseases, 10th Revision codes for stroke: I60 through I69.
Data source: National Vital Statistics System and National Center for Health Statistics.
40
36
35
33
30
27
25
Percent of Patients
25
21 21
20
18
17
15
15 14
11
10
8
0
White Men White Women Black Men Black Women
45-64 years of age 65-74 years of age ≥75 years of age
Chart 13-7. Probability of death within 1 year after first stroke.

Source: Pooled data from the Framingham Heart Study, Atherosclerosis Risk in Communities Study, Cardiovascular Health
Study, Multi-Ethnic Study of Atherosclerosis, Coronary Artery Risk Development in Young Adults, and Jackson Heart Study of
the National Heart, Lung, and Blood Institute.

CLINICAL STATEMENTS
80
AND GUIDELINES
70 67 66
60 57
Percent of Patients 51
50
45
43
40
36
33
29
30 27
25
19
20
10
0
Chart 13-8. Probability of death within 5 years after first stroke.

25
22
20 20
20 19 19
16
Percent of Patients
15 14
12
11
10 10
10
5
5
0
Chart 13-9. Probability of death with recurrent stroke in 5 years after first stroke.

CLINICAL STATEMENTS
AND GUIDELINES
Chart 13-10. Trends in carotid endarterectomy and carotid stenting procedures (United States: 1993–2014).
Carotid endarterectomy: International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM) 38.12 (all-
listed); carotid stenting: ICD-9-CM 00.63 (all-listed).
Source: Nationwide Inpatient Sample, Healthcare Cost and Utilization Project, Agency for Healthcare Research and Quality.
Chart 13-11. Age-standardized global prevalence rates of cerebrovascular disease per 100 000, both sexes, 2015.
Chart 13-12. Age-standardized global prevalence rates of hemorrhagic stroke per 100 000, both sexes, 2015.
Chart 13-13. Age-standardized global prevalence rates of ischemic stroke per 100 000, both sexes, 2015.
Chart 13-14. Age-standardized global mortality rates of cerebrovascular disease per 100 000, both sexes, 2015.
Chart 13-15. Age-standardized global mortality rates of hemorrhagic stroke per 100 000, both sexes, 2015.
Chart 13-16. Age-standardized global mortality rates of ischemic stroke per 100 000, both sexes, 2015.
behalf of the American Heart Association Advocacy Coordinating Committee

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AND GUIDELINES
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14. CONGENITAL CARDIOVASCULAR outcomes.5 Health outcomes continue to improve for
CLINICAL STATEMENTS
congenital cardiovascular defects, including survival,
DEFECTS AND KAWASAKI DISEASE
AND GUIDELINES
leading to a population shift toward adulthood. There
ICD-9 745 to 747, ICD-10 Q20 to Q28. See is a growing population of adults with both congenital
Tables 14-1 through 14-4 and Charts 14-1 heart defects and adult medical diagnoses,6 which adds
through 14-7 to the complexity of their management7,8 and empha-
sizes the need for coordinated care by adult congenital
Click here to return to the Table of Contents heart disease specialists.9
Congenital cardiovascular defects are structural prob-

lems that arise from abnormal formation of the heart
Prevalence
or major blood vessels. ICD-9 lists 25 congenital heart (See Tables 14-1 through 14-3)
defect codes, of which 21 designate specific anatomic The population with congenital heart defects has grown
or hemodynamic lesions; however, there are many more substantially over the past several decades, related
lesions that are not well described by ICD-9 or ICD-10 primarily to better surgical outcomes and improved
codes because of the wide diversity of congenital car- medical management; this has led to an aging of the
diovascular malformations, as well as varying classifica- congenital cardiovascular defects population.10 The
tions of nomenclature. Defects range in severity from 32nd Bethesda Conference estimated that the total
tiny septal communications or defects between cham- number of adults living with congenital cardiovascular
bers that can resolve spontaneously to major malforma- defects in the United States in 2000 was 800 000.1,11
tions that may require multiple surgical procedures in In 2002, the estimated prevalence of congenital car-
infancy. In fact, on occasion a lesion can be so severe diovascular defects was 650 000 to 1.3 million in all
that it leads to in utero demise. As such, congenital age groups.12 The annual birth prevalence of congeni-
heart defects are serious and common conditions that tal cardiovascular defects ranged from 2.4 to 13.7 per
have a significant impact on morbidity, mortality, and 1000 live births (Table 14-2). In the United States, 1
healthcare costs in children and in adults.1 Some types in 150 adults is expected to have some form of con-
of congenital cardiovascular defects are associated with genital heart defect, including mild lesions such as a
diminished quality of life,2 on par with what is seen in well-functioning bicuspid aortic valve, as well as more
other chronic pediatric health conditions,3 as well as def-
severe disease such as HLHS.7 The estimated prevalence

icits in cognitive functioning4 and neurodevelopmental of congenital cardiovascular defects ranges from 2.5%
for hypoplastic right heart syndrome to 20.1% for VSD
in children and from 1.8% for TGA to 20.1% for VSD
in adults (Table 14-3). In population data from Canada,
the measured prevalence of congenital heart defects
ASD atrial septal defect
AV atrioventricular
in the general population was 13.11 per 1000 chil-
CABG coronary artery bypass graft dren and 6.12 per 1000 adults in the year 2010.13 The
CDC Centers for Disease Control and Prevention expected growth rates of the congenital heart defects
CI confidence interval population vary from 1% to 5% per year depending on
DM diabetes mellitus age and the distribution of lesions.12
Estimates of the distribution of lesions in the con-
HD heart disease genital heart defects population using available data
HLHS hypoplastic left heart syndrome vary based on proposed assumptions. If all those born
ICD-9 International Classification of Diseases, 9th Revision with congenital heart defects between 1940 and 2002
ICD-10 International Classification of Diseases, 10th Revision were treated, there would be ≈750 000 survivors with
ICU intensive care unit
simple lesions, 400 000 with moderate lesions, and
KD Kawasaki disease
NH non-Hispanic
180 000 with complex lesions; in addition, there would
NHIS National Health Interview Survey be 3.0 million people alive with bicuspid aortic valves.12
NHLBI National Heart, Lung, and Blood Institute Without treatment, the number of survivors in each
NIS Nationwide Inpatient Sample group would be 400 000, 220 000, and 30 000, respec-
OR odds ratio tively. The actual numbers surviving were projected to
RR relative risk
be between these 2 sets of estimates as of more than
RV right ventricle
STS Society of Thoracic Surgeons
a decade ago.12 The most common types of defects in
TGA transposition of the great arteries children are VSD, 620 000 people; ASD, 235 000 peo-
TOF tetralogy of Fallot ple; valvar pulmonary stenosis, 185 000 people; and
UI uncertainty interval patent ductus arteriosus, 173 000 people.12 The most
VSD ventricular septal defect common lesions seen in adults are ASD and TOF.11

Limited information is available about the prevalence ≈25%, or 2.4 per 1000 live births, require invasive
CLINICAL STATEMENTS
of congenital heart defects outside of North America treatment in the first year of life (Table 14-2).
AND GUIDELINES
and Western Europe.14 A study of 4 Chinese provinces

found the prevalence of congenital HD among those Birth Prevalence of Specific Defects
from birth to 18 years of age was 1.7%.15 A popula- • The National Birth Defects Prevention Network
tion-based study in Himachal, India, showed the popu- for 13 states in the United States from 2004 to
lation prevalence was 0.6% of people.16 2006 showed the average birth prevalence of 21
selected major birth defects. These data indicated
that there are >6100 estimated annual cases
Birth Prevalence of 5 cardiovascular defects: truncus arteriosus
The incidence of disorders present from at or before birth, (0.07/1000 births), TGA (0.3/1000 births), TOF
such as congenital heart disease, is generally described as (0.4/1000 births), AV septal defect (0.47/1000
the birth prevalence. The incidence (birth prevalence) of births), and HLHS (0.23/1000 births).24,25
congenital heart defects in the United States is commonly • Metropolitan Atlanta Congenital Defects Program
reported as being between 4 and 10 per 1000, clustering data for specific defects at birth showed the fol-
around 8 per 1000 live births.17 Using “recalled” diagno- lowing: VSD, 4.2/1000 births; ASD, 1.3/1000
ses of congenital heart defects from the NHIS combined births; valvar pulmonic stenosis, 0.6/1000 births;
with other national databases (US Census, National Vital TOF, 0.5/1000 births; aortic coarctation, 0.4/1000
Statistics System, Human Mortality Database), the birth births; AV septal defect, 0.4/1000 births; and TGA
prevalence is 3.3 and 3.2 per 1000 for males and females, (0.2/1000 births).22
respectively.18 Birth prevalence in Europe is reported as • Bicuspid aortic valve occurs in 13.7 per 1000 peo-
6.9 per 1000 births; birth prevalence in Asia is reported as ple; these defects might not require treatment in
9.3 per 1000.14 The overall birth prevalence of congenital infancy or childhood but can cause problems later
heart defects at the Bhabha Atomic Research Centre in adulthood.26
Hospital in Mumbai, India, from 2006 through 2011
was 13.28 per 1000 live births.19
Variations in birth prevalence rates could be related Mortality
to the age at detection; major defects can be identified (See Tables 14-1 and 14-4 and Charts 14-1
in the prenatal or neonatal period, but minor defects through 14-5)
might not be detected until later stages, including adult- Overall mortality attributable to congenital heart
hood, which makes it challenging to estimate birth prev- defects:
alence and population prevalence. To distinguish more
• In 2015 (NHLBI tabulation):
serious defects, some studies report the number of new
— Mortality related to congenital cardiovascular
cases of sufficient severity to result in death or an inva-
defects was 3128 deaths (Table 14-1), a 14%
sive procedure within the first year of life, in addition
decrease from 2005.
to overall birth prevalence. Birth prevalence rates are
— Congenital cardiovascular defects (ICD-10
likely to increase over time because of improved tech-
Q20–Q28) were the most common cause
nique and utilization of and advancements in screening,
of infant deaths resulting from birth defects
including fetal cardiac ultrasound,20 screening by pulse
(ICD-10 Q00–Q99); 24.0% of infants who
oximetry,21 and echocardiography during infancy.
died of a birth defect had a heart defect
Overall Birth Prevalence (ICD-10 Q20-Q24).
(See Table 14-2) — The age-adjusted death rate (deaths per
• According to population-based data from the 100 000 people) attributable to congenital
Metropolitan Atlanta Congenital Defects Program cardiovascular defects was 1.0, a 16.7%
(Atlanta, GA), congenital heart defects occurred decrease from 2005.
in 1 of every 111 to 125 births (live, still, or >20 • According to a review of Norwegian national
weeks’ gestation) from 1995 to 1997 and from mortality data in live-born children with congeni-
1998 to 2005. Some defects showed variations tal heart defects from 1994 to 2009, the all-cause
by sex and racial distribution.22 mortality rate was 17.4% for children with severe
• According to population-based data from congenital heart defects and 3.0% for children
Alberta, Canada, there was a total birth preva- with nonsevere congenital heart defects, with
lence of 12.42 per 1000 total births (live, still, or declining mortality rates over the analysis period
>20 weeks’ gestation).23 related to declining operative mortality and more
• An estimated minimum of 40 000 infants are frequent pregnancy terminations.27
expected to be affected by congenital heart • Death rates attributed to congenital heart defects
defects each year in the United States. Of these, decrease as gestational age advances toward

40 weeks.28 In-hospital mortality of infants with • Congenital cardiovascular defect–related mortal-
CLINICAL STATEMENTS
major congenital heart defects is independently ity varies substantially by age, with infants show-
AND GUIDELINES
associated with late-preterm birth (OR, 2.70; 95% ing the highest mortality rates from 1999 to 2015
CI, 1.69–4.33) compared with delivery at later (Chart 14-4).
gestational ages.29 Similarly, postoperative mortal- • The US 2015 age-adjusted death rate (deaths per
ity of infants with congenital heart defects born 100 000 people) attributable to congenital cardio-
near term (37 weeks) is 1.34 (95% CI, 1.05–1.71; vascular defects was 1.1 for NH white males, 1.6
P=0.02) higher than those born full term,30,31 with for NH black males, 0.9 for Hispanic males, 0.8 for
higher complication rates and longer length of NH white females, 1.1 for NH black females, and
stay. The presence of congenital heart defects 0.8 for Hispanic females. Infant (<1 year of age)
substantially increases mortality of very low-birth- mortality rates were 31.4 for NH white infants,
weight infants; in a study of very low-birth-weight 45.7 for NH black infants, and 31.4 for Hispanic
infants, the mortality rate with serious congenital infants (Chart 14-5).42
heart defects was 44% compared with 12.7% • Mortality after congenital heart surgery also dif-
in very low-birth-weight infants without serious fers between races/ethnicities, even after adjust-
congenital heart defects.32 ment for access to care. The risk of in-hospital
• Analysis of the STS Congenital Heart Surgery mortality for minority patients compared with
Database, a voluntary registry with self-reported white patients is 1.22 (95% CI, 1.05–1.41) for
data for a 3-year cycle (2013–2016) from 116 Hispanics, 1.27 (95% CI, 1.09–1.47) for NH
centers performing congenital heart defects sur- blacks, and 1.56 (95% CI, 1.37–1.78) for other
gery (112 based in 40 US states, 3 in Canada, NH people.43 Similarly, another study found that
and 1 in Turkey),33 showed that of 122 193 total a higher risk of in-hospital mortality was associ-
patients who underwent an operation with ana- ated with nonwhite race (OR, 1.36; 95% CI,
lyzable data, the aggregate hospital discharge 1.19–1.54) and Medicaid insurance (OR, 1.26;
mortality rate was 3.0% (95% CI, 2.9–3.1).34 The 95% CI, 1.09–1.46).44 One center’s experience
mortality rate was 8.6% (95% CI, 8.2–9.1) for suggested race was independently associated
neonates,35 2.8% (95% CI, 2.6–3.0) for infants,36 with neonatal surgical outcomes only in patients
1.0% (95% CI, 0.9–1.1) for children (>1 year to with less complex congenital heart defects.45
18 years of age),37 and 1.5% (95% CI, 1.3–1.8) Another center found that a home monitoring
for adults (>18 years of age).38 program can reduce mortality even in this vulner-
• The Japan Congenital Cardiovascular Surgery able population46
Database reported similar surgical outcomes for • The population-weighted mortality rate for sur-
congenital HD from 28 810 patients operated on gery for congenital heart defects is slightly higher
between 2008 and 2012, with 2.3% and 3.5% in males (5.1%) than females (4.6%) <20 years
mortality at 30 and 90 days, respectively.40 old (Table 14-4).
• In population-based data from Canada, 8123 • Data from the HCUP’s Kids’ Inpatient Database
deaths occurred among 71 686 patients with from 2000, 2003, and 2006 show male children
congenital heart defects followed up for nearly 1 had more congenital heart defects surgeries in
million patient-years.7 infancy, more high-risk surgeries, and more proce-
• Among 12 644 adults with congenital HD fol- dures to correct multiple cardiac defects. Female
lowed up at a single Canadian center from 1980 infants with high-risk congenital heart defects had
to 2009, 308 patients in the study cohorts (19%) a 39% higher adjusted mortality than males.38,46
died.41 According to CDC multiple-cause death data
• Trends in age-adjusted death rates attributable to from 1999 to 2006, sex differences in mortality
congenital cardiovascular defect mortality show over time varied with age. Between the ages of
a downward decline from 1999 to 2015 (Chart 18 and 34 years, mortality over time decreased
14-1); this also varies by race/ethnicity and sex significantly in females but not in males.47
(Charts 14-2 and 14-3). • In studies that examined trends since 1979, age-
• From 1999 to 2015, there was a downward adjusted death rates declined 22% for critical
decline in the age-adjusted death rates attrib- congenital heart defects48 and 39% for all con-
utable to congenital cardiovascular defects in genital heart defects,49 and deaths tended to
black, white, and Hispanic people (Chart 14-2), occur at progressively older ages. CDC mortality
in both males and females (Chart 14-3), and in data from 1979 to 2005 showed all-age death
age groups 1 to 4 years, 5 to 14 years, 5 to 24 rates had declined by 60% for VSD and 40%
years, and ≥25 years (Chart 14-4) in the United for TOF.50 Population-based data from Canada
States. showed overall mortality decreased by 31% and

the median age of death increased from 2 to 23 2013, which represents 27% of all birth-defect
CLINICAL STATEMENTS
years between 1987 and 2005.7 associated hospital costs.57

AND GUIDELINES
• Further analysis of the Kids’ Inpatient Database • Among pediatric hospitalizations (age 0–20 years)
from 2000 to 2009 showed a decrease in HLHS in the HCUP 2012 Kids’ Inpatient Database58:
stage 3 mortality by 14% and a decrease in — Pediatric hospitalizations with congenital
stage 1 mortality by 6%.51 Surgical interven- heart defects (4.4% of total pediatric hospi-
tions are the primary treatment for reducing talizations) accounted for $6.6 billion in hos-
mortality. A Pediatric Heart Network study of pitalization spending (23% of total pediatric
15 North American centers revealed that even hospitalization costs).
in lesions associated with the highest mortality, — 26.7% of all congenital heart defect costs
such as HLHS, aggressive palliation can lead to an were attributed to critical congenital car-
increase in the 12-month survival rate, from 64% diovascular defects, with the highest costs
to 74%.52 attributable to HLHS, coarctation of the
• Surgical interventions are common in adults aorta, and TOF.
with congenital heart defects. Mortality rates — Median hospital cost was $51 302 ($32 088–
for 12 congenital heart defect procedures were $100 058) in children who underwent car-
examined with data from 1988 to 2003 reported diac surgery, $21 920 ($13 068–$51 609) in
in the NIS. A total of 30 250 operations were children who underwent cardiac catheter-
identified, which yielded a national estimate of ization, $4134 ($1771–$10 253) in chil-
152 277±7875 operations. Of these, 27% were dren who underwent noncardiac surgery,
performed in patients ≥18 years of age. The over- and $23 062 ($5529–$71 887) in children
all in-hospital mortality rate for adult patients admitted for medical treatments. These
with congenital heart defects was 4.71% (95% data are presented as median and inter-
CI, 4.19%–5.23%), with a significant reduction in quartile range.
mortality observed when surgery was performed — The mean cost of congenital heart defects
on such adult patients by pediatric versus non- was higher in infancy ($36 601) than in older
pediatric heart surgeons (1.87% versus 4.84%; ages and in those with critical congenital
P<0.0001).53 For adults with congenital heart heart defects ($52 899).
defects, specialist care is a key determinant of
• Other studies confirm the high cost of HLHS. An

mortality and morbidity. In a single-center report analysis of 1941 neonates with HLHS showed
of 4461 adult patients with congenital heart a median cost of $99 070 for stage 1 palliation
defects with 48 828 patient-years of follow-up, (Norwood or Sano procedure), $35 674 for stage
missed appointments and delay in care were pre- 2 palliation (Glenn procedure), $36 928 for stage
dictors of mortality.54 3 palliation (Fontan procedure), and $289 292 for
transplantation.59
• Other congenital heart defect lesions are less
Hospitalizations costly. In 2124 patients undergoing congenital
(See Table 14-1) heart operations between 2001 and 2007, total
• In 2014, the total number of hospital discharges costs for the surgeries were $12 761 (ASD repair),
for congenital cardiovascular defects for all ages $18 834 (VSD repair), $28 223 (TOF repair), and
was 39 000 (Table 14-1). $55 430 (arterial switch operation).60
• Hospitalization of infants with congenital heart
defects is common; one third of patients with
congenital heart defects require hospitalization
Risk Factors
during infancy,55,56 often in an ICU. • Numerous intrinsic and extrinsic nongenetic risk
• Although the most common congenital heart factors contribute to congenital heart defects.61,62
defect lesions were shunts, including patent duc- • Intrinsic risk factors for congenital heart defects
tus arteriosus, VSDs, and ASDs, TOF accounted include various genetic syndromes. Twins are at
for a higher proportion of in-hospital death than higher risk for congenital heart defects63; one
any other birth defect. report from Kaiser Permanente data showed
monochorionic twins were at particular risk (RR,
11.6; CI, 9.2–14.5).64 Known risks generally focus
Cost on maternal exposures, but a study of paternal
• Using HCUP 2013 NIS data, one study noted that occupational exposure documented a higher inci-
hospitalization costs for individuals of all ages with dence of congenital heart defects with paternal
congenital heart defects exceeded $6.1 billion in exposure to phthalates.65

• Other paternal exposures that increase risk for during pregnancy.61 An observational study of
CLINICAL STATEMENTS
congenital heart defects include paternal anes- folic acid supplementation in Hungarian females
AND GUIDELINES
thesia, which has been implicated in TOF (3.6%); showed a decrease in the incidence of congenital
sympathomimetic medication and coarctation of heart defects, including VSD (OR, 0.57; 95% CI,
the aorta (5.8%); pesticides and VSDs (5.5%); 0.45–0.73), TOF (OR, 0.53; 95% CI, 0.17–0.94),
and solvents and HLHS (4.6%).66 dextro-TGA (OR, 0.47; 95% CI, 0.26–0.86), and
• Known maternal risks include maternal smok- ASD secundum (OR, 0.63; 95% CI, 0.40–0.98).80
ing67,68 during the first trimester of pregnancy, A US population-based case-control study
which has also been associated with a ≥30% showed an inverse relationship between folic acid
increased risk of the following lesions in the fetus: use and the risk of TGA (Baltimore-Washington
ASD, pulmonary valvar stenosis, truncus arte- Infant Study, 1981–1989).81
riosus, TGA,69 and septal defects (particularly for • An observational study from Quebec, Canada,
heavy smokers [≥25 cigarettes daily]).70 Maternal of 1.3 million births from 1990 to 2005 found
smoking might account for 1.4% of all congenital a 6% per year reduction in severe congenital
heart defects. heart defects using a time-trend analysis before
• Exposure to secondhand smoke has also been and after public health measures were instituted
implicated as a risk factor.71 that mandated folic acid fortification of grain and
• Air pollutants can also increase the risk of con- flour products in Canada.82
genital heart defects. In a retrospective review • Maternal infections, including rubella and chla-
of singleton infants born in Florida from 2000 mydia, have been associated with congenital
to 2009, maternal exposure during pregnancy heart defects.83,84
to the air pollutant benzene was associated with • High altitude has also been described as a risk fac-
an increased risk in the fetus of critical and non- tor for congenital heart defects; Tibetan children
critical congenital heart defects (1.33; 95% CI, living at 4200 to 4900 m had a higher prevalence
1.07–1.65).72 of congenital heart defects (12.09 per 1000) than
• Maternal binge drinking73 is also associated with those living at lower altitudes of 3500 to 4100 m;
an increased risk of congenital cardiac defects, patent ductus arteriosus and ASD contributed to
and the combination of binge drinking and smok- the increased prevalence.85
ing can be particularly dangerous: Mothers who
smoke and report any binge drinking in the 3

months before pregnancy are at an increased risk Screening
of giving birth to a child with congenital heart Pulse oximetry screening for critical congenital heart
defects (adjusted OR, 12.65).73 defects, a group of defects requiring intervention within
• Maternal obesity is also associated with congeni- the first days (or first year) of life, was recommended by
tal heart defects. A meta-analysis of 14 studies the US Department of Health and Human Services on
of females without gestational DM showed October 15, 2010.86 It was incorporated as part of the
infants born to mothers who were moderately US recommended uniform screening panel for new-
and severely obese, respectively, had 1.1 and 1.4 borns in 2011 and has been endorsed by the AHA and
times greater risk of congenital heart defects than the American Academy of Pediatrics.87 By December
infants born to normal-weight mothers.74–76 The 2014, 43 states had adopted this hospital screening
risk of TOF was 1.9 times higher among infants approach for identification of previously unidentified
born to mothers with severe obesity than among (by fetal cardiac ultrasound) newborn critical congenital
infants born to normal-weight mothers.75 heart disease,88 and several studies have demonstrated
• Maternal DM, including gestational DM, has also the benefit of such screening.89–91 Challenges remain
been associated with cardiac defects, both iso- in the implementation of pulse oximetry screening in
lated (congenital heart defect[s] as the only major certain populations, such as in neonatal ICUs, at higher
congenital anomaly) and multiple (congenital elevations where normal saturation may be lower, and
heart defect[s] plus ≥1 noncardiac major congeni- for in-home births.
tal anomalies).77,78 Pregestational DM is also asso- • Several key factors contribute to effective screen-
ciated with congenital heart defects, specifically ing, including probe placement (postductal),
TOF.79 oximetry cutoff (<95%), timing (>24 hours of
• Preeclampsia is also a risk factor for congenital life), and altitude (<2643 ft, 806 m).
heart defects, although not critical defects.80 • If fully implemented, screening would identify
• Folate deficiency is a well-accepted risk for con- 1189 additional infants with critical congenital
genital defects, including congenital heart defects, heart defects and would yield 1975 false-positive
and folic acid supplementation is recommended results.92

• A simulation model estimates that screening the to be overrepresented in larger cohorts of patients
CLINICAL STATEMENTS
entire United States for critical congenital heart with specific forms of congenital cardiovascular
AND GUIDELINES
defects with pulse oximetry would uncover 875 defects.101 The most common copy number vari-
infants (95% UI, 705–1060) who truly have non- ant is del22q11, which encompasses the T-box
syndromic congenital heart defects versus 880 transcription factor (TBX1) gene and presents
(95% UI, 700–1080) false-negative screenings as DiGeorge syndrome and velocardiofacial syn-
(no heart defects).93 drome. Others include del17q11, which causes
• It has been estimated that 29.5% (95% CI, William syndrome.102
28.1%–31.0%) of nonsyndromic children with • Single point mutations are also a cause of con-
critical congenital heart defects are diagnosed genital cardiovascular defects and include muta-
after 3 days and thus might benefit from pulse tions in a core group of cardiac transcription
oximetry screening.94 factors (NKX2.5, TBX1, TBX5, and MEF2),102 ZIC3,
• A meta-analysis of 13 studies that included and the NOTCH1 gene (dominantly inherited and
229 421 newborns found pulse oximetry had a found in ≈5% of cases of bicuspid aortic valve)
sensitivity of 76.5% (95% CI, 67.7%–83.5%) for and related NOTCH signaling genes.103
detection of critical congenital heart defects and • More recent advances in whole-exome sequenc-
a specificity of 99.9% (95% CI, 99.7%–99.9%), ing have suggested that 10% of sporadic severe
with a false-positive rate of 0.14% (95% CI, cases of congenital cardiovascular defects are
0.06%–0.33%).95 caused by de novo mutations,104 particularly in
• The cost of identifying a newborn with critical chromatin-regulating genes.
congenital heart defects has been estimated at • There also exist rare monogenic congenital car-
$20 862 per newborn detected and $40 385 per diovascular defects, including monogenic forms
life-year gained (2011 US dollars).93 of ASD, heterotaxy, severe mitral valve prolapse,
• Reports outside of the United States have shown and bicuspid aortic valve.102
similar performance of pulse oximetry screening • There is no consensus currently on the role, type,
in identifying critical congenital heart defects,96 and utility of clinical genetic testing in people
with a sensitivity and specificity of pulse oximetry with congenital cardiovascular defects,102 but it is
screening for critical congenital heart defects of being used increasingly, for example, to assist in
diagnosis of possible underlying syndromes.
100% and 99.7%, respectively.
Genetics Kawasaki Disease

• Congenital cardiovascular defects have a herita- ICD-9 446.1; ICD-10 M30.3.
ble component. There is a greater concordance Mortality—3. Any-mention mortality—10 (2015 NHLBI
of congenital cardiovascular defects in monozy- tabulation).
gotic than dizygotic twins.97 Among parents with • KD is an acute inflammatory illness character-
ASD or VSD, 2.6% and 3.7%, respectively, have ized by fever, rash, nonexudative limbal sparing
children who are similarly affected, 21 times the conjunctivitis, extremity changes, red lips and
estimated population frequency.98 However, a strawberry tongue, and a swollen lymph node.
large fraction of congenital cardiovascular defects In areas where bacille Calmette-Guerin vaccina-
occur in families with no other history of con- tion is common, the site can reactivate in KD.105
genital cardiovascular defects, which suggests the The most feared consequence of this vasculitis is
possibility of de novo genetic events. coronary artery aneurysms, which can result in
• Large chromosomal abnormalities are associated coronary ischemic events and other cardiovascu-
with come congenital cardiovascular defects. lar outcomes in the acute period or years later.106
For example, aneuploidies such as trisomy 13, The cause of KD is unknown, but it could be an
18, and 21 account for 9% to 18% of congeni- immune response to an acute infectious illness
tal heart defects.99 The specific genes respon- based in part on genetic susceptibilities.107,108 This
sible for congenital cardiovascular defects that is supported by variation in incidence related to
are disrupted by these abnormalities are diffi- geography, race/ethnicity, sex, age, and season.109
cult to identify. There are studies that suggest The Nationwide Longitudinal Survey in Japan has
that DSCAM and COL6A contribute to Down shown breastfeeding is protective against devel-
syndrome–associated congenital cardiovascular oping KD.110
defects.100 • In 2014, there were 6000 all-listed diagnoses
• Copy number variants also contribute to congeni- discharges for KD, with 4000 males and 2000
tal cardiovascular defects and have been shown females (HCUP, unpublished NHLBI tabulation).

• The incidence of KD is highest in Japan, at 322.45 early spring months, except in Hawaii, where no
CLINICAL STATEMENTS
patients per 100 000 children aged 0 to 4 years,111 clear seasonal trend is seen.122 KD can recur in 2%
AND GUIDELINES
followed by Taiwan at 164.6/100 000 in children to 4% of children who have already experienced
<5 years old112 and Korea, where the rate reached KD.123
113.1/100 000 children <5 years old in 2008.113 • Treatment of KD rests on diminishing the inflam-
Measured over 4 years, from 2008 through 2012, matory response with intravenous immunoglob-
the incidence of KD in Shanghai rose from 30.3 to ulin infusion, which reduces the incidence of
71.9 per 100 000 children aged 0 to 4 years.114 coronary artery aneurysms from ≈25% to ≈2%.
• KD is much less common in the United States, Addition of prednisolone to the standard regimen
with an incidence of 20.8/100 000 children of intravenous immunoglobulin for patients with
aged <5 years in 2006.115 The incidence of KD is severe KD appears to result in further reductions
lower in Italy, 17.6 per 100 000 children <5 years in the incidence of coronary artery anomalies (RR,
of age,116 and even lower in Germany, affect- 0.20; 95% CI, 0.12–0.28),124 a result supported
ing 7.2 of 100 000 children <5 years of age, by a meta-analysis of steroid treatment in 9 tri-
although this low rate might be affected by lack als that included 1011 patients with KD.125 Other
of recognition.117 anti-inflammatory treatments have also been
• The incidence of KD is rising worldwide, including used, based on limited data.126
in the United States. US hospitalizations for KD • Risk factors for coronary artery abnormalities
rose from 17.5/100 000 children aged <5 years include late diagnosis and treatment, young age
in 2000 to 19/100 000 children <5 years of age (<6 months), male sex, Asian background,127
in 2009.118,119 Japan experienced its highest-ever and initial coronary artery dimensions.128 Long-
incidence rate in 2012.120 In addition to geo- term prognosis in children with coronary artery
graphic variation in the incidence of KD, the age aneurysms is predicted in part by coronary artery
of children affected can also differ. In northern size at 1 month of illness, with the 10-year isch-
Europe (Finland, Sweden, and Norway), 67.8% of emia event-free and aneurysm persistence prob-
patients with KD were <5 years of age, compared ability being 87.5% and 20.6%, respectively.129
with 86.4% of patients in Japan (P<0.001).121 Successful surgical treatment (eg, CABG) of late
• Race-specific incidence rates indicate that KD is sequelae of symptomatic coronary artery stenoses
most common among Americans of Asian and
has been described.130

Pacific Island descent (30.3/100 000 children <5
years of age), occurs with intermediate frequency
in NH blacks (17.5/100 000 children <5 years of Global Burden of Congenital HD
age) and Hispanics (15.7/100 000 children <5 (See Charts 14-6 and 14-7)
years of age), and is least common in whites
(12.0/100 000 children <5 years of age).115 US • The GBD 2015 Study used statistical models
states with higher Asian American populations and data on incidence, prevalence, case fatality,
have higher rates of KD; for example, rates are excess mortality, and cause-specific mortality to
2.5-fold higher in Hawaii than in the continental estimate disease burden for 315 diseases and
United States.119 injuries in 195 countries and territories.
• Boys have a 1.5-fold higher incidence of KD than — Age-standardized mortality rates of congeni-
girls.119 Although KD can be seen as late as ado- tal heart anomalies are lowest in high-income
lescence, 76.8% of children with KD are <5 years countries and South Africa (Chart 14-6).131
of age.115,118,119 There are seasonal variations in — The prevalence of congenital heart anomalies
KD: KD is more common during the winter and is highest in Central Europe (Chart 14-7).131

Table 14-1. Congenital Cardiovascular Defects

CLINICAL STATEMENTS
Estimated Prevalence, Mortality, 2015, Hospital Discharges,

AND GUIDELINES
Population Group 2002, All Ages All Ages* 2014, All Ages
Both sexes 2.4 million26a 3128 39 000
Males … 1751 (56%)† 21 000
Females … 1377 (44%)† 18 000
NH white males … 1035 …
NH white females … 812 …
NH black males … 328 …
NH black females … 229 …
Hispanic males … 295 …
Hispanic females … 257 …
NH Asian or Pacific Islander males … 63 …
NH Asian or Pacific Islander females … 55 …
NH American Indian or Alaska Native … 38 …

*Mortality for Hispanic, NH American Indian or Alaska Native, and NH Asian and Pacific Islander people should be interpreted
with caution because of inconsistencies in reporting Hispanic origin or race on the death certificate compared with censuses,
surveys, and birth certificates. Studies have shown underreporting on death certificates of American Indian or Alaska Native, Asian
and Pacific Islander, and Hispanic decedents, as well as undercounts of these groups in censuses.
†These percentages represent the portion of total congenital cardiovascular mortality that is for males vs females.
Sources: Mortality: Centers for Disease Control and Prevention/National Center for Health Statistics, 2015 Mortality Multiple
Cause-of-Death—United States. These data represent underlying cause of death only. Hospital discharges: Healthcare Cost and
Utilization Project, National (Nationwide) Inpatient Sample, 2014, Agency for Healthcare Research and Quality; data include those
inpatients discharged alive, dead, or status unknown.
Table 14-2. Annual Birth Prevalence of Congenital

Cardiovascular Defects in the United States14,24

Estimated Number
Rate per 1000 (Variable With
Type of Presentation Live Births Yearly Birth Rate)
Fetal loss Unknown Unknown
Invasive procedure during the
2.4 9200
first year
Detected during first year* 8 36 000
Bicuspid aortic valve 13.7 54 800
*Includes stillbirths and pregnancy termination at <20 weeks’ gestation;

includes some defects that resolve spontaneously or do not require treatment.

Table 14-3. Estimated Prevalence of Congenital Cardiovascular Defects and Percent
CLINICAL STATEMENTS
Distribution by Type, United States, 2002* (in Thousands)
AND GUIDELINES
Prevalence, n Percent of Total
Type Total Children Adults Total Children Adults
Total 994 463 526 100 100 100
VSD† 199 93 106 20.1 20.1 20.1
ASD 187 78 109 18.8 16.8 20.6
Patent ductus arteriosus 144 58 86 14.2 12.4 16.3
Valvular pulmonic stenosis 134 58 76 13.5 12.6 14.4
Coarctation of aorta 76 31 44 7.6 6.8 8.4
Valvular aortic stenosis 54 25 28 5.4 5.5 5.2
TOF 61 32 28 6.1 7 5.4
AV septal defect 31 18 13 3.1 3.9 2.5
TGA 26 17 9 2.6 3.6 1.8
Hypoplastic right-heart syndrome 22 12 10 2.2 2.5 1.9
Double-outlet RV 9 9 0 0.9 1.9 0.1
Single ventricle 8 6 2 0.8 1.4 0.3
Anomalous pulmonary venous connection 9 5 3 0.9 1.2 0.6
Truncus arteriosus 9 6 2 0.7 1.3 0.5
HLHS 3 3 0 0.3 0.7 0
Other 22 12 10 2.1 2.6 1.9
Average of the low and high estimates, two thirds from low estimate.13 ASD indicates atrial septal defect; AV,
atrioventricular; HLHS, hypoplastic left heart syndrome; RV, right ventricle; TGA, transposition of the great arteries; TOF,
tetralogy of Fallot; and VSD, ventricular septal defect.
*Excludes an estimated 3 million bicuspid aortic valve prevalence (2 million in adults and 1 million in children).
†Small VSD, 117 000 (65 000 adults and 52 000 children); large VSD, 82 000 (41 000 adults and 41 000 children).
Source: Data derived from Hoffman et al.12

Table 14-4. Surgery for Congenital Heart Disease

CLINICAL STATEMENTS
Population,
AND GUIDELINES
Sample Weighted
Surgery for congenital heart disease, N 14 888 25 831
Deaths, N 736 1253
Mortality rate, % 4.9 4.8
By sex (81 missing in sample)
Male, N 8127 14 109
Deaths, N 420 714
Female, N 6680 11 592
Deaths, N 315 539
By type of surgery
ASD secundum surgery, N 834 1448
Deaths, N 3 6
Norwood procedure for HLHS, N 161 286
Deaths, N 42 72
In 2003, 25 000 cardiovascular operations for congenital cardiovascular

defects were performed on children <20 years of age. Inpatient mortality rate
after all types of cardiac surgery was 4.8%. Nevertheless, mortality risk varies
substantially for different defect types, from 0.4% for ASD repair to 25.2% for
first-stage palliation for HLHS. Fifty-five percent of operations were performed
in males. In unadjusted analysis, mortality after cardiac surgery was somewhat
higher for males than for females (5.1% vs 4.6%). ASD indicates atrial septal
defect; and HLHS, hypoplastic left heart syndrome.

Source: Data derived from Ma et al.132
Chart 14-1. Trends in age-adjusted death rates attributable to congenital cardiovascular defects, 1999 to 2015.
Source: National Center for Health Statistics, National Vital Statistics System.

CLINICAL STATEMENTS
AND GUIDELINES
Chart 14-2. Trends in age-adjusted death rates attributable to congenital cardiovascular defects by race/ethnicity,
1999 to 2015.
Chart 14-3. Trends in age-adjusted death rates attributable to congenital cardiovascular defects by sex, 1999 to
2015.

CLINICAL STATEMENTS
AND GUIDELINES
Chart 14-4. Trends in age-specific death rates attributable to congenital cardiovascular defects by age at death,
1999 to 2015.
Chart 14-5. Age-adjusted death rates attributable to congenital cardiovascular defects, by sex and race/ethnicity, 2015.
Chart 14-6. Age-standardized global mortality rates of congenital heart anomalies per 100 000, both sexes, 2015.
Chart 14-7. Age-standardized global prevalence rates of congenital heart anomalies per 100 000, both sexes, 2015.

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CLINICAL STATEMENTS
YT, Gao XM. Prevalence of congenital heart disease in Xinjiang multi-ethnic
1. Warnes CA, Williams RG, Bashore TM, Child JS, Connolly HM, Dearani JA,
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region of China. PLoS One. 2015;10:e0133961. doi: 10.1371/journal.
del Nido P, Fasules JW, Graham TP Jr, Hijazi ZM, Hunt SA, King ME, Landzberg pone.0133961.
MJ, Miner PD, Radford MJ, Walsh EP, Webb GD. ACC/AHA 2008 guide- 16. Bhardwaj R, Kandoria A, Marwah R, Vaidya P, Singh B, Dhiman P, Sood
lines for the management of adults with congenital heart disease: a report A, Sharma A. Prevalence of congenital heart disease in rural population
of the American College of Cardiology/American Heart Association Task of Himachal: a population-based study. Indian Heart J. 2016;68:48–51.
Force on Practice Guidelines (Writing Committee to Develop Guidelines on doi: 10.1016/j.ihj.2015.08.022.
the Management of Adults With Congenital Heart Disease). Circulation. 17. Shuler CO, Black GB, Jerrell JM. Population-based treated prevalence
2008;118:e714–e833. doi: 10.1161/CIRCULATIONAHA.108.190690. of congenital heart disease in a pediatric cohort. Pediatr Cardiol.
2. Fteropoulli T, Stygall J, Cullen S, Deanfield J, Newman SP. Quality of life 2013;34:606–611. doi: 10.1007/s00246-012-0505-3.
of adult congenital heart disease patients: a systematic review of the 18. Benziger CP, Stout K, Zaragoza-Macias E, Bertozzi-Villa A, Flaxman AD.
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journal.pgen.1006335. Kotani K, Tsogzolbaatar EO, Yanagawa H. Epidemiologic features of
104. Zaidi S, Choi M, Wakimoto H, Ma L, Jiang J, Overton JD, Romano- Kawasaki disease in Japan: results of the 2009-2010 nationwide survey.
Adesman A, Bjornson RD, Breitbart RE, Brown KK, Carriero NJ, Cheung J Epidemiol. 2012;22:216–221.
YH, Deanfield J, DePalma S, Fakhro KA, Glessner J, Hakonarson H, Italia 121. Salo E, Griffiths EP, Farstad T, Schiller B, Nakamura Y, Yashiro M,
MJ, Kaltman JR, Kaski J, Kim R, Kline JK, Lee T, Leipzig J, Lopez A, Mane Uehara R, Best BM, Burns JC. Incidence of Kawasaki disease in north-
SM, Mitchell LE, Newburger JW, Parfenov M, Pe’er I, Porter G, Roberts ern European countries. Pediatr Int. 2012;54:770–772. doi: 10.1111/j.
AE, Sachidanandam R, Sanders SJ, Seiden HS, State MW, Subramanian 1442-200X.2012.03692.x.
S, Tikhonova IR, Wang W, Warburton D, White PS, Williams IA, Zhao 122. Holman RC, Christensen KY, Belay ED, Steiner CA, Effler PV, Miyamura
H, Seidman JG, Brueckner M, Chung WK, Gelb BD, Goldmuntz E, J, Forbes S, Schonberger LB, Melish M. Racial/ethnic differences in the
Seidman CE, Lifton RP. De novo mutations in histone-modifying genes incidence of Kawasaki syndrome among children in Hawaii. Hawaii Med
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105. Kumar A, Singh S. BCG site reactivation in Kawasaki disease. Arthritis LB, Nakamura Y, Yashiro M, Belay ED. Recurrent Kawasaki disease: USA
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Numano F, Burns JC. The spectrum of cardiovascular lesions requiring T, Hara T, Hamaoka K, Ogawa S, Miura M, Nomura Y, Fuse S, Ichida F,
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15. DISORDERS OF HEART RHYTHM Abbreviations Used in Chapter 15 Continued
CLINICAL STATEMENTS
EMPHASIS-HF Eplerenone in Mild Patients Hospitalization and Survival
AND GUIDELINES
Study in Heart Failure
through 15-12 EPIC-Norfolk European Prospective Investigation Into Cancer and
Nutrition—Norfolk Cohort
Click here to return to the Table of Contents ESRD end-stage renal disease
FIT Henry Ford Exercise Testing
Bradyarrhythmias GBD Global Burden of Disease
ICD-9 426.0, 426.1, 427.81; ICD-10 I44.0 to GWAS genome-wide association studies
I44.3, I49.5. HD heart disease
2015: Mortality—1094. Any-mention mortality—5921. HF heart failure
2014: Hospital discharges—94 000. HR hazard ratio
Pacemakers: ICD-9-CM 37.7 to 37.8, 00.50, 00.53.
ICD-9-CM International Classification of Diseases, 9th Revision,
Mean hospital charges: $83 521; in-hospital death Clinical Modification
rate: 1.46%; mean length of stay: 5.1 days. ICD-10 International Classification of Diseases, 10th Revision
IQR interquartile range
AV Block JLNS Jervell and Lange-Nielsen syndrome
Look AHEAD Look: Action for Health in Diabetes
Prevalence and Incidence LQTS long-QT syndrome
• In a healthy sample of participants from the ARIC LV left ventricular
study (mean age 53 years), the prevalence of LVEF left ventricular ejection fraction
MET metabolic equivalent
Abbreviations Used in Chapter 15 MI myocardial infarction
ACCORD Action to Control Cardiovascular Risk in Diabetes NCDR National Cardiovascular Data Registry
AF atrial fibrillation NCHS National Center for Health Statistics
AMI acute myocardial infarction NH non-Hispanic
ARIC Atherosclerosis Risk in Communities study NHAMCS National Hospital Ambulatory Medical Care Survey
ARVC arrhythmogenic right ventricular cardiomyopathy NHDS National Hospital Discharge Survey
ASSERT Asymptomatic Atrial Fibrillation and Stroke Evaluation in NHLBI National Heart, Lung, and Blood Institute
Pacemaker Patients and the Atrial Fibrillation Reduction NSTEMI non–ST -segment–elevation myocardial infarction
Atrial Pacing Trial OHCA out-of-hospital cardiac arrest
AV atrioventricular OPERA Oulu Project Elucidating Risk of Atherosclerosis
BMI body mass index OR odds ratio
BNP B-type natriuretic peptide ORBIT-AF Outcomes Registry for Better Informed Treatment of
BP blood pressure Atrial Fibrillation
CABG coronary artery bypass graft PAR population attributable risk
CAD coronary artery disease PREVEND Prevention of Renal and Vascular End-Stage Disease
CARDIA Coronary Artery Risk Development in Young Adults PVC premature ventricular contraction
CHA2DS2-VASc Clinical prediction rule for estimating the risk of stroke PVT polymorphic ventricular tachycardia
based on congestive heart failure, hypertension, QALY quality-adjusted life-year
diabetes mellitus, and sex (1 point each); age ≥75 y and QTc corrected QT interval
stroke/transient ischemic attack/thromboembolism (2
points each); plus history of vascular disease, age 65–74
RE-LY Randomized Evaluation of Long-term Anticoagulant
y, and (female) sex category
Therapy
CHADS2 Clinical prediction rule for estimating the risk of stroke
RR relative risk
based on congestive heart failure, hypertension, age
≥75 y, diabetes mellitus (1 point each), and prior stroke/ RWS Romano-Ward syndrome
transient ischemic attack/thromboembolism (2 points) SBP systolic blood pressure
CHARGE-AF Cohorts for Heart and Aging Research in Genomic SCD sudden cardiac death
Epidemiology–Atrial Fibrillation SNP single-nucleotide polymorphism
CHD coronary heart disease STEMI ST-segment–elevation myocardial infarction
CHS Cardiovascular Health Study STROKESTOP Systematic ECG Screening for Atrial Fibrillation
CI confidence interval Among75-Year-Old Subjects in the Region of Stockholm
CKD chronic kidney disease and Halland, Sweden
CPVT catecholaminergic polymorphic ventricular tachycardia SVT supraventricular tachycardia
CVD cardiovascular disease TAVR transcatheter aortic valve replacement
DALY disability-adjusted life-year TdP torsade de pointes
DM diabetes mellitus UI uncertainty interval
ECG electrocardiogram USD US dollars
ED emergency department VF ventricular fibrillation
EF ejection fraction VT ventricular tachycardia
(Continued ) WPW Wolff-Parkinson-White

first-degree AV block was 7.8% in black males, and all-cause mortality (HR, 1.44; 95% CI, 1.09–
CLINICAL STATEMENTS
3.0% in black females, 2.1% in white males, 1.91).14 Compared with people with a PR inter-
AND GUIDELINES
and 1.3% in white females.1 Lower prevalence val ≤200 ms, those with a PR interval >200 ms
estimates were noted in the relatively younger had an absolute increased risk per year of 1.04%
population (mean age 45 years) of the CARDIA for AF, 0.53% for pacemaker implantation, and
study at its year 20 follow-up examination: 2.6% 2.05% for death (Chart 15-1).14
in black males, 1.9% in black females, 1.2% in • Patients with abnormalities of AV conduction
white males, and 0.1% in white females.2 may be asymptomatic or may experience seri-
• The prevalence of PR interval prolongation was ous symptoms related to bradycardia, ventricular
observed to be 2.1% in Finnish middle-aged arrhythmias, or both.14
people, but the authors noted that the PR inter- • Decisions about the need for a pacemaker are
val normalized in follow-up in 30% of these influenced by the presence or absence of symp-
people.3 toms directly attributable to bradycardia and the
• Mobitz II second-degree AV block is rare in likelihood of the arrhythmia to progress to com-
healthy individuals (≈0.003%), whereas Mobitz I plete heart block. Permanent pacing improves
(Wenckebach) is observed in 1% to 2% of healthy survival in patients with third-degree AV block,
young people, especially during sleep.4,5 especially if syncope has occurred.16
• The prevalence of third-degree AV block in the • In a large prospective regional French registry of
general adult population is ≈0.02% to 0.04%.6,7 6662 STEMI patients (2006–2013), high-degree
• Third-degree AV block is very rare in appar- AV block was noted in 3.5% of individuals. In the
ently healthy people. Johnson et al8 found majority of cases (63.7%), high-degree AV block
only 1 case among >67 000 symptom-free US was present on admission. Although patients with
Air Force males; Rose et al,9 in their study of high-degree AV block on admission or occurring
>18 000 civil servants, did not find any cases. On during the first 24 hours of hospitalization had
the other hand, among 293 124 patients with higher in-hospital mortality rates than patients
DM and 552 624 with hypertension enrolled without heart block, it was not an indepen-
with Veterans Health Administration hospitals, dent marker of mortality risk after multivariable
third-degree AV block was present in 1.1% and analysis.17
• Although there is little evidence to suggest that
0.6%, respectively.10
• Investigators have evaluated more contemporary pacemakers improve survival in patients with iso-
results from a novel, long-term ambulatory elec- lated first-degree AV block,18 it is recognized that
trocardiographic monitoring system to measure marked first-degree AV block (PR >300 ms) can
the burden and timing of various arrhythmias. lead to symptoms even in the absence of higher
The ZIO Patch is a lightweight, lead-wire-free, sin- degrees of AV block.19
gle-patient-use electrocardiographic monitor that Prognosis
adheres to the left upper chest and records and • Investigators at Northwestern University com-
stores up to 14 days of continuous, beat-to-beat pared older adult outpatients (>60 years old)
ECG. After evaluating 122 815 ZIO Patch record- with (N=470) and without (N=2090) asymp-
ings contributed by 122 454 patients, high-grade tomatic bradycardia. Over a mean follow-up of
AV block (defined as either Mobitz II or complete 7.2 years, patients with asymptomatic brady-
heart block) was present in 1486 tracings (1.2% cardia had a higher adjusted incidence of pace-
of all tracings).11 maker insertion (HR, 2.14; 95% CI, 1.30–3.51;
• Congenital complete AV block is estimated to P=0.003), which appeared after a lag time of 4
occur in 1 of 15 000 to 20 000 live births,12 An years. However, the absolute rate of pacemaker
English register study estimated the incidence implantation was low (<1% per year), and
of infant complete AV block as 2.1 per 100 000 asymptomatic bradycardia was not associated
live births.13 Congenital complete heart block with a higher risk of death.20
could be attributable to transplacental transfer of
maternal anti-SSA/Ro or SSB/La antibodies.12 Risk Factors
• In healthy individuals without CVD or its risk
Complications factors from MESA, PR interval was longer with
(See Chart 15-1) advancing age, in males compared with females,
• In the FHS, PR interval prolongation (>200 ms) and in blacks compared with whites.21
was associated with an increased risk of AF • Although first-degree AV block and Mobitz type I
(HR, 2.06; 95% CI, 1.36–3.12),14,15 pacemaker second-degree AV block can occur in apparently
implantation (HR, 2.89; 95% CI, 1.83–4.57),14 healthy people, presence of Mobitz II second- or

third-degree AV block usually indicates underlying Complications
CLINICAL STATEMENTS
HD, including CHD and HF.5 (See Chart 15-2)
AND GUIDELINES
• Reversible causes of AV block include electro- • In a small prospective study of 35 patients ≥45
lyte abnormalities, drug-induced AV block, peri- years of age with sinus node dysfunction, 57%
operative AV block attributable to hypothermia, experienced symptoms over a 4-year follow-up
or inflammation near the AV conduction sys- period if untreated; 31% experienced syncope
tem after surgery in this region. Some condi- over the same period.31
tions might warrant pacemaker implantation • Approximately 50% of patients with sinus node
because of the possibility of disease progres- dysfunction develop tachy-brady syndrome over
sion even if the AV block reverses transiently a lifetime; such patients have a higher risk of
(eg, sarcoidosis, amyloidosis, and neuromuscu- stroke and death. The survival of patients with
lar diseases).16 sinus node dysfunction appears to depend pri-
• TAVR that uses a balloon-expandable valve is marily on the severity of underlying cardiac
associated with an increased rate of perma- disease and is not significantly changed by pace-
nent pacemaker implantation if there is heavy maker therapy.32–34
calcification and right bundle-branch block • In a retrospective study,35 patients with sinus
present.22,23 node dysfunction who had pacemaker therapy
• Long sinus pauses and AV block can occur during were followed up for 12 years; at 8 years, mor-
sleep apnea. In the absence of symptoms, these tality among those with ventricular pacing was
abnormalities are reversible and do not require 59% compared with 23% among those with
pacing.24 atrial pacing. This discrepancy can be attributed
to selection bias. For instance, the physiological
Prevention
or anatomic disorder (eg, fibrosis of conductive
• Detection and correction of reversible causes of
tissue) that led to the requirement for the particu-
acquired AV block could be of potential impor-
lar pacemaker might have influenced prognosis,
tance in preventing symptomatic bradycardia and
rather than the type of pacemaker used.
other complications of AV block.16
• In a multicenter study from the Netherlands of
• In utero detection of congenital AV block is pos-
people with bradycardia treated with pacemaker
sible by echocardiography.25
implantation, the actuarial 1-, 3-, 5-, and 7-year

survival rates were 93%, 81%, 69%, and 61%,
Sinus Node Dysfunction respectively. Individuals without CVD at baseline
had similar survival rates as age- and sex-matched
Prevalence and Incidence
control subjects.36
• The prevalence of sinus node dysfunction has
• With sinus node dysfunction, the incidence of
been estimated to be between 403 and 666 per
sudden death is extremely low, and pacemaker
million, with an incidence rate of 63 per million
implantation does not appear to alter longevity.16,37
per year requiring pacemaker therapy.26
• SVT including AF was prevalent in 53% of patients
• Sinus node dysfunction occurs in 1 of every 600
with sinus node dysfunction.33
cardiac patients >65 years of age and accounts
• On the basis of records from the NHDS, age-
for ≈50% of implantations of pacemakers in the
adjusted pacemaker implantation rates increased
United States.27,28
progressively from 370 per million in 1990 to 612
• Sinus node dysfunction is commonly present with
per million in 2002. This escalating implantation
other causes of bradyarrhythmias (carotid sinus
rate is attributable to increasing implantation for
hypersensitivity in 33% of patients and advanced
isolated sinus node dysfunction; implantation
AV conduction abnormalities in 17%).26,29
for sinus node dysfunction increased by 102%,
• The incidence rate of sick sinus syndrome was
whereas implantation for all other indications did
0.8 per 1000 person-years of follow-up in 2 bira-
not increase (Chart 15-2).38
cial US cohorts, ARIC and CHS.30 The incidence
• In patients paced for sick sinus syndrome, the
increased with advancing age (HR, 1.73; 95%
CHA2DS2-VASc score is associated with an
CI, 1.47–2.05 per 5-year increment), and blacks
increased risk of stroke and death, even in those
were at 41% lower risk of sick sinus syndrome
patients without AF at baseline.39
than their white counterparts (HR, 0.59; 95% CI,
0.37–0.98). Investigators projected that in the Risk Factors
United States, the number of new cases of sick • The causes of sinus node dysfunction can be clas-
sinus syndrome per year would rise from 78 000 sified as intrinsic (secondary to pathological condi-
in 2012 to 172 000 in 2060. tions involving the sinus node) or extrinsic (caused

by depression of sinus node function by external 604 middle-aged individuals in the Finnish OPERA
CLINICAL STATEMENTS
factors such as drugs or autonomic influences).40 study, 7 (1.2%) fulfilled the diagnostic criteria for
AND GUIDELINES
• Idiopathic degenerative disease is probably the inappropriate sinus tachycardia.47

most common cause of sinus node dysfunction.41 • Of 1383 participants in the Baltimore Longitudinal
• Collected data from 28 different studies on atrial Study of Aging undergoing maximal exercise test-
pacing for sinus node dysfunction showed a ing, 6% exhibited SVT during the test; increas-
median annual incidence of second- and third- ing age was a significant risk factor. Only 16%
degree AV block of 0.6% (range, 0%–4.5%) exhibited >10 beats of SVT, and only 4% were
and an overall prevalence of 2.1% (range, symptomatic. Over an average of 6 years of fol-
0%–11.9%). This suggests that the degenera- low-up, people with exercise-induced SVT were
tive process also affects the specialized conduc- more likely to develop SVT or AF.48
tion system, although the rate of progression is • In a study of males applying for a pilot’s license,
slow and does not dominate the clinical course of the surface ECG revealed that the prevalence of
disease.42 ectopic atrial tachycardia was estimated to be
• IHD may be responsible for one third of sinus 0.34% in asymptomatic patients and 0.46% in
node dysfunction cases. Transient sinus node symptomatic patients.49
dysfunction can complicate MI; it is common
Complications
during inferior MI and is caused by autonomic
• Rare cases of incessant SVT can lead to a tachy-
influences. Cardiomyopathy, long-standing
cardia-induced cardiomyopathy,50 and rare cases
hypertension, infiltrative disorders (eg, amyloi-
of sudden death attributed to SVT as a trigger
dosis and sarcoidosis), collagen vascular disease, have been described.51
and surgical trauma can also result in sinus node • Among 2 350 328 females included in Taiwan’s
dysfunction.43,44 national birth registry between 2001 and 2012,
• In the CHS and ARIC studies, factors associated 769 experienced paroxysmal SVT during preg-
with incident sick sinus syndrome included white nancy. Compared with those females without par-
(versus black) race, higher mean BMI, height, oxysmal SVT during pregnancy, paroxysmal SVT
prevalent hypertension, lower heart rate, right during pregnancy was associated with a higher
bundle-branch block, N-terminal pro-BNP, cys- risk for maternal morbidity, cesarean delivery, low
tatin C, and history of a major cardiovascular birth weight, preterm labor, fetal stress, and obvi-
event.30 ous fetal abnormalities.52
• A California administrative database study sug-
SVT (Excluding AF and Atrial Flutter) gested that after the exclusion of people with
ICD-9 427.0; ICD-10 I47.1. diagnosed AF, SVT was associated with an
adjusted doubling of the risk of stroke in follow-
Mortality—155. Any-mention mortality—1413. Hospital up (HR, 2.10; 95% CI, 1.69–2.62). The absolute
discharges—15 000 (6000 male; 9000 female). stroke rate was low, however. The cumulative
stroke rate was 0.94% (95% CI, 0.76%–1.16%)
over 1 year in patients with SVT versus 0.21%
(See Chart 15-3)
(95% CI, 0.21%–0.22%; P<0.001, log-rank test)
• Data from the Marshfield Epidemiologic Study
in those without SVT.53
Area in Wisconsin suggested the incidence of
documented paroxysmal SVT was 35 per 100 000 Specific Types
person-years. The mean age at SVT onset was 57 • Among those presenting for invasive electrophysi-
years, and both female sex and age >65 years ological study and ablation, AV nodal reentrant
were significant risk factors (Chart 15-3).45 tachycardia (a circuit that requires 2 AV nodal
• A review of ED visits from 1993 to 2003 revealed pathways) is the most common mechanism of
that an estimated 550 000 visits were for SVT SVT54,55 and usually represents the majority of
(0.05% of all visits; 95% CI, 0.04%–0.06%), or cases (56% of 1 series of 1754 cases from Loyola
≈50 000 visits per year. Of these patients, 24% University Medical Center).55
(95% CI, 15%–34%) were admitted to the hos- • AV reentrant tachycardia (an arrhythmia that
pital, and 44% (95% CI, 32%–56%) were dis- requires the presence of an extranodal connection
charged without specific follow-up.46 between the atria and ventricles or specialized
• The prevalence of SVT that is clinically undetected conduction tissue) is the second most com-
is likely much greater than the estimates from ED mon56,57 type of SVT (27% in the Loyola series),55
visits and electrophysiology procedures would and atrial tachycardia is the third most common
suggest. For example, among a random sample of (17% in the Loyola series).55

• In the pediatric population, AV reentrant tachy- the shortest R-R interval during AF) can help risk
CLINICAL STATEMENTS
cardia is the most common SVT mechanism, fol- stratify these patients.63,68
AND GUIDELINES
lowed by AV nodal reentrant tachycardia and • In a single-center prospective registry study of
then atrial tachycardia.58 2169 patients who agreed to undergo an electro-
• AV reentrant tachycardia prevalence decreases physiology study for WPW syndrome from 2005 to
with age, whereas AV nodal reentrant tachycardia 2010, 1168 patients (206 asymptomatic) under-
and atrial tachycardia prevalence increase with went radiofrequency ablation, none of whom had
advancing age.55 malignant arrhythmias or VF in up to 8 years of
• The majority of AV reentrant tachycardia patients follow-up. Of those who did not receive radiofre-
in the Loyola series were males (55%), whereas quency ablation (N=1001; 550 asymptomatic) in
the majority of patients with AV nodal reentrant follow-up, 1.5% had VF, most of whom (13 of
tachycardia (70%) or atrial tachycardia (62%) 15) were children. The authors noted that poor
were females.55 prognosis was related to accessory pathway elec-
• Multifocal atrial tachycardia is an arrhythmia that trophysiological properties rather than patient
is commonly confused with AF and is character- symptoms.69
ized by 3 distinct P-wave morphologies, irregular • In a meta-analysis of 20 studies involving 1869
R-R intervals, and a rate >100 beats per minute. It asymptomatic patients with a WPW electrocar-
is uncommon in both children56 and adults,57 with diographic pattern followed up for a total of
a prevalence in hospitalized adults estimated at 11 722 person-years, the risk of sudden death in
0.05% to 0.32%.59,60 The average age of onset a random effects model that was used because of
in adults is 70 to 72 years. Adults with multifo- heterogeneity across studies was estimated to be
cal atrial tachycardia have a high mortality rate, 1.25 (95% CI, 0.57–2.19) per 1000 person-years.
with estimates around 45%, but this is generally Risk factors for sudden death included male sex,
ascribed to the underlying condition(s).57,61 inclusion in a study of children (<18 years of age),
and inclusion in an Italian study.70
WPW Syndrome • Although some studies in asymptomatic children
with ventricular preexcitation suggest a benign
Prevalence
prognosis,66,71 others suggest that electrophysi-
• WPW syndrome was observed in 0.11% of
ological testing can identify a group of asymp-
males and 0.04% of females among 47 358

tomatic children with a risk of sudden death or
ECGs from adults participating in 4 large Belgian
VF as high as 11% over 19 months of follow-
epidemiological studies.59 In a study of 32 837
up.72 In a pediatric hospital retrospective review
Japanese students who were required by law to
of 444 children with WPW syndrome, 64% were
receive ECGs before entering school, WPW was
symptomatic at presentation, and 20% had onset
reported in 0.073%, 0.070%, and 0.174% of
of symptoms during follow-up. The incidence of
elementary, junior high, and high school students,
sudden death was 1.1 per 1000 person-years in
respectively.60
patients without structural HD.73
Complications
• WPW syndrome, a diagnosis reserved for those
with both ventricular preexcitation (evidence of an Subclinical Atrial Tachyarrhythmias,
anterograde conducting AV accessory pathway on Unrecognized AF, Screening for AF
a 12-lead ECG) and tachyarrhythmias,62 deserves Device-Detected AF
special attention because of the associated risk of • Pacemakers and defibrillators have increased cli-
sudden death. Sudden death is generally attrib- nician awareness of the frequency of subclinical
uted to rapid heart rates in AF conducting down AF and atrial high-rate episodes in people with-
an accessory pathway and leading to VF.63,64 Of out a documented history of AF. Several studies
note, AF is common in WPW patients, and surgi- have suggested that device-detected high-rate
cal or catheter ablation of the accessory pathway atrial tachyarrhythmias are surprisingly frequent
often results in elimination of the AF.65 and are associated with an increased risk of AF,68
• Asymptomatic adults with ventricular preex- thromboembolism,68,74 and total mortality.68
citation appear to be at no increased risk of • Investigators in the ASSERT study prospectively
sudden death compared with the general popu- enrolled 2580 patients with a recent pacemaker
lation,63,64,66,67 although certain characteristics or defibrillator implantation who were ≥65 years
found during invasive electrophysiological study of age, had a history of hypertension, and had
(including inducibility of AV reentrant tachycardia no history of AF. They classified individuals by
or AF, accessory pathway refractory period, and presence versus absence of subclinical atrial

tachyarrhythmias (defined as atrial rate >190 • In a community-based study in Sweden

CLINICAL STATEMENTS
beats per minute for >6 minutes in the first 3 (STROKESTOP study), half of the population 75
AND GUIDELINES
months) and conducted follow-up for 2.5 years.75 to 76 years of age were invited to a stepwise
Subclinical atrial tachyarrhythmias in the first 3 screening program for AF, and 7173 participated
months occurred in 10.1% of the patients and in the screening, of whom 218 had newly diag-
were associated with the following75: nosed AF (3.0%; 95% CI, 2.7%–3.5%) and an
— An almost 6-fold higher risk of clinical AF additional 666 (9.3%; 95% CI, 8.6%–10.0%)
(HR, 5.56; 95% CI, 3.78–8.17; P<0.001) had previously diagnosed AF. Of the 218 newly
— A more than doubling in the adjusted risk diagnosed AF cases, only 37 were diagnosed by
of the primary end point, ischemic stroke or screening electrocardiography, whereas intermit-
systemic embolism (HR, 2.50; 95% CI, 1.28– tent monitoring detected 4 times as many cases.
4.89; P<0.008) Of those individuals with newly diagnosed AF,
— An annual ischemic stroke or systemic embo- 93% initiated treatment with oral anticoagulant
lism rate of 1.69% (versus 0.69% in those drugs.81
without) • There have been 2 recent systematic reviews
— A 13% PAR for ischemic stroke or systemic regarding the effectiveness of screening to detect
embolism unknown AF.
— Over the subsequent 2.5 years of follow- — Lowres et al82 identified 30 separate studies
up, an additional 34.7% of the patients had that included outpatient clinics or community
subclinical atrial tachyarrhythmias, which screening. In individuals without a prior diag-
were 8-fold more frequent than clinical AF nosis of AF, they observed that 1.0% (95%
episodes. CI, 0.89%–1.04%) of those screened had
• A pooled analysis of 5 prospective studies in AF (14 studies, N=67 772), whereas among
patients without permanent AF revealed that those individuals ≥65 years of age, 1.4%
over 2 years of follow-up, cardiac implanted elec- (95% CI, 1.2%–1.6%; 8 studies, N=18 189)
tronic devices detected ≥5 minutes of AF in 43% had AF.
of the patients (total N=10 016). Adjustment for — Another systematic review by Moran et al83
CHADS2 score and anticoagulation revealed that observed that in individuals >65 years of
AF burden was associated with an increased risk age, systematic screening (OR, 1.57; 95% CI,
of stroke.76 1.08–2.26) and opportunistic screening (OR,
• The temporal association of AF and stroke 1.58; 95% CI, 1.10–2.29) were associated
risk was evaluated in a case-crossover analysis with enhanced detection of AF. The number
among 9850 patients with cardiac implant- needed to screen by either method was ≈170
able electronic devices enrolled in the Veterans individuals.
Health Administration healthcare system. The • At present, the detection of AF, even in an asymp-
OR for an acute ischemic stroke was the highest tomatic stage, is the basis for risk stratification
within a 5-day period after a qualifying AF epi- for stroke and appropriate decision making on
sode, which was defined as at least 5.5 hours of the need for anticoagulant drugs. Ongoing trials
AF on a given day. This estimate reduced as the are evaluating the risks and benefits of antico-
period after the AF occurrence extended beyond agulation among patients at high risk for stroke
30 days.77 but without a prior history of AF. The findings
from these studies will help to determine opti-
Community Screening mal strategies for subclinical AF screening and
• The incidence of detecting previously undiag- treatment.78
nosed AF by screening depends on the underlying
risk of AF in the population studied, the intensity
and duration of screening, and the method used AF and Atrial Flutter
to detect AF.78 Prevalence
• Methods vary in their sensitivity and specific- (See Chart 15-4)
ity in the detection of undiagnosed AF, increas- • Estimates of the prevalence of AF in the United
ing from palpation, to devices such as handheld States ranged from ≈2.7 million to 6.1 million in
single-lead ECGs, modified BP devices, and 2010,84,85 and AF prevalence is estimated to rise to
plethysmographs78 12.1 million in 2030 (Chart 15-4).86
• There has been increasing interest in the use of • In the European Union, the prevalence of AF in
smart phone technology to aid in community adults >55 years of age was estimated to be 8.8
screening.79,80 million (95% CI, 6.5–12.3 million) in 2010 and

was projected to rise to 17.9 million in 2060 Lifetime Risk and Cumulative Risk
CLINICAL STATEMENTS
(95% CI, 13.6–23.7 million).87 (See Chart 15-6)
AND GUIDELINES
• Data from a California health plan suggest • Participants of largely European ancestry in the
that compared with whites, blacks (OR, 0.49; NHLBI-sponsored FHS were followed up from
95% CI, 0.47–0.52), Asians (OR, 0.68; 95% CI, 1968 to 1999. At 40 years of age, remaining
0.64–0.72), and Hispanics (OR, 0.58; 95% CI, lifetime risks for AF were 26.0% for males and
0.55–0.61) have a significantly lower adjusted 23.0% for females. At 80 years of age, lifetime
prevalence of AF.88 risks for AF were 22.7% for males and 21.6% for
• Among Medicare patients aged ≥65 years females (Chart 15-6).92 In further analysis, count-
who were diagnosed from 1993 to 2007, the ing only those who had development of AF with-
prevalence of AF increased ≈5% per year, from out prior or concurrent HF or MI, lifetime risk for
≈41.1 per 1000 beneficiaries to 85.5 per 1000 AF was ≈16%.92 Estimates of lifetime risks of AF
beneficiaries.89 were similar in the Rotterdam Study.93
— In 2007 in the 5% Medicare sample, there • In a medical insurance database study from the
were 105 701 older adults with AF: 3.7% Yunnan Province in China, the estimated lifetime
were black, 93.8% were white, and 2.6% risk of AF at age 55 years was 21.1% (95% CI,
were other/unknown race.89 19.3%–23.0%) for females and 16.7% (95% CI,
— The prevalence rate per 1000 beneficiaries 15.4%–18.0%) for males.94
was 46.3 in blacks, 90.8 in whites, and 47.5 • Investigators from the NHLBI-sponsored ARIC
in other/unknown race.89 study observed that the cumulative risk of AF was
21% in white males, 17% in white females, and
Incidence 11% in African Americans of both sexes by 80
(See Table 15-1 and Chart 15-5) years of age.95
• Investigators from MESA estimated the age- and
sex-adjusted incidence rate of hospitalized AF Mortality
per 1000 person-years (95% CI) as 11.2 (9.8– (See Chart 15-7)
12.8) in NH whites, 6.1 (4.7–7.8) in Hispanics, ICD-9 427.3; ICD-10 I48.
5.8 (4.8–7.0) in NH blacks, and 3.9 (2.5–6.1) in In 2015, AF was the underlying cause of death in
Chinese.90 23 862 people and was listed on 148 672 US death
• Five years after diagnosis with AF, the cumulative certificates (any-mention mortality). In addition, the
incidence rate of mortality, HF, MI, stroke, and age-adjusted mortality rate was 6.3 per 100 000 peo-
gastrointestinal bleeding was higher in older age ple in 2015.96
groups (80–84, 85–89, and ≥90 years old) than in • In adjusted analyses from the FHS, AF was associ-
younger age groups (67–69, 70–74, and 75–79 ated with an increased risk of death in both males
years of age) (Table 15-1). (OR, 1.5; 95% CI, 1.2–1.8) and females (OR, 1.9;
• Data from California administrative databases 95% CI, 1.5–2.2).97 Furthermore, there was an
were analyzed with regard to racial variation in interaction with sex, such that AF appeared to
incidence of AF. After adjustment for AF risk fac- diminish the survival advantage typically observed
tors, compared with their white counterparts, in females.
lower incidence rates were found in blacks (HR, • Although there was significant between-study
0.84; 95% CI, 0.82–0.85; P<0.001), Hispanics heterogeneity (P<0.001), a meta-analysis con-
(HR, 0.78; 95% CI, 0.77–0.79; P<0.001), and firmed that the adjusted risk of death was signifi-
Asians (HR, 0.78; 95% CI, 0.77–0.79; P<0.001) cantly stronger in females than in males with AF
(Chart 15-5).91 (RR, 1.12; 95% CI, 1.07–1.17).98
• In a Medicare sample, the incidence of AF was • In Medicare beneficiaries ≥65 years of age with
≈28 per 1000 person-years and did not change new-onset AF, mortality decreased modestly but
substantively between 1993 and 2007. Of indi- significantly between 1993 and 2007. In 2007,
viduals with incident AF in 2007, ≈55% were the age- and sex-adjusted mortality at 30 days
females, 91% were white, 84% had hyperten- was 11%, and at 1 year, it was 25%.89
sion, 36% had HF, and 30% had cerebrovascular • An observational study from Rochester County,
disease.89 MN, of >4600 patients diagnosed with first
• Using data from a health insurance claims data- AF showed that risk of death within the first 4
base covering 5% of the United States, the inci- months after the AF diagnosis was high. The most
dence of AF was estimated at 1.6 million cases in common causes of CVD death were CAD, HF, and
2010 and was projected to increase to 2.6 million ischemic stroke, which accounted for 22%, 14%,
cases in 2030.86 and 10%, respectively, of the early deaths (within

the first 4 months) and 15%, 16%, and 7%, risk of death compared with patients with neither
CLINICAL STATEMENTS
respectively, of the late deaths.99 event.118

AND GUIDELINES
• Although stroke is the most feared complication Stroke

of AF, a recent clinical trial (RE-LY) reported that (See Chart 15-7)
stroke accounted for only ≈7.0% of deaths in AF, • Stroke rates per 1000 patient-years declined in
with SCD (22.25%), progressive HF (15.1%), and AF patients taking anticoagulant drugs, from
noncardiovascular death (35.8%) accounting for 46.7 in 1992 to 19.5 in 2002, for ischemic stroke
the majority of deaths.100 but remained fairly steady for hemorrhagic stroke
• AF is also associated with increased mortality (range, 1.6–2.9).119
in individuals with other cardiovascular condi- • Before the widespread use of anticoagulant
tions and procedures, including HF,101,102 HF with drugs, after accounting for standard stroke risk
preserved EF103,104 and reduced EF,103 MI,105,106 factors, AF was associated with a 4- to 5-fold
CABG107,108 (both short-term and long-term108), increased risk of ischemic stroke.120 Although
and stroke.109 In noncardiovascular conditions, AF the RR of stroke associated with AF did not vary
is also associated with an increased risk of death, (≈3- to 5-fold increased risk) substantively with
including in DM,110 ESRD,111 sepsis,112,113 and non- advancing age, the proportion of strokes attribut-
cardiac surgery.114 able to AF increased significantly. In the FHS, AF
• In Medicare unadjusted analysis, blacks and accounted for ≈1.5% of strokes in individuals 50
Hispanics had a higher risk of death than their to 59 years of age and ≈23.5% in those 80 to 89
white counterparts with AF; however, after adjust- years of age.120
ment for comorbidities, blacks (HR, 0.95; 95% CI, • AF was also an independent risk factor for ischemic
0.93–0.96; P<0.001) and Hispanics (HR, 0.82; stroke severity, recurrence, and mortality.109 In an
95% CI, 0.80–0.84; P<0.001) had a lower risk of observational study, at 5 years only 39.2% (95%
death than whites with AF.115 In contrast, in the CI, 31.5%–46.8%) of ischemic stroke patients
population-based ARIC study, the rate difference with AF were alive, and 21.5% (95% CI, 14.5%–
for all-cause mortality for individuals with versus 31.3%) had experienced recurrent stroke.121 In 1
without AF was 106.0 (95% CI, 86.0–125.9) in study, individuals who had AF and were not treated
blacks, which was higher than the 55.9 (95% CI, with anticoagulant drugs had a 2.1-fold increase in
48.1–63.7) rate difference in mortality observed
risk for recurrent stroke and a 2.4-fold increase in

for whites.116 risk for recurrent severe stroke.122
Complications • Studies have demonstrated an underutilization
of warfarin therapy. In a recent meta-analysis,
Thromboembolism Excluding Stroke males and individuals with prior stroke were more
• In a Danish population-based registry of individ- likely to receive warfarin, whereas factors associ-
uals 50 to 89 years of age discharged from the ated with lower use included alcohol and drug
hospital, individuals with new-onset AF had an abuse, noncompliance, warfarin contraindica-
elevated risk of thromboembolic events to the tions, dementia, falls, both gastrointestinal and
aorta, renal mesenteric, pelvic, and peripheral intracranial hemorrhage, renal impairment, and
arteries. The event rate was 2 to 10 per 1000 advancing age.123 The underutilization of antico-
person-years. Compared with referents in the agulation in AF has been demonstrated to be a
Danish population, the RR of diagnosed extracra- global problem.124
nial embolism was 4.0 (95% CI, 3.5–4.6) in males • In Medicare analyses that were adjusted for
and 5.7 (95% CI, 5.1–6.3) in females.117 comorbidities, blacks (HR, 1.46; 95% CI, 1.38–
Extracranial Systemic Embolic Events 1.55; P<0.001) and Hispanics (HR, 1.11; 95% CI,
• Investigators pooled data from 4 large contem- 1.03–1.18; P<0.001) had a higher risk of stroke
porary randomized anticoagulation trials and than whites with AF.115 The increased risk per-
observed 221 systemic emboli in 91 746 person- sisted in analyses adjusted for anticoagulant ther-
years of follow-up. Systemic embolic rate was 0.24 apy status. Additional analyses from the Medicare
versus a stroke rate of 1.92 per 100 person-years. registry demonstrate that the addition of African
Compared with individuals experiencing stroke, American race to the CHA2DS2-VASc scoring sys-
patients experiencing systemic emboli were more tem significantly improved the prediction of stroke
likely to be females (56% versus 47%; P=0.01) events among newly diagnosed AF patients ≥65
but had similar mean age and CHADS2 score as years of age.125
those with stroke. Both stroke (RR, 6.79; 95% CI, • A meta-analysis that examined stroke risk by sex
6.22–7.41) and systemic emboli (RR, 4.33; 95% and presence of AF reported that AF conferred
CI, 3.29–5.70) were associated with an increased a multivariable-adjusted 2-fold stroke risk in

females compared with males (RR, 1.99; 95% CI, a composite cardiovascular outcome (out-of-
CLINICAL STATEMENTS
1.46–2.71); however, the studies were noted to hospital death or hospitalization for stroke, MI, or
AND GUIDELINES
be significantly heterogeneous.98 hemorrhage).136
Anticoagulation Undertreatment Heart Failure
• In the NCDR’s Practice Innovation and Clinical (See Chart 15-7)
Excellence Registry of outpatients with AF, less • AF and HF share many antecedent risk factors,
than half of high-risk patients, defined as those and ≈40% of people with either AF or HF will
with a CHA2DS2-VASc score ≥4, were receiving an develop the other condition.102
oral anticoagulant prescription.126 • In the community, estimates of the incidence of
Cognition HF in individuals with AF ranged from 3.3102 to
Individuals with AF have an adjusted 2-fold increased 4.4137 per 100 person-years of follow-up.
risk of dementia.127 • Among older adults with AF in Medicare, the 5-year
• A meta-analysis of 21 studies indicated that AF event rate was high, with rates of death and HF
was associated with an increased risk of cogni- exceeding those for stroke (see Chart 15-7). Higher
tive impairment in patients after stroke (RR, 2.70; event rates after new-onset AF were associated
95% CI, 1.82–4.00) and in patients without a his- with older age and higher mean CHADS2 score.138
tory of stroke (RR 1.37; 95% CI, 1.08–1.73). The • Investigators examined the incidence rate of HF
risk of dementia was similarly increased (RR, 1.38; in individuals with systolic dysfunction versus pre-
95% CI, 1.22–1.56).128 served LVEF (<40% versus >50%, respectively)
• In individuals with AF in Olmsted County, MN, the in a Netherlands community-based cohort study
cumulative rate of dementia at 1 and 5 years was (PREVEND). Per 1000 person-years, the incidence
2.7% and 10.5%, respectively.129 rate of systolic HF was 12.75 versus 1.99 for those
with versus those without AF, with a multivari-
Physical Disability and Subjective Health
able-adjusted HR of AF of 5.79 (95% CI, 2.40–
• AF has been associated with physical disability,
13.98). Corresponding numbers for preserved EF
poor subjective health,130,131 and diminished qual-
were 4.90 versus 0.85 with and without AF, with
ity of life.132 A recent systematic review suggested
a multivariable-adjusted HR of AF of 4.80 (95%
that among people with AF, moderate-intensity
CI, 1.30–17.70).139
activity improved exercise capacity and quality of
life.133 Myocardial Infarction

(See Chart 15-7)
Falls
• In the REGARDS study, in models that adjusted
• In the REGARDS study, AF was significantly asso-
for standard risk factors, AF was associated with a
ciated with an adjusted higher risk of falls (10%)
70% increased risk of incident MI (HR, 1.96; 95%
than among those without AF (6.6%; OR, 1.22;
CI, 1.52–2.52); the risk was higher in females and
95% CI, 1.04–1.44). The presence of a history of
blacks. In individuals with AF, the age-adjusted
both AF and falls was associated with a signifi-
incidence rate per 1000 person-years was 12.0
cantly higher risk of mortality (per 1000 person-
(95% CI, 9.6–14.9) in those with AF compared
years: AF plus falls, 51.2; AF and no falls, 34.4;
with 6.0 (95% CI, 5.6–6.6) in those without AF.140
no AF and falls, 29.8; no AF and no falls, 15.6).
• In ARIC, AF was associated with an adjusted
Compared with those with neither AF nor falls,
increased risk of NSTEMI (HR, 1.80; 95% CI, 1.39–
those with both conditions had an adjusted
2.31) but not STEMI (P for comparison HR=0.004).132
2-fold increased risk of death (HR, 2.12; 95% CI,
1.64–2.74).134 Furthermore, the adjusted association between AF
• A systematic review and Markov decision analytic and NSTEMI was stronger in females (HR, 2.72;
modeling report focused on people with AF ≥65 95% CI, 1.98–3.74) than in males (HR, 1.21; 95%
years of age noted that warfarin treatment was CI, 0.82–1.78; Pinteraction<0.0002).
associated with 12.9 QALYs per patient with typi- • The CHS also observed a higher risk of incident MI
cal risks of stroke and falls versus 10.15 QALYs for in individuals with AF who were black (HR, 3.1;
those treated with neither warfarin nor aspirin. Of 95% CI, 1.7–5.6) than in whites (HR, 1.6; 95%
interest, sensitivity analyses of the probability of CI, 1.2–2.1; Pinteraction=0.03).141
falls or stroke did not substantively influence the Chronic Kidney Disease
results.135 • In a Japanese community-based study, individuals
• A Medicare study noted that patients at high risk with AF had approximately a doubling in increased
for falls with a CHADS2 score of at least 2 who risk of developing kidney dysfunction or protein-
had been prescribed warfarin had a 25% lower uria, even in those without baseline DM or hyper-
risk (HR, 0.75; 95% CI, 0.61–0.91; P=0.004) of tension. Per 1000 person-years of follow-up, the

incidence of kidney dysfunction was 6.8 in those Hospitalizations and Ambulatory Care
CLINICAL STATEMENTS
without and 18.2 in those with AF at baseline.142 Visits

AND GUIDELINES
• In a Kaiser Permanente study of people with CKD,

new-onset AF was associated with an adjusted • According to HCUP data in 2014, there were
1.67-fold increased risk of developing ESRD com- 454 000 hospital discharges with AF and atrial
pared with those without AF (74 versus 64 per flutter as the principal diagnosis, evenly split
1000 person-years of follow-up).143 between males and females (unpublished NHLBI
tabulation).
SCD and VF • The rate per 100 000 discharges increased with
• Among 2763 postmenopausal women with CHD advancing age, from 16.4 in those aged 18 to
enrolled in the Heart and Estrogen/Progestin 44 years, 149.6 in those 45 to 64 years, 593.1 in
Replacement Study, investigators sought to those 65 to 84 years, to 1159.5 in individuals ≥85
develop an SCD prediction model and identified years; however, 52.4% of all hospital discharges
AF as an independent risk factor, with an HR of for AF occurred in patients 65 to 84 years old.149
1.92 (95% CI, 1.02–3.61).144
• On the basis of Medicare and MarketScan data-
• In a study that examined data from 2 population-
bases, annually, people with AF (37.5%) are
based studies, AF was associated with a doubling
approximately twice as likely to be hospitalized as
in the risk of SCD after accounting for baseline
age- and sex-matched control subjects (17.5%).150
and time-varying confounders. In ARIC, the unad-
• In 2014, there were 7 084 000 physician office vis-
justed incidence rate was 1.30 (95% CI, 1.14–
its and 418 000 ED visits for AF (NHAMCS, NHLBI
1.47) in those without AF and 2.89 (95% CI,
tabulation).
2.00–4.05) in those with AF; corresponding rates
in CHS were 3.82 (95% CI, 3.35–4.35) and 12.00 Cost
(95% CI, 9.45–15.25), respectively. The multivari- (See Chart 15-8)
able-adjusted HR associated with AF for sudden • Investigators examined Medicare and Optum
death was 2.47 (95% CI, 1.95–3.13).145 Touchstone databases (2004–2010) to esti-
• An increased risk of VF was observed in a mate costs attributed to nonvalvular AF versus
community-based case-control study from the propensity-matched control subjects in 2014 US
Netherlands. Individuals with ECG-documented dollars151:
VF during OHCA were matched with non-VF com- — For patients aged 18 to 64 years, average
munity control subjects. The prevalence of AF in per capita medical spending was $38 861
the 1397 VF cases was 15.4% versus 2.6% in the (95% CI, $35 781–$41 950) versus $28 506
community control subjects. Individuals with AF (95% CI, $28 409–$28 603) for matched
had an overall adjusted 3-fold increased risk of VF patients without AF. Corresponding numbers
(adjusted OR, 3.1; 95% CI, 2.1–4.5). The associa- for patients ≥65 years old were $25 322 for
tion was similar across age and sex categories and those with AF (95% CI, $25 049–$25 595)
was observed in analyses of individuals without versus $21 706 (95% CI, $21 563–$21 849)
comorbidities, without AMI, and not using antiar- for matched non-AF patients.
rhythmic or QT-prolonging drugs.146 — The authors estimated that the incremental
AF Type and Complications cost of AF was $10 355 for commercially
• A meta-analysis of 12 studies reported that com- insured patients and $3616 for Medicare
pared with paroxysmal AF, nonparoxysmal AF patients.
was associated with a multivariable-adjusted — Estimating that the prevalence of diagnosed
increased risk of thromboembolism (HR, 1.355; versus undiagnosed nonvalvular AF was
95% CI, 1.151–2.480; P<0.001) and death (HR, 0.83% versus 0.07% for individuals 18 to 64
1.217; 95% CI, 1.085–1.365; P<0.001).147 years of age and 8.8% versus 1.1% for those
• In the FHS, atrial flutter had a much lower inci- ≥65 years of age, the investigators estimated
dence rate (36 per 100 000 person-years) than AF that the incremental cost of undiagnosed AF
(578 per 100 000 person-years). Although based was $3.1 billion (95% CI, $2.7–3.7 billion).
on only 112 individuals, in age- and sex-adjusted • Investigators examined Medicare and MarketScan
analyses, incident atrial flutter was associated with databases (2004–2006) to estimate costs attrib-
a 5-fold hazard of AF (HR, 5.0; 95% CI, 3.1–8.0). uted to AF in 2008 US dollars (Chart 15-8)152:
Compared with AF, atrial flutter was associated — Annual total direct costs for AF patients were
with a similar age- and sex-adjusted increased risk ≈$20 670 versus ≈$11 965 in the control
of HF, stroke, and death; however, the risk of MI group, for an incremental per-patient cost of
was higher in people with atrial flutter.148 $8705.

— Extrapolating to the US population, it is substantially, from $2932 (IQR, $2232‒$3870) to
CLINICAL STATEMENTS
estimated that the incremental cost of AF $4719 (IQR, $3124‒$7209).158
AND GUIDELINES
was ≈$26 billion, of which $6 billion was
attributed to AF, $9.9 billion to other cardio- Risk Factors
vascular expenses, and $10.1 billion to non- (See Chart 15-9)
cardiovascular expenses. Standard Risk Factors
— In individuals in a commercial claims data • Hypertension accounted for ≈14%159 to 22%160
set (MarketScan) of nonrepeat stroke admis- of AF cases.
sions, AF was associated with an adjusted • In MESA, the population attributable fraction
$4905 higher cost (2012 US $) than in of AF attributable to hypertension appeared
patients with stroke without AF. The higher to be higher in US NH blacks (33.1%), Chinese
cost was observed regardless of age (all <65 (46.3%), and Hispanics (43.9%) than in NH
years), sex, urban versus rural setting, or whites (22.2%).90
region.153 • ARIC,161 the FHS,25,162,163 and the Women’s Health
Study164 have developed risk prediction models to
Secular Trends
predict new-onset AF. Predictors of increased risk
• During 50 years of observation of the FHS
of new-onset AF include advancing age, European
(1958–1967 to 1998–2007), the age-adjusted
prevalence and incidence of AF approximately ancestry, body size (greater height and BMI), elec-
quadrupled. However, when only AF that was trocardiographic features (LV hypertrophy, left
ascertained on ECGs routinely collected in the atrial enlargement), DM, BP (SBP and hyperten-
FHS was considered, the prevalence but not the sion treatment), and presence of CVD (CHD, HF,
incidence increased, which suggests that part of valvular HD).
the changing epidemiology was attributable to • More recently, the ARIC, CHS, and FHS investi-
enhanced surveillance. Although the prevalence gators developed and validated a risk prediction
of most risk factors changed over time, the haz- model for AF in blacks and whites, which was rep-
ards associated with specific risk factors did not licated in 2 European cohorts.165 The CHARGE-AF
change. Hence, the PAR associated with BMI, model has been validated in a US multiethnic
hypertension treatment, and DM increased (con- cohort including Hispanics166 and in a UK cohort
sistent with increasing prevalence). Over time, the (EPIC Norfolk).167

multivariable-adjusted hazards of stroke and mor- • Other consistently reported risk factors for AF
tality associated with AF declined by 74% and include clinical and subclinical hyperthyroid-
25%, respectively.154 ism,168,169 CKD,170 and moderate171 or heavy alco-
• Between 2000 and 2010 in Olmsted County, MN, hol consumption.172
age- and sex-adjusted incidence rates and sur- Borderline Risk Factors
vival did not change over time.155 However, over a • Data from the ARIC study indicated that having
similar time frame in the United Kingdom (2001– at least 1 elevated risk factor explained 50% and
2013), the incidence of nonvalvular AF increased having at least 1 borderline risk factor explained
modestly from 5.9 (95% CI, 5.8–6.1) per 1000 6.5% of incident AF cases. The estimated overall
patient-years to 6.9 (95% CI, 6.8–7.1) per 1000 incidence rate per 1000 person-years at a mean
patient-years, with the largest increase observed age of 54.2 years was 2.19 for those with optimal
in those >80 years of age.156 risk, 3.68 for those with borderline risk, and 6.59
• In data from the ARIC study, the prevalence of AF for those with elevated risk factors.160
in the setting of MI increased slightly, from 11%
to 15%, between 1987 and 2009; however, the Family History and Genetics
increased risk of death (OR, 1.47; 95% CI, 1.07– (See Table 15-2)
2.01) in the year after MI accompanied by AF did • Although unusual, early-onset lone AF has long
not change over time.157 been recognized to cluster in families.173,174 In the
• Between 1999 and 2013, among Medicare fee-for- past decade, the heritability of AF in the commu-
service beneficiaries, rates of hospitalization for AF nity has been appreciated. In studies from the
increased ≈1% per year. Although the median hos- FHS:
pital length of stay, 3 days (IQR, 2.0–5.0 days), did — Adjusted for coexistent risk factors, having at
not change, the mortality declined by 4% per year, least 1 parent with AF was associated with
and hospital readmissions at 30 days declined by 1% a 1.85-fold increased risk of AF in the adult
per year. During the same years, median Medicare offspring (multivariable-adjusted 95% CI,
inpatients costs per hospitalization increased 1.12–3.06; P=0.02).175

— A history of a first-degree relative with AF • Risk of drug-induced LQTS (ie, acquired LQTS)
CLINICAL STATEMENTS
also was associated with an increased risk of also appears to have genetic components; rare
AND GUIDELINES
AF (HR, 1.40; 95% CI, 1.13–1.74).161 The risk variants in LQTS-related genes have been associ-
was greater if the first-degree relative’s age ated with drug-induced LQTS.191
of onset was ≤65 years (HR, 2.01; 95% CI, • Brugada syndrome affects an estimated 3 in
1.49–2.71) and with each additional affected 10 000 people, is inherited in an autosomal
first-degree relative (HR, 1.24; 95% CI, 1.05– dominant pattern with variable penetrance and
1.46).176 Similar findings were reported from expressivity, and is more prevalent in males than
Sweden.177 females. Most mutations that cause Brugada
• Mutations in genes coding channels (sodium and syndrome occur in genes within or related to
potassium), gap junction proteins, and signaling the sodium channel (SCN5A)192 and in the L-type
have been described, often in lone AF or familial calcium channel α-subunit (CACNA1C) and
AF series, but they are responsible for few cases β-subunit (CACNB2B). The yield of genetic testing
of AF in the community.178 for these mutations is relatively low, with up to
• Meta-analyses of GWAS have revealed novel sus- 65% of patients not having an identifiable muta-
ceptibility loci near chromosomes 4q25 (upstream tion, but can help with SCD risk stratification and
of PITX2),179–181 16q22 (ZFHX3),179,182 and 1q21 screening of family members.193
(KCNN3),180 as well as ≈18 novel susceptibility • ARVC is inherited in an autosomal dominant
loci in several published meta-analyses183 that manner but with low penetrance and high vari-
included individuals with AF of European and ability in clinical presentations. Mutations in 15
Japanese ancestry.184 Although an area of inten- genes cause ARVC and 2 related diseases, Naxos
sive inquiry, the causative SNPs and the functional disease and Carvajal syndrome; mutations in des-
basis of the associations have not been revealed. mosomal proteins are responsible for the majority
• Racial variation in AF incidence is complex and not of cases, with mutations in plakophilin 2 (PKP2)
fully understood. One study suggests that genetic accounting for >40% of cases.194 Clinical genetic
markers of European ancestry are associated with testing for ARVC is available, and identification
an increased risk of incident AF.185 of the causative mutation is considered a major
• Some studies suggest that genetic markers of AF criterion in the revised ARVC diagnostic criteria,194
could improve risk prediction for AF over models but mutations are identified in only 50% of cases.
that include clinical factors.164 • The majority of CPVT is inherited in an autosomal

• Many cardiac arrhythmias are heritable traits; dominant manner and is caused by mutations in
for example, common AF has a heritability of the cardiac ryanodine receptor 2/calcium release
62%.186 gene (RYR2), although a less common autosomal
• There are monogenic (mendelian) forms of car- recessive form exists that is caused by mutations
diac arrhythmias caused primarily by mutations in in the cardiac calsequestrin (CASQ2) gene.193
ion channel genes that have strong effects and Clinical genetic testing is able to identify a caus-
have high penetrance in families, including LQTS, ative mutation in 60% of patients with CPVT and
CPVT, ARVC, and Brugada syndrome.187 can be useful for diagnosis; after the causative
• There are up to 15 subtypes of LQTS, each char- mutation is identified in the proband, first-degree
acterized by unique clinical manifestations based relatives should be offered genetic testing to
on syncope, QT interval, T-wave changes on an enable presymptomatic diagnosis and preventive
ECG, and genetic mutations (Table 15-2). LQTS is measures.187
usually inherited in an autosomal dominant pat- • There are monogenic forms of AF that are caused
tern and has a prevalence of up to 1 in 3000, with by mutations in genes encoding potassium chan-
patients with LQT1, LQT2, and LQT3 constituting nel subunits (KCNQ1, KCNJ2, KCNA5) or sodium
>90% of LQTS.188,189 channel subunits (SCN1B, SCN2B), as well as the
• Clinical genetic testing will identify a genetic connexin-40 gene. These rare mutations do not
mutation in >75% of patients and can help with appear to be a cause of common AF.
diagnosis, SCD risk prediction, and screening in • GWAS, including the largest to date, which
at-risk family members. included >17 000 case subjects and >150 000
• Treatment of LQTS includes consideration of control subjects, have identified 26 genetic loci
β-blockers for prophylaxis of arrhythmias, restric- that are associated with common AF, with the
tion of competitive sports, and insertion of an strongest finding for common variants near the
implantable cardioverter-defibrillator for patients paired-like homeodomain transcription factor
with very high-risk features (ie, syncope, QTc 2 (PITX2) gene195 and others in potassium and
>500 ms, or family history of SCD).190 sodium channel genes.

• Whole exome/genome sequencing studies have 5.9; 95% CI, 3.4–10.3; P<0.001) than those
CLINICAL STATEMENTS
identified rare mutations in additional genes, with <3% weight loss (39.6% AF free). In addi-
AND GUIDELINES
including MYL4.196 Studies in non-European pop- tion, those losing at least 10% weight reported
ulations have identified race-specific gene vari- fewer symptoms.201a
ants for AF.195 • Data from some studies suggested that vigorous-
• Genetic risk scores could also identify patients at intensity exercise 5 to 7 days per week was associ-
higher risk of cardioembolic stroke197; however, ated with a slightly increased risk of AF (HR, 1.20;
the utility of clinical genetic testing for AF-related P=0.04).133 In contrast, a meta-analysis suggested
genetic variants is unclear. that more intensive physical activity was not asso-
• Clinical genetic testing is recommended in ciated with excess risk of AF (RR, 1.0; 95% CI,
LQTS and CPVT in the setting of a strong clini- 0.82–1.22), but the heterogeneity statistic was
cal index of suspicion and can be considered in significant.203
patients who meet task force diagnostic criteria • A multiracial longitudinal study from Detroit, MI,
for ARVC. Genetic testing is also recommended reported a dose-response relation between objec-
in families with LQTS, CPVT, Brugada syndrome, tively assessed exercise capacity and lower risk of
and ARVC if a mutation has been identified in new-onset AF.204 In unadjusted analyses, the inci-
the proband.187 dence rates of AF over 5 years were 3.7%, 5.0%,
• Genetic studies of other arrhythmia phenotypes, 9.5%, and 18.8% for >11, 10 to 11, 6 to 9, and
such as idiopathic VF, and of electrocardiographic <6 METs, respectively. Every 1-higher peak MET
parameters have identified genetic loci in ion was associated with an adjusted 7% lower risk
channel genes and novel genetic loci; such stud- of AF (HR, 0.93; 95% CI, 0.92–0.94). The protec-
ies could expand our knowledge of the genetic tive association of fitness was observed in all sub-
architecture of cardiac arrhythmias.188 groups examined but was particularly beneficial in
obese individuals (Chart 15-10).
Prevention • An Australian study of consecutive overweight
(See Charts 15-9 and 15-10) and obese patients with AF who agreed to par-
• On the basis of data from ARIC, the high- ticipate in an exercise program reported that
est PAR for AF was hypertension, followed by individuals who achieved lower improvement in
BMI, smoking, cardiac disease, and DM (Chart cardiorespiratory fitness (<2 METs gain) had lower
15-9).160 AF-free survival (40%; HR, 3.9; 95% CI, 2.1–7.3;

• A meta-analysis of 8 studies suggested that cur- P<0.001) than those with greater improvement in
rent smoking was associated with an increased fitness (≥2 METs gain, 89% AF free).205
risk of AF (pooled RR, 1.39; 95% CI, 1.11–1.75). • Although heterogeneous in their findings, mod-
Compared with noncurrent smokers, current est-sized short-term studies suggested that the
smokers had a 21% higher risk of incident AF use of statins might prevent AF; however, larger
(pooled RR, 1.21; 95% CI, 1.03–1.42), which sug- longer-term studies do not provide support
gests that smoking cessation is associated with a for the concept that statins are effective in AF
reduced risk of AF.198 prevention.206
• A meta-analysis of 5 population-based studies • Treatment of obstructive sleep apnea has been
reported that obese individuals have a 49% higher noted to decrease risk of recurrent AF, after car-
risk (RR, 1.49; 95% CI, 1.36–1.64) for developing dioversion207 and ablation,208 but its role in pri-
AF than their nonobese counterparts.199 mary prevention is unproven.
• A causal relationship between higher BMI and • In a national outpatient registry of AF patients
incident AF gained further support from a genetic (ORBIT-AF), 93.5% had indications for guideline-
mendelian randomization study, which observed based primary or secondary prevention in addition
that a BMI gene score that included 39 SNPs was to oral anticoagulant drugs; however, only 46.6%
associated with a higher risk of AF.200 received all guideline-indicated therapies, consis-
• An observational prospective Swedish study tent with an underutilization of evidence-based
revealed that individuals having bariatric surgery preventive therapies for comorbid conditions in
had a 29% lower risk (HR, 0.79; 95% CI, 0.60– individuals with AF.208 Predictors of not receiving
0.83; P<0.001) of developing AF in 19 years of all guideline-indicated therapies included frailty,
median follow-up than matched referents.201 comorbid illness, geographic region, and anti-
• In adjusted analyses, overweight and obese indi- arrhythmic drug therapy. Factors most strongly
viduals with paroxysmal or persistent AF who associated with the 17.1% warfarin discontinua-
achieved at least 10% weight loss were 6-fold tion rate in the first year prescribed included hos-
more likely to be AF free (86.2% AF free; HR, pitalization because of bleeding (OR, 10.9; 95%

CI, 7.9–15.0), prior catheter ablation (OR, 1.8; Awareness

CLINICAL STATEMENTS
95% CI, 1.4–2.4), noncardiovascular/nonbleed- • In REGARDS, a US national biracial study, com-

AND GUIDELINES
ing hospitalization (OR, 1.8; 95% CI, 1.4–2.2), pared with whites, blacks had approximately one
cardiovascular hospitalization (OR, 1.6; 95% CI, third the likelihood (OR, 0.32; 95% CI, 0.20–0.52)
1.3–2.0), and permanent AF (OR, 0.25; 95% CI, of being aware that they had AF.189 The REGARDS
0.17–0.36).209 investigators also reported that compared with
• There are increasingly more data supporting the individuals aware of their diagnosis, individuals
importance of risk factor modification for second- who were unaware of their AF had a 94% higher
ary prevention of AF recurrence and improved risk of mortality in follow up.214
symptoms.
Global Burden of AF
— In individuals referred for catheter abla-
(See Table 15-3 and Charts 15-11 and 15-12)
tion, those who agreed to aggressive risk
• The vast majority of research on the epidemiol-
factor modification had lower symptom ogy of AF has been conducted in Europe and
burden in follow-up and higher adjusted North America. Investigators from the GBD proj-
AF-free survival (HR, 4.8; 95% CI, 2.0–11.4; ect noted that the global prevalence, incidence,
P<0.001).202 mortality, and DALYs associated with AF increased
— Observational data suggest that overweight from 1990 to 2010.215
and obese individuals with symptomatic AF • The GBD 2015 study used statistical models and
who opt to participate in weight loss and data on incidence, prevalence, case fatality, excess
aggressive risk factor management interven- mortality, and cause-specific mortality to estimate
tions have fewer hospitalizations, cardiover- disease burden for 315 diseases and injuries in
sions, and ablation procedures than their 195 countries and territories.216
counterparts who decline enrollment. The — Mortality attributable to AF is highest in
risk factor management group was associ- Northern Europe and lowest in sub-Saharan
ated with a predicted 10-year cost savings of Africa (Chart 15-11).
$12 094.210 — Prevalence of AF is highest in Northern
Europe, Central Europe, and the United
Prevention: Randomized Data
States (Chart 15-12).
• Intensive glycemic control was not found to pre-
• Although AF accounted for <1% of global

vent incident AF in the ACCORD study.110
deaths, in 2015 the age-adjusted mortality rate
• In the Look AHEAD randomized trial of individ-
per 100 000 was 3.3 (95% CI, 2.7–4.0); how-
uals with type 2 DM who were overweight to
ever, globally between 1990 and 2015, the
obese, an intensive lifestyle intervention asso-
death rate declined 3.9% (UI, −5.9 to −1.7%;
ciated with modest weight loss did not signifi-
Table 15-3).216
cantly affect the rate of incident AF (6.1 versus
• Investigators conducted a prospective registry of
6.7 cases per 1000 person-years of follow up;
>15 000 AF patients presenting to EDs in 47 coun-
multivariable HR, 0.99; 95% CI, 0.77–1.28); tries. They observed substantial regional variabil-
however, AF was not prespecified as a primary ity in annual AF mortality: South America (17%)
or secondary outcome.211 and Africa (20%) had double the mortality rate
• Randomized trials of overweight or obese patients of North America, Western Europe, and Australia
referred to an Adelaide, Australia, arrhythmia (10%; P<0.001). HF deaths (30%) exceeded
clinic for management of symptomatic parox- deaths attributable to stroke (8%).217
ysmal or persistent AF demonstrated that indi-
viduals randomized to a weight loss intervention
reported lower symptom burden.212 Tachycardia
• Meta-analyses have suggested that renin-angio- ICD-9 427.0, 427.1, 427.2; ICD-10 I47.1,
tensin system blockers might be useful in pri- I47.2, I47.9.
mary and secondary (recurrences) prevention
2015: Mortality—900. Any-mention mortality—7183.
of AF in trials of hypertension, after MI, in HF,
2014: Hospital discharges— 64 000 (42 000 male,
and after cardioversion.109,213 However, the stud-
22 000 female).
ies were primarily secondary or post hoc analy-
ses, and the results were fairly heterogeneous. Premature Ventricular Contractions
Recently, in an analysis of the EMPHASIS-HF trial, • In the population-based CHS, a study of older
in 1 of many secondary outcomes, eplerenone adults without HF or systolic dysfunction studied
was nominally observed to reduce the incidence by Holter monitor (median duration, 22.2 hours),
of new-onset AF.129 0.011% of all heart beats were PVCs, and 5.5%

of participants had nonsustained VT. Over follow- Torsade de Pointes
CLINICAL STATEMENTS
up, baseline PVC percentage was significantly Prevalence and Incidence
AND GUIDELINES
associated with an adjusted increased odds of • By extrapolating data from non-US registries,237
decreased LVEF (OR, 1.13; 95% CI, 1.05–1.21) it has been estimated that 12 000 cases of drug-
and an increased adjusted risk of incident HF (HR, induced TdP occur annually in the United States.232
1.06; 95% CI, 1.02–1.09) and death (HR, 1.04; • A prospective, active surveillance, Berlin-based
95% CI, 1.02–1.06).218 registry of 51 hospitals observed that the annual
Monomorphic VT incidence of symptomatic drug-induced QT pro-
longation in adults was 2.5 per million males and
4.0 per million females. The authors reported 42
• In 634 patients with implantable cardioverter-
potentially associated drugs, including metoclo-
defibrillators who had structural HD (including pramide, amiodarone, melperone, citalopram,
both primary and secondary prevention patients) and levomethadaone. The mean age of patients
followed up for a mean 11±3 months, ≈80% of with QT prolongation/TdP was 57±20 years, and
potentially clinically relevant ventricular tachyar- the majority of the cases occurred in females
rhythmias were attributable to VT amenable to (66%) and out of the hospital (60%).238
antitachycardia pacing (which implies a stable cir- • The prevalence of drug-induced prolongation
cuit and therefore monomorphic VT).219 Because of QT interval and TdP is 2 to 3 times higher in
therapy might have been delivered before spon- females than in males.231
taneous resolution occurred, the proportion of • With the majority of QT-interval–prolonging
these VT episodes with definite clinical relevance drugs, drug-induced TdP can occur in 3% to 15%
is not known. of patients.229
• Among 2099 subjects (mean age, 52 years; • Antiarrhythmic drugs with QT-interval–prolonging
52.2% male) without known CVD, exercise- potential carry a 1% to 3% risk of TdP over 1 to 2
induced nonsustained VT occurred in nearly 4% years of exposure.239
and was not independently associated with total
mortality.220 Complications
• Drug-induced TdP can result in morbidity that
Complications requires hospitalization and in mortality attribut-
• Although the prognosis of those with VT or fre- able to SCD in ≤31% of patients.232,240
quent PVCs in the absence of structural HD is • In a cohort of 459 614 Medicaid and Medicaid-
good,221,222 a potentially reversible cardiomyopa- Medicare enrollees aged 30 to 75 years who were
thy can develop in patients with very frequent taking antipsychotic medications, the incidence
PVCs,223,224 and some cases of sudden death of sudden death or ventricular arrhythmia was
attributable to short-coupled PVCs have been 3.4 per 1000 person-years.241
described.225,226
Risk Factors
Polymorphic VT • TdP is usually related to administration of
Prevalence and Incidence QT-interval–prolonging drugs.242 An up-to-date
• During ambulatory cardiac monitoring, PVT prev- list of drugs with the potential to cause TdP is
alence ranged from 0.01% to 0.15%227,228; how- available at a website maintained by the University
ever, among patients who developed SCD during of Arizona Center for Education and Research on
ambulatory cardiac monitoring, PVT was detected Therapeutics.243
in 30% to 43%.228–230 • Specific risk factors for drug-induced TdP include
• In the setting of AMI, the prevalence of PVT prolonged QT interval, female sex, advanced age,
ranged from 1.2% to 2%.231,232 bradycardia, hypokalemia, hypomagnesemia, LV
systolic dysfunction, and conditions that lead to
Complications elevated plasma concentrations of causative drugs,
• The presentation of PVT can range from a brief, such as kidney disease, liver disease, drug interac-
asymptomatic, self-terminating episode to recur- tions, or some combination of these.232,244,245
rent syncope or SCD.233 • Predisposition was also noted in patients who
• The overall hospital discharge rate (survival) of had a history of ventricular arrhythmia and who
PVT has been estimated to be ≈28%.234 experienced a recent symptomatic increase in the
Risk Factors frequency and complexity of ectopy.246
• PVT in the setting of a normal QT interval is most • Drug-induced TdP rarely occurs in patients with-
frequently seen in the context of acute ischemia out concomitant risk factors. An analysis of 144
or MI.235,236 published articles describing TdP associated with

noncardiac drugs revealed that 100% of the • Both common and rare genetic variants have
CLINICAL STATEMENTS
patients had at least 1 risk factor, and 71% had at been shown to increase the propensity for drug-
AND GUIDELINES
least 2 risk factors.247 induced QT interval prolongation.249,250

• A combination of data mining of electronic health
records, adverse events, and laboratory science Prevention
demonstrated that the combination of ceftriax- • Appropriate monitoring when a QT-interval–
one and lansoprazole resulted in significantly lon- prolonging drug is administered is essential. Also,
ger QTc intervals and a 1.4 times higher likelihood prompt withdrawal of the offending agent should
of having a QTc interval >500 ms.248 be initiated.251
Table 15-1. Cumulative Incidence Rate Over 5 Years

After AF Diagnosis, by Age*
Age Heart Myocardial Gastrointestinal
Group, y Mortality Failure Infarction Stroke Bleeding
67–69 28.8 11.0 3.3 5.0 4.4
70–74 32.3 12.1 3.6 5.7 4.9
75–79 40.1 13.3 3.9 6.9 5.9
80–84 52.1 15.1 4.3 8.1 6.4
85–89 67.0 15.8 4.4 8.9 6.6
≥90 84.3 13.7 3.6 6.9 5.4
All values are percentages.

AF indicates atrial fibrillation.
*See Chart 15-7.
Adapted from Piccini et al138 by permission of the European Society of
Cardiology. Copyright © 2013, The Authors.
Table 15-2. LQTS-Related Genes

LQTS Gene Protein % of LQTS Clinical Syndrome Clinical Presentation
LQT1 KCNQ1 Kv7.1 45 RWS; JLNS Prolonged QT, syncope with physical
activity (with congenital sensorineural
hearing loss for JLNS)
LQT2 KCNH2 Kv11.1 45 RWS Prolonged QT, syncope with sudden
emotion or noise
LQT3 SCN5A Nav1.5 7 RWS; Brugada Prolonged QT, syncope at rest,
syndrome characteristic ECG pattern (Brugada)
LQT4 ANK2 Ankyrin-B Unknown Prolonged QT Prolonged QT, atrial arrhythmias
LQT5 KCNE1 minK <1 RWS; JLNS Prolonged QT (with congenital
sensorineural hearing loss for JLNS)
LQT6 KCNE2 miRP1 <1 RWS Prolonged QT
LQT7 KCNJ2 Kir2.1 <1 Andersen-Tawil Periodic paralysis, high-frequency
syndrome bidirectional ventricular tachycardia,
prolonged QT
LQT8 CACNA1C Cav1.2 <1 Timothy syndrome Prolonged QT with syndactyly and facial
and neurodevelopmental changes
LQT9 CAV3 CAV3 Unknown Caveolinopathy Prolonged QT
LQT10 SCN4B Navbeta4 <1 RWS Prolonged QT
LQT11 AKAP9 Yotiao Unknown Prolonged QT
LQT12 SNTA1 Alpha1 syntrophin Unknown Prolonged QT
LQT13 KCNJ5 Kir3.4 Unknown RWS Prolonged QT
LQT14 CALM1 <1 RWS Prolonged QT
LQT15 CALM2 <1 RWS Prolonged QT
JLNS indicates Jervell and Lange-Nielsen syndrome; LQTS, long-QT syndrome; and RWS, Romano-Ward syndrome.
Data derived from Pagon et al252 and Goldenberg et al.189

Table 15-3. Global Mortality for AF and Atrial Flutter
CLINICAL STATEMENTS
Both Sexes Male Female
AND GUIDELINES
Deaths Prevalence Deaths Prevalence Deaths Prevalence
Total number (millions) 0.2 (0.2 to 0.2) 33.3 (30.0 to 37.2) 0.1 (0.1 to 0.1) 19.1 (17.1 to 21.4) 0.1 (0.1 to 0.1) 14.2 (12.8 to 15.9)
Percent change in total
112.2 (106.0 to 118.6) 81.9 (79.7 to 84.3) 131.4 (122.5 to 139.7) 87.8 (85.1 to 90.6) 99.0 (92.7 to 106.4) 74.5 (71.6 to 77.4)
number 1990 to 2015
Percent change in total
36.7 (34.0 to 39.6) 28.2 (27.2 to 29.1) 42.5 (39.0 to 46.1) 30.1 (29.0 to 31.3) 32.4 (29.6 to 35.7) 25.7 (24.6 to 26.8)
number 2005 to 2015
Rate per 100 000 3.3 (2.7 to 4.0) 518.9 (466.4 to 581.0) 3.6 (2.9 to 4.4) 647.8 (582.5 to 726.1) 3.1 (2.5 to 3.7) 408.6 (365.6 to 457.9)
Percent change in
−3.9 (−5.9 to −1.7) −4.5 (−5.4 to −3.5) −2.8 (−5.5 to −0.3) −4.3 (−5.2 to −3.2) −5.5 (−8.0 to −2.5) −6.4 (−7.7 to −5.0)
rate 1990 to 2015
Percent change in
−3.4 (−4.9 to −1.9) −2.5 (−3.1 to −1.9) −2.7 (−4.8 to −0.7) −2.1 (−2.8 to −1.3) −4.4 (−6.2 to −2.3) −3.6 (−4.3 to −2.8)
rate 2005 to 2015

Reprinted from Global Burden of Disease Study 2015216 with permission. Copyright © 2016, University of Washington.
400
350
Incidence (per 10,000 person-years)
300
250
200
150
100
50
0
Pacemaker implantation Atrial fibrillation All-cause mortality
Outcome
PR Interval >200 ms PR interval ≤ 200ms
Chart 15-1. Long-term outcomes in individuals with prolonged PR interval (>200 ms; first-degree atrioventricular
block) compared with individuals with normal PR interval in the FHS.
FHS indicates Framingham Heart Study.
Data derived from Cheng et al.14

CLINICAL STATEMENTS
AND GUIDELINES
Chart 15-2. Primary indications (in thousands) for pace-

maker placement between 1990 and 2002 from the
NHDS, NCHS.
AV indicates atrioventricular; NCHS, National Center for
Health Statistics; and NHDS, National Hospital Discharge
Survey.
Data derived from Birnie et al.38
140
120
Incidence (per 100,000 person years)
100
80
60
40
20
0
≤ 19 20-64 ≥ 65
Age
Total Male Female
Chart 15-3. Incidence rate of paroxysmal supraventricular tachycardia per 100 000 person-years by age and sex.
Data derived from Orejarena et al.45

CLINICAL STATEMENTS
14
AND GUIDELINES
12
12.1
10
AF prevalence (millions)
9.3
8
5.1
4
2
2.3
0
1995 2000 2005 2010 2015 2020 2025 2030
Year
Chart 15-4. Current and future US prevalence projections for AF.

Projections assume no increase (red dashed line) or logarithmic growth (blue dashed line) in incidence of AF from 2007.
Data derived from Go et al84; and modified from Colilla et al86 with permission from Elsevier. Copyright © 2013, Elsevier Inc.
70
60
Incidence (per 1000 person years)
50
40
30
20
10
0
Men Women Men Women Men Women Men Women
65-69 70-74 75-79 >80
Age (years)
Hispanic Asian Black White
Chart 15-5. Atrial fibrillation incidence by race.

Incidence increases with advancing age among different races and sexes in the United States.
Data derived from Dewland et al.91

CLINICAL STATEMENTS
AND GUIDELINES
Chart 15-6. Lifetime cumulative risk for atrial fibrillation (AF) at different ages (through age 94 years) by sex.
With increasing incidence of AF with aging, lifetime risk is unchanged.
Reprinted from Lloyd-Jones et al.92 Copyright © 2004, American Heart Association, Inc.
50
45
40
Cumulative Incidence (%)
35
30
25
20
15
10
0
0 1 2 3 4 5
Years after AF diagnosis
Death Heart failure Myocardial Infarction Stroke Gastrointestinal bleeding
Chart 15-7. Cumulative incidence of events in the 5 years after diagnosis of incident AF in Medicare patients.
Reprinted from Piccini et al138 by permission of the European Society of Cardiology. Copyright © 2013, The Authors.

CLINICAL STATEMENTS
2005 2001
AND GUIDELINES
USD 26 billion USD 6.65 billion
Inpatient AF
Outpatient/Pharmacy
Indirect inpatient
Indirect outpatient/pharmacy
Chart 15-8. AF cost estimates, where AF is diagnosed in inpatient and outpatient encounters.
Indirect costs are incremental costs of inpatient and outpatient visits.
AF indicates atrial fibrillation; and USD, US dollars.
Adapted from Kim et al,150 copyright © 2011, American Heart Association, Inc.; and from Coyne et al152 with permission from
the International Society for Pharmacoeconomics and Outcomes Research (ISPOR), copyright © 2006, International Society for
Pharmacoeconomics and Outcomes Research (ISPOR).
25
Population attributable fraction (%)
20
15
10
0
Hypertension BMI ≥ 25 Smoking Diabetes Cardiac disease
Mellitus
Risk factor
Chart 15-9. Population attributable fraction of major risk factors for atrial fibrillation in the ARIC study.
ARIC indicates Atherosclerosis Risk in Communities; BMI, body mass index (in kg/m2); cardiac disease, patients with history of
coronary artery disease or heart failure; and smoking, current smoker.
Data derived from Huxley et al.160

CLINICAL STATEMENTS
AND GUIDELINES
Chart 15-10. Time-to-event analysis of incidence of atrial fibrillation by category of METs in the FIT Project
between 1991 and 2009.
The P value was determined by a log-rank test.
FIT indicates Henry Ford Exercise Testing; and METs, metabolic equivalents.
Reprinted from Qureshi et al.204 Copyright © 2015, American Heart Association, Inc.
Chart 15-11. Age-standardized global mortality rates of atrial fibrillation and flutter per 100 000, both sexes, 2015.
Chart 15-12. Age-standardized global prevalence rates of atrial fibrillation per 100 000, both sexes, 2015.
Cardiovascular Medicine. 3rd ed. Baltimore, MD: Lippincott Williams &

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P, Jansky P, Avezum A, Sigamani A, Damasceno A, Reilly P, Grinvalds cardia, and torsades de pointes. Acad Emerg Med. 1999;6:609–617.
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AND GUIDELINES
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pointes due to noncardiac drugs: most patients have easily identifiable Nickerson DA, George AL Jr, Roden DM. Novel rare variants in congenital
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16. SUDDEN CARDIAC ARREST Abbreviations Used in Chapter 16 Continued
CLINICAL STATEMENTS
QTc corrected QT interval
AND GUIDELINES
ROC Resuscitation Outcomes Consortium
through 16-4 RR relative risk
RV right ventricular
Click here to return to the Table of Contents SBP systolic blood pressure
SCA sudden cardiac arrest
Cardiac Arrest (Including VF and SD standard deviation
Ventricular Flutter) SUDS Sudden Unexpected Death Study
ICD-9 427.4, 427.5; ICD-10 I46.0, I46.1, UCL upper confidence limit
VF ventricular fibrillation
I46.9, I49.0. VT ventricular tachycardia
2015: Mortality—17 668. Any-mention mortality—
366 807.
Cardiac arrest is the cessation of cardiac mechani-
cal activity, as confirmed by the absence of signs of cir-
culation.1 SCA has various operational definitions, but
AED automated external defibrillator
SCA in general is unexpected cardiac arrest that might
result in attempts to restore circulation. If attempts
ARIC Atherosclerosis Risk in Communities Study are unsuccessful, this situation is referred to as SCD.
ARVC arrhythmogenic right ventricular cardiomyopathy SCA results from many disease processes; a consensus
AV atrioventricular statement by the International Liaison Committee on
BMI body mass index Resuscitation recommends categorizing cardiac arrest
BP blood pressure
into events with external causes (drowning, trauma,
CARDIA Coronary Artery Risk Development in Young Adults asphyxia, electrocution, and drug overdose) or medi-
CARES Cardiac Arrest Registry to Enhance Survival cal causes.2 Because of fundamental differences in
CHS Cardiovascular Health Study underlying pathogenesis and the system of care, epide-
CI confidence interval miological data for OHCA and IHCA are collected and
reported separately. For similar reasons, data for infants
CPC Cerebral Performance Index
(aged <1 year), children (aged 1–18 years), and adults
CPR cardiopulmonary resuscitation

CPVT catecholaminergic polymorphic ventricular tachycardia are reported separately.
DCM dilated cardiomyopathy
DM diabetes mellitus Incidence
ECG electrocardiogram (See Tables 16-1 through 16-6)
eGFR estimated glomerular filtration rate
• The ROC clinical trial network maintained a reg-
EMS emergency medical services istry of EMS-assessed and EMS-treated OHCA in
GWAS genome-wide association studies multiple regions of the United States from 2005
GWTG Get With the Guidelines to 2015 (Tables 16-1 through 16-3).
HCM hypertrophic cardiomyopathy • The ongoing CARES registry estimates the inci-
HD heart disease
dence of EMS-treated OHCA among individuals
HF heart failure of any age in the United States (Tables 16-3 to
HR hazard ratio 16-6).
ICD-9 International Classification of Diseases, 9th Revision • Incidence of EMS-assessed OHCA in people of
ICD-10 International Classification of Diseases, 10th Revision any age is 110.8 individuals per 100 000 popula-
tion (95% CI, 108.9–112.6), or 356 461 people
IHCA in-hospital cardiac arrest
(quasi CI, 350 349–362 252) based on extrapo-
LCL lower confidence limit lation from the ROC registry of OHCA (ROC
LQTS long-QT syndrome Investigators, unpublished data, July 7, 2016)
LV left ventricular to the total population of the United States
MI myocardial infarction (325 193 000 as of June 9, 20173).
NH non-Hispanic
• Incidence of EMS-treated OHCA of suspected car-
OHCA out-of-hospital cardiac arrest
diac cause in people of any age is 57 individuals
OR odds ratio per 100 000 population based on the CARES reg-
PEA pulseless electrical activity istry of EMS-treated OHCA.4
PVT polymorphic ventricular tachycardia • Ongoing registries for GWTG recorded the inci-
(Continued ) dence of IHCA events in 300 hospitals in the

United States. Incidence of IHCA is reported population of hospitalized patients in the United
CLINICAL STATEMENTS
either in crude numbers, per-1000 bed-days, or States.10

AND GUIDELINES
per hospital admissions. • Mean incidence of IHCA per 1000 bed-days in

2003 to 2010 data was 0.337 (SD 0.215) for ICU,
OHCA: Adult
0.109 (SD 0.079) for telemetry wards, and 0.134
(See Tables 16-1 to 16-3)
(SD 0.098) for unmonitored wards.9
• Incidence of EMS-assessed cardiac arrest in
• Incidence of IHCA was 1.6 per 1000 hospital
adults is 140.7 individuals per 100 000 popula-
admissions, with a median across hospitals of
tion (95% CI, 138.3–143.1), or 347 322 adults
1.5 (IQR, 1.2–2.2) in the UK National Cardiac
(95% CI, 341 397–353 246) based on extrapo-
Arrest Audit database between 2011 and 2013
lation from the ROC registry of OHCA (ROC
(144 hospitals and 22 628 patients ≥16 years of
Investigators, unpublished data, July 7, 2016)
age).11
to the total population of the United States3
• According to 2003 to 2010 GWTG data, for adult
(Table 16-1).
IHCA, 59% (50 514) occurred in the ICU and 41%
• Incidence of EMS-treated OHCA in adults was
(34 687) on inpatient wards among 85 201 events
73.0 individuals per 100 000 population (95% CI,
at 445 hospitals.9
71.2–74.7), or 180 202 adults (95% CI, 175 759–
• According to 2016 GWTG data, location of adult
184 399) in the ROC registry (Table 16-1). In
IHCA was 53.7% in the ICU, operating room, or
the Oregon SUDS 2002 to 2003 data, ≈60% of
ED and 46.3% in noncritical care areas among
EMS-assessed adult OHCAs had resuscitation
22 960 events at 300 hospitals (Table 16-4).
attempted,5 whereas in the ROC registry, ≈52%
• Initial recorded cardiac rhythm was VF or VT or
of EMS-assessed adult OHCA had resuscitation
attempted (Table 16-1). shockable in 16.1% of IHCAs in 2016 GWTG
• In 2015, the incidence of EMS-treated OHCA data (Table 16-4).
was 66 per 100 000. Incidence of EMS-treated OHCA: Children
OHCA with initial shockable rhythm was 13.5 per (See Tables 16-1 and 16-3)
100 000 (Table 16-2). • Age- and sex-adjusted incidence rate of EMS-
• Age- and sex-adjusted incidence of EMS-treated assessed OHCA in children was 8.3 per 100 000
SCA of suspected cardiac cause was 60 (95% CI, person-years (75.3 for infants [<1 years], 3.7 for
54–66) per 100 000 per year (≈234 085 per year children [1–11 years], and 6.3 for adolescents
in the United States) in the Oregon SUDS 2002 to [12–19 years] per 100 000 person-years) in the
2004 data.6 ROC Epistry from 2007 to 2012.12
• Location of OHCA is most often a home or resi- • Incidence of EMS-assessed OHCA was 7037
dence (68.5%), followed by public settings (21%) (quasi CI, 6214–7861) children in the United
and nursing homes (10.5%) (Table 16-4).7 States based on extrapolation from ROC for indi-
• OHCA is witnessed by a layperson in 37% of
viduals <18 years of age in the United States (ROC
cases or by an EMS provider in 12% of cases. For
Investigators, unpublished data, July 7, 2016)
51% of cases, collapse is not witnessed.7
(Table 16-1).
• Initial recorded cardiac rhythm was VF or VT or
• Location of EMS-treated OHCA was at home for
shockable by an automated external defibrillator
89.5% of children ≤1 year old, 77.1% of children
in 19.8% of EMS-treated OHCAs in 2016 (Table
1 to 12 years old, and 72.9% of children 13 to
16-4).
18 years old in the CARES 2016 data. Location
• Among 10.9 million registered participants in 40
was in a public place for 10.2% of children ≤1
marathons and 19 half marathons, the overall
years old, 22.7% of children 1 to 12 years old,
incidence of cardiac arrest was 0.54 per 100 000
and 26.8% of children 13 to 18 years old (Table
participants (95% CI, 0.41–0.70).8 Those with
16-4).13
cardiac arrest were more often male and were
• Incidence of SCD was 0.24 per 100 000 athlete-
running a marathon versus a half marathon.
years in high school athletes screened every 3
IHCA: Adult years between 1993 and 2012 with standard pre-
(See Table 16-4) participation evaluations during Minnesota State
• Incidence of adult IHCA was a mean 0.580 (SD High School League activities.14
0.325) events per 1000 inpatient bed-days based • Incidence of nontraumatic OHCA was 1 per
on 85 201 events at 445 hospitals in GWTG 2003 43 770 athlete participant-years in a longitudinal
to 2010 data.9 study of students 17 to 24 years of age partici-
• Incidence of IHCA is 209 000 people each year pating in National Collegiate Athletic Association
based on extrapolation of GWTG data to the total sports from 2004 to 2008. Incidence of cardiac

arrest was higher among blacks than among Investigators, unpublished data, July 7, 2016)
CLINICAL STATEMENTS
whites and among males than among females.15 (Table 16-1).
AND GUIDELINES
• Age- and sex-adjusted incidence of adult SCD
IHCA: Children
after OHCA was 60 (95% CI, 54–66) per 100 000
(See Table 16-4)
per year, or 183 001 deaths per year (95% UI,
• Incidence of IHCA was 1.8 CPR events per 100
164 218–203 205) in the United States, based on
pediatric (<18 years) ICU admissions (sites range
Oregon SUDS 2002 to 2004 data.6
from 0.6 to 2.3 per 100 ICU admissions) in the
• In-hospital mortality for patients hospitalized after
Collaborative Pediatric Critical Care Research
treatment for cardiac arrest was 57.8% according
Network dataset of 10 078 pediatric ICU admis-
to 2009 US NIS data.18
sions from 2011 to 2013.16
• Large regional variations in survival to hospital
• Per 2016 GWTG data, location of IHCA for chil-
discharge (range, 3.4%–22.0%) and survival
dren was 87.5% in the ICU, operating room, or
with functional recovery (range, 0.8%–20.1%)
ED and 12.5% in noncritical care areas among
495 events at 69 hospitals (Table 16-4). are observed between 132 counties in the United
• Initial recorded cardiac arrest rhythm was asys- States.19 Variation in rates of layperson CPR
tole and pulseless electrical activity in 874 chil- explained much of this variation.
dren (84.8%) and VF or VT or shockable in • Age-adjusted survival to hospital admission was
10.7% of 495 children at 69 hospitals in GWTG- lower for blacks (6.0%) and Hispanics (8.6%) than
Resuscitation in 2016 (Table 16-4). for whites (11.3%) among 4053 cardiac arrests in
New York City in 2002 to 2003.20 This disparity
persisted to 30 days after hospital discharge.
Lifetime Risk • In the 2016 CARES registry, survival to hospital
• Infants have a higher incidence of SCD (12.8 admission after EMS-treated nontraumatic OHCA
per 100 000) than older children (1.1–2.0 per was 29.0% for all presentations, with higher
100 000). Among adults, risk of SCD increases survival rates in public places (39.5%) and lower
exponentially with age, surpassing the risk for survival rates in homes/residences (27.5%) and
infants by age 40 years (20.3 per 100 000) (Chart nursing homes (18.2%) (Table 16-6).
16-1). • Among runners with cardiac arrest during mara-
• SCD appears among the multiple causes of thons or half marathons, 71% died; those who
death on 13.5% of death certificates (366 807 died were younger (mean±SD, 39±9 years of age)
of 2 712 630), which suggests that 1 of every than those who did not die (mean±SD, 49±10
7.4 people in the United States will die of SCD.17 years of age), were more often male, and were
Because some people survive SCA, the lifetime more often running a full marathon.8
risk of cardiac arrest is even higher. IHCA: Adult
(See Table 16-4 and Chart 16-2)
Mortality • Survival to hospital discharge was 25.8% of
(See Table 16-7 and Chart 16-1) 22 960 adult IHCAs at 300 hospitals in GWTG
2016 data (Chart 16-2). Among survivors, 84.6%
• In 2015, primary-cause SCD mortality was 17 668, had good functional status at hospital discharge.
and any-mention SCD mortality in the United • Unadjusted survival rate after IHCA was 18.4%
States was 366 807 (Table 16-7).17 in the UK National Cardiac Arrest Audit database
• Mortality rates for any mention of SCD by age are between 2011 and 2013. Survival was 49% when
provided in Chart 16-1.
the initial rhythm was shockable and 10.5% when
OHCA: Adult the initial rhythm was not shockable.11
(See Tables 16-1 to 16-4 and 16-6) • Survival to discharge is lower for black patients
• Survival to hospital discharge after EMS-treated (25.2%) than for white patients (37.4%) after
OHCA was 10.8% (95% CI, 10.6%–11.1%), and IHCA.21 Lower rates of survival to discharge for
survival with good functional status was 9.0% blacks reflect lower rates of both successful
(95% CI, 8.7%–9.2%) based on 59 759 cases in resuscitation (55.8% for blacks versus 67.4% for
CARES for 2016.7 whites) and postresuscitation survival (45.2% ver-
• Survival to hospital discharge after EMS-treated sus 55.5%). The hospital where patients received
cardiac arrest was 11.4% (95% CI, 10.4%– care explained much of the racial variation in
12.4%) for patients of any age and 11.4% postresuscitation survival (adjusted RR for hos-
(95% CI, 10.3%–12.4%) for adults in the ROC pital, 0.92; 95% CI, 0.88–0.96; adjusted RR for
Epistry (January 1, 2015, to June 30, 2015) (ROC race, 0.99; 95% CI, 0.92–1.06).

OHCA: Children • Rates of layperson-initiated CPR and layperson

CLINICAL STATEMENTS
(See Tables 16-1 and 16-5) use of automated external defibrillators have
AND GUIDELINES
• Survival to hospital discharge after EMS-treated increased over time (Table 16-3).
nontraumatic cardiac arrest was 13.2% (95%
CI, 7.0%–19.4%) for children in the ROC Epistry
from January 1, 2015, to June 30 2015 (ROC
Complications
Investigators, unpublished data, July 7, 2016) (See Table 16-4)
(Table 16-1).22 • Survivors of cardiac arrest experience multiple
• Survival to hospital discharge was 6.4% for 991 medical problems related to critical illness, includ-
children ≤1 year old, 14.4% for 397 children 1 to ing impaired consciousness and cognitive deficits.
12 years old, and 19.9% for 306 children 13 to As many as 18% of survivors of OHCA, 40% of
18 years old in CARES 2016 data (Table 16-4). adult survivors of IHCA, and 72% of child survi-
• Among 91 children discharged from the hospital vors of IHCA have moderate to severe functional
after OHCA in King County, WA, from 1976 to impairment at hospital discharge (Table 16-4).
2007, survival was 92% at 1 year, 86% at 5 years, • Functional impairments are associated with
and 77% at 20 years.23 reduced function, reduced quality of life, and
shortened lifespan.25,26
IHCA: Children
• Functional recovery continues in some children
• Survival to hospital discharge after IHCA was
over the first 12 months after OHCA27 and over
37.9% in 495 children 0 to 18 years old and
the first 6 to 12 months after OHCA in adults.28
27.9% in 165 neonates (0–30 days old) per 2016
GWTG data (GWTG-Resuscitation unpublished
data for 2016). Healthcare Utilization and Cost
• Survival to hospital discharge for children with • In the Oregon SUDS, the estimated societal bur-
IHCA in the ICU was 45% in the Collaborative den of SCD in the United States was 2 million
Pediatric Critical Care Research Network from years of potential life lost for males and 1.3 million
2011 to 2013.16 years of potential life lost for females, accounting
for 40% to 50% of the years of potential life lost
from all cardiac disease.6
Secular Trends
• Among males, estimated deaths attributable
(See Tables 16-2 and 16-3; Charts 16-2
to SCD exceeded all other individual causes of
and 16-3) death, including lung cancer, accident, CLRD,
• Survival after IHCA increased between 2000 and cerebrovascular disease, DM, prostate cancer, and
2015 in GWTG data (Chart 16-2). colorectal cancer.6
• Age-adjusted death rates for any mention of SCD • A study in Denmark of 1218 OHCA patients
declined from 138 per 100 000 person-years in between 2002 and 2010 demonstrated that
1999 to 98 per 100 000 person-years by 2015 transport to a non–tertiary care center versus a
(Chart 16-3). tertiary care center after return of spontaneous
• Incidence of EMS-treated OHCA increased from circulation or with ongoing resuscitation was
47 per 100 000 to 66 per 100 000 between 2008 independently associated with increased risk of
and 2015 in the ROC Epistry (ROC Investigators, death (HR, 1.32; 95% CI, 1.09–1.59).29
unpublished data, July 7, 2016) (Table 16-2).
• Unadjusted survival to hospital discharge after
EMS-treated OHCA increased from 10.2% in
Risk Factors
2006 to 12.4% in 2015 in the ROC Epistry (ROC (See Chart 16-4)
Investigators, unpublished data, July 7, 2016) • The underlying cause of OHCA varies by age
(Table 16-3). group. Chart 16-4 illustrates the causes of OHCA
• In-hospital mortality for patients hospitalized by age group based on a retrospective cohort of
after treatment for cardiac arrest decreased from OHCA patients 0 to 35 years of age treated in
69.6% in 2001 to 57.8% in 2009 according to US King County, WA, between 1980 and 2009.30
NIS data.18 • A large proportion of patients with OHCA have
• Survival to hospital discharge after IHCA in chil- coronary atherosclerosis.31 Approximately 5% to
dren increased from 14.3% in 2000 to 43.4% in 10% of SCD cases occur in the absence of CAD or
2009 (adjusted rate ratio per year, 1.08; 95% CI, structural HD.32 Twenty-five percent of those with
1.01–1.16) without an increased rate of neuro- EMS-treated OHCA have no symptoms before the
logical disability among survivors over time.24 onset of arrest.33

• Prior HD was associated with risk for OHCA in • Risk of SCD in prospective cohorts who were ini-
CLINICAL STATEMENTS
1275 health maintenance organization enrollees tially free of CVD when recruited in 1987 to 1993
AND GUIDELINES
50 to 79 years of age. Incidence of OHCA was was associated with male sex, black race, DM,
6.0 per 1000 person-years in subjects with any current smoking, and SBP.35
clinically recognized HD compared with 0.8 per • In patients with implanted defibrillators, rate of first
1000 person-years in subjects without HD. In sub- ventricular dysrhythmia or death within 4 years was
groups with HD, incidence was 13.7 per 1000 higher among black patients (42%) than whites
person-years in subjects with prior MI and 21.9 (34%; adjusted HR, 1.60; 95% CI, 1.18–2.17).43
per 1000 person-years in subjects with HF.34 • A study in New York City found the age-adjusted
• A logistic model incorporating age, sex, race, cur- incidence of OHCA per 10 000 adults was 10.1
rent smoking, SBP, use of antihypertensive medi- among blacks, 6.5 among Hispanics, and 5.8
cation, DM, serum potassium, serum albumin, among whites.20
HDL-C, eGFR, and QTc interval, derived in 13 677 • A family history of cardiac arrest in a first-degree
adults, correctly stratified 10-year risk of SCD in a relative is associated with an ≈2-fold increase in
separate cohort of 4207 adults (c-statistic 0.820 risk of cardiac arrest.15,44
in ARIC and 0.745 in CHS).35 • Age- and sex-adjusted prevalence of electrocar-
• Four lifestyle factors (smoking, exercise, diet and diographic abnormalities associated with SCD
weight) were associated with SCD in a study of was 0.6% to 1.1% in a sample of 7889 Spanish
81 722 females in the Nurses’ Health Study who citizens aged ≥40 years, including Brugada syn-
were followed up from 1984 to 2010. Relative drome in 0.13%, QTc <340 ms in 0.18%, and QTc
risk of SCD (N=321) was 0.54 (95% CI, 0.34– ≥480 ms in 0.42%.45
0.86) for females with 1 low-risk factor, 0.41 • The US National Registry of Sudden Death in
(95% CI, 0.25–0.65) for those with 2 low-risk Athletes (1980–2011) of 2406 SCDs in competi-
factors, 0.33 (95% CI, 0.20–0.54) for 3 low-risk tive athletes (mean age 19 years) revealed a higher
factors, and 0.08 (95% CI, 0.03–0.23) for 4 low- estimated incidence of SCD in black athletes than
risk factors.36 in white athletes and in males than in females.
• OHCA rates were higher in census tracts from Of these athletes, 842 deaths (35%) were adju-
the lowest socioeconomic quartile relative to the dicated to have a cardiovascular cause, including
highest socioeconomic quartile (incidence rate HCM (36%), anomalous coronary artery (19%),
ratio, 1.9; 95% CI, 1.8–2.0) in 9235 cases from myocarditis (7%), ARVC (5%), CAD (4%), mitral
the ROC Epistry (from 2006 to 2007).37 valve prolapse (4%), aortic rupture (3%), aortic
• In the US National Registry of Sudden Death in stenosis (2%), DCM (2%), and LQTS (2%).38
Athletes from 1980 to 2011, there were 1306 • Exome sequencing in younger (<51 years) dece-
SCDs in young athletes (mean 19±6 years of age) dents who died of sudden unexplained death or
participating in organized sports. The most com- suspected arrhythmic death has revealed likely
mon causes of SCD in 842 young athletes with pathogenic variants in channel or cardiomyopa-
confirmed diagnoses were HCM (36%), coronary thy-related genes for 29% to 34% of cases.46,47
artery anomalies (19%), myocarditis (7%), ARVC Among children with exertion-related deaths,
(5%), CAD (4%), and commotio cordis (3%).38 pathogenic mutations were present in 10 of 11
• Abnormal vital signs during the 4 hours preceding decedents (91%) 1 to 10 years old and 4 of 21
IHCA occurred in 59.4% and at least 1 severely decedents (19%) 11 to 19 years old.48
abnormal vital sign occurred in 13.4% of 7851
Long-QT Syndrome
patients in the 2007 to 2010 GWTG data.39
• Hereditary LQTS is a genetic channelopathy char-
• Early warning score systems using both clinical cri-
acterized by prolongation of the QT interval (typi-
teria and vital signs can identify hospital patients
cally >460 ms) and susceptibility to ventricular
with a higher risk of IHCA.40
tachyarrhythmias that lead to syncope and SCD.
Genetics and Family History Associated With SCD Investigators have identified mutations in 15
• The majority of OHCA in the general population genes leading to this phenotype (LQT1 through
results directly from CAD.41 Risk factors are thus LQT15).49,50 LQT1 (KCNQ1), LQT2 (KCNH2), and
similar to those for CAD. LQT3 (SCN5A) mutations account for the majority
• Arrhythmic cardiac arrest not attributable to CAD (≈80%) of the typed mutations.51,52
is associated with structural HD in about one • Prevalence of LQTS was estimated at 1 per 2000
third of cases and primary arrhythmic disorders, live births from ECG-guided molecular screening
often with a genetic basis, in the other two thirds of ≈44 000 infants (mostly white) born in Italy.53
of cases.42 A similar prevalence was found among nearly

8000 Japanese schoolchildren screened by use of (IQR, 4–7.1 years), 6 patients had aborted sudden
CLINICAL STATEMENTS
an ECG-guided molecular screening approach.54 death (24%) and 4 (16%) had syncope.64 Sixteen
AND GUIDELINES
LQTS has been reported among those of African patients (84%) had a familial or personal history
descent, but its prevalence is not well assessed.55 of cardiac arrest. A gene mutation associated
• There is variable penetrance and a sex-time inter- with short-QT syndrome was identified in 5 of 21
action for LQTS symptoms. Risk of cardiac events probands (24%).
is 21% among males and 14% among females
by 12 years of age. Risk of events during adoles- Brugada Syndrome
cence (ages 12–18 years) is equivalent between • Brugada syndrome is an acquired or inher-
sexes (≈25% for both sexes). Risk of cardiac ited channelopathy characterized by persistent
events in young adulthood (ages 18–40 years) is ST-segment elevation in the precordial leads (V1–
16% among males and 39% among females.51 V3), right bundle-branch block, and susceptibility
• Individuals may be risk stratified for increased to ventricular arrhythmias and SCD.65 Brugada
risk of SCD56 according to their specific long-QT syndrome is associated with mutations in at least
mutation and their response to β-blockers.57 12 ion channel–related genes.65,66
• Among 403 patients from the LQTS Registry • In a meta-analysis of 24 studies, prevalence was
from birth through age 40 years, multivariate estimated at 0.4% worldwide, with regional prev-
analysis demonstrated that patients with multiple alence of 0.9%, 0.3%, and 0.2% in Asia, Europe,
LQTS gene mutations had a 2.3-fold (P=0.015) and North America, respectively.67 Prevalence is
increased risk for life-threatening cardiac events higher in males (0.9%) than females (0.1%).65,68–72
(comprising aborted cardiac arrest, implant- • Cardiac event rates for Brugada syndrome patients
able defibrillator shock, or SCD) compared with followed up prospectively in northern Europe
patients with a single mutation.58 (31.9 months) and Japan (48.7 months) were
similar: 8% to 10% in patients with prior aborted
Short-QT Syndrome sudden death, 1% to 2% in those with history
• Short-QT syndrome is an inherited mendelian of syncope, and 0.5% in asymptomatic patients.
condition characterized by shortening of the QT Predictors of poor outcome include clinical history
interval (typically QT <320 ms) and predisposition of syncope or ventricular tachyarrhythmias, family
to AF, ventricular tachyarrhythmias, and sudden history of sudden death, and a spontaneous early
death. Mutations in 5 ion channel genes have repolarization pattern on ECG.73,74

been described (SQT1–SQT5).59 • Among patients with Brugada syndrome, first-
• Prevalence of a QTc Bazett interval shorter than degree AV block, syncope, and spontaneous type
320 ms in a population of 41 767 young, predom- 1 ST-segment elevation were independently asso-
inantly male Swiss conscripts was 0.02%.60 ciated with risk of sudden death or implantable
• Prevalence of QT interval ≤320 ms in 18 825 cardioverter-defibrillator–appropriate therapies.75
apparently healthy people from the United
Kingdom aged 14 to 35 years between 2005 and Catecholaminergic PVT
2013 was 0.1%.61 Short QT intervals were associ- • CPVT is a familial condition characterized by adren-
ated with male sex and Afro-Caribbean ethnicity. ergically induced ventricular arrhythmias associ-
• Prevalence of QT interval ≤340 ms in 99 380 unique ated with syncope and sudden death. Arrhythmias
patients aged ≤21 years at Cincinnati Children’s include frequent ectopy, bidirectional VT, and PVT
Hospital between 1993 and 2013 was 0.05%.62 Of with exercise or catecholaminergic stimulation
these children, 15 of 45 (33%) were symptomatic. (such as emotion, or medicines such as isoproter-
• Among 53 patients from the European Short QT enol). Mutations in genes encoding RYR2 (CPVT1)
Syndrome Registry (75% males, median age 26 are found in the majority of patients and result in
years),63 89% had a familial or personal history a dominant pattern of inheritance.76 Mutations in
of cardiac arrest. Twenty-four patients received genes encoding CASQ2 (CPVT2) are found in a
an implantable cardioverter-defibrillator, and 12 small minority and result in a recessive pattern of
received long-term prophylaxis with hydroquini- inheritance. Mutations have also been described in
dine. During a median follow-up of 64 months, 2 KCNJ2 (CPVT3), TRDN, ANK2, and CALM1.76
patients received an appropriate implantable car- • Prevalence of CPVT is not estimable from case
dioverter-defibrillator shock, and 1 patient expe- series. Of 101 patients with CPVT, the majority had
rienced syncope. Nonsustained PVT was recorded experienced symptoms before 21 years of age.77
in 3 patients.63 • In small series (N=27–101) of patients followed
• In an international case series of 15 centers that up over a mean of 6.8 to 7.9 years, 27% to 62%
included 25 patients ≤21 years of age with short- experienced cardiac symptoms, and fatal or near-
QT syndrome who were followed up for 5.9 years fatal events occurred in 13% to 31%.77–79

• Risk factors for cardiac events included younger • Nonsustained VT is a risk factor for sudden
CLINICAL STATEMENTS
age at diagnosis and absence of β-blocker death,86,87 particularly in younger patients.
AND GUIDELINES
therapy. A history of aborted cardiac arrest and Nonsustained VT in those ≤30 years of age is
absence of β-blocker therapy were risk factors for associated with a 4.35-greater odds of sudden
fatal or near-fatal events.77 death (95% CI, 1.5–12.3).87
• A history of syncope is also a risk factor for sudden
Arrhythmogenic RV Dysplasia/Cardiomyopathy
death in these patients,88 particularly if the syncope
• Arrhythmogenic RV dysplasia or cardiomyopathy
was recent before the initial evaluation and not
is a form of genetically inherited structural HD
attributable to a neurally mediated event.89
that presents with fibrofatty replacement of the
• The presence of LV outflow tract obstruction
myocardium, which increases risk for palpitations,
with pressure gradients ≥30 mm Hg appears to
syncope, and sudden death.59 Twelve ARVC loci
increase the risk of sudden death by ≈2-fold.90,91
have been described (ARVC1–ARVC12). Disease-
The presence of LV outflow tract obstruction has
causing genes for 8 of these loci have been iden-
tified, the majority of which are in desmosomally a low positive predictive value (7%–8%) but a
related proteins.80 high negative predictive value (92%–95%) for
• Of 100 patients in the Johns Hopkins Arrhythmo predicting sudden death.91,92
genic Right Ventricular Dysplasia Registry, 51 were • The rate of malignant ventricular arrhythmias
males and 95 were white, with the rest being of detected by implantable cardioverter-defibrillators
black, Hispanic, or Middle Eastern origin. Twenty- appears to be similar between HCM patients with
two percent of the 87 index cases and 32% of all a family history of sudden death in ≥1 first-degree
the identified cases had evidence of the familial relative and those with at least 1 of the risk fac-
form of ARVC.81 tors described above.93
• The most common presenting symptoms were • The risk of sudden death increases with the num-
palpitations (27%), syncope (26%), and SCD ber of risk factors.94
(23%).81 Early Repolarization Syndrome
• During a median follow-up of 100 patients with • Early repolarization, observed in ≈4% to 19%
arrhythmogenic right ventricular dysplasia for 6 of the population95–98 (more commonly in young
years, 47 patients received an implantable cardio- males95,97,99 and in athletes96) has conventionally
verter-defibrillator, 29 of whom received appropriate been considered a benign finding.

implantable cardioverter-defibrillator shocks. At the • A syndrome in which ≥1-mm positive deflections
end of follow-up, 66 patients were alive. Twenty- (sometimes referred to as “J waves”) occurred in
three patients died at study entry, and 11 died dur- the S wave of ≥2 consecutive inferior or lateral
ing follow-up (91% of deaths were attributable to leads was significantly more common among
SCA).81 Similarly, the annual mortality rate was 2.3% patients with idiopathic VF than among control
for 130 patients with ARVC from Paris, France, who subjects.95,96 Given an estimated risk of idiopathic
were followed up for a mean of 8.1 years.82 VF in the general population (among those aged
Hypertrophic Cardiomyopathy 35–45 years) of 3.4 per 100 000, the positive pre-
(Please refer to Chapter 19, Cardiomyopathy and Heart dictive value of such J-wave findings in a person
Failure, for statistics regarding the general epidemiol- 35 to 45 years of age increases the chances of
ogy of HCM.) having idiopathic VF to 11 per 100 000.96
• Over a mean follow-up of 8±7 years, 6% of HCM • Shocks from an automatic implantable cardio-
patients experienced SCD.83 verter-defibrillator occur more often and earlier in
• Among 1866 sudden deaths in athletes between survivors of idiopathic VF with early repolarization
1980 and 2006, HCM was the most common syndrome (HR, 3.9; 95% CI, 1.4–11.0).100
cause of cardiovascular sudden death (in 251 • In an analysis of the Social Insurance Institution’s
cases, or 36% of the 690 deaths that could be Coronary Disease Study in Finland, J-point eleva-
reliably attributed to a cardiovascular cause).44 tion was identified in 5.8% of 10 864 people.97
• The risk of sudden death increases with increasing Those with inferior-lead J-point elevation more
maximum LV wall thickness,84,85 and the risk for often were male and more often were smokers;
those with wall thickness ≥30 mm is 18.2 per 1000 had a lower resting heart rate, lower BMI, lower
patient-years (95% CI, 7.3–37.6),85 or approxi- BP, shorter QTc, and longer QRS duration; and
mately twice that of those with maximal wall thick- were more likely to have electrocardiographic
ness <30 mm.84,85 Of note, an association between evidence of CAD. Those with lateral J-point
maximum wall thickness and sudden death has not elevation were more likely to have LV hypertro-
been found in every HCM population.85 phy. Before and after multivariable adjustment,

subjects with J-point elevation ≥1 mm in the infe- (median, 6.81%), based on training data from the
CLINICAL STATEMENTS
rior leads (N=384) had a higher risk of cardiac AHA, the American Red Cross, and the Health &
AND GUIDELINES
death (adjusted RR, 1.28; 95% CI, 1.04–1.59) Safety Institute, the largest providers of CPR train-
and arrhythmic death (adjusted RR, 1.43; 95% CI, ing in the United States.104 Training rates were
1.06–1.94); however, these patients did not have lower in rural areas, counties with high propor-
a significantly higher rate of all-cause mortality. tions of black or Hispanic residents, and counties
Before and after multivariable adjustment, sub- with lower median household income.
jects with J-point elevation >2 mm (N=36) had an • Prevalence of reported current training in CPR was
increased risk of cardiac death (adjusted RR, 2.98; 18%, and prevalence of having CPR training at
95% CI, 1.85–4.92), arrhythmic death (adjusted some point was 65% in a survey of 9022 people
RR, 3.94; 95% CI, 1.96–7.90), and death of any in the United States in 2015.105 The prevalence of
cause (adjusted RR, 1.54; 95% CI, 1.06–2.24). CPR training was lower in Hispanic/Latino people,
• In CARDIA, 18.6% of 5069 participants had early older people, people with less formal education,
repolarization restricted to the inferior and lateral and lower-income groups.
leads at baseline; by year 20, only 4.8% exhibited • Those with prior CPR training include 90% of
an early repolarization pattern.98 Younger age, citizens in Norway,106 68% of citizens in Victoria,
black race, male sex, longer exercise duration and Australia,107 61.1% of laypeople in the United
QRS duration, and lower BMI, heart rate, QT index, Kingdom,108 and 49% of people in South Korea,109
and Cornell voltage were associated with the pres- according to surveys.
ence of baseline early repolarization. Persistence of • Laypeople with knowledge of automated exter-
the electrocardiographic pattern from baseline to nal defibrillators include 69.3% of people in the
year 20 was associated with black race (OR, 2.62; United Kingdom, 66% in Philadelphia, PA, and
95% CI, 1.61–4.25), BMI (OR, 0.62 per 1 SD; 95% 32.6% in the Republic of Korea.108–110 A total
CI, 0.40–0.94), serum triglyceride levels (OR, 0.66 of 58% of Philadelphia respondents110 but only
per 1 SD; 95% CI, 0.45–0.98), and QRS duration 2.1% of UK respondents108 reported that they
(OR, 1.68 per 1 SD; 95% CI, 1.37–2.06) at baseline. would actually use an automated external defi-
• Evidence from families with a high penetrance brillator during a cardiac arrest.
of the early repolarization syndrome associated • Laypeople in the United States initiated CPR in
with a high risk of sudden death suggests that
34.4% of OHCAs recorded in the 2005 to 2014

the syndrome can be inherited in an autosomal CARES data set and in 40.7% of OHCAs in CARES
dominant fashion.101 A meta-analysis of GWAS 2016 data19 (Table 19-6). Layperson CPR rates in
performed in population-based cohorts failed to Asian countries range from 10.5% to 40.9%.111
identify any genetic variants.102 • Laypeople in the United States are less likely to
Genome-Wide Association Studies initiate CPR for people with OHCA in low-income
• GWAS on cases of arrhythmic death attempt to black neighborhoods (OR, 0.49; 95% CI, 0.41–
identify previously unidentified genetic variants 0.58)112 or in predominantly Hispanic neighbor-
and biological pathways associated with poten- hoods (OR, 0.62; 95% CI, 0.44–0.89) than in
tially lethal ventricular arrhythmias and risk of high-income white neighborhoods.113
sudden death. Limitations of these studies are • Laypeople from Hispanic and Latino neighbor-
the small number of samples available for analy- hoods in Denver, CO, report that barriers to learn-
sis and the heterogeneity of case definition. The ing or providing CPR include lack of recognition
number of loci uniquely associated with SCD is of cardiac arrest events and lack of understanding
much smaller than for other complex diseases. In about what a cardiac arrest is and how CPR can
addition, studies do not consistently identify the save a life, as well as fear of becoming involved
same variants. A pooled analysis of case-control with law enforcement114
and cohort GWAS identified a rare (1.4% minor
allele frequency) novel marker at the BAZ2B locus
(bromodomain adjacent zinc finger domain 2B)
Global Burden
that was associated with a risk of arrhythmic • International comparisons of cardiac arrest epi-
death (OR, 1.9; 95% CI, 1.6–2.3).103 demiology must take into account differences in
case ascertainment. OHCA usually is identified
through EMS systems, and regional and cultural
Awareness and Treatment differences in use of EMS affect results.115
• Median annual CPR training rate for US coun- • A systematic review of international epidemiology
ties was 2.39% (25th–75th percentiles, 0.88%– of OHCA from 1991 to 2007 included 30 studies
5.31%) and ranged from 0.00% to >4.07% from Europe, 24 from North America, 7 from Asia,

and 6 from Australia.116 Estimated incidence per discharge was 8.7%. Among children (<18 years
CLINICAL STATEMENTS
100 000 population of EMS-assessed OHCA was old), crude incidence was 5.6 per 100 000.118
AND GUIDELINES
86.4 in Europe, 98.1 in North America, 52.5 in • Hospitals in Beijing, China, reported IHCA inci-
Asia, and 112.9 in Australia. Estimated incidence dence of 17.5 events per 1000 admissions.119
per 100 000 population of EMS-treated OHCA
was 40.6 in Europe, 47.3 in North America, 45.9
in Asia, and 51.1 in Australia. The proportion of Future Research
cases with VF was highest in Europe (35.2%) and • The absence of standards for monitoring and
lowest in Asia (11.2%). reporting the incidence and outcomes of cardiac
• A prospective data collection concerning arrest remains a barrier to population research in
10 682 OHCA cases from 27 European coun- the United States (ROC Investigators, unpublished
tries in October 2014 found an incidence of 84 data, July 7, 2016). Cardiac arrest is a syndrome
per 100 000 people, with CPR attempted in 19 that results from many disease processes, and
to 104 cases per 100 000 people.115 Return of diagnosis codes are often assigned to those dis-
pulse occurred in 28.6% (range for countries, eases rather than to cardiac arrest. Consequently,
9%–50%), with 10.3% (range, 1.1%–30.8%) of incidence of cardiac arrest is underestimated from
people on whom CPR was attempted surviving to administrative data. Finally, regional and cultural
hospital discharge or 30 days. differences in use of EMS systems could affect
• Western Australia reports an age- and sex- ascertainment of OHCA in current registries.
adjusted incidence of 87.6 EMS-attended cardiac Regimenting and increasing the rigor of reporting
arrests per 100 000 population, with resuscita- of cardiac arrest will improve the understanding
tion attempted in 45%.117 Survival to hospital of the epidemiology of this syndrome.
Table 16-1. Annual Incidence of OHCA in US Sites of the ROC, June 1,

2014, to May 31, 2015
Annual No. of US Cases
Incidence per
100 000 (95% CI) N 95% LCL 95% UCL
EMS assessed
Any age 110.8 (108.9–112.6) 356 461 350 349 362 252
Adults 140.7 (138.3–143.1) 347 322 341 397 353 246
Children 9.4 (8.3–10.5) 7037 6214 7861
EMS treated
Any age 57.3 (56.0–58.7) 184 343 180 161 188 847
Adults 73.0 (71.2–74.7) 180 202 175 759 184 399
Children 7.3 (6.3–8.3) 5465 4716 6214
VF*
Any age 12.1 (11.5–12.7) 38 928 36 997 40 858
Adults 15.8 (15.0–16.6) 39 003 37 028 40 978
Children 0.5 (0.3–0.8) 374 225 599
Bystander-witnessed VF
Any age 7.0 (6.5–7.5) 22 520 20 912 24 129
Adults 9.2 (8.6–9.8) 22 710 21 229 24 192
Children 0.3 (0.1–0.5) 225 75 374
Assumes total US population is 321 716 000.10 CI indicates confidence interval; EMS, emergency

medical services; LCL, lower confidence limit; OHCA, out-of-hospital cardiac arrest; ROC, Resuscitation
Outcomes Consortium; UCL, upper confidence limit; and VF, ventricular fibrillation.
*The estimated number of annual VF cases of any age is less than the estimated number of cases in
adults alone because of rounding and missing information about patient age.
Source: ROC Investigators, unpublished data; data time frame is June 1, 2014, to May 31, 2015.
Population growth of 0.93% per year has been added from the 2010 population. In 2013, 23.27% of
the population was <18 years of age; this is used for annual number of case estimates for adults and
children.

Table 16-2. Trend in Incidence Rates* for EMS-Treated

CLINICAL STATEMENTS
OHCA
AND GUIDELINES
Incidence of EMS-Treated
OHCA With Initial
Incidence of EMS-Treated Shockable Rhythm per
Year OHCA per 100 000 People 100 000 People
2008 47.1 9.8
2009 57.7 11.9
2010 59.9 12.4
2011 61.6 13
2012 62.9 13.8
2013 64.9 13.2
2014 68.1 14.4
2015 66 13.5
EMS indicates emergency medical services; and OHCA, out-of-hospital

cardiac arrest.
*Incidence rates were calculated using the subset of ROC (Resuscitation
Outcomes Consortium) EMS agencies from 7 US sites that participated
continuously from 2008 to 2015. The total yearly population of the regions
covered by these agencies was adjusted using the 2000 and 2010 US census
to account for yearly population increases. The population at risk consisted
of people living in all census tracts where an ROC agency arrives and treats
a patient, even if the agency does not treat all patients in that tract. The
population represents the number of people who live within the census tracts
served by the EMS agencies and does not account for people who commute
into the area during business hours.
Table 16-3. Trends in Layperson Response and Outcomes for EMS-Treated OHCA13
2006 2007 2008 2009 2010 2011 2012 2013 2014 2015 2016
Survival to hospital discharge, %
ROC 10.2 10.1 11.9 10.3 11.1 11.3 12.4 11.9 12.7 12.4 …
CARES … … … … … 10.5 10 10.6 10.8 10.6 10.8
Survival if first rhythm shockable, %
ROC 25.9 29 33.6 27.8 30.1 30.9 34.1 32.7 33.5 30.2 …
CARES … … … … … … … … 29.3 29.1 29.5
First rhythm shockable, %
ROC 23.7 21.7 21.9 20.9 20.8 21.4 21.7 20.2 20.8 21.3 …
CARES … … … … … 23.2 23.1 23.2 20.4 20.1 19.8
Layperson-initiated CPR, %
ROC 36.5 37.9 37.4 39.1 38.6 38.6 42.8 43 44.5 43.6 …
CARES … … … … … 38 37.8 40.4 40.4 40.6 40.7
Layperson use of AED, %
ROC 3.2 3.3 3.9 4.5 4 3.9 5.1 6 6.6 6.7 …
CARES … … … … … 4.4 4 4.6 4.9 5.4 5.7
AED shock by layperson, %
ROC 2 1.6 1.8 1.8 2 1.8 2 2.2 2.2 2.3 …
CARES … … … … … 1.7 1.6 1.6 1.6 1.7 1.7
AED indicates automated external defibrillator; CARES, Cardiac Arrest Registry to Enhance Survival; EMS, emergency medical services,
OHCA, out-of-hospital cardiac arrest; and ROC, Resuscitation Outcomes Consortium.
Source: Data reported by ROC and CARES.

Table 16-4. Characteristics of and Outcomes for OHCA Table 16-6. Outcomes of EMS-Treated Nontraumatic
CLINICAL STATEMENTS
and IHCA OHCA in Adults (Age ≥18 Years): CARES Registry 2016
AND GUIDELINES
OHCA IHCA Survival
With Good
Adults Children Adults Children
Survival to Survival to Neurological
Survival to hospital discharge 10.8 10.7 26.4 49.5 Presenting Hospital Hospital Function In-Hospital
Characteristics (n) Admission Discharge (CPC 1 or 2) Mortality*
Good functional status at 9.0 8.2 15.9 13.9
hospital discharge All presentations
29.0 10.8 9 62.8
(59 759)
VF/VT/shockable 20.2 7.2 16.1 10.7
Home/residence
PEA … … 52.3 45.2 27.5 9.1 7.3 66.9
(40 685)
Asystole … … 23.6 26.9
Nursing home
18.2 4.4 2.4 75.8
Unknown … … 8 17.2 (6477)
Public setting 21.1 16.1 … … Public setting

39.5 19.9 17.8 49.6
(12 596)
Home 68.1 83.6 … …
Unwitnessed
Nursing home 10.8 0.3 … … 18.6 4.7 3.5 74.7
(29 906)
Arrest in ICU, operating … … 53.7 87.5 Bystander
room, or ED witnessed 38.7 16.7 14.1 56.8
Noncritical care area … … 46.3 12.5 (22 518)
EMS provider
Values are percentages. ED indicates emergency department; ICU, intensive 41.4 18.0 15.0 56.5
witnessed (7333)
care unit; IHCA, in-hospital cardiac arrest; OHCA, out-of-hospital cardiac arrest;
PEA, pulseless electrical activity; VF, ventricular fibrillation; and VT, ventricular Shockable
tachycardia. presenting rhythm 49.5 29.4 26.3 40.6
Data are from CARES (Cardiac Arrest Registry to Enhance Survival) 2016, (12 045)
based on 61 523 emergency medical services -treated OHCA cases, and from
Get With the Guidelines 2016, based on 22 960 adult IHCAs in 300 hospitals Nonshockable
and 495 child IHCAs in 69 hospitals. presenting rhythm 23.8 6.1 4.6 74.4
(47 707)
Bystander CPR
29.8 12.6 10.6 57.7
(24 215)
Table 16-5. Outcomes of EMS-Treated Nontraumatic
OHCA in Children: CARES Registry 2016 No bystander CPR
25.1 7.5 6.0 70.1

(28 202)
Survival
With Good Values are percentages. CARES indicates Cardiac Arrest Registry to Enhance
Survival to Survival to Neurological Survival; CPC, Cerebral Performance Index; CPR, cardiopulmonary resuscitation;
Age Hospital Hospital Function (CPC In-Hospital EMS, emergency medical services; and OHCA, out-of-hospital cardiac arrest.
Groups (n) Admission Discharge 1 or 2) Mortality* *Percentage of patients admitted to hospital who die before hospital
discharge.
<1 y (991) 18.5 6.4 4.8 65.4 Modified from CARES.13
1–12 y (397) 33.2 14.4 10.1 56.6
13–18 y (306) 43.8 19.9 16.7 54.6
Values are percentages. CARES indicates Cardiac Arrest Registry to Enhance

Survival; CPC, Cerebral Performance Category; EMS, emergency medical
services; and OHCA, out-of-hospital cardiac arrest.
*Percentage of patients admitted to hospital who die before hospital
discharge.
Data derived from CARES.13

Table 16-7. Sudden Cardiac Arrest (ICD-10 Codes

CLINICAL STATEMENTS
146.0, 146.1, 146.9, 149.0)

AND GUIDELINES
Number of Number of
Deaths as Deaths as Any-
Underlying Mention Cause,
Population Group Cause, All Ages All Ages
Both sexes 17 668 366 807
Males 9311 186 268
Females 8357 180 539
NH white males 7038 135 613
NH white females 6272 129 901
NH black males 1572 24 354
NH black females 1451 25 855
Hispanic males 398 17 080
Hispanic Females 327 16 056
NH Asian/Pacific Islander males 229 7056
NH Asian/Pacific Islander females 258 6891
NH American Indian/Alaska Native 78 2325
ICD-10 indicates International Classification of Diseases, 10th Revision; and

NH, non-Hispanic.
Data derived from Centers for Disease Control and Prevention WONDER
(Wide-ranging Online Data for Epidemiologic Research) database.17
Chart 16-1. Death rates for any mention of sudden cardiac death by age, 2015.
Data derived from Centers for Disease Control and Prevention WONDER (Wide-ranging Online Data for Epidemiologic
Research) database.17 Accessed April 16, 2017.

CLINICAL STATEMENTS
AND GUIDELINES
Chart 16-2. Temporal trends in survival to hospital discharge after pulseless IHCA in GWTG-Resuscitation from
2000 to 2016.
GWTG indicates Get With the Guidelines; IHCA, in-hospital cardiac arrest; PEA, pulseless electrical activity; VF, ventricular
fibrillation; and VT, ventricular tachycardia.
Source: GWTG-Resuscitation; unpublished data.
Chart 16-3. Age-adjusted death rates for any mention of sudden cardiac death, 1999 to 2015.
Data derived from Centers for Disease Control and Prevention WONDER (Wide-ranging Online Data for Epidemiologic
Research) database.17 Accessed April 16, 2017.

CLINICAL STATEMENTS
Primary Ages 0-2 Ages 3 - 13

AND GUIDELINES
Arrhythmia, 8% Other, 4%
Myocarditis,
4% HCM, 18% Congenital,
21%
Long QT,
14% Myocarditis,
11%
Congenital
, 84% Mitral Valve Primary
Prolapse, 7% Arrhythmia,
Other, 18% 11%
Congenital,
Ages 14 - 24 Ages 25 - 35
Myocarditis, 4%
HCM, 2% 2%
Long
QT, Primary
8% Arrhythmia,
Congenital, 14%
23%
DCM, 14% CAD, 43%
Myocarditis, Other, 19%

4%
Other, 26% Primary
Arrhythmia,
23% Mitral Valve DCM, 11%
Prolapse,
2% HCM, 3% Long QT, 2%
Chart 16-4. Detailed causes of cardiac arrest by age group in children and young adults in King County, WA
(1980–2009).
CAD indicates coronary artery disease; DCM, dilated cardiomyopathy; and HCM, hypertrophic cardiomyopathy. “Other” cor-
responds to all other causes.
Reprinted from Meyer et al.30 Copyright © 2012, American Heart Association, Inc.
3. US population data (population clock). United States Census Bureau web-

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AND GUIDELINES
76. Lieve KV, Wilde AA. Inherited ion channel diseases: a brief review. tion and prevention of sudden death with implantable defibrillators in
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105. Blewer AL IS, Leary M, Dutwin D, McNally B, Anderson ML, Morrison survival from out-of-hospital cardiac arrest according to neighbor-
CLINICAL STATEMENTS
LJ, Aufderheide TA, Daya M, Idris A, Callaway CW, Kudenchuk PJ, Vilke hood ethnicity. Am J Emerg Med. 2014;32:1041–1045. doi: 10.1016/j.
AND GUIDELINES
GM, Abella BS. Cardiopulmonary resuscitation training disparities in ajem.2014.06.019.

the United States. J Am Heart Assoc. 2017;6:e006124. doi: 10.1161/ 114. Sasson C, Haukoos JS, Ben-Youssef L, Ramirez L, Bull S, Eigel B, Magid
JAHA.117.006124. DJ, Padilla R. Barriers to calling 911 and learning and performing cardio-
106. Bakke HK, Steinvik T, Angell J, Wisborg T. A nationwide survey of first aid pulmonary resuscitation for residents of primarily Latino, high-risk neigh-
training and encounters in Norway. BMC Emerg Med. 2017;17:6. doi: borhoods in Denver, Colorado. Ann Emerg Med. 2015;65:545–552.e2.
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107. Bray JE, Smith K, Case R, Cartledge S, Straney L, Finn J. Public cardio- 115. Nishiyama C, Brown SP, May S, Iwami T, Koster RW, Beesems SG, Kuisma
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17. SUBCLINICAL ATHEROSCLEROSIS Abbreviations Used in Chapter 17 Continued

CLINICAL STATEMENTS
CLINICAL STATEMENTS
See Table 17-1 and Charts 17-1 through 17-8 MASALA Mediators of Atherosclerosis in South Asians Living in
AND GUIDELINES
AND GUIDELINES
America
Atherosclerosis, a systemic disease process in which MRI magnetic resonance imaging

fatty deposits, inflammation, and scar tissue build up NHLBI National Heart, Lung, and Blood Institute
within the walls of arteries, is the underlying cause NNT number needed to treat
of the majority of clinical cardiovascular events.
NNT5 5-year number needed to treat
Atherosclerosis can develop in large and small arteries
PWV pulse wave velocity
ABI ankle-brachial index
RR relative risk
TIA transient ischemic attack
TIPS The Indian Polycap Study
BMI body mass index
BNP B-type natriuretic peptide
BP blood pressure supplying a variety of end organs, including the heart,
CAC coronary artery calcification
brain, kidneys, and extremities. There can be significant
variability in which arteries and locations are affected in
individual patients, although atherosclerosis is often a
systemic disease. In recent decades, advances in imag-
CHD coronary heart disease ing technology have allowed for improved ability to
detect and quantify atherosclerosis at all stages and in
CHS Cardiovascular Health Study

CKD chronic kidney disease multiple different vascular beds. Early identification of
subclinical atherosclerosis could lead to more aggres-
sive lifestyle modifications and medical treatment to
CONFIRM Coronary CT Angiography Evaluation for Clinical Outcomes:
An International Multicenter Registry prevent clinical manifestations of atherosclerosis such
as MI, stroke, or renal failure. Two modalities, CT of
the chest for evaluation of CAC and B-mode ultrasound
of the neck for evaluation of carotid artery IMT, have
been used in large studies with outcomes data and can
DBP diastolic blood pressure help define the burden of atherosclerosis in individuals
DM diabetes mellitus before they develop clinical events such as heart attack
ESRD end-stage renal disease or stroke. Another commonly used method for detect-
ing and quantifying atherosclerosis in the peripheral
arteries is the ABI. Data on cardiovascular outcomes
FMD flow-mediated dilation
are beginning to emerge for additional modalities that
FRS Framingham Risk Score
measure anatomic and functional measures of subclini-
HBP high blood pressure cal disease, including brachial artery reactivity testing,
HDL high-density lipoprotein aortic and carotid MRI, and tonometric methods of
HDL-C high-density lipoprotein cholesterol measuring vascular compliance or microvascular reac-
HF heart failure tivity. Further research could help to define the role
HR hazard ratio
of these techniques in cardiovascular risk assessment.
Some guidelines have recommended that screening for
subclinical atherosclerosis, especially by CAC or IMT,
JUPITER Justification for the Use of Statins in Primary Prevention: An
might be appropriate in people at intermediate risk
Intervention Trial Evaluating Rosuvastatin
for CHD (eg, 10-year estimated risk of 10%–20%) but
not for lower-risk general population screening or for
LV left ventricular people with preexisting CHD or most other high-risk
(Continued ) conditions.1,2

According to the latest ACC/AHA cholesterol man- Prevalence

CLINICAL STATEMENTS
agement guidelines, when treatment decisions are (See Table 17-1 and Charts 17-1 through 17-3)
AND GUIDELINES
uncertain after 10-year ASCVD risk is estimated, the • The NHLBI’s FHS reported CAC measured in 3238
patient and clinician should take into consideration white adults in age groups ranging from <45
any additional factors that modify the risk estimate, years of age to ≥75 years of age.8
including an elevated CAC score or an ABI <0.9.3 — Overall, 32.0% of females and 52.9% of
There are still limited data demonstrating whether males had prevalent CAC.
screening with these and other imaging modalities — Among participants at intermediate risk
can improve patient outcomes or whether it only according to FRS, 58% of females and 67%
increases downstream medical care costs. A recently of males had prevalent CAC.
published report in a large cohort randomly assigned • The NHLBI’s CARDIA study measured CAC in
to coronary calcium screening or not showed such 3043 black and white adults 33 to 45 years of
screening to result in an improved risk factor profile age (at the CARDIA year 15 examination).8
without increasing downstream medical costs.4 In — Overall, 15.0% of males, 5.1% of females,
addition, a recent cost-effectiveness analysis based 5.5% of those 33 to 39 years of age, and
on data from MESA5 reported that CAC testing and 13.3% of those 40 to 45 years of age had
statin treatment for those with CAC >0 was cost- prevalent CAC. Overall, 1.6% of partici-
effective (<$50 000 per QALY) in intermediate-risk pants had an Agatston score that exceeded
scenarios (CHD risk 5%–10%) considering less favor- 100.
able statin assumptions ($1.00 per pill). Furthermore,
• Chart 17-1 shows the prevalence of CAC by eth-
a recent MESA analysis compared these CAC-based
nicity and sex in adults 33 to 45 years of age. The
treatment strategies to a “treat all” strategy and to
prevalence of CAC was lower in black males than
treatment according to the Adult Treatment Panel
in white males but was similar in black and white
III guidelines, with clinical and economic outcomes
females at these ages.8
modeled over both 5- and 10-year time horizons.6
• The NHLBI’s Jackson Heart Study recently reported
The results consistently demonstrated that it is both
outcomes with presence of elevated CAC (>100)
cost-saving and more effective to scan intermediate-
in 4416 African American participants (mean age
risk patients for CAC and to treat those with CAC
54 years; 64% females) followed up for 6 years.9
≥1 than to use treatment based on established risk

— CAC >100 was noted in 14% of those with-
assessment guidelines.6
out any metabolic syndrome or DM, 26% of
those with metabolic syndrome, and 41% of
those with DM.
Coronary Artery Calcification
— At 6-year follow-up, 265 CVD events were
Background noted in this cohort.
• CAC is a measure of the burden of atheroscle- — High CAC scores were significantly associ-
rosis in the heart arteries and is measured by ated with CVD events among those with nei-
CT. Other components of the atherosclerotic ther metabolic syndrome nor DM (HR, 4.3;
plaque, including fatty (eg, cholesterol-rich 95% CI, 2.0–9.5), those with metabolic syn-
components) and fibrotic components, often drome (HR, 2.2; 95% CI, 1.1–4.4), and those
accompany CAC and can be present even in the with DM (HR, 3.4; 95% CI, 1.6–8.7).
absence of CAC. — In comparison, the presence of PAD was not
• The presence of any CAC, which indicates that predictive of CVD events in either group.
at least some atherosclerotic plaque is present, • The NHLBI’s MESA measured CAC in 6814 par-
is defined by an Agatston score >0. Clinically ticipants 45 to 84 years of age, including white
significant plaque, frequently an indication for (N=2619), black (N=1898), Hispanic (N=1494),
more aggressive risk factor management, is often and Chinese (N=803) males and females.10
defined by an Agatston score ≥100 or a score — Chart 17-2 shows the prevalence of CAC by
≥75th percentile for one’s age and sex; however, sex and ethnicity in US adults 45 to 84 years
although they predict short- to intermediate-term of age in MESA.
risk, absolute CAC cutoffs offer more prognostic — The prevalence and 75th percentile levels of
information across all age groups in both males CAC were highest in white males and low-
and females.7 An Agatston score ≥400 has been est in black and Hispanic females. Significant
noted to be an indication for further diagnostic ethnic differences persisted after adjustment
evaluation (eg, exercise testing or myocardial per- for risk factors, with the RR of coronary cal-
fusion imaging) for CAD. cium being 22% less in blacks, 15% less in

Hispanics, and 8% less in Chinese than in factors made no notable difference in CAC trends
CLINICAL STATEMENTS
whites. in any ethnic group.13
AND GUIDELINES
• Table 17-1 shows the 75th percentile levels of
CAC and Incidence of Cardiovascular Events
CAC by sex and race at selected ages in MESA.
(See Charts 17-4 and 17-5)
— In a comparison of MESA with the MASALA
• The NHLBI’s MESA reported on the association of
study, which is a community-based cohort
CAC scores with first CHD events over a median
of South Asians in the United States (mean
age 58 years), the age-adjusted prevalence follow-up of 3.9 years among a population-based
of CAC was similar among white (68.8%) sample of 6722 males and females (39% white,
and South Asian (67.9%) males, with these 27% black, 22% Hispanic, and 12% Chinese).14
groups having a greater prevalence of CAC — Chart 17-4 shows the HRs associated with
than Chinese (57.8%), African-American CAC scores of 1 to 100, 101 to 300, and
(51.2%), and Hispanic (57.9%) males. In >300 compared with those without CAC
contrast, the age-adjusted prevalence of (score=0), after adjustment for standard risk
CAC was lower in South Asian females factors. People with CAC scores of 1 to 100
(36.8%) than in white females (42.6%) and had ≈4 times greater risk and those with
females of other races/ethnicities.11 CAC scores >100 were 7 to 10 times more
• To date, sparse research exists on the prevalence likely to experience a coronary event than
of subclinical atherosclerosis, including CAC, in those without CAC.
rural areas of the United States. A study reported — CAC provided similar predictive value for
the distribution of CAC scores among 1607 coronary events in whites, Chinese, blacks,
(mean age 56 years; 56% females) community- and Hispanics (HRs ranging from 1.15–1.39
dwelling asymptomatic individuals from central for each doubling of coronary calcium).
Appalachia. Overall, 44% had a CAC score of 0, • In MESA, CAC was noted to be highly predic-
whereas the prevalence of those with mild (1–99), tive of CHD event risk across all age groups in a
moderate (100–399), and severe (≥400) CAC was follow-up that extended to 8.5 years, which sug-
29%, 15%, and 11%, respectively.12 gests that once CAC is known, chronological age
• The prevalence of CAC varies widely according to has less importance. Compared with a CAC score
baseline risk profile, including global scores such of 0, CAC >100 imparted an increased multi-
as the FRS. In a report from MESA,13 the preva- variable-adjusted CHD event risk in the younger
lence of CAC among individuals with a very low individuals (45–54 years old), with an HR of 12.4
FRS (≤2.5%) was 22%, and it was 39% among (95% CI, 5.1–30.0). The respective risk was simi-
those with an FRS 10-year risk for CHD of 2.5% lar even in the very elderly (75–84 years of age),
to 5%. In recent studies from MESA, the preva- with an HR of 12.1 (95% CI, 2.9–50.2).16
lence of CAC in those with no lipid abnormalities • In another report of a community-based sample,
was 42%,14 and nearly one fifth (22%) of people not referred for clinical reasons, the South Bay
in MESA with no known traditional CVD risk fac- Heart Watch examined CAC in 1461 adults (aver-
tors had presence of CAC.15 age age 66 years) with coronary risk factors, with
• In a 2005 update,13 the 10-year trends in CAC a median of 7.0 years of follow-up.17
among individuals without clinical CVD in MESA • Chart 17-5 shows the HRs associated with
were reported (Chart 17-3). After adjustment for increasing CAC scores (relative to CAC=0 and
age, sex, ethnicity, and type of CT scanner, the <10% risk category) in low-risk (<10%), inter-
proportion of participants with no CAC decreased mediate-risk (10%–15% and 16%–20%), and
over time from 40.7% to 32.6% (P=0.007), and high-risk (>20%) FRS categories of estimated risk
the proportions increased from 29.9% to 37.0% for CHD in 10 years. Increasing CAC scores fur-
(P=0.01) for those with a CAC score ranging from ther predicted risk in intermediate- and high-risk
1 to 99 and from 14.7% to 17.7% (P=0.14) for groups.17
those with a CAC score of 100 to 299, whereas • In a study of healthy adults 60 to 72 years of age
the proportion with a CAC score ≥400 decreased who were free of clinical CAD, predictors of the
from 9.1% to 7.2% (P=0.11). Trends in CAC progression of CAC were assessed. Predictors
among the 4 racial/ethnic groups revealed a sig- tested included age, sex, race/ethnicity, smoking
nificant trend toward increased prevalence of status, BMI, family history of CAD, CRP, several
CAC in African Americans but not in any other measures of DM, insulin levels, BP, and lipids.
group. Among African Americans, the CAC prev- Insulin resistance, in addition to the traditional
alence ratio (year 10 versus baseline) was 1.27 cardiac risk factors, independently predicts pro-
(P<0.001 for test for trend). Adjustment for risk gression of CAC.18 Clinically, however, it is not yet

recommended to conduct serial scanning of CAC 802 events; mean follow-up 5.18 years). The RR
CLINICAL STATEMENTS
to measure effects of therapeutic interventions. for all-cause mortality or cardiovascular events

AND GUIDELINES
• A publication from MESA also used CAC, in par- or both comparing a total CAC score ≥10 with
ticular, and carotid IMT to stratify CHD and CVD a score <10 was 5.47 (95% CI, 2.59–11.53;
event risk in people with metabolic syndrome and I2=82.4%, P<0.001). For people with a CAC score
DM; those with low levels of CAC or carotid IMT <10, the posttest probability of the composite
had CHD and CVD event rates as low as many outcome was ≈1.8%, which represents a 6.8-fold
people without metabolic syndrome and DM. reduction from the pretest probability, which sug-
Those with DM who had CAC scores <100 had gests that low or absent CAC could facilitate risk
annual CHD event rates of <1%.19 stratification by enabling the identification of peo-
• It is noteworthy, as demonstrated in MESA in ple at low risk within this high-risk population.24
5878 participants with a median of 5.8 years of • Recent studies have suggested CAC also pre-
follow-up, that the addition of CAC to standard dicts cardiac events beyond stroke and MI. In the
risk factors resulted in significant improvement Rotterdam Study, CAC independently predicted
of classification of risk for incident CHD events, incident HF during a median follow-up of 6.8
placing 77% of people in the highest or lowest years. Those with severe CAC (>400) after adjust-
risk categories compared with 69% based on risk ment for risk factors had a 4.1-fold higher risk
factors alone. An additional 23% of those who (95% CI, 1.7–10.1) of HF than those with CAC
experienced events were reclassified as high risk, scores of 0 to 10.25 In addition, CAC substantially
and 13% with events were reclassified as low improved the risk classification of subjects (net
risk.20 The contribution of CAC to risk prediction reclassification index, 34.0%).
has also been observed in other cohorts, includ- • In MESA, during a median follow-up period of
ing both the Heinz Nixdorf Recall Study21 and the 8.5 years, after accounting for risk factors, higher
Rotterdam Study.22 CAC scores were associated with increased risk
• The prospective Dallas Heart Study recently for AF (CAC=0: HR, 1.0 [referent]; CAC=1–100:
reported the prognostic value of CAC scores in a HR, 1.4 [95% CI, 1.01–2.0]; CAC=101–300: HR,
relatively younger cohort (44.4±9.0 years of age). 1.6 [95% CI, 1.1–2.4]; CAC >300: HR, 2.1 [95%
Among the 2084 participants who were followed CI, 1.4–2.9]). The addition of CAC to the FHS AF
up for a median of 9 years, compared with indi- risk score yielded relative integrated discrimination
viduals with CAC=0, those with CAC scores of 10 improvement of 0.10 (95% CI, 0.061–0.15).26
to 99 and >100 were associated with an HR (95% • Investigators from MESA recently reported a
CI) of 3.43 (1.36–8.56) and 5.64 (2.28–13.97) for higher CAC burden was also associated with
CHD events, respectively. The addition of CAC to non-CVD outcomes. During a median follow-up
the traditional risk factor model resulted in sig- of 10.2 years, accounting for demographics and
nificant improvement in the C statistic (Δ=0.03; traditional risk factors, participants with severe
P=0.003), as well as a net correct reclassification CAC (>400) were at an increased risk of cancer
of 22%.23 (HR, 1.53; 95% CI, 1.18–1.99), CKD (HR, 1.70;
• In the Heinz Nixdorf Recall Study,21 CAC indepen- 95% CI, 1.21–2.39), pneumonia (HR, 1.97; 95%
dently predicted stroke during a mean follow-up CI, 1.37–2.82), chronic obstructive pulmonary
of 7.9 years. Cox proportional hazards regres- disease (HR, 2.71; 95% CI, 1.60–4.57), and hip
sions were used to examine CAC as a predictor of fracture (HR, 4.29; 95% CI, 1.47–12.50) com-
stroke in addition to established vascular risk fac- pared with those with CAC=0.27
tors (age, sex, SBP, LDL-C, HDL-C, DM, smoking, • An absence of CAC, observed in 40% to 50% of
and AF). Study participants who had a stroke had individuals, confers a very low risk for future car-
significantly higher CAC values at baseline than diovascular events. In a meta-analysis of 13 stud-
the remaining subjects (median 104.8 [quartile 1, ies assessing the relationship of CAC with adverse
14.0; quartile 3, 482.2] versus 11.2 [quartile 1, cardiovascular outcomes that included 71 595
0; quartile 3, 106.2]; P<0.001). In a multivariable asymptomatic patients, 29 312 patients (41%)
Cox regression, log10(CAC+1) was an indepen- did not have any evidence of CAC.28 In a follow-
dent stroke predictor (HR, 1.52; 95% CI, 1.19– up that averaged 3 to 5 years, 154 of 29 312
1.92; P=0.001). CAC discriminated stroke risk patients without CAC (0.47%) experienced a car-
specifically in participants in the low (<10%) and diovascular event compared with 1749 of 42 283
intermediate (10%–20%) FRS categories.21 patients with CAC (4.14%). The cumulative RR
• A meta-analysis24 also highlighted the utility of was 0.15 (95% CI, 0.11–0.21; P<0.001). These
CAC testing in the diabetic population. In this findings were confirmed in MESA, which reported
meta-analysis, 8 studies were included (n=6521; a rate of 0.52% for CHD events during a median

of 4 years of follow-up among people with no with CAC >0 at baseline, HRs per 100-U annual
CLINICAL STATEMENTS
detectable CAC.29 change in CAC were 1.2 and 1.3, respectively, and
AND GUIDELINES
• The value of CAC=0 has been confirmed in vari- for those with annual progression ≥300 versus no
ous high-risk groups. For example, in MESA, 38% progression, HRs were 3.8 and 6.3, respectively.33
of those with DM had CAC=0, and the annual- Progression of CAC in MESA was also shown to
ized CHD and CVD event rates were 0.4% and be greater in those with metabolic syndrome and
0.8%, respectively.19 A publication15 from MESA DM than in those with neither condition, and
demonstrated a low hard CHD event rate per progression of CAC in each of these conditions
1000 years during a median follow-up of 7.1 was associated with a greater future risk of CHD
years across the entire spectrum of baseline FRS events.34
(0%–6%: 0.9; 6%–10%: 1.1; 10%–20%: 1.9; • Furthermore, a recent study from MESA spe-
>20%: 2.5). Among high-risk individuals consid- cifically demonstrated association of CAC pro-
ered for various polypill criteria in MESA,30 based gression with incident AF. Presence of any CAC
on age and risk factors, the prevalence of CAC=0 progression (>0 per year) in the 5-year follow-up
ranged from 39% to 59%, and the respective was associated with 1.55-fold higher risk for AF
rate of CHD events varied from 1.2 to 1.9 events (95% CI, 1.10–2.19). The risk of AF increased
per 1000 person-years during a median follow-up with higher levels of CAC progression: (1–100
of 7.6 years. per year: HR, 1.47 [95% CI, 1.03–2.09]; 101–300
• Furthermore, a recent study from MESA demon- per year: HR, 1.92 [95% CI, 1.15–3.20]; >300 per
strated that during a median 10-year follow-up, year: HR, 3.23 [95% CI, 1.48–7.05]).35
among 13 negative risk markers (CAC=0, carotid • In MESA, greater adherence to a healthy lifestyle,
IMT <25th percentile, absence of carotid plaque, based on a healthy lifestyle score, was associ-
brachial FMD >5% change, ABI >0.9 and <1.3, ated with slower progression of CAC and lower
high-sensitivity CRP <2 mg/L, homocysteine <10 mortality rates relative to those with the most
µmol/L, N-terminal pro-BNP <100 pg/mL, no unhealthy lifestyle.36
microalbuminuria, no family history of CHD [any/
premature], absence of metabolic syndrome, and Carotid IMT
healthy lifestyle), CAC=0 had the lowest diag-
Background
nostic likelihood ratio for all CHD (0.41) and CVD

(0.54).31 • Carotid IMT measures the thickness of 2 layers
• A recent meta-analysis that pooled data from 3 (the intima and media) of the wall of the carotid
studies, including data from MESA, evaluated arteries, the largest conduits of blood going to
13 262 asymptomatic patients (mean age 60 the brain. Carotid IMT is thought to be an even
years, 50% men) without apparent CVDs. During earlier manifestation of atherosclerosis than CAC,
a mean follow-up of 7.2 years, the pooled risk because thickening precedes the development of
ratio of incident stroke with CAC >0 was 2.95 frank atherosclerotic plaque. Carotid IMT meth-
(95% CI, 2.18–4.01; P<0.001) compared with ods are still being refined, so it is important to
CAC=0. Furthermore, there was an increasing know which part of the artery was measured
risk with higher CAC score (0.12% per year for (common carotid, internal carotid, or bulb) and
CAC=0, 0.26% per year for CAC 1–99, 0.41% whether near and far walls were both measured.
per year for CAC 100–399, and 0.70% per year This information can affect the average-thickness
for CAC ≥400).32 measurement that is usually reported.
• Unlike CAC, everyone has some thickness to the
CAC Progression and Risk layers of their arteries, but people who develop
• A recent report of 4609 individuals who had base- atherosclerosis have greater thickness. Ultrasound
line and repeat cardiac CT found that progression of the carotid arteries can also detect plaques and
of CAC provided incremental information over determine the degree of narrowing of the artery
baseline score, demographics, and cardiovas- they might cause. Epidemiological data high-
cular risk factors in predicting future all-cause lighted in the section “Prevalence and Association
mortality.33 With Incident Cardiovascular Events” indicate
• More recently, data from 6778 people in MESA that high-risk levels of thickening might be con-
showed annual CAC progression was an average sidered as those in the highest quartile or quintile
of 25 Agatston units, and among those without for one’s age and sex, or ≥1 mm.
CAC at baseline, a 5-U annual change in CAC • Although ultrasound is commonly used to diag-
was associated with HRs of 1.4 and 1.5 for total nose plaque in the carotid arteries in people who
and hard CHD events, respectively. Among those have had strokes or who have bruits (sounds of

turbulence in the artery), guidelines are limited as • Among both females and males in MESA, blacks
CLINICAL STATEMENTS
to screening of asymptomatic people with carotid had the highest common carotid IMT, but they
AND GUIDELINES
IMT to quantify atherosclerosis or predict risk. were similar to whites and Hispanics in internal
However, some organizations have recognized carotid IMT. Chinese participants had the lowest
that carotid IMT measurement by B-mode ultra- carotid IMT, in particular in the internal carotid, of
sonography can provide an independent assess- the 4 ethnic groups41 (Chart 17-8).
ment of coronary risk.37 • The NHLBI’s CHS reported follow-up of 4476 males
and females ≥65 years of age (mean age 72 years)
Prevalence and Association With Incident who were free of CVD at baseline.42 Mean maxi-
Cardiovascular Events mal common carotid IMT was 1.03±0.20 mm,
(See Charts 17-6 and 17-7) and mean internal carotid IMT was 1.37±0.55
• The Bogalusa Heart Study measured carotid IMT in mm. After a mean follow-up of 6.2 years, those
518 black and white males and females at a mean with maximal combined carotid IMT in the highest
age of 32±3 years. These males and females were quintile had a 4- to 5-fold greater risk for incident
healthy but overweight.38 heart attack or stroke than those in the bottom
— The mean values of carotid IMT for the dif- quintile. After adjustment for other risk factors,
ferent segments are shown in Chart 17-6 by there was still a 2- to 3-fold greater risk for the
sex and race. Males had significantly higher top versus the bottom quintile.
carotid IMT in all segments than females, • In MESA, during a median follow-up of 3.3 years,
and blacks had higher common carotid and an IMT rate of change of 0.5 mm per year was
carotid bulb IMTs than whites. associated with an HR of 1.23 (95% CI, 1.02–
— Even at this young age, after adjustment for 1.48) for incident stroke. The upper quartile of
age, race, and sex, carotid IMT was associ- IMT rate of change had an HR of 2.18 (95% CI,
ated significantly and positively with waist 1.07–4.46) compared with the lower 3 quartiles
circumference, SBP, DBP, and LDL-C. Carotid combined.43
IMT was inversely correlated with HDL-C • A study of 441 individuals ≤65 years of age with-
levels. Participants with greater numbers out a history of CAD, DM, or hyperlipidemia who
of adverse risk factors (0, 1, 2, 3, or more) were examined for carotid IMT found 42% had
had stepwise increases in mean carotid IMT high-risk carotid ultrasound findings (carotid IMT
levels. ≥75th percentile, adjusted for age, sex, and race

• Updates from an individual-participant meta- or presence of plaque). Among those with an
analysis involving 15 population-based cohorts FRS ≤5%, 38% had high-risk carotid ultrasound
worldwide that included 60 211 individuals findings.44
(46 788 whites, 7200 blacks, 3816 Asians, and • Conflicting data have been reported on the
2407 Hispanics) demonstrated differing asso- contribution of carotid IMT to risk prediction. In
ciations between risk factors and burden of 13 145 participants in the NHLBI’s ARIC study, the
carotid IMT according to racial/ethnic groups.39 addition of carotid IMT, combined with identifica-
Specifically, association between age and tion of plaque presence or absence, to traditional
carotid IMT was weaker in blacks and Hispanics, risk factors reclassified risk in 23% of individuals
SBP was more strongly associated with carotid overall, with a net reclassification improvement of
IMT in Asians, and HDL-C and smoking were 9.9%. There was a modest but statistically signifi-
associated less with carotid IMT in blacks (Chart cant improvement in the area under the receiver
17-7). operating characteristic curve, from 0.742 to
• In a subsequent analysis, the Bogalusa investi- 0.755.45 In contrast, data reported recently from
gators examined the association of risk factors the Carotid Atherosclerosis Progression Study
measured since childhood with carotid IMT mea- reflected a net reclassification improvement of
sured in these young adults.40 Higher BMI and −1.4%, which was not statistically significant.46
LDL-C levels measured at 4 to 7 years of age were • In the Rotterdam Study, 3580 nondiabetic indi-
associated with increased risk for being >75th viduals aged 55 to 75 years were followed up for
percentile for carotid IMT in young adulthood. a median of 12.2 years. In older males, addition
Higher SBP and LDL-C and lower HDL-C in young of carotid IMT to Framingham risk factors did not
adulthood were also associated with having high improve prediction of hard CHD or stroke. In older
carotid IMT. These data highlight the importance females, addition of carotid IMT to Framingham
of adverse risk factor levels in early childhood and risk factors yielded a net reclassification improve-
young adulthood in the early development of ment of 8.2% (P=0.03) for hard CHD and 8.0%
atherosclerosis. (P=0.06) for stroke.47

• A recent study from a consortium of 14 popu- for risk factors, the HRs for major adverse car-
CLINICAL STATEMENTS
lation-based cohorts consisting of 45 828 indi- diac events were 1.45 (95% CI, 0.67–3.14)
AND GUIDELINES
viduals followed up for a median of 11 years and 2.36 (95% CI, 1.13–4.92) with increasing
demonstrated little additive value of common carotid plaque burden tertile. Net reclassification
carotid IMT to FRS for purposes of discrimina- improved significantly with carotid plaque burden
tion and reclassification as far as incident MI and (0.23).53
stroke were concerned. The C statistics of the • Two large, population-based prospective stud-
model with FRS alone (0.757; 95% CI, 0.749– ies have aimed to elucidate the association of
0.764) and with addition of common carotid IMT carotid ultrasound findings with outcomes
(0.759; 95% CI, 0.752–0.766) were similar. The with shared pathogenesis of atherosclerosis.
net reclassification improvement with the addition Among 15 792 individuals aged 45 to 64 years
of common carotid IMT was small (0.8%; 95% (26% blacks, 56% females) followed up for a
CI, 0.1%–1.6%). In those at intermediate risk, median of 22.7 years, mean carotid IMT in the
the net reclassification improvement was 3.6% fourth quartile (>0.81 mm) versus first quartile
among all individuals (95% CI, 2.7%–4.6%).48 (<0.62) was significantly associated with ESRD.54
• Among nearly 13 590 participants in the ARIC Investigators from the FHS demonstrated that
study aged 45 to 64 years, each 1-SD increase in additional information obtained from carotid
carotid IMT was associated with incident HF (HR, ultrasound regarding the degree of carotid
1.20; 95% CI, 1.16–1.25) in a 20-year follow-up stenotic burden was predictive of cerebral
after accounting for major CVD risk factors and microbleeds detected on brain MRI, which are
CHD. Similar associations were also noted across recognized as a marker of stroke and dementia,
all race and sex groups.49 This relationship was in 1243 participants (56.9±8.8 years old; 53%
found to be much stronger among those without females). Carotid stenosis ≥25% was associated
established DM.50 with a 2.2-fold (95% CI, 1.10–4.40) increased
• A recent study51 from 3 population-based cohorts risk of cerebral microbleed, whereas no associa-
(ARIC, N=13 907; MESA, N=6640; and the tion was noted with carotid IMT.54
Rotterdam Study, N=5220) demonstrated that
both a higher carotid IMT and presence of carotid
plaque were independently associated with an CAC and Carotid IMT
increased risk of incident AF. In this study, a 1-SD • In the NHLBI’s MESA, a study of white, black,
increase in carotid IMT and presence of carotid Chinese, and Hispanic adults 45 to 84 years of
plaque were associated with a meta-analyzed age, carotid IMT and CAC were found to be com-
HR (95% CI) of 1.12 (1.08–1.16) and1.30 (1.19– monly associated, but patterns of association dif-
1.42), respectively.51 fered somewhat by sex and race.41
• A recent study from the same consortium of a — Common and internal carotid IMT were
population-based cohort reported no added value greater in females and males who had CAC
of measurement of mean common carotid IMT in than in those who did not, regardless of
individuals with HBP for improving cardiovascu- ethnicity.
lar risk prediction. For those at intermediate risk, — Overall, CAC prevalence and scores were
the addition of mean common carotid IMT to associated with carotid IMT, but associations
an existing cardiovascular risk score resulted in a were somewhat weaker in blacks than in
small but statistically significant improvement in other ethnic groups.
risk prediction.52 — In general, blacks had the thickest carotid
• In a recent study, however, carotid plaque burden IMT of all 4 ethnic groups, regardless of the
measured via 3-dimensional carotid ultrasound presence of CAC.
showed promise in improving CVD risk predic- — Common carotid IMT differed little by race/
tion. The prospective BioImage Study enrolled ethnicity in females with any CAC, but
5808 asymptomatic US adults (mean age 69 among females with no CAC, IMT was
years; 56.5% females). Carotid plaque areas from higher among blacks (0.86 mm) than in the
both carotid arteries were summed as the carotid other 3 groups (0.76–0.80 mm).
plaque burden. The primary end point was the • In a more recent analysis from MESA, the inves-
composite of major adverse cardiac events (car- tigators reported on follow-up of 6779 males
diovascular death, MI, and ischemic stroke). In a and females in 4 ethnic groups over 9.5 years
2.7-year median follow-up, major adverse cardiac and compared the predictive utility of carotid
events occurred in 216 patients (4.2%), of which IMT, carotid plaque, and CAC (presence and
82 (1.5%) were primary events. After adjustment burden).55

— CAC presence was a stronger predictor of may be equivocal. It is also of interest because of
CLINICAL STATEMENTS
incident CVD and CHD than carotid ultra- its ability to detect and possibly quantitate over-
AND GUIDELINES
sound measures. all plaque burden and certain characteristics of

— Mean IMT ≥75th percentile (for age, sex, and plaques that might make them prone to rupture,
race) alone did not predict events. Compared such as positive remodeling or low attenuation.
with traditional risk factors, C statistics for • Compared with the established value of CAC
CVD (C=0.756) and CHD (C=0.752) increased scanning for risk reclassification in asymptom-
the most by the addition of CAC presence atic patients, there are limited data regarding
(CVD, 0.776; CHD, 0.784; P<0.001), fol- the utility of CT angiography in asymptomatic
lowed by carotid plaque presence (CVD, people. This was recently assessed by the inves-
C=0.760; CHD, C=0.757; P<0.05). tigators of the CONFIRM registry,58 from which
— Compared with risk factors (C=0.782), >7500 asymptomatic subjects with CAC and CT
carotid plaque presence (C=0.787; P=0.045) angiography were followed up for death and
but not CAC (C=0.785; P=0.438) improved nonfatal MI for a median of 2 years. Overall,
prediction of stroke/TIA. 2.2% either died or experienced nonfatal MI,
• Investigators from the NHLBI’s CARDIA and MESA and in multivariable models, compared with
studies examined the burden and progression of those without atherosclerosis, there was increas-
subclinical atherosclerosis among adults <50 years ing risk across groups with increasing degrees
of age. Ten-year and lifetime risks for CVD were of atherosclerosis measured by CT angiography.
estimated for each participant, and the partici- However, after the inclusion of CAC in the multi-
pants were stratified into 3 groups: (1) those with variable risk model, CT angiography did not pro-
low 10-year (<10%) and low lifetime (<39%) pre- vide incremental prognostic value over this short
dicted risk for CVD; (2) those with low 10-year period of follow-up.58 In another study from the
(<10%) but high lifetime (≥39%) predicted risk; CONFIRM registry, it was noted that coronary CT
and (3) those with high 10-year risk (>10%). The angiography provided incremental prognostic
latter group had the highest burden and greatest utility for prediction of mortality and nonfatal MI
progression of subclinical atherosclerosis. Given for asymptomatic individuals with moderately
the young age of those studied, ≈90% of partici- high CAC scores but not for those with lower
or higher CAC scores. The value of coronary CT
pants were at low 10-year risk, but of these, half

had high predicted lifetime risk. Compared with angiography over the FRS was demonstrated in
those with low short-term/low lifetime predicted individuals with a CAC score >100 (increment in
risks, those with low short-term/high lifetime pre- C statistic, 0.24; net reclassification index, 0.62;
dicted risk had significantly greater burden and all P<0.001) but not among those with CAC
progression of CAC and significantly greater bur- scores ≤100 (all P>0.05).59
den of carotid IMT, even at these younger ages. • Because of the limited outcome data in asymp-
These data confirm the importance of early expo- tomatic people, as well as the associated expense
sure to risk factors for the onset and progression and risk of CT angiography (including generally
of subclinical atherosclerosis.56 higher radiation levels than with CT scanning to
detect CAC), current guidelines do not recom-
mend its use as a screening tool for assessment of
Carotid IMT Progression and Risk cardiovascular risk in asymptomatic people.2
To date, few studies have comprehensively studied the
impact of carotid IMT progression on CVD outcomes.
Measures of Vascular Function and
Data from a comprehensive meta-analysis of individual
participant data demonstrated that common carotid Incident CVD Events
artery IMT progression in people with DM ranged Background
between −0.09 and 0.04 mm per year in a follow-up of • Measures of arterial tonometry (stiffness) are
3.6 years; however, this change was not associated with based on the concept that pulse pressure has
cardiovascular outcomes. The HR for a 1-SD increase in been shown to be an important risk factor for
common carotid artery IMT progression was 0.99 (95% CVD. Arterial tonometry offers the ability to
CI, 0.91–1.08).57 directly and noninvasively measure central PWV in
the thoracic and abdominal aorta.
• Brachial FMD is a marker for nitric oxide release
CT Angiography from the endothelium that can be measured by
• CT angiography is widely used to aid in the diag- ultrasound. Impaired FMD is an early marker of
nosis of CAD, particularly when other test results CVD.

• Recommendations have not been specific, how- Comparison of Measures
CLINICAL STATEMENTS
ever, as to which, if any, measures of vascular • In MESA, a comparison of 6 risk markers—CAC,
AND GUIDELINES
function might be useful for CVD risk stratifica- ABI, high-sensitivity CRP, carotid IMT, brachial
tion in selected patient subgroups. Because of the FMD, and family history of CHD—and their clini-
absence of significant prospective data relating cal utility over FRS was evaluated in 1330 interme-
these measures to outcomes, the latest guidelines diate-risk individuals. After 7.6 years of follow-up,
do not recommend measuring either FMD or arte- CAC, ABI, high-sensitivity CRP, and family history
rial stiffness for cardiovascular risk assessment in were independently associated with incident CHD
asymptomatic adults.2 in multivariable analyses (HRs of 2.6, 0.79, 1.28,
and 2.18, respectively), but carotid IMT and bra-
Arterial Tonometry and CVD
chial FMD were not. CAC provided the highest
• The Rotterdam Study measured arterial stiffness
incremental improvement over the FRS (0.784 for
in 2835 elderly participants (mean age 71 years).60
both CAC and FRS versus 0.623 for FRS alone), as
They found that as aortic PWV increased, the RR
well as the greatest net reclassification improve-
of CHD was 1.72 (second versus first tertile) and
ment (0.659).65 Furthermore, in MESA, the values
2.45 (third versus first tertile). Results remained
of 13 negative markers (CAC score of 0, carotid
robust even after accounting for carotid IMT, ABI,
IMT <25th percentile, absence of carotid plaque,
and pulse pressure.
brachial FMD >5% change, ABI >0.9 and <1.3,
• A study from Denmark of 1678 individuals aged
high-sensitivity CRP <2 mg/L, homocysteine <10
40 to 70 years found that each 1-SD increment in
µmol/L, N-terminal pro-BNP <100 pg/mL, no
aortic PWV (3.4 m/s) increased CVD risk by 16%
microalbuminuria, no family history of CHD [any/
to 20%.61
premature], absence of metabolic syndrome,
• The FHS measured several indices of arterial stiff-
and healthy lifestyle) were compared for all and
ness, including PWV, wave reflection, and central
hard CHD and all CVD events over the 10-year
pulse pressure.60 They found that not only was
follow-up. After accounting for CVD risk factor,
higher PWV associated with a 48% increased
absence of CAC had the strongest negative pre-
risk of incident CVD events, but PWV additionally
dictive value, with an adjusted mean diagnostic
improved CVD risk prediction (integrated discrimi-
likelihood ratio of 0.41 (SD, 0.12) for all CHD and
nation improvement of 0.7%, P<0.05).
0.54 (SD, 0.12) for CVD, followed by carotid IMT
• A study from the Jackson Heart Study suggested

<25th percentile (diagnostic likelihood ratio, 0.65
peripheral arterial tonometry to be associated
[SD, 0.04] and 0.75 [SD, 0.04], respectively).31
with LV hypertrophy. A total of 440 African
• Similar findings were also noted in the Rotterdam
American participants (mean age 59±10 years,
Study, in which among 12 CHD risk markers,
60% women) underwent both peripheral arterial
improvements in FRS predictions were most sta-
tonometry and cardiac MRI evaluations between
tistically and clinically significant with the addition
2007 and 2013. Age- and sex-adjusted Pearson
of CAC scores.66
correlation analysis suggested that natural log-
transformed LV mass index was negatively cor-
related with reactive hyperemia index (coefficient Utility for Risk Stratification for
−0.114; P=0.02) after accounting for age, sex, Treatment
BMI, DM, hypertension, ratio of TC and HDL-C,
• CAC has been examined in multiple studies for
smoking, and history of CVD.62
its potential to identify those most likely and not
FMD and CVD likely to benefit from treatment.
• MESA measured FMD in 3026 participants (mean • A total of 950 participants from MESA who met
age 61 years) who were free of CVD. As FMD JUPITER clinical trial entry criteria (risk factors plus
increased (ie, improved brachial function), the LDL-C <130 mg/dL and CRP ≥2 mg/L) were identi-
risk of CVD was 16% lower.63 FMD also improved fied and stratified according to CAC scores of 0,
CVD risk prediction compared with the FRS by 1 to 100, or >100; CHD event rates were calcu-
improving net reclassification by 29%. lated, and the NNT was calculated by applying the
• A recent meta-analysis assessed the relation of benefit found in JUPITER to the event rates found
FMD with CVD events. Thirteen studies involving in each of these groups. For CHD, the predicted
11 516 individuals without established CVD, with NNT5 was 549 for those with CAC of 0, 94 for
a mean duration of 2 to 7.2 years and adjusted scores of 1 to 100, and 24 for scores >100.65
for age, sex, and risk factors, reported a multi- • In a similar fashion, 2 studies extrapolated the
variate RR of 0.93 (95% CI, 0.90–0.96) per 1% NNT5 for LDL-C lowering by statins, applying the
increase in brachial FMD.64 30% RR reduction associated with a 1 mmol/L

(39 mg/dL) reduction in LDL-C from a Cochrane • A study from MESA also examined the role of
CLINICAL STATEMENTS
meta-analysis of statin therapy in primary pre- CAC testing to define the target population to
AND GUIDELINES
vention across the spectrum of lipid abnormali- treat with a polypill.30 The NNT5 to prevent 1
ties (LDL-C ≥130 mg/dL, HDL-C <40 mg/dL for event was estimated by applying the expected
males or <50 mg/dL for females, and triglyc- 62% CHD event reduction associated with the
erides ≥150 mg/dL), as well as across 10-year use of the polypill (based on TIPS). The estimated
FRS categories (0%–6%, 6%–10%, 10%–20%, NNT5 to prevent 1 CHD event ranged from 170 to
and >20%). The estimated NNT5 for prevent- 269 for patients with CAC=0, from 58 to 79 for
ing 1 CVD event across dyslipidemia categories those with CAC scores from 1 to 100, and from
in this MESA cohort ranged from 23 to 30 in 25 to 27 for those with CAC scores >100,30 which
those with CAC ≥100.67 The NNT5 was 30 in enabled significant reductions in the population
participants with no lipid abnormality and CAC considered for treatment with more selective use
>100, whereas it was 154 in those with 3 lipid of the polypill and, as a result, avoidance of treat-
abnormalities and CAC of 0.67 A very high NNT5 ment of those who were unlikely to benefit.
of 186 and 222, respectively, was estimated to • Within the scope of the new ACC/AHA guide-
prevent 1 CHD event in the absence of CAC lines, recent data from MESA demonstrated that
among those with 10-year FRS of 11% to 20% among those for whom statins were recom-
and >20%. The respective estimated NNT5 was mended, 41% had CAC=0 and had 5.2 ASCVD
as low as 36 and 50 with the presence of a very events per 1000 person-years. Among 589 par-
high CAC score (>300) among those with 10-year ticipants (12%) considered for moderate-intensity
FRS of 0% to 6% and 6% to 10%, respectively.30 statin treatment, 338 (57%) had CAC=0, with an
These collective data show the utility of CAC in ASCVD event rate of 1.5 per 1000 person-years.
identifying those most likely to benefit from statin Of participants eligible (recommended or consid-
treatment across the spectrum of risk profiles ered) for statins, 44% (1316 of 2966) had CAC=0
with an appropriate NNT. at baseline and an observed 10-year ASCVD event
• Similarly, CAC testing also identified appropriate rate of 4.2 per 1000 person-years. The study
candidates who might derive the highest benefit results highlighted that among the intermediate-
with aspirin therapy. In MESA, individuals with risk range of 5% to 20%, nearly half (48%) had
CAC ≥100 had an estimated net benefit with CAC=0, and their 10-year ASCVD risk was below
aspirin regardless of their traditional risk status; the threshold recommended for statin therapy
the estimated NNT5 was 173 for individuals clas- (4.5%).69 These findings were recently confirmed
sified as having <10% FRS and 92 for individuals in the Jackson Heart Study. Among 2812 African
with ≥10% FRS, and the estimated 5-year num- American individuals aged 40 to 75 years with-
ber needed to harm was 442 for a major bleed.68 out prevalent ASCVD followed up for a median
Conversely, individuals with zero CAC had unfa- of 10 years, participants who were statin eligible
vorable estimates (estimated NNT5 of 2036 for by ACC/AHA guidelines experienced a 10-year
individuals with <10% FRS and 808 for individu- ASCVD event rate of 8.1 per 1000 person-years.
als with ≥10% FRS; estimated 5-year number However, in the absence of CAC, the 10-year
needed to harm of 442 for a major bleed). Sex- observed ASCVD risk was below the threshold of
specific and age-stratified analyses showed simi- statin recommendation set by the guidelines, at
lar results. 3.1 per 1000 person-years.70

Table 17-1. CAC Scores for the 75th Percentile of
CLINICAL STATEMENTS
Males and Females of Different Racial/Ethnic Groups,
AND GUIDELINES
at Specified Ages
75th Percentile CAC Scores*
Age, y Black Chinese Hispanic White
Women
45 0 0 0 0
55 0 2 0 1
65 26 45 19 54
75 138 103 116 237
Men
45 0 3 0 0
55 15 34 27 68
65 95 121 141 307
75 331 229 358 820
CAC indicates coronary artery calcification.

*The 75th percentile CAC score is the score at which 75% of people of the
same age, sex, and race have a score at or below this level and 25% of people
of the same age, sex, and race have a higher score.
Source: MESA (Multi-Ethnic Study of Atherosclerosis) CAC Tools website.71
20
18 17.6
Proportion (%) With Detectable Calcium
16
14
12 11.3
10
6 5.2 4.9
0
Males Females
White Black
Chart 17-1. Prevalence (%) of detectable coronary calcium in the CARDIA study: US adults 33 to 45 years of age
(2000–2001).
P<0.0001 across race-sex groups.
CARDIA indicates Coronary Artery Risk Development in Young Adults.
Data derived from Loria et al.8

CLINICAL STATEMENTS
80
AND GUIDELINES
70.4
70
Proportion (%) With Detectable Calcium

59.2
60 56.5
52.1
50
44.6
41.9
40 36.5
34.9
30
20
10
0
White Black Hispanic Chinese
Males Females
Chart 17-2. Prevalence (%) of detectable coronary calcium in MESA: US adults 45 to 84 years of age.
P<0.0001 across ethnic groups in both males and females.
MESA indicates Multi-Ethnic Study of Atherosclerosis.
Data derived from Bild et al.10
Chart 17-3. Ten-year trends in coronary artery calcification in individuals without clinical cardiovascular disease
in MESA.
MESA indicates Multi-Ethnic Study of Atherosclerosis.
Adapted from Bild et al.13

CLINICAL STATEMENTS
12
AND GUIDELINES
9.7
Hazard Ratio (HR) Compared to CAC=0

10
8 7.7
7.1
6.8
3.9
4 3.6
2
1.0 1.0
0
0 1-100 101-300 >300
Coronary Calcium Scores
Major CHD Events Any CHD Events
Chart 17-4. HRs for CHD events associated with coronary calcium scores: US adults 45 to 84 years of age (reference
group, CAC=0).
All HRs P<0.0001. Major CHD events included myocardial infarction and death attributable to CHD; any CHD events included
major CHD events plus definite angina or definite or probable angina followed by revascularization.
CAC indicates coronary artery calcification; CHD, coronary heart disease; and HR, hazard ratio.
Data derived from Detrano et al.14
Chart 17-5. HRs for coronary heart disease events associated with coronary calcium scores: US adults (reference
group, CAC=0 and Framingham Risk Score <10%).
Coronary heart disease events included nonfatal myocardial infarction and death attributable to coronary heart disease.
CAC indicates coronary artery calcification; and HR, hazard ratio.
Data derived from Greenland et al.17

CLINICAL STATEMENTS
1.0
AND GUIDELINES
0.89 0.89 0.89

0.9
0.81
0.8
0.71 0.71
0.69 0.69 0.70
0.7 0.67 0.66
Mean Carotid IMT (mm)
0.65
0.6
0.5
0.4
0.3
0.2
0.1
0.0
Common Carotid Carotid Bulb Internal Carotid
White Females Black Females White Males Black Males
Chart 17-6. Mean values of carotid IMT for different carotid artery segments in younger adults by race and sex
(Bogalusa Heart Study).
IMT indicates intima-media thickness.
Data derived from Urbina et al.38

CLINICAL STATEMENTS
AND GUIDELINES
Chart 17-7. Association between cardiovascular risk

factors and mean common carotid intima-media thick-
ness, by ethnicity.
Point estimates for betas; lines represent 95% confidence
intervals.
HDL indicates high-density lipoprotein.
Reprinted from Gijsberts et al.39 Copyright © 2015, Gijsberts et al.

CLINICAL STATEMENTS
1.2
1.13
AND GUIDELINES
1.11
1.04
1.0
0.91
0.87 0.86 0.87
0.83
Mean Carotid IMT (mm)

0.8
0.6
0.4
0.2
0.0
Common Carotid Internal Carotid
White Black Hispanic Chinese
Chart 17-8. Mean values of carotid IMT for different carotid artery segments in older adults, by race.
IMT indicates intima-media thickness.
Data derived from Manolio et al.41
of Atherosclerosis (MESA). PLoS One. 2015;10:e0116377. doi: 10.1371/

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A, Holewijn S, Ikeda A, Kavousi M, Kitagawa K, Kitamura A, Koffijberg 10.1161/CIRCULATIONAHA.111.081380.
H, Lonn EM, Lorenz MW, Mathiesen EB, Nijpels G, Okazaki S, O’Leary 59. Cho I, Chang HJ, Ó Hartaigh B, Shin S, Sung JM, Lin FY, Achenbach S,
DH, Polak JF, Price JF, Robertson C, Rembold CM, Rosvall M, Rundek T, Heo R, Berman DS, Budoff MJ, Callister TQ, Al-Mallah MH, Cademartiri F,
Salonen JT, Sitzer M, Stehouwer CD, Witteman JC, Moons KG, Bots ML. Chinnaiyan K, Chow BJ, Dunning AM, DeLago A, Villines TC, Hadamitzky
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jama.2012.9630. prognostic utility of coronary CT angiography for asymptomatic patients
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51. Chen LY, Leening MJ, Norby FL, Roetker NS, Hofman A, Franco OH, Pan of arterial stiffness in the general population. Circulation. 2006;113:664–
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rial stiffness and the risk of atrial fibrillation: the Atherosclerosis Risk in Vasan RS, Mitchell GF, Fox ER. The association of endothelial function and
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and the Rotterdam Study. J Am Heart Assoc. 2016;5:e002907. doi: Americans: the Jackson Heart Study. J Am Soc Hypertens. 2017;11:258–
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Holewijn S, Ikeda A, Kavousi M, Kitagawa K, Kitamura A, Ikram MA, Lonn tion for incident cardiovascular events in a population-based study: the
EM, Lorenz MW, Mathiesen EB, Nijpels G, Okazaki S, O’Leary DH, Polak multi-ethnic study of atherosclerosis. Circulation. 2009;120:502–509. doi:
JF, Price JF, Robertson C, Rembold CM, Rosvall M, Rundek T, Salonen JT, 10.1161/CIRCULATIONAHA.109.864801.
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57. Lorenz MW, Price JF, Robertson C, Bots ML, Polak JF, Poppert H, Kavousi CIRCOUTCOMES.113.000690.
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Willeit P, Steinmetz H, Desvarieux M, Xie W, Schmidt C, Norata GD, Suarez statin candidates according to American College of Cardiology/American
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Care. 2015;38:1921–1929. doi: 10.2337/dc14-2732. Murthy VL. Subclinical atherosclerosis, statin eligibility, and outcomes in
58. Cho I, Chang HJ, Sung JM, Pencina MJ, Lin FY, Dunning AM, Achenbach African American Individuals: the Jackson Heart Study. JAMA Cardiol.
S, Al-Mallah M, Berman DS, Budoff MJ, Callister TQ, Chow BJ, Delago A, 2017;2:644–652. doi: 10.1001/jamacardio.2017.0944.
Hadamitzky M, Hausleiter J, Maffei E, Cademartiri F, Kaufmann P, Shaw 71. MESA CAC score reference values. MESA CAC Tools website. http://www.
LJ, Raff GL, Chinnaiyan KM, Villines TC, Cheng V, Nasir K, Gomez M, Min mesa-nhlbi.org/Calcium/input.aspx. Accessed July 16, 2014.

18. CORONARY HEART DISEASE, Abbreviations Used in Chapter 18 Continued
CLINICAL STATEMENTS
ACUTE CORONARY SYNDROME, AND FINRISK Finnish population survey on risk factors for
AND GUIDELINES
chronic, noncommunicable diseases
ANGINA PECTORIS GBD Global Burden of Disease
GWAS genome-wide association studies
through 18-15 HCUP Healthcare Cost and Utilization Project
Click here to return to the Table of Contents HD heart disease
HF heart failure
HR hazard ratio
Coronary Heart Disease ICD-9 International Classification of Diseases, 9th
ICD-9 410 to 414, 429.2; ICD-10 I20 to I25 Revision
(includes MI ICD-10 I21 to I22). ICD-10 International Classification of Diseases, 10th

Revision
Prevalence IHD ischemic heart disease
(See Tables 18-1 and 18-2 and Charts 18-1 JHS Jackson Heart Study
JUPITER Justification for the Use of Statins in Primary
through 18-4) Prevention: An Intervention Trial Evaluating
• On the basis of data from NHANES 2011 to 2014 Rosuvastatin
(unpublished NHLBI tabulation), an estimated LDL-C low-density lipoprotein cholesterol
16.5 million Americans ≥20 years of age have LV left ventricular
MEPS Medical Expenditure Panel Survey
ACC American College of Cardiology MI-GENES Myocardial Infarction Genes Study
ACEI angiotensin-converting enzyme inhibitor NAMCS National Ambulatory Medical Care Survey
ACS acute coronary syndrome NCDR National Cardiovascular Data Registry
ACTION Acute Coronary Treatment and Intervention NCHS National Center for Health Statistics
Outcomes Network NH non-Hispanic
AHA American Heart Association NHAMCS National Hospital Ambulatory Medical Care
AMI acute myocardial infarction Survey
AP angina pectoris NHANES National Health and Nutrition Examination
ARB angiotensin receptor blocker Survey
ARIC Atherosclerosis Risk in Communities study NHDS National Hospital Discharge Survey
ASCOT Anglo-Scandinavian Cardiac Outcomes Trial NHIS National Health Interview Study
ASCVD atherosclerotic cardiovascular disease NHLBI National Heart, Lung, and Blood Institute
BEST Randomized Comparison of Coronary Artery NIS Nationwide Inpatient Sample
Bypass Surgery and Everolimus-Eluting Stent NSTEMI non–ST-segment–elevation myocardial infarction
Implantation in the Treatment of Patients With OR odds ratio
Multivessel Coronary Artery Disease
BMI body mass index
BP blood pressure
PRECOMBAT Premier of Randomized Comparison of Bypass
BRFSS Behavioral Risk Factor Surveillance System Surgery Versus Angioplasty Using Sirolimus
CABG coronary artery bypass graft Stents in Patients With Left Main Coronary
CAD coronary artery disease Artery Disease
CARDIA Coronary Artery Risk Development in Young PROVE IT-TIMI 22 Pravastatin or Atorvastatin Evaluation and
Adults Infection Therapy–Thrombolysis in Myocardial
CARDIoGRAMplusC4D Coronary Artery Disease Genome-wide Infarction 22
Replication and Meta-analysis (CARDIoGRAM) RCT randomized controlled trial
plus the Coronary Artery Disease Genetics (C4D) REGARDS Reasons for Geographic and Racial Differences
CARE Cholesterol and Recurrent Events in Stroke
CHD coronary heart disease SBP systolic blood pressure
CHS Cardiovascular Health Study SE standard error
CI confidence interval SES socioeconomic status
CKD chronic kidney disease SHS Strong Heart Study
CRUSADE Can Rapid Risk Stratification of Unstable Angina SNP single-nucleotide polymorphism
Patients Suppress Adverse Outcomes With Early STEMI ST-segment–elevation myocardial infarction
Implementation of the ACC/AHA Guidelines SYNTAX Synergy Between PCI With Taxus and Cardiac
CVD cardiovascular disease Surgery
D2B door-to-balloon TC total cholesterol
DBP diastolic blood pressure TRACE-CORE Transitions, Risks, and Actions in Coronary
DM diabetes mellitus Events–Center for Outcomes Research and
ED emergency department Education
EMS emergency medical services UA unstable angina
FHS Framingham Heart Study WHI Women’s Health Initiative
(Continued ) YLL years of life lost

CHD (Table 18-1). The prevalence of CHD was Incidence

CLINICAL STATEMENTS
higher for males than females for all ages (Chart (See Table 18-1 and Charts 18-5 through 18-7)
AND GUIDELINES
18-1). • Approximately every 40 seconds, an American

• Total CHD prevalence is 6.3% in US adults ≥20 will have an MI (AHA computation).
years of age. CHD prevalence is 7.4% for males • On the basis of data from the 2005 to 2014 ARIC
and 5.3% for females. study of the NHLBI5:
— Among NH whites, CHD prevalence is 7.7% — This year, ≈720 000 Americans will have a
for males and 5.3% for females. new coronary event (defined as first hospi-
— Among NH blacks, CHD prevalence is 7.1% talized MI or CHD death), and ≈335 000 will
for males and 5.7% for females. have a recurrent event.
— Among Hispanics, CHD prevalence is 5.9% — The estimated annual incidence of MI is
for males and 6.1% for females. 605 000 new attacks and 200 000 recurrent
— Among NH Asians, CHD prevalence is 5.0% attacks. Of these 805 000 first and recurrent
for males and 2.6% for females. events, it is estimated that 170 000 are silent.
• On the basis of data from the 2015 NHIS1: — Average age at first MI is 65.6 years for males
— Among American Indian/Alaska Natives ≥18 and 72.0 years for females.
years of age, the CHD prevalence estimate is • In the REGARDS study, 37% of adjudicated MIs
9.3%. had a primary hospital discharge diagnosis of MI,
• According to data from NHANES 2011 to 2014 whereas 63% had a primary hospital discharge
(unpublished NHLBI tabulation), the overall preva- diagnosis other than MI, which suggests that
lence for MI is 3.0% in US adults ≥20 years of age. most MIs that result in hospitalization might be
By age groups, males have a higher prevalence of occurring during hospitalization for other acute
MI than females for all age groups except 20 to illnesses.6
39 years (Chart 18-2). MI prevalence is 3.8% for • Self-reported income and education were asso-
males and 2.3% for females. ciated with incident CHD (defined as definite or
— Among NH whites, MI prevalence is 4.0% for probable MI or acute CHD death) in the REGARDS
males and 2.4% for females. study. Those reporting low income and low edu-
— Among NH blacks, MI prevalence is 3.3% for cation had twice the incidence of CHD as those
males and 2.2% for females.
reporting high income and high education (10.1

— Among Hispanics, MI prevalence is 2.9% for versus 5.2 per 1000 person-years, respectively).7
males and 2.1% for females. • Annual numbers for MI or fatal CHD in the NHLBI-
— Among NH Asians, MI prevalence is 2.6% for sponsored ARIC study and CHS stratified by age
males and 0.7% for females. and sex are displayed in Chart 18-5. Incidence of
• Data from NHANES indicate that between 2001 heart attacks stratified by age, race, and sex is
and 2012, the age-adjusted prevalence of CHD displayed in Chart 18-6.
declined from 10.3% to 8.0%.2 • Incidence of MI by age, sex, and race in the NHLBI-
• According to data from NHANES 2011 to 2014 sponsored ARIC study is displayed in Chart 18-7.
(unpublished NHLBI tabulation), the overall preva- Black males have a higher incidence of MI in all
lence for angina is 3.4% in US adults ≥20 years of age groups.
age (Table 18-2). • Among 24 443 US adult participants in the
• According to data from NHANES for the period REGARDS study, the incidence of CHD (nonfatal
1988 to 2012, angina prevalence declined in MI or fatal CHD) per 1000 person-years was 9.0
NH whites (from 4.0% to 2.1%) but not in NH among NH black males, 8.1 among NH white
blacks (from 4.9% to 4.4%) and in both males males, 5.0 among NH black females, and 3.4
and females ≥65 years old (males from 5.1% to among NH white females. NH blacks had a higher
2.9%, females from 5.6% to 2.4%).3 risk for fatal CHD, which was explained by risk
• Data from the BRFSS 2015 survey indicated that factors. No racial differences were present for
4.2% of respondents had been told that they nonfatal CHD.8
had had an MI. The highest prevalence was in • In 9498 participants in the ARIC study, whites had
Kentucky (5.9%), and the lowest was in Hawaii a higher rate of clinically recognized MI compared
(2.6%) (age-adjusted) (Chart 18-3).4 with blacks (5.04 versus 3.24 per 1000 person-
• In the same survey, 3.9% of respondents had years, P=0.002).9
been told that they had angina or CHD. The high-
est prevalence was in West Virginia (6.2%), and Trends in Incidence
the lowest was in Colorado and Hawaii (2.5%) • The overall body of literature suggests that
(age-adjusted) (Chart 18-4).4 the incidence of MI has declined significantly

over time, including over the past decade.10 to 2000 to 9.4% in 2011 to 2012. The proportion
CLINICAL STATEMENTS
Geographic differences in patient populations, of US adults with 10-year predicted ASCVD risk of
AND GUIDELINES
temporal changes in the criteria used to diag- 7.5% to <20% was 23.9% in 1999 to 2000 and
nose MI, and differences in study methodology 26.8% in 2011 to 2012.16
increase the complexity of interpreting these • For adults with optimal risk factors (TC of 170
studies, however. mg/dL, HDL-C of 50 mg/dL, SBP of 110 mm Hg
• In Olmsted County, MN, between 1995 and without antihypertensive medication use, no DM,
2012, the population rate of MI declined 3.3% and not a smoker), 10-year CVD risk ≥7.5% will
per year; however, these declines varied among occur at age 65 years for white males, 70 years
types of MI, with the greatest declines occurring for black males and females, and 75 years for
for prehospital fatal MI.11 white females.17
• Data from Kaiser Permanente Northern • In the REGARDS study, the adjusted HR for CHD
California showed that the age- and sex- death associated with any versus no stroke symp-
adjusted incidence rate of hospitalizations for toms was 1.50 (95% CI, 1.10–2.06).18 Individuals
MI declined from 274 per 100 000 person-years with atherosclerotic stroke should be included
in 1999 to 208 per 100 000 person-years in among those deemed to be at high risk (20%
2008. Furthermore, the age- and sex-adjusted over 10 years) of further atherosclerotic coronary
incidence rate of hospitalizations for STEMI events. For primary prevention, ischemic stroke
decreased from 133 per 100 000 person-years in should be included among CVD outcomes in
1999 to 50 per 100 000 person-years in 2008 (P absolute risk assessment algorithms. The inclu-
linear trend <0.001). The trajectory of the age- sion of atherosclerotic ischemic stroke as a high-
and sex-adjusted incidence rate of hospitaliza- risk condition has important implications because
tions for NSTEMI did not change significantly over the number of people considered to be at high
the entire study period, although it did show a risk will increase over time.19
significant decline after troponin became widely • A survey of US family physicians, general inter-
used to diagnose MI.12 nists, and cardiologists published in 2012 found
• According to data from ARIC and the REGARDS that 41% of respondents reported using global
study, between 1987 to 1996 and 2003 to 2009, CHD risk assessment at least occasionally.20 It
the incidence of CHD declined from 3.9 to 2.2 is unclear whether physicians are using global
per 1000 person-years in people without DM and CHD risk prediction more since the publication
from 11.1 to 5.4 per 1000 person-years among of the 2013 ACC/AHA cholesterol management
those with DM.13 guideline.21
• Among Medicare beneficiaries between 2002 • Lifetime risk for CHD varies drastically as a func-
and 2011, the incidence of MI hospitalization tion of risk factor profile. At 55 years of age and
declined from 1485 to 1122 per 100 000 per- with an optimal risk factor profile, lifetime risk
son-years. The incidence of MI as the primary for CHD is 3.6% for males and <1% for females;
reason for hospitalization decreased over time with ≥2 major risk factors, it is 37.5% for males
(from 1063 to 677 per 100 000 person-years and 18.3% for females.22
between 2002 and 2011), whereas the percent- • The ASCVD tool might overestimate risk across
age of MIs as a secondary reason for hospital- all strata of risk compared with external con-
ization increased (from 190 to 245 per 100 000 temporary cohorts (Physicians’ Health Study,
person-years). The percentage of MIs that were Women’s Health Study, and WHI Observational
attributable to a secondary diagnosis increased Study), as well as in reanalysis of the origi-
from 28% to 40%.14 nal validation cohorts. However, some of the
• Among Medicare beneficiaries, the incidence of subsequent analyses were not conducted in
primary hospitalization for MI between 2002 and comparable populations as the original study
2011 declined by 36.6% among NH whites (from cohorts.23
1057 to 670 per 100 000 person-years between
Mortality
2002 and 2011) and by 26.4% among NH blacks
• Based on 2015 mortality data1:
(from 966 to 711 per 100 000 person-years
— CHD mortality was 366 801, and CHD any-
between 2002 and 2011).15
mention mortality was 536 339 (unpublished
Predicted Risk NHLBI tabulation) (Table 18-1).
• The percentage of US adults with a 10-year pre- — MI mortality was 114 023. MI any-mention
dicted ASCVD risk (using pooled-cohort risk mortality was 151 863 (unpublished NHLBI
equations) ≥20% decreased from 13.0% in 1999 tabulation) (Table 18-1).

• From 2005 to 2015, the annual death rate attrib- • Compared with nonparticipants, participants in
CLINICAL STATEMENTS
utable to CHD declined 34.4% and the actual the Supplemental Nutrition Assistance Program
AND GUIDELINES
number of deaths declined 17.7% (unpublished have twice the risk of CVD mortality, which likely
NHLBI tabulation). reflects differences in socioeconomic, environ-
• CHD age-adjusted death rates per 100 000 were mental, and behavioral characteristics.28
135.3 for NH white males, 145.4 for NH black
Temporal Trends in Mortality
males, and 97.9 for Hispanic males; for NH white
females, the rate was 71.2; for NH black females, • The decline in CHD mortality rates in part reflects
it was 86.7; and for Hispanic females, it was 56.0 the shift in the pattern of clinical presentations
(unpublished NHLBI tabulation). of AMI. In the past decade, there has been a
• 77% of CHD deaths occurred out of the hospital. marked decline in STEMI (from 133 to 50 cases
According to NCHS mortality data, 280 780 CHD per 100 000 person-years).12
deaths occur out of the hospital or in hospital EDs • In Olmsted County, MN, the age- and sex-adjusted
annually (NCHS, AHA tabulation). 30-day case fatality rate decreased by 56% from
• The estimated average number of YLL because 1987 to 2006.29
of an MI death is 16.6 (unpublished NHLBI • Among Medicare fee-for-service beneficiaries,
tabulation). between 1999 and 2011, the 30-day mortality
• Approximately 35% of the people who experi- rate after hospitalized MI declined by 29.4%.30
ence a coronary event in a given year will die from Declines in 30-day mortality after MI occurred
it, and ≈14% who experience a heart attack (MI) in all US census divisions between 2000 and
will die of it (AHA computation). 2008.31
• Researchers investigating variation in hospital- • In a community-based study of Worcester, MA,
specific 30-day risk-stratified mortality rates for the percentage of patients dying after cardiogenic
patients with AMI found teaching status, num- shock during their hospitalization for MI declined
ber of hospital beds, AMI volume, cardiac facili- from 47.1% in 2001 to 2003 to 28.6% in 2009
ties available, urban/rural location, geographic to 2011.32
region, hospital ownership type, and SES profile • Between 2001 and 2011 in the NIS, in-hospital
of the patients were all significantly associated mortality did not change for patients with STEMI
with mortality rates. However, a substantial pro- with a PCI (3.40% and 3.52% in 2001 and 2011,
portion of variation in outcomes for patients with respectively) or CABG (5.79% and 5.70% in 2001
AMI between hospitals remains unexplained by and 2011, respectively) and increased for patients
measures of hospital characteristics.24 with no intervention (12.43% and 14.91% in
• Life expectancy after AMI treated in hospitals with 2001 and 2011, respectively). In-hospital mortal-
high performance on 30-day mortality measures ity declined for patients with NSTEMI undergoing
compared with low-performing hospitals was on CABG (from 4.97% to 2.91%) or no procedure
average between 0.74 and 1.14 years longer.25 (from 8.87% to 6.26%) but did not change for
• Among 194 071 adults who were hospitalized for patients with NSTEMI undergoing PCI (1.73%
an AMI in the 2009 to 2010 NIS, in-hospital mor- and 1.45%).33
tality for those <65 years of age was higher for • Among US males <55 years of age, CHD mortality
Hispanic females (3.7%) than for black females declined an annual 5.5% per year between 1979
(3.1%) and white females (2.5%). Differences and 1989; a smaller decline was present in 1990
were smaller for males <65 years of age. Among to 1999 (1.2% per year) and in 2000 to 2011
older adults (≥65 years), in-hospital mortality was (1.8% per year). Among US females <55 years of
8.0% for white females and between 6% and age, CHD mortality declined an annual 4.6% per
8% for other race-sex groups.26 year in 1979 to 1989, with no decline between
• In a study using data from the Cooperative 1990 and 1999 and a decline of 1.0% in 2000 to
Cardiovascular Project, survival and life expec- 2011.34
tancy after AMI were higher in whites than in • Reflecting trends in change in type and sever-
blacks (7.4% versus 5.7%). White patients living ity of AMI, studies worldwide have documented
in high SES areas showed the longest life expec- a reduction in HF and mortality after MI. In a
tancy. Gaps in life expectancy between white and nationwide Swedish registry of 199 851 patients
black patients were largest amongst high SES admitted with AMI from 1996 to 2008, the inci-
areas, with smaller differences in medium and dence of HF decreased from 46% to 28%, with
low SES areas. These differences attenuated but a greater decline in individuals with STEMI com-
did not disappear after adjustment for patient pared with NSTEMI.35 The in-hospital, 30-day, and
and treatment characteristics.27 1-year mortality rates for those with HF decreased

from 19% to 13%, 23% to 17%, and 36% to and increased with age from 6% (25–34 years) to
CLINICAL STATEMENTS
31%, respectively (all P<0.001). In an Australian 33% (≥65 years).42
AND GUIDELINES
registry of 20 812 consecutive patients with first • Among 2009 females and 976 males <55 years
MI, the prevalence of HF after MI declined from of age hospitalized for MI, only 48.7% of females
28.1% in 1996 to 1998 to 16.5% in 2005 to 2007 and 52.9% of males reported being told they
(P<0.001), with a decline in mortality after MI in were at risk for HD or a heart problem. Also,
both individuals with and without HF (P<0.05 50.3% of females and 59.7% of males reported
for both).36 In Olmsted County, MN, from 1990 their healthcare provider discussing HD and things
to 2010, there was a decline in mortality associ- they could do to take care of their heart.43
ated with HF after MI, but this risk was greater for • Among US adults with CHD, between 1999
delayed HF than for early-onset HF after MI.37 to 2000 and 2011 to 2012, the use of statins
• Taking into account past trends in CHD mortal- increased from 36% to 73%, aspirin use increased
ity from 1980, and considering age-period and from 4% to 28%, ACEI or ARB use increased from
cohort effects, CHD mortality is likely to con- 33% to 46%, and β-blocker use increased from
tinue its decades-long decline, with a reduction 27% to 57%.44
in deaths by 2030 of 27%; however, race dispari-
Time of Symptom Onset and Arrival at Hospital
ties will persist.38 Recent reports have suggested
• A meta-analysis of 48 studies enrolling >1.8 mil-
a slowing down of all CVD and HD mortality in
lion patients showed that off-hours presentation
recent years.39,40
for MI was associated with higher short-term
Risk Factors mortality. In addition, those patients with STEMI
(See Charts 18-8 and 18-9) who presented off hours had longer D2B times.45
• Risk factors for CHD act synergistically to increase • Data from CRUSADE and the NCDR ACTION
CHD risk. Those with fewer risk factors have lower Registry–GWTG showed a longer median time to
10-year risk of CHD (Chart 18-8).41 hospital presentation in females (3 hours) than in
• Only a small percentage of US females and males males (2.8 hours; P<0.001), which did not change
have low CHD risk defined by SBP <120 mm Hg over time from 2002 to 2007.46
and DBP <80 mm Hg; cholesterol <200 mg/dL; • Data from Worcester, MA, indicate that the
BMI <25 kg/m2; currently not smoking cigarettes; median time from symptom onset to hospital
and no prior MI or DM (Chart 18–9). arrival did not improve from 2001 through 2011.
In 2009 to 2011, 48.9% of patients reached the
Awareness of Warning Signs and Risk for HD hospital within 2 hours of symptom onset com-
• Females’ awareness that CVD is their leading pared with 45.8% in 2001 to 2003.47
cause of death increased from 30% in 1997 to • An analysis of data from the NCDR ACTION
56% in 2012.42 Registry–GWTG showed that 60% of 37 634
• In 2012, NH black and Hispanic females had STEMI patients used EMS to get to the hospital.
lower awareness than white females that HD/ Older adults, females, adults with comorbidities,
heart attack is the leading cause of death for and sicker patients were more likely to use EMS
females.42 than their counterparts. Hospital arrival time was
• The percentages of females in 2012 identifying shorter for those who used EMS (89 minutes) than
warning signs for a heart attack were as fol- for those who used self-transport (120 minutes).48
lows: pain in the chest—56%; pain that spreads • Among patients hospitalized for ACS between
to the shoulder, neck, or arm—60%; shortness 2001 and 2011 in the NIS, those with STEMI
of breath—38%; chest tightness—17%; nau- admitted on the weekend versus on a weekday
sea—18%; and fatigue—10%.42 had a 3% higher odds of in-hospital mortality.
• The 5 most commonly cited HD prevention strat- Those admitted on the weekend versus weekday
egies in 2012 were maintaining a healthy BP for non–ST-elevation ACS had a 15% higher odds
(78%), seeing the doctor (78%), and increas- of in-hospital mortality. The excess mortality asso-
ing fiber intake, eating food with antioxidants, ciated with weekend versus weekday admission
and maintaining healthy cholesterol levels (each decreased over time.49
66%).42 • A retrospective analysis of the NHAMCS data
• Among online survey participants, 21% from 2004 to 2011 that reviewed 15 438 visits
responded that their doctor had talked to them related to ACS symptoms suggested that blacks
about HD risk. Rates were lower among Hispanic have a 30% longer waiting time than whites, the
females (12%) than whites (22%) or blacks (22%) reasons for which are unclear.50

• The timing of hospital admission influences man- 59% of individuals were referred to cardiac reha-
CLINICAL STATEMENTS
agement of MI. A study of the NIS database bilitation post-PCI, with significant site-specific
AND GUIDELINES
from 2003 to 2011 indicated that admission on variation.59

a weekend for NSTEMI was associated with a • In a community-based analysis of residents in
significantly reduced odds for coronary angiogra- Olmsted County, MN, discharged with first MI
phy (OR, 0.88; 95% CI, 0.89–0.90; P<0.001) and between 1987 and 2010, 52.5% participated in
early invasive strategy (OR, 0.48; 95% CI, 0.47– cardiac rehabilitation. The overall rate of partici-
0.48; P<0.001), with consequences of greater pation did not change during the study period.
mortality.51 Cardiac rehabilitation was associated with reduc-
tions in all-cause mortality and readmission.60 A
Complications
dose-response association between rehabilita-
Rehospitalizations tion session attendance and lower risk of MI
• The burden of rehospitalizations for AMI may be and death was similarly seen in elderly Medicare
substantial: A retrospective cohort study of 78 085 beneficiaries.61
Medicare beneficiaries ≥66 years of age without
recent CHD history who were hospitalized for Mortality
AMI in 2000 to 2010 reported that 20.6% had • In a pooled analysis of individuals after PCI in sev-
at least 1 rehospitalization during the 10 years eral RCTs, those with STEMI had a greater risk of
after the index MI. Among patients with a CHD death within the first 30 days after PCI than those
rehospitalization, 35.9% had ≥2 CHD rehospital- with stable IHD, whereas those with NSTEMI had
izations. Males and patients ≥85 years of age had a greater risk of death during the entire 2 years of
greater rate ratios for first rehospitalization.52 follow up.62
• A study of 3 250 194 Medicare beneficiaries • From the NCDR registry, in 2014 the unadjusted
admitted for PCI found that readmission rates rate of acute kidney injury was 2.6% (versus
declined slightly from 16.1% in 2000 to 15.4% in 2.3% in 2011), of blood transfusion was 1.4%
2012. The majority of readmissions were because (versus 1.9% in 2011), of postprocedural stroke
of chronic IHD (26.6%), HF (12%), and chest was 0.2% (versus 0.2% in 2011), of emergency
pain/angina (7.9%). A minority (<8%) of total CABG surgery was 0.2% (versus 0.3% in 2011),
readmissions were for AMI, UA, or cardiac arrest/ and of vascular access site injury was 1.3% (ver-
cardiogenic shock.53 sus 1.2% in 2011).63

• Rehospitalization can be influenced by clinical, • STEMI confers greater in-hospital risks than
psychosocial, and sociodemographic characteris- NSTEMI, including death (6.4% for STEMI, 3.4%
tics not accounted for in traditional Centers for for NSTEMI), cardiogenic shock (4.4% versus
Medicare & Medicaid Services claims-based mod- 1.6%, respectively), and bleeding (8.5% versus
els, including prior PCI, CKD, low health literacy, 5.5%, respectively).63
lower serum sodium levels, and lack of cigarette • On the basis of pooled data from the FHS, ARIC,
smoking.54 CHS, MESA, CARDIA, and JHS studies of the
• In a study of 3 central Massachusetts hospi- NHLBI (1995–2012), within 1 year after a first MI
tals, the 90-day rehospitalization rate declined (unpublished NHLBI tabulation):
from 31.5% in 2001 to 2003 to 27.3% in 2009 — At ≥45 years of age, 18% of males and 23%
to 2011. Crude 30-day rehospitalization rates of females will die.
decreased from 20.5% in 2001 to 2003 to 15.8% — At 45 to 64 years of age, 3% of white males,
in 2009 to 2011.55,56 5% of white females, 9% of black males,
Cardiac Rehabilitation and 10% of black females will die.
• In the NCDR ACTION Registry–GWTG, cardiac — At 65 to 74 years of age, 14% of white
rehabilitation referral after patients were admit- males, 18% of white females, 22% of black
ted with a primary diagnosis of STEMI or NSTEMI males, and 21% of black females will die.
increased from 72.9% to 80.7% between 2007 — At ≥75 years of age, 27% of white males,
and 2012.57 29% of white females, 19% of black males,
• An analysis of Medicare claims data revealed that and 31% of black females will die.
only 13.9% of Medicare beneficiaries enroll in • In part because females have MIs at older ages
cardiac rehabilitation after an AMI, and only 31% than males, they are more likely to die of MI
enroll after CABG. Older people, females, non- within a few weeks.
whites, and individuals with comorbidities were • Within 5 years after a first MI:
less likely to enroll in cardiac rehabilitation pro- — At ≥45 years of age, 36% of males and 47%
grams.58 In the NCDR between 2009 and 2012, of females will die.

— At 45 to 64 years of age, 11% of white included aspirin at arrival, aspirin at discharge,
CLINICAL STATEMENTS
males, 17% of white females, 16% of black ACEI or ARB for LV systolic dysfunction, smok-
AND GUIDELINES
males, and 28% of black females will die. ing cessation advice/counseling, β-blocker at dis-
— At 65 to 74 years of age, 25% of white charge, and PCI within 90 minutes of arrival.64
males, 30% of white females, 33% of black
Hospital Discharges and Ambulatory Care Visits
males, and 44% of black females will die.
(See Table 18-1 and Chart 18-10)
— At ≥75 years of age, 55% of white males,
• From 2004 to 2014, the number of inpatient dis-
60% of white females, 61% of black males,
charges from short-stay hospitals with CHD as the
and 64% of black females will die.
first-listed diagnosis decreased from 1 879 000 to
• Of those who have a first MI, the percentage with
1 021 000 (unpublished NHLBI tabulation) (Table
a recurrent MI or fatal CHD within 5 years is as
18-1).
follows:
• From 1997 through 2014, the number of hospi-
— At ≥45 years of age, 17% of males and 21%
tal discharges for CHD was higher for males than
of females.
females (Chart 18-10).
— At 45 to 64 years of age, 11% of white
• In 2014, there were 11 713 000 physician office
visits for CHD (NAMCS, NHLBI tabulation). In
males, and 32% of black females.
2014, there were 501 000 ED visits with a primary
diagnosis of CHD (NAMCS, NHAMCS, NHLBI
tabulation).
• Total office visits for angina declined from 3.6
million per year in 1995 to 1998 to 2.3 million
per year in 2007 to 2010 based on data from the
and 20% of black females.
NAMCS and NHAMCS.65
• The percentage of people with a first MI who will
• In a systematic review, secondary adherence (pro-
have HF in 5 years is as follows:
portion of days covered ≥80%) in the year after
— At ≥45 years of age, 16% of males and 22%
ACS ranged from 54% to 62% for ACEI/ARBs,
of females.
67% to 69% for antiplatelet agent use, 64%
— At 45 to 64 years of age, 6% of white males,
to 65% for β-blockers, and 57% to 65% for
statins.66
and 25% of black females.
• In the GWTG-CAD registry, quality-of-care mea-
sures were lowest for ACEI/ARB use (88.2% and
72.8% for those undergoing PCI and CABG,
respectively) and highest for aspirin at discharge
(98.5% and 96.8% for PCI and CABG, respec-
tively) among patients hospitalized for ACS
and 19% of NH black females.
between 2003 and 2008. Shorter length of stay
• The percentage of people with a first MI who
was associated with appropriate use of medical
will have an incident stroke within 5 years is as
therapy.67
follows:
• In the CathPCI registry, a composite of use of
— At ≥45 years of age, 4% of males and 7% of
evidence-based medical therapies, including
females.
aspirin, P2Y12 inhibitors, and statins, was high
— At ≥45 years of age, 5% of white males, 6%
(89.1% in 2011 and 93.3% in 2014). However,
of white females, 4% of black males, and
in the ACTION-GWTG registry, metrics that were
10% of black females.
shown to need improvement were defect-free
• The median survival time (in years) after a first MI
care (median hospital performance rate of 78.4%
is as follows:
in 2014), P2Y12 inhibitor use in eligible medically
— At ≥45 years of age, 8.2 for males and 5.5
treated AMI patients (56.7%), and the use of
for females.
aldosterone antagonists in patients with LV sys-
— At ≥45 years of age, 8.4 for white males, 5.6
tolic dysfunction and either DM or HF (12.8%).63,68
for white females, 7.0 for black males, and
5.5 for black females. Operations and Procedures
• In a sample of >4000 US hospitals, core pro- • In 2014, an estimated 480 000 percutaneous
cess measures for MI improved between 2006 transluminal coronary angioplasties, 371 000
and 2011. The median performance rates were inpatient bypass procedures, 1 016 000 inpa-
high and increased from 96% in 2006 to 99% in tient diagnostic cardiac catheterizations, 86 000
2011 for the composite measure. Core processes carotid endarterectomies, and 351 000 pacemaker

procedures were performed for inpatients in the an OR for in-hospital mortality of 0.92 (95% CI,
CLINICAL STATEMENTS
United States (unpublished NHLBI tabulation). 0.91–0.93) and an OR for 6-month mortality of
AND GUIDELINES
• In an analysis of the BEST, PRECOMBAT, and 0.94 (95% CI, 0.93–0.95).76

SYNTAX trials comparing individuals with MI and • In 2014, from the CathPCI registry, median D2B
who had left main or multivessel CAD, the out- time for primary PCI for STEMI was 59 minutes
comes of CABG versus PCI were examined. CABG for patients receiving PCI in the presenting hospi-
was associated with a lower risk of recurrent MI tal and 105 minutes for patients transferred from
and repeat revascularizations.69 In 5-year follow-up another facility for therapy.63
of the SYNTAX trial, the greater MI-related death • The importance of adherence to optimal medical
in PCI patients was associated with the presence therapy was highlighted in an 8-hospital study of
of DM, 3-vessel disease, or high SYNTAX scores.70 NSTEMI patients, in which medication nonadher-
• In the NIS, 2001 to 2011, improvement in mortal- ence was associated with a composite outcome
ity differed by MI type and intervention: adjusted of all-cause mortality, nonfatal MI, and reinter-
in-hospital mortality improved for individuals vention (HR, 2.79; 95% CI, 2.19–3.54; P<0.001).
with NSTEMI, regardless of intervention received, In propensity-matched analysis, CABG outcomes
whereas for STEMI, a decline in adjusted in-hospi- were favorable compared with PCI in patients
tal mortality was significant for those who under- nonadherent to medical therapy (P=0.001), but
went PCI (OR, 0.83; 95% CI, 0.73–0.94), but no outcomes were similar in medicine-adherent
significant improvement was observed for those patients (P=0.574).77
who received CABG or without intervention.33
• In the NIS, isolated CABG procedures decreased Cost
by 25.4% from 2007 to 2011 (326 to 243 cases • The estimated direct costs of HD in 2013 to 2014
per million adults), particularly at higher-volume (average annual) were $100.9 billion (MEPS,
centers. Low-volume centers were associated NHLBI tabulation).
with greater risk of all-cause in-hospital mortal- • The estimated direct and indirect cost of HD in
ity in multivariable analysis (OR, 1.39; 95% CI, 2013 to 2014 (average annual) was $204.8 billion
1.24–1.56; P< 0.001).71 (MEPS, NHLBI tabulation).
• According to the NIS, the number of PCI proce- • Among Medicare beneficiaries admitted with
dures declined by 38% between 2006 and 2011. AMI, the median length of hospital stay was 1
Among patients with stable IHD, a 61% decline in day shorter in 2008 than in 1998 to 1999; how-
PCI occurred over this time period.72 ever, overall expenditures per patient increased
• In Washington State, the overall number of PCIs by 16.5%, with three fourths of the increase in
decreased by 6.8% between 2010 and 2013, expenditures occurring 31 to 365 days after the
with a 43% decline in the number of PCIs per- date of hospital admission.78 A study of the NIS
formed for elective indications.73 from 2001 to 2011 showed that costs per hospi-
• However, in Massachusetts, age- and sex-adjusted talization increased significantly for patients who
rates of coronary revascularization (PCI or CABG) underwent intervention, but not for those with-
declined from 423 to 258 per 100 000 residents out intervention.33
(39% decline) between 2003 and 2012. Rates • MI ($12.1 billion) and CHD ($9.0 billion) were 2
of elective PCI declined by 50% over the period, of the 10 most expensive conditions treated in US
whereas rates of PCI in the setting of MI declined hospitals in 2013.79
by 16%.74 • Between 2013 and 2030, medical costs of CHD
• Among Medicare fee-for-service beneficiaries, the are projected to increase by ≈100%.80
total number of revascularization procedures per- • A meta-analysis of 15 randomized trials esti-
formed peaked in 2010 and declined by >4% per mated costs for patients with stable CAD as low-
year through 2012. In-hospital and 90-day mor- est for medical therapy ($3069 and $13 864 at 1
tality rates declined after CABG surgery overall, and 3 years, respectively) and highest for CABG
as well as among patients presenting for elective ($27 003 and $28 670 at 1 and 3 years, respec-
CABG or CABG after NSTEMI.75 tively). PCI costs were between those of medical
• Between 2011 and 2014, the use of femoral therapy and CABG costs and were higher with
access declined (from 88.8% to 74.5%) and drug-eluting stents than with bare-metal stents
radial access increased (from 10.9% to 25.2%).63 and balloon angioplasty.81
• Among patients presenting for PCI after STEMI in • In a multipayer administrative claims database of
the NCDR, D2B time decreased from a median of patients with incident inpatient PCI admissions
86 to 63 minutes between 2005 and 2011. Each between 2008 and 2011, post-PCI angina and
10-minute shorter D2B time was associated with chest pain were common and costly ($32 437

versus $17 913; P< 0.001 at 1 year comparing Stable AP
CLINICAL STATEMENTS
those with and without angina/chest pain).82 ICD-9 413; ICD-10 I20.1 to I20.9.
AND GUIDELINES
Prevalence
Acute Coronary Syndrome (See Table 18-2 and Charts 18-11 and 18-12)
ICD-9 410, 411; ICD-10 I20.0, I21, I22. • According to data from NHANES 2011 to 2014,
the prevalence of AP among adults (≥20 years of
• In 2014, there were 633 000 ACS principal diag-
age) is 8 700 000 (Table 18-2).
nosis discharges. Of these, an estimated 389 000
• The prevalence of AP increased with age from
were males, and 244 000 were females. This esti-
<1% among males and females 20 to 39 years
mate was derived by adding the principal diag-
of age to >10% among males and females ≥80
noses for MI (609 000) to those for UA (24 000)
years of age (Chart 18-11).
(NHDS, NHLBI).
• On the basis of data from NHANES from 1998
• When secondary discharge diagnoses in 2014
to 2004 and the six 2-year surveys from 2001 to
were included, the corresponding number of
2012, in 2009 to 2012, there were an average of
inpatient hospital discharges was 1 339 000
3.4 million people ≥40 years of age in the United
unique hospitalizations for ACS; 785 000 were
States with angina each year, compared with 4
males, and 554 000 were females. Of the total,
million in 1988 to 1994. Declines in angina symp-
957 000 were for MI alone, and 382 000 were for
toms have occurred for NH whites but not for NH
UA alone (HCUP, NHLBI).
blacks.3
• In a study using the NIS and the State Inpatient
• From 1988 to 1994 through 2009 to 2012, the
Databases for the year 2009, mean charge per
prevalence of AP symptoms has declined among
ACS discharge was $63 578 (median $41 816).
whites but not blacks (Chart 18-12).3
Mean charges, however, were greater for the first
• In Americans ≥40 years of age with health insur-
compared with the second admission ($71 336
ance, age-adjusted angina prevalence declined
versus $53 290, respectively).83
from 7.6% in 2001 to 2002 to 5.2% in 2011 to
• On the basis of medical, pharmacy, and disability
2012 (P for trend <0.001), whereas in those with-
insurance claims data from 2007 to 2010, short-
out health insurance, there was an increase from
term productivity losses associated with ACS were
4.7% to 7.6%, albeit not statistically significant.2
estimated at $7493 per disability claim, with long-

term productivity losses of $52 473 per disability Incidence
claim. ACS also resulted in substantial wage losses, (See Table 18-2 and Chart 18-13)
from $2263 to $20 609 per disability claim, for • The annual rates per 1000 population of new epi-
short- and long-term disability, respectively.84 sodes of AP for nonblack males are 28.3 for those
• The percentage of ACS or MI cases with 65 to 74 years of age, 36.3 for those 75 to 84
ST-segment elevation appears to be declining. In years of age, and 33.0 for those ≥85 years of age.
an analysis of 46 086 hospitalizations for ACS in For nonblack females in the same age groups, the
the Kaiser Permanente Northern California study, rates are 14.1, 20.0, and 22.9, respectively. For
the percentage of MI cases with ST-segment ele- black males, the rates are 22.4, 33.8, and 39.5,
vation decreased from 47.0% to 22.9% between and for black females, the rates are 15.3, 23.6,
1999 and 2008.74 and 35.9, respectively (CHS, NHLBI).
• After adjustment for clinical differences and the • The incidence of AP for adults ≥45 years of age
severity of CAD by angiogram, 30-day mortality is higher in males (370 000) than it is in females
after ACS is similar in males and females.85 (195 000) (Table 18-2).
• According to data from the NIS, between 2001 • In the FHS, the incidence of AP increased from
and 2011, the use of PCI for patients with ACS ages 45 to 54 years to ages 75 to 84 years and
declined by 15%.72 was lower among participants ≥85 years of age
• On the basis of administrative claims data for US than among those 75 to 84 years of age (Chart
Medicare beneficiaries, hospitalization for ACS 18-13).
(MI or UA) decreased from 2.4% in 1992 to 1.7%
in 2009. UA decreased from 1.5% in 1997 to
0.6% in 2009.86 Genetics/Family History
• In a report from the TRACE-CORE study, the Family History as a Risk Factor
average profile of a first ACS patient showed a • CHD and MI are heritable. A parental history of
high psychosocial burden, including depression MI increases the risk of MI, especially when 1 par-
(41.7%), high perceived stress (34.5%), and ent had a premature MI before 50 years of age,
impaired cognition (15.2%).87 with paternal history of premature MI shown to

approximately double the risk of a heart attack in independent genetic variants, and all have small
CLINICAL STATEMENTS
males and increase the risk in females by ≈70%.88 effect sizes.

AND GUIDELINES
• Sibling history of CVD has been shown to increase • Over the past decade, the application of GWAS
the odds of CVD in males and females by 45% to large cohorts of CHD case and control subjects
(OR, 1.45; 95% CI, 1.10–1.91) in models that has identified many consistent genetic variants
account for CVD risk factors.89 associated with CHD.
• Family history of premature angina, MI, angio- • The first GWAS identified the now most consis-
plasty, or bypass surgery increases lifetime risk by tently replicated genetic marker for CHD and MI
≈50% for both HD (from 8.9% to 13.7%) and in European-derived populations, on chromo-
CVD mortality (from 14.1% to 21%).90 some 9p21.3.93 The frequency of the primary SNP
• In the FHS, addition of a family history of prema- is very common (50% of the white population is
ture CVD provided improved prognostic value estimated to harbor 1 risk allele, and 23% har-
over traditional risk factors.91 bors 2 risk alleles).94
• Among people with a family history, coronary
— The 10-year HD risk for a 65-year-old male
artery calcium is a robust marker of ASCVD risk.88
with 2 risk alleles at 9p21.3 and no other
• In premature ACS (age ≤55 years), a greater per-
traditional risk factors is ≈13.2%, whereas
centage of females (28%) than males (20%) have
a similar male with 0 alleles would have a
a family history of CAD (P=0.008). Compared
10-year risk of ≈9.2%. The 10-year HD risk
with patients without a family history, patients
for a 40-year-old female with 2 alleles and
with a family history of CAD have a higher preva-
no other traditional risk factors is ≈2.4%,
lence of traditional CVD risk factors.92
whereas a similar female with 0 alleles
Prevalence would have a 10-year risk of ≈1.7%.94
• Among adults ≥20 years of age, 12.2% (SE 0.5%) • The 9p21.3 genetic locus has also been asso-
reported having a parent or sibling with a heart ciated with CHD in individuals of East Asian
attack or angina before the age of 50 years. The ancestry (OR per risk allele, 1.3; 95% CI,
racial/ethnic breakdown from NHANES 2011 to 1.25–1.35).95
2014 is as follows (unpublished NHLBI tabulation): • The 9p21.3 genetic locus is also associated with
— For NH whites, 12.2% (SE 0.9%) for males, CAC,96 premature atherosclerosis,97 ischemic
14.7% (SE 0.9%) for females. stroke,98 HF,99 PAD,100 and aortic aneurysm.101
— For NH blacks, 8.1% (SE 0.9%) for males, — After this initial GWAS discovery, investigators
12.0% (SE 0.9%) for females. combined cohorts in efforts to increase sam-
— For Hispanics, 7.4% (SE 0.7%) for males, ple size and thus power to identify additional
10.1% (SE 0.9%) for females. CHD genes. The CARDIoGRAMplusC4D
— For NH Asians, 5.7% (SE 0.9%) for males, Consortium represents the largest genetic
5.3% (SE 0.8%) for females. study of CAD to date. Although the ORs are
• HD occurs as people age, so the prevalence of modest, these are common alleles, which
family history will vary depending on the age at suggests that the attributable risk could be
which it is assessed. The breakdown of reported substantial. Additional analysis suggested
family history of heart attack by age of survey that loci associated with CAD were involved
respondent in the US population as measured by
in lipid metabolism and inflammation
NHANES 2011 to 2014 is as follows (unpublished
pathways.102
NHLBI tabulation):
— Relatedly, the relationship between genetic
— Age 20 to 39 years, 8.7% (SE 0.8%) for
variants associated with CHD and measured
males, 9.7% (SE 0.8%) for females.
CHD risk factors is complex, with some
genetic markers associated with multiple risk
factors and other markers showing no asso-
ciation with risk factors.103
• The association of SNPs with incident CHD was
— Age ≥80 years, 8.1% (SE 2.1%) for males,
investigated in a large multiethnic study of mul-
13.7% (SE 2.7%) for females.
tiple cohorts in the United States (including
Genetics NHANES, WHI, the Multiethnic Cohort Study,
• For the past 20 years, candidate gene studies CHS, ARIC, CARDIA, Hispanic Community Health
have been conducted to identify the genetic vari- Study/Study of Latinos, and SHS).104 SNPs, includ-
ants underlying the heritability of CHD, but very ing in 9p21, APOE, and LPL, were associated with
few have identified consistent, replicated, and incident CHD in individuals of European ancestry,

but not African Americans. Effect sizes were primary prevention measures even in patients
CLINICAL STATEMENTS
greater for those ≤55 years of age and in females. with a high genetic risk.
AND GUIDELINES
• More recently, genetic studies of CHD have
focused on the coding regions of the genome
(exons) and have identified additional genes and
Global Burden
SNPs for CHD, including loss-of-function muta- (See Table 18-3 and Charts 18-14
tions in the angiopoietin-like 4 (ANGPTL4) gene, and 18-15)
which is an inhibitor of lipoprotein lipase.105 These • Globally, it is estimated that 110.6 million people
mutations are associated with low plasma triglyc- live with IHD, and it is more prevalent in males
erides and high HDL-C. than in females (64.4 and 46.1 million people,
• Whole-genome sequencing studies, which offer respectively). The number of people with IHD
a deeper and more comprehensive coverage of increased by 73.3% from 1990 to 2015, although
the genome, have recently identified 13 variants the rate per 100 000 decreased 7.4% over the
with large effects on blood lipids, with 5 of these same time period (Table 18-3).112
also being associated with CHD (PCSK9, APOA1, • The GBD 2015 Study used statistical models and
ANGPTL4, and LDLR).106 data on incidence, prevalence, case fatality, excess
mortality, and cause-specific mortality to estimate
Clinical Utility of Genetic Markers
disease burden for 315 diseases and injuries in
• Recent advances have demonstrated the utility
195 countries and territories.112
of genetics in CAD risk prediction. In 48 421 indi-
— IHD mortality rates are generally lower than
viduals enrolled in the Malmo Diet and Cancer
150 per 100 000 for most of the world but
Study and 2 primary prevention trials (JUPITER,
exceed 300 per 100 000 in Eastern Europe
ASCOT) and 2 secondary prevention trials of lipid-
and Central Asia (Chart 18-14).
lowering (CARE, PROVE-IT TIMI22), a genetic risk
— Russia has the highest prevalence rates of
score consisting of 27 variants of genetic risk for
IHD in the world (Chart 18-15).
CAD improved risk prediction above models that
incorporated traditional risk factors and family
history.107 Future Research
• In the Malmo Diet and Cancer Study, application
• Although the prevalence of CHD has decreased

of an additional 23 SNPs known to be associated over the past decade, it remains the leading
with CAD resulted in greater discrimination and cause of mortality in both the underdeveloped
reclassification (both P<0.0001).108 In the FINRISK and developed world. There are substantial gaps
and FHS cohorts, with a sample size of 12 676 in our knowledge of the determinants of social
individuals, a genetic risk score incorporating disparities in the occurrence and outcomes of
49 310 SNPs based on the CARDIoGRAMplusC4D CHD that might have profound implications for
Consortium data showed that the combination of prevention and health care. Crucially, a better
genetic risk score with the FRS improved 10-year understanding of how these disparities originate
cardiac risk prediction, particularly in those ≥60 and are maintained over the life course will be
years of age.109 essential to design comprehensive strategies to
• In the MI-GENES trial of intermediate-risk improve CVD health in the coming years.
patients, patient knowledge of their genetic risk • Large population and trial studies with col-
score resulted in lower levels of LDL-C than a con- laborations have yielded tremendous strides in
trol group managed by conventional risk factors the understanding of the genetics of CHD. Yet
alone, which suggests the influence of genetic knowledge gaps include the “missing heritabil-
risk score in risk prevention.110 ity” possibility, which consists of additional com-
• Even in individuals with high genetic risk, preven- mon variants of modest effect size, rare variants
tion strategies have added benefit. For example, of greater effect size, structural differences in
in 4 studies across 55 685 participants, genetic deoxyribonucleic acid sequences, and epigen-
and lifestyle factors were independently associ- etic modifications. Larger studies, whole-genome
ated with CHD, but even in participants at high sequencing, and combined efforts with ’omics
genetic risk, a favorable lifestyle was associated data could yield additional insights into the basis
with a nearly 50% lower relative risk of CHD than of CHD. The primary function of the majority
was an unfavorable lifestyle.111 of SNPs associated with CHD identified thus far
• Collectively, these results may suggest future roles remains poorly understood. Ultimately, the bio-
for incorporation of genetic risk score in clinical logical mechanisms of these significant variants
practice and emphasize the need for traditional must be investigated to enable understanding of

the pathophysiology of CAD and development The extensive literature on the excess morbidity
CLINICAL STATEMENTS
of further therapeutic agents and drug targets. and mortality in ethnic and racial minorities in the
AND GUIDELINES
Despite the significant advances, it is noteworthy United States thus highlights the need for incor-
that the overwhelming majority of genetic data poration of these minority groups into population
represent that of NH whites of European ancestry. and genetic studies.
Table 18-1. Coronary Heart Disease

New and Hospital
Prevalence, CHD, Prevalence, MI, Recurrent MI New and Discharges
Population 2011–2014 2011–2014 and Fatal CHD, Recurrent MI, Mortality,* CHD, Mortality,* MI, CHD, 2014 All
Group Age ≥20 y Age ≥20 y Age ≥35 y Age ≥35 y 2015 All Ages 2015 All Ages Ages
Both sexes 16 500 000 (6.3%) 7 900 000 (3.0%) 1 055 000 805 000 366 801 114 023 1 021 000
Males 9 100 000 (7.4%) 4 700 000 (3.8%) 610 000 470 000 209 298 (57.1%)† 65 211 (57.2%)† 649 000
Females 7 400 000 (5.3%) 3 200 000 (2.3%) 445 000 335 000 157 503 (42.9%)† 48 812 (42.8%)† 372 000
NH white males 7.7% 4.0% 520 000‡ … 167 236 52 393 …
NH white females 5.3% 2.4% 370 000‡ … 124 614 38 407 …
NH black males 7.1% 3.3% 90 000‡ … 21 006 6400 …
NH black females 5.7% 2.2% 75 000‡ … 18 048 5723 …
Hispanic males 5.9% 2.9% … … 13 416 4246 …
Hispanic females 6.1% 2.1% … … 9639 3106 …
NH Asian males 5.0% 2.6% … … 5154 1516§ …
NH Asian females 2.6% 0.7% … … 3767 1167§ …
NH American
Indian or Alaska 9.3%‖¶ … … … 2044 624 …
Native
CHD includes people who responded “yes” to at least 1 of the questions in “Has a doctor or other health professional ever told you that you had coronary heart
disease, angina or angina pectoris, heart attack, or myocardial infarction?” Those who answered “no” but were diagnosed with Rose angina are also included (the
Rose questionnaire is only administered to survey participants >40 years of age). CHD indicates coronary heart disease; ellipses (…), data not available; MI, myocardial
infarction; and NH, non-Hispanic.
*Mortality for Hispanic, NH American Indian or Alaska Native, and NH Asian and Pacific Islander people should be interpreted with caution because of inconsistencies
in reporting Hispanic origin or race on the death certificate compared with censuses, surveys, and birth certificates. Studies have shown underreporting on death
certificates of American Indian or Alaska Native, Asian and Pacific Islander, and Hispanic decedents, as well as undercounts of these groups in censuses.
†These percentages represent the portion of total CHD and MI mortality that is for males vs females.
‡Estimates include Hispanics and non-Hispanics. Estimates for whites include other nonblack races.
§Includes Chinese, Filipino, Hawaiian, Japanese, and Other Asian or Pacific Islander.
‖National Health Interview Survey, National Center for Health Statistics 2015; data are weighted percentages for Americans ≥18 years of age.1
¶Estimate considered unreliable or does not meet standards of reliability or precision.
Sources: Prevalence: National Health and Nutrition Examination Survey 2011 to 2014 (National Center for Health Statistics) and National Heart, Lung, and Blood
Institute. Percentages for racial/ethnic groups are age adjusted for Americans ≥20 years of age. Age-specific percentages are extrapolated to the 2014 US population
estimates. These data are based on self-reports. Incidence: Atherosclerosis Risk in Communities study (2005–2014), National Heart, Lung, and Blood Institute.
Mortality: Centers for Disease Control and Prevention/National Center for Health Statistics, 2015 Mortality Multiple Cause-of-Death–United States. Mortality for NH
Asians includes Pacific Islanders. Hospital discharges: Healthcare Cost and Utilization Project, Hospital Discharges, 2014 (data include those inpatients discharged
alive, dead, or status unknown).

Table 18-2. Angina Pectoris*
CLINICAL STATEMENTS
Prevalence, 2011–2014, Incidence of Hospital Discharges,
AND GUIDELINES
Population Group Age ≥20 y Stable AP, Age ≥45 y 2014, All Ages
Both sexes 8 700 000 (3.4%) 565 000 10 000
Males 4 200 000 (3.5%) 370 000 5000
Females 4 500 000 (3.3%) 195 000 5000
NH white males 3.7% … …
NH white females 3.3% … …
NH black males 3.5% … …
NH black females 3.3% … …
Hispanic males 2.7% … …
Hispanic females 3.8% … …
NH Asian or Pacific Islander males 2.0% … …
NH Asian or Pacific Islander females 1.3% … …
AP indicates angina pectoris; ellipses (…), data not available; and NH, non-Hispanic.
*AP is chest pain or discomfort that results from insufficient blood flow to the heart muscle. Stable AP is predictable chest pain on
exertion or under mental or emotional stress. The incidence estimate is for AP without myocardial infarction.
Sources: Prevalence: National Health and Nutrition Examination Survey 2011 to 2014 (National Center for Health Statistics) and
National Heart, Lung, and Blood Institute; percentages for racial/ethnic groups are age adjusted for US adults ≥20 years of age. AP
includes people who either answered “yes” to the question of ever having angina or AP or who were diagnosed with Rose angina
(the Rose questionnaire is only administered to survey participants >40 years of age). Estimates from National Health and Nutrition
Examination Survey 2011 to 2014 (National Center for Health Statistics) were applied to 2014 population estimates (≥20 years of age).
Incidence: AP uncomplicated by a myocardial infarction or with no myocardial infarction (Framingham Heart Study [the original cohort
and the Offspring Cohort 1986–2009], National Heart, Lung, and Blood Institute). Hospital discharges: Healthcare Cost and Utilization
Project, Hospital Discharges, 2014; data include those inpatients discharged alive, dead, or status unknown.
Table 18-3 Global Burden of Ischemic Heart Disease and Trends, Global Burden of Disease112
Both Sexes Males Females

Deaths Prevalence Deaths Prevalence Deaths Prevalence
Total number
8.9 (8.8 to 9.1) 110.6 (100.7 to 121.8) 4.9 (4.7 to 5.0) 64.4 (58.7 to 71.0) 4.0 (3.9 to 4.1) 46.1 (42.1 to 50.8)
(millions)
Percent change
total number 48.9 (45.9 to 52.2) 73.3 (71.7 to 74.9) 56.5 (52.0 to 62.2) 76.0 (73.9 to 78.0) 40.8 (37.2 to 44.5) 69.6 (67.7 to 71.5)
1990 to 2015
Percent change
total number 16.6 (14.6 to 18.6) 25.9 (24.6 to 27.2) 19.7 (16.8 to 23.0) 26.0 (24.5 to 27.6) 12.9 (10.6 to 15.5) 25.7 (24.3 to 27.0)
2005 to 2015
Rate per 100 000 142.1 1662.6 172.8 2044.7 115.0 1312.4
(139.5 to 145.2) (1518.5 to 1828.0) (168.2 to 177.5) (1864.2 to 2250.8) (112.3 to 118.1) (1198.4 to 1446.6)
Percent change −25.2
−7.4 (−8.2 to −6.5) −23.9 (−25.9 to −21.3) −8.3 (−9.3 to −7.3) −27.9 (−29.8 to −26.0) −7.2 (−8.3 to −6.1)
rate 1990 to 2015 (−26.6 to −23.7)
Percent change −12.8
−3.4 (−4.2 to −2.6) −10.9 (−12.9 to −8.6) −4.1 (−5.1 to −3.1) −15.4 (−17.1 to −13.5) −2.7 (−3.7 to −1.7)
rate 2005 to 2015 (−14.2 to −11.4)
Reprinted from Global Burden of Disease Study 2015112 with permission. Copyright © 2016, University of Washington.

CLINICAL STATEMENTS
35
AND GUIDELINES
30.6
30
25
Percent of Population 21.7
19.7
20
15
11.0
10
6.1
5.4
5
0.6 0.7
0
20-39 40-59 60-79 80+
Age (Years)
Males Females
Chart 18-1. Prevalence of coronary heart disease by age and sex (NHANES: 2011–2014).
20
18 17.5
16
14
12 11.0 11.0
10
6 5.2
4
2.6
1.9
2
0.3 0.3
0
20 - 39 40 - 59 60 - 79 80+
Age (Years)
Males Females
Chart 18-2. Prevalence of myocardial infarction by age and sex (NHANES: 2011–2014).
Myocardial infarction includes people who answered “yes” to the question of ever having had a heart attack or myocardial
infarction.

CLINICAL STATEMENTS
AND GUIDELINES
Chart 18-3. “Ever told you had a heart attack (myocardial infarction)?” Age-adjusted prevalence by state, BRFSS
Prevalence & Trends Data.4
Source: Centers for Disease Control and Prevention, National Center for Chronic Disease Prevention and Health Promotion,
Division of Population Health.
Chart 18-4. “Ever told you had angina or coronary heart disease?” Age-adjusted prevalence by state, BRFSS
Prevalence & Trends Data.4
Source: Centers for Disease Control and Prevention, National Center for Chronic Disease Prevention and Health Promotion,
Division of Population Health

CLINICAL STATEMENTS
AND GUIDELINES
Chart 18-5. Annual number of adults per 1000 having diagnosed heart attack or fatal CHD by age and sex (ARIC
surveillance: 2005–2014 and CHS).
These data include myocardial infarction and fatal CHD but not silent myocardial infarction.
ARIC indicates Atherosclerosis Risk in Communities; CHD, coronary heart disease; and CHS, Cardiovascular Health Study.
Chart 18-6. Incidence of heart attack or fatal CHD by age, sex, and race (ARIC Surveillance: 2005–2014).
ARIC indicates Atherosclerosis Risk in Communities; CHD, coronary heart disease; and MI, myocardial infarction.

CLINICAL STATEMENTS
AND GUIDELINES
Chart 18-7. Incidence of myocardial infarction by age, sex, and race (ARIC Surveillance: 2005–2014).
ARIC indicates Atherosclerosis Risk in Communities.
Source: Unpublished data from ARIC, National Heart, Lung, and Blood Institute.
Chart 18-8. Estimated 10-year coronary heart disease risk in adults 55 years of age according to levels of various
risk factors (FHS).
FHS indicates Framingham Heart Study; and HDL-C, high-density lipoprotein cholesterol.
Data derived from Wilson et al.41

CLINICAL STATEMENTS
AND GUIDELINES
Chart 18-9. Prevalence of low coronary heart disease risk, overall and by sex (NHANES: 1971–2006).
Low risk is defined as systolic blood pressure <120 mm Hg and diastolic blood pressure <80 mm Hg; cholesterol <200 mg/dL;
body mass index <25 kg/m2; currently not smoking cigarettes; and no prior myocardial infarction or diabetes mellitus.
Source: Personal communication with the National Heart, Lung, and Blood Institute, June 28, 2007.
Chart 18-10. Hospital discharges for coronary heart disease by sex (United States: 1997–2014).
Hospital discharges include people discharged alive, dead, and “status unknown.”
Source: Healthcare Cost and Utilization Project, Agency for Healthcare Research and Quality and National Heart, Lung, and
Blood Institute.

CLINICAL STATEMENTS
AND GUIDELINES
Chart 18-11. Prevalence of angina pectoris by age and sex (NHANES: 2011–2014).
Angina pectoris includes people who either answered “yes” to the question of ever having angina or angina pectoris or who
were diagnosed with Rose angina.
Chart 18-12. Secular trends in age- and sex-standardized prevalence rates of angina for adults aged ≥40 years in
the United States, by race, for angina symptoms defined using the Rose questionnaire.
Reprinted from Will et al.65 Copyright © 2014, American Heart Association, Inc.

CLINICAL STATEMENTS
AND GUIDELINES
Chart 18-13. Incidence of angina pectoris (deemed uncomplicated on the basis of physician interview of patient)
by age and sex (FHS 1986–2009).
FHS indicates Framingham Heart Study.
Data derived from the National Heart, Lung, and Blood Institute.
Chart 18-14. Age-standardized global mortality rates of ischemic heart disease per 100 000, both sexes, 2015.
Chart 18-15. Age-standardized global prevalence rates of ischemic heart disease per 100 000, both sexes, 2015.
C, Cushman M, Howard V, Howard G; for the REGARDS Investigators.

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Whittaker JC, de Faire U, Kivimaki M, Kumari M, Hypponen E, Power C, F, Hyde C, Cannon CP, Sacks F, Poulter N, Sever P, Ridker PM, Braunwald
Humphries SE, Talmud PJ, Price J, Morris RW, Ye S, Casas JP, Hingorani E, Melander O, Kathiresan S, Sabatine MS. Genetic risk, coronary heart
AD. Comparative analysis of genome-wide association studies signals for disease events, and the clinical benefit of statin therapy: an analysis of
lipids, diabetes, and coronary heart disease: Cardiovascular Biomarker primary and secondary prevention trials. Lancet. 2015;385:2264–2271.
Genetics Collaboration. Eur Heart J. 2012;33:393–407. doi: 10.1093/ doi: 10.1016/S0140-6736(14)61730-X.
eurheartj/ehr225. 108. Tada H, Melander O, Louie JZ, Catanese JJ, Rowland CM, Devlin JJ,
104. Franceschini N, Carty C, Bůzková P, Reiner AP, Garrett T, Lin Y, Vöckler Kathiresan S, Shiffman D. Risk prediction by genetic risk scores for cor-
JS, Hindorff LA, Cole SA, Boerwinkle E, Lin DY, Bookman E, Best LG, onary heart disease is independent of self-reported family history. Eur
Bella JN, Eaton C, Greenland P, Jenny N, North KE, Taverna D, Young Heart J. 2016;37:561–567. doi: 10.1093/eurheartj/ehv462.
AM, Deelman E, Kooperberg C, Psaty B, Heiss G. Association of genetic 109. Abraham G, Havulinna AS, Bhalala OG, Byars SG, De Livera AM, Yetukuri
variants and incident coronary heart disease in multiethnic cohorts: the L, Tikkanen E, Perola M, Schunkert H, Sijbrands EJ, Palotie A, Samani NJ,
PAGE study. Circ Cardiovasc Genet. 2011;4:661–672. doi: 10.1161/ Salomaa V, Ripatti S, Inouye M. Genomic prediction of coronary heart dis-
CIRCGENETICS.111.960096. ease. Eur Heart J. 2016;37:3267–3278. doi: 10.1093/eurheartj/ehw450.
105. Stitziel NO, Stirrups KE, Masca NG, Erdmann J, Ferrario PG, Konig IR, 110. Kullo IJ, Jouni H, Austin EE, Brown SA, Kruisselbrink TM, Isseh IN, Haddad
Weeke PE, Webb TR, Auer PL, Schick UM, Lu Y, Zhang H, Dube MP, Goel RA, Marroush TS, Shameer K, Olson JE, Broeckel U, Green RC, Schaid DJ,
A, Farrall M, Peloso GM, Won HH, Do R, van Iperen E, Kanoni S, Kruppa Montori VM, Bailey KR. Incorporating a genetic risk score into coronary
J, Mahajan A, Scott RA, Willenberg C, Braund PS, van Capelleveen heart disease risk estimates: effect on low-density lipoprotein cholesterol
JC, Doney AS, Donnelly LA, Asselta R, Merlini PA, Duga S, Marziliano levels (the MI-GENES Clinical Trial). Circulation. 2016;133:1181–1188.
N, Denny JC, Shaffer CM, El-Mokhtari NE, Franke A, Gottesman O, doi: 10.1161/CIRCULATIONAHA.115.020109.
Heilmann S, Hengstenberg C, Hoffman P, Holmen OL, Hveem K, Jansson 111. Khera AV, Emdin CA, Drake I, Natarajan P, Bick AG, Cook NR, Chasman
JH, Jockel KH, Kessler T, Kriebel J, Laugwitz KL, Marouli E, Martinelli N, DI, Baber U, Mehran R, Rader DJ, Fuster V, Boerwinkle E, Melander O,
McCarthy MI, Van Zuydam NR, Meisinger C, Esko T, Mihailov E, Escher Orho-Melander M, Ridker PM, Kathiresan S. Genetic risk, adherence to
SA, Alver M, Moebus S, Morris AD, Muller-Nurasyid M, Nikpay M, Olivieri a healthy lifestyle, and coronary disease. N Engl J Med. 2016;375:2349–
O, Lemieux Perreault LP, AlQarawi A, Robertson NR, Akinsanya KO, 2358. doi: 10.1056/NEJMoa1605086.
Reilly DF, Vogt TF, Yin W, Asselbergs FW, Kooperberg C, Jackson RD, 112. Global Burden of Disease Study 2015. Global Burden of Disease Study
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Ford I, Jukema JW, Kee F, Kuulasmaa K, Nordestgaard BG, Perola M, org/gbd-results-tool. Accessed June 1, 2017.

19. CARDIOMYOPATHY AND HEART Abbreviations Used in Chapter 19 Continued
CLINICAL STATEMENTS
FAILURE MI myocardial infarction
AND GUIDELINES
MRI magnetic resonance imaging
See Table 19-1 and Charts 19-1 through 19-7 NAMCS National Ambulatory Medical Care Survey
Click here to return to the Table of Contents NH non-Hispanic
Cardiomyopathy NHDS National Hospital Discharge Survey
ICD-9 425; ICD-10 I42. NHLBI National Heart, Lung, and Blood Institute
2015: Mortality—23 118. Any-mention mortality— OR odds ratio
45 399. PA physical activity
Using HCUP data for cardiomyopathy in 2014, there PAR population attributable risk
were 16 000 inpatient hospitalizations for which car- PPCM peripartum cardiomyopathy
PVC premature ventricular contraction
diomyopathy was the principal diagnosis and 966 000
where it was included among all-listed diagnoses RR relative risk
(NHLBI unpublished tabulation). SBP systolic blood pressure
ACEI angiotensin-converting enzyme inhibitor
ACR albumin-to-creatinine ratio Hypertrophic Cardiomyopathy
AF atrial fibrillation • Approximately 1 in 500 individuals have unex-
AHA American Heart Association plained LV hypertrophy, of which 20% to 30%
ARB angiotensin receptor blocker are likely to have a sarcomere mutation suggest-
ing clinically expressed HCM; however, not all
BMI body mass index
BNP B-type natriuretic peptide people with sarcomere mutations manifest clini-
BP blood pressure cal HCM because of incomplete penetrance even
CAD coronary artery disease among members of the same family (see Family
CARDIA Coronary Artery Risk Development in Young Adults Study History and Genetics for more details).1
CHA Chicago Heart Association Detection Project in Industry

CHD coronary heart disease Dilated Cardiomyopathy
CHS Cardiovascular Health Study • The most commonly recognized causes of DCM
are mutations in a diverse group of genes that are
inherited in an autosomal dominant fashion with
CVD cardiovascular disease age-dependent penetrance and variable clinical
DCM dilated cardiomyopathy expression (see Family History and Genetics for
DM diabetes mellitus more details).
ED emergency department • Data from multiple Washington, DC–area hospi-
tals showed that blacks with idiopathic DCM have
GBD Global Burden of Disease 1- and 2-year survival rates of 71.5% and 63.6%,
GWAS genome-wide association study respectively, whereas whites with idiopathic
GWTG-HF Get With the Guidelines–Heart Failure DCM have survival rates of 92.0% and 86.3%,
HbA1c hemoglobin A1c (glycosylated hemoglobin) respectively.2
HCM hypertrophic cardiomyopathy
HCUP Healthcare Cost and Utilization Project Peripartum Cardiomyopathy
HD heart disease • Data from Kaiser Permanente indicate that the
Health ABC Health, Aging, and Body Composition
incidence of PPCM is 4.84 per 10 000 live births
HF heart failure
HR hazard ratio
(95% CI, 3.98–5.83). PPCM is associated with
ICD-10 International Classification of Diseases, 10th Revision higher maternal and neonatal death rates and
ICD-9 International Classification of Diseases, 9th Revision worse neonatal outcomes.3
IHD ischemic heart disease • NHDS data suggest a trend toward an increase in
INTERMACS Interagency Registry for Mechanically Assisted Circulatory the incidence of PPCM in the United States from
Support
LV left ventricular
1990 through 1993 (1 case per 3189 live births) to
LVAD left ventricular assist device 2000 through 2002 (1 case per 2289 live births),
LVEF left ventricular ejection fraction which could be related to a rise in maternal age,
MESA Multi-Ethnic Study of Atherosclerosis increase in multifetal pregnancies, and increased
(Continued ) disease awareness and detection.4

• Population data from the Southern California lived with disability from cardiomyopathy and
CLINICAL STATEMENTS
Kaiser healthcare system between 1996 and 2005 myocarditis increased 22%, from 3.1 to 3.7 years.
AND GUIDELINES
show the highest incidence of PPCM in blacks (1 in • Chart 19-1 shows the incidence of PPCM
1421), followed by Asians (1 in 2675) and whites globally.13
(1 in 4075), with the lowest rates in Hispanics (1 • The GBD 2015 Study used statistical models and
in 9861).5 data on incidence, prevalence, case fatality, excess
• In a prospective cohort of PPCM, 13% of females mortality, and cause-specific mortality to estimate
had major events (death, cardiac transplantation, disease burden for 315 diseases and injuries in
or implantation of an LVAD) or persistent severe 195 countries and territories.12
cardiomyopathy at 12 months. Black females — The highest mortality rates attributed to
had worse LV dysfunction at presentation and cardiomyopathy and myocarditis were in
at 6 and 12 months postpartum compared with Eastern Europe (Chart 19-2).
nonblack females.6 — The prevalence of cardiomyopathy and myo-
carditis was highest in South Africa (Chart
Youth 19-3).
• Since 1996, the NHLBI-sponsored Pediatric
Cardiomyopathy Registry has collected data on
children with newly diagnosed cardiomyopathy in Heart Failure
New England and the Central Southwest (Texas, ICD-9 428; ICD-10 I50.
Oklahoma, and Arkansas).7 2015: Mortality—75 251. Any-mention mortality—
— The overall incidence of cardiomyopathy is 330 610. 2014: Hospital Discharges—900 000.
1.13 cases per 100 000 among children <18
years of age. Prevalence
— Among children <1 year of age, the inci- (See Table 19-1 and Chart 19-4)
dence is 8.34, and among children 1 to 18 • On the basis of data from NHANES 2011 to 2014,
years of age, it is 0.70 per 100 000. an estimated 6.5 million Americans ≥20 years
— The annual incidence is higher in black chil- of age had HF (Chart 19-4). This represents an
dren than in white children, in boys than in increase from an estimated 5.7 million US adults
girls, and in New England (1.44 per 100 000) with HF based on NHANES 2009 to 2012 (NHLBI
than in the Central Southwest (0.98 per unpublished tabulation).

100 000). • Projections show that the prevalence of HF will
• The estimated annual incidence of HCM in chil- increase 46% from 2012 to 2030, resulting in >8
dren was 4.7 per 1 million children, with higher million people ≥18 years of age with HF.14
incidence in New England than in the Central Incidence
Southwest region and in boys than in girls.8 Long- (See Table 19-1 and Chart 19-5)
term outcomes of children with HCM suggest • Data from the NHLBI-sponsored CHA, ARIC, and
that 9% progress to HF and 12% to SCD.9 See CHS cohorts indicate that HF incidence approaches
Chapter 15 (Disorders of Heart Rhythm) for statis- 21 per 1000 population after 65 years of age.15
tics regarding sudden death in HCM. • Data from Kaiser Permanente indicated an
• The estimated annual incidence of DCM in chil- increase in the incidence of HF among the elderly
dren <18 years of age is 0.57 per 100 000 over- and improved HF survival, resulting in increased
all, with higher incidence in boys than girls (0.66 HF prevalence, with both trends being more pro-
versus 0.47 cases per 100 000) and blacks than nounced in males.16
whites (0.98 versus 0.46 cases per 100 000). The • Data from Olmsted County, MN, indicate that the
most commonly recognized causes of DCM were age- and sex-adjusted incidence of HF declined
myocarditis (46%) and neuromuscular disease substantially, from 315.8 per 100 000 in 2000
(26%).10 The 5-year incidence rate of SCD among to 219.3 per 100 000 in 2010, with a greater
children with DCM is 3%.11 rate reduction for HF with reduced EF (−45.1%;
Global Burden of Cardiomyopathy 95% CI, −33.0% to −55.0%) than for HF with
(See Charts 19-1 through 19-3) preserved EF (−27.9%; 95% CI, −12.9% to
• Between 1990 and 2015, the global number of −40.3%).17
deaths attributable to cardiomyopathy and myo- • In the CARDIA study, HF before 50 years of age
carditis increased 31%, from 269 302 to 353 725, was more common among blacks than whites.
but the age-adjusted death rate decreased slightly Hypertension, obesity, and systolic dysfunction
from 5.1 to 4.8 per 100 000.12 Globally, the years were important risk factors that may be targets
for prevention.18

• On the basis of data from the 2005 to 2014 com- implantable cardioverter-defibrillators, and car-
CLINICAL STATEMENTS
munity surveillance component of the ARIC study diac resynchronization therapies.22 Contemporary
AND GUIDELINES
of the NHLBI: evidence from the GWTG-HF registry suggests
— There are 1 000 000 new HF cases annually that ≈47% of individuals admitted to the hospi-
(495 000 males and 505 000 females) (Table tal with HF should have had initiation of ≥1 new
19-1). medication on discharge.23 In a large Swedish
— Black males have the highest incidence of HF registry of patients with HF with preserved EF,
across all age groups (Chart 19-5). statins improved 1-year cardiovascular hospital-
• In MESA, African Americans had the highest risk ization, mortality, and cardiovascular mortality.24
of developing HF, followed by Hispanic, white, Accordingly, 5-year survival of HF diagnosis after
and Chinese Americans (4.6, 3.5, 2.4, and 1.0 per an MI in Olmstead County, MN, improved in
1000 person-years, respectively). This higher risk 2001 to 2010 versus 1990 to 2000, from 54% to
reflected differences in the prevalence of hyper- 61%.25
tension, DM, and low SES.19 African Americans • Some data suggest that improvements in sur-
had the highest proportion of incident HF not vival could be leveling off over time. Data from
preceded by clinical MI (75%).19 the Rochester Epidemiology Project in Olmsted
Lifetime Risk County, MN, showed improved survival after
• Because most forms of HF tend to present in older HF diagnosis between 1979 and 200026; how-
age, and the population is aging, lifetime risk ever, 5-year mortality did not decline from 2000
for HF in the community is high. Data from the to 2010 and remained high at ≈50% (52.6%
NHLBI-sponsored CHA, ARIC, and CHS cohorts overall; 24.4% for 60-year-olds and 54.4% for
indicated the following15: 80-year-olds), Importantly, mortality was more
— Overall, at age 45 years through age 95 years, frequently ascribed to noncardiovascular causes
lifetime risks for HF were high (20%–45%). (54.3%), and the risk of noncardiovascular death
— Lifetime risks for HF were 30% to 42% in was greater in HF with preserved EF than in HF
white males, 20% to 29% in black males, with reduced EF.17
32% to 39% in white females, and 24% to • Given improvements in HF survival overall, the
46% in black females. number of individuals carrying a diagnosis of HF
— Lifetime risk for HF was higher with higher at death has increased. Mortality associated with
BP and BMI at all ages. HF is substantial, such that 1 in 8 deaths has HF
— The lifetime risk of HF occurring for people mentioned on the death certificate (NCHS, NHLBI
with BMI ≥30 kg/m2 was double that of unpublished tabulation).27 The number of underly-
those with BMI <25 kg/m2. ing cause of deaths attributable to HF was 27.7%
— The lifetime risk of HF occurring for people higher in 2015 (75 251) than it was in 2005
with BP >160/90 mm Hg was 1.6 times that (58 933) (NCHS, NHLBI unpublished tabulation).
of those with BP <120/90 mm Hg. • In 2015, HF was the underlying cause in 75 251
deaths (33 667 males and 41 584 females).27 Table
Mortality 19-1 shows the numbers of these deaths that
(See Table 19-1) were coded for HF as the underlying cause.
• Survival after the onset of HF in older adults • In 2015, the overall any-mention age-adjusted
has improved, as indicated by data from Kaiser death rate for HF was 87.9 per 100 000, with
Permanente16; however, improvements in HF sur- variation across racial/ethnic groups: in males,
vival have not been even across all demograph- the rates were 107.4 for NH whites, 112.6 for
ics. Among Medicare beneficiaries, the overall NH blacks, 47.0 for NH Asians or Pacific Islanders,
1-year HF mortality rate declined slightly from 100.9 for NH American Indians or Alaska Natives,
1998 to 2008 but remained high at 29.6%, and and 67.5 for Hispanics; in females, the respec-
rates of decline were uneven across states.20 In tive rates were 79.6 for NH whites, 83.9 for NH
the NHLBI’s ARIC study, the 30-day, 1-year, and blacks, 33.3 for NH Asians or Pacific Islanders,
5-year case fatality rates after hospitalization for 75.0 for NH American Indians or Alaska Natives,
HF were 10.4%, 22%, and 42.3%, respectively, and 48.8 for Hispanics.27
and blacks had a greater 5-year case fatality rate
than whites (P<0.05).21 Risk Factors
• Observed mortality declines have been primar- • Traditional risk factors for HF are common in the
ily attributed to evidence-based approaches to US adult population. Data from NHANES indicate
treat HF risk factors and the implementation of that at least 1 HF risk factor is present in up to one
ACEIs, β-blockers, coronary revascularization, third of the US adult population.28

• Traditional factors account for a considerable pro- a J-shaped relationship.33 Inflammatory

CLINICAL STATEMENTS
portion of HF risk. Data from Olmstead County, markers (interleukin-6 and tumor necrosis
AND GUIDELINES
MN, indicate that CHD, hypertension, DM, obe- factor-α), serum albumin levels, and cigarette
sity, and smoking are responsible for 52% of smoking exposure additionally were associ-
incident HF cases in the population, with ORs or ated with increased HF risk.38–40
RRs and their PARs as follows29: CHD OR, 3.1 and — In the CHS, baseline cardiac high-sensitivity
overall PAR, 20% (highest in males, 23% versus troponin and changes in high-sensitivity tro-
16% in females); cigarette smoking RR, 1.4 and ponin levels were significantly associated
PAR, 14%; hypertension RR, 1.4 and PAR, 20% with incident HF.41 Conversely, circulating
(highest in females, 28% versus 13% in males); individual and total omega-3 fatty acid con-
obesity RR, 2.0 and PAR, 12%; DM OR, 2.7 and centrations were associated with lower inci-
PAR, 12%; dietary sodium intake RR, 1.4 and dence of HF.42
PAR, not available30; and valvular HD RR, 1.5 and — In the ARIC study, white blood cell count,
PAR, 2%.20 CRP, albuminuria, HbA1c among individuals
• Racial disparities in risks for HF persist, as shown without DM, cardiac troponin, PVCs, and
in the Health ABC Study, a US cohort of 2934 socioeconomic position over the life course
adults aged 70 to 79 years followed up for 7 were all identified as risk factors for HF.43–48
years.31 Among blacks, a greater proportion of — In MESA, plasma N-terminal pro-BNP pro-
HF risk (68% versus 49% among whites) was vided incremental prognostic information
attributable to modifiable risk factors, including beyond the traditional risk factors and the
elevated SBP, elevated fasting glucose level, CHD, MRI-determined LV mass index for incident
LV hypertrophy, and smoking. LV hypertrophy was symptomatic HF.49
3-fold more prevalent in blacks than in whites.
CHD (PAR, 23.9% for white participants, 29.5% LV Function
for black participants) and uncontrolled BP (PAR, • Measures of impaired systolic or diastolic LV func-
21.3% for white participants, 30.1% for black tion are common precursors to clinical HF.
participants) had the highest PARs in both races.31 — In the FHS, the prevalence of asymptom-
Hispanics carry a predominance of HF risk factors atic LV systolic dysfunction was 5% and
and healthcare disparities, which suggests a rela- diastolic dysfunction was 36%. LV systolic
tively elevated HF risk in this population as well.32 and diastolic dysfunction were associated
• Dietary and lifestyle factors also impact HF risk. with increased risk of incident HF. Measures
Among 20 900 male physicians in the Physicians’ of major organ system dysfunction (higher
Health Study, the lifetime risk of HF was higher serum creatinine, lower ratios of forced expi-
in males with hypertension, whereas healthy life- ratory volume in 1 second to forced vital
style factors (normal weight, not smoking, regu- capacity, and lower hemoglobin concentra-
lar PA, moderate alcohol intake, consumption of tions) were also associated with an adjusted
breakfast cereals, and consumption of fruits and increased risk of new-onset HF.50
vegetables) were related to lower risk of HF.33 In — In Olmsted County, MN, diastolic dysfunction
the ARIC study, greater adherence to the AHA’s (HR, 1.81; 95% CI, 1.01–3.48) was observed
Life Simple 7 guidelines (better profiles in smok- to progress with advancing age and was
ing, BMI, PA, diet, cholesterol, BP, and glucose) associated with an increased risk of incident
was associated with a lower lifetime risk of HF, as clinical HF during 6 years of subsequent fol-
well as more optimal echocardiographic param- low-up after adjustment for age, hyperten-
eters of cardiac structure and function.34 sion, DM, and CAD.51
• Multiple nontraditional risk factors for HF have — With respect to variation by race/ethnic-
been identified. ity, presence of asymptomatic LV sys-
— In the NHLBI-sponsored FHS, circulating BNP, tolic dysfunction in MESA was higher in
urinary ACR, elevated serum γ-glutamyl African Americans than in whites, Chinese,
transferase, and higher levels of hematocrit and Hispanics (1.7% overall and 2.7% in
were identified as risk factors for incident blacks). After 9 years of follow-up, asymp-
HF.30,35,36 Circulating concentrations of resis- tomatic LV dysfunction was associated with
tin were also associated with incident HF increased risk of overt HF (HR, 8.69; 95% CI,
independent of prevalent coronary disease, 4.89–15.45), as well as CVD and all-cause
obesity, insulin resistance, and inflamma- mortality.52
tion.37 Circulating adiponectin concentra- — In the Echocardiographic Study of Hispanic/
tions were also related to incident HF, with Latinos, more than half (50.3%) of

middle-aged or older Hispanics had some • Rates of HF rehospitalization or cardiovascular
CLINICAL STATEMENTS
form of cardiac dysfunction (systolic, dia- death were greatest for those previously hospital-
AND GUIDELINES
stolic, or both), although fewer than 1 in 20 ized for HF.62
Hispanic/Latinos had symptomatic or clini- • Although Hispanic patients hospitalized with HF
cally recognized HF.53 were significantly younger than NH whites, the
• LV function is variably abnormal in the setting of prevalence of DM, hypertension, and overweight/
clinically overt HF. obesity was higher among them. In multivari-
— Among individuals with symptomatic HF in ate analysis, a 45% lower in-hospital mortality
Olmstead County, MN, 55% had HF with risk was observed among Hispanics with HF with
preserved EF, and this presentation was asso- preserved EF compared with NH whites but not
ciated with a high mortality rate comparable among those with HF with reduced EF.63
to that of HF with reduced EF.54 • On the basis of data from the community sur-
— Over a 15-year follow-up period, survival veillance component of the ARIC study of the
trends improved among individuals with HF NHLBI64:
with reduced EF but not among those with — The average incidence of hospitalized HF for
HF with preserved EF in Olmstead County.55 those aged ≥55 years was 11.6 per 1000
— As a group, patients with HF with preserved people per year; recurrent hospitalized HF
EF are older, are more likely to be female, was 6.6 per 1000 people per year.
and have greater prevalence of hypertension, — Age-adjusted annual hospitalized HF inci-
obesity, and anemia than those with HF with dence was highest for black males (15.7 per
reduced EF.56 1000), followed by black females (13.3 per
1000), white males (12.3 per 1000), and
Hospital Discharges/Ambulatory Care Visits white females (9.9 per 1000).
(See Table 19-1 and Chart 19-6) — Of incident hospitalized HF events, 53% had
• Hospital discharges for HF (including discharged HF with reduced EF and 47% had preserved
alive, dead, and status unknown) are shown for EF. Black males had the highest proportion
the United States (1997–2014) by sex in Chart of hospitalized HF with reduced EF (70%);
19-6. Discharges for HF decreased from 2004 white females had the highest proportion of
to 2014, with principal diagnosis discharges of hospitalized HF with preserved EF (59%).

1 042 000 and 900 000, respectively (NCHS, NHLBI — Age-adjusted 28-day and 1-year case fatality
unpublished tabulation).57 In 2014, there were after hospitalized HF was 10.4% and 29.5%,
2 371 000 physician office visits with a primary respectively, and did not differ by race or sex.
diagnosis of HF (NAMCS, NHLBI unpublished tab- • Data from Olmsted County, MN, indicate that
ulation). In 2014, there were 459 000 ED visits for among those with HF, hospitalizations were par-
HF (NHAMCS, NHLBI unpublished tabulation). ticularly common among males and did not differ
• Among 1077 patients with HF in Olmsted County, by HF with reduced EF versus preserved EF, with
MN, hospitalizations were common after HF diag- 63% of hospitalizations for noncardiovascular
nosis, with 83% patients hospitalized at least causes. Among those with HF, hospitalization
once and 43% hospitalized at least 4 times. More rates for cardiovascular causes did not change
than one half of all hospitalizations were related over time, whereas those for noncardiovascular
to noncardiovascular causes.58 causes increased from 2000 to 2010.17
• Among Medicare beneficiaries, the overall HF hos- Cost
pitalization rate declined substantially from 1998 See Chapter 25 (Economic Cost of Cardiovascular
to 2008 but at a lower rate for black males,59 and Disease) for further statistics.
the temporal trend findings were uneven across • In 2012, total cost for HF was estimated to be
states. $30.7 billion (2010$), of which 68% was attribut-
• In the GWTG-HF Registry, only one tenth of eli- able to direct medical costs.14
gible HF patients received cardiac rehabilitation • Projections suggest that by 2030, the total cost
referral at discharge after hospitalization for HF.60 of HF will increase almost 127%, to $69.7 billion,
• Among Medicare part D coverage beneficiaries, from 2012, amounting to ≈$244 for every US
HF medication adherence (ACEI/ARB, β-blockers, adult.14
and diuretic agents) after HF hospitalization • Implantable cardioverter-defibrillators could be
discharge decreased over 2 to 4 months after cost-effective in the guideline-recommended
discharge, followed by a plateau over the subse- groups of individuals with HF with reduced EF;
quent year for all 3 medication classes.61 however, the benefit might not be as great in

certain populations, particularly individuals with • Elevated LVAD index admission costs could be
CLINICAL STATEMENTS
a high all-cause mortality (represented by risk related to procurement costs and length of stay.
AND GUIDELINES
factors including age ≥75 years, New York Heart Hospital readmissions also contribute significantly
Association functional class III, LVEF ≤20%, BNP to overall cost of LVAD therapy: with continuous-
≥700 pg/mL, SBP ≤120 mm Hg, AF, DM, chronic flow LVAD, 44% of patients were readmitted
lung disease, and CKD).65,66 within 30 days of discharge, with a median cost
• The costs associated with treating HF comorbidi- of $7546. The most common causes of readmis-
ties and HF exacerbations in youths are signifi- sion were gastrointestinal bleeding, infection, and
cant, totaling nearly $1 billion in inpatient costs, stroke, with device malfunction and arrhythmias
and may be rising.67 the most costly causes of readmission. There was
no difference in survival between patients who
Open Heart Transplant and Assist Device
were and were not readmitted, although median
Placement in the United States
follow-up was only 11 months.73
(See Chart 19-7)
From September 1987 to December 2012, 40 253 peo- LVAD and Open Heart Transplant Disparities
ple were waiting for heart transplants, with a median • The 7th INTERMACS report did not specifically
survival of 2.3 years; 26 943 received transplants, with address the influence of race or ethnicity on mor-
median survival of 9.5 years. Life-years saved were tality after LVAD procedures but did report that a
465 296; life-years saved per patient were 5.0. higher mortality was seen in females (HR, 1.16;
• The 7th INTERMACS report of >15 000 LVAD P=0.005).68
implantations from June 2006 to December 2014 • In the United Network for Organ Sharing
revealed 80% survival at 1 year and 70% at 2 Database of 18 085 patients who had open heart
years.68 transplantation performed at 102 centers, blacks
• The number of patients receiving LVADs increased had a higher adjusted 1-year mortality, particu-
from 98 in 2006 to 2423 in 2014. larly at poor-performing centers (observed-to-
• The proportion of LVADs as destination therapy expected mortality ratio >1.2; OR, 1.37 [95% CI,
increased from 14.7% in 2006 to 2007 to 19.6% 1.12–1.69]; P=0.002).74 Compared with whites
in 2008 to 2010, 41.6% in 2011 to 2013, and and Hispanics, a higher proportion of blacks were
45.7% in 201468 (Chart 19-7). treated at centers with higher than expected mor-
• The NIS reported 2038 LVAD implantations from tality, which persisted after adjustment for insur-
2005 to 2011, with 127 in 2005 and increasing to ance type and education level.
506 procedures in 2011.69
• In-hospital mortality with LVAD implantation
decreased significantly from 47.2% in 2005 to Family History and Genetics
12.7% in 2011. An inflection point was seen with • HCM and familial DCM are the most common
a sharp rise in LVAD implantation and decrease mendelian cardiomyopathies, with autosomal
in the in-hospital mortality rate in 2008. Average dominant or recessive transmission, in addition to
hospital length of stay decreased from the pulsa- X-linked and mitochondrial inheritance.
tile LVAD (pre-2008) to the continuous-flow LVAD • Familial DCM accounts for up to 50% of cases of
(2008–2011) eras.70 The mean cost of LVAD- DCM, with a prevalence of 1 in 2500, but is likely
related hospitalization increased from $194 380 underestimated.75 Familial DCM often displays an
in 2005 to $234 808 in 2011.71 age-dependent penetrance.76 Up to 40% of cases
• In a Markov model analysis, compared with non- have an identifiable genetic cause.75
bridged heart transplant recipients (who did not • Given the heterogeneous nature of the under-
receive an LVAD bridge), receiving a bridge-to- lying genetics, manifestation of the disease is
transplantation LVAD increased survival, with highly variable, even in cases for which the causal
greater associated cost (range, $84 964 per life- mutation has been identified.77 Variants in the
year to $119 574 per life-year for high-risk and β-myosin heavy chain gene (MYH7) were some
low-risk patients, respectively). Open heart trans- of the earliest to be associated with familial
plantation increased life expectancy and was cost- HCM,78,79 with >30 other genes implicated since,
effective (8.5 years with <$100 000 per QALY each accounting for <5% of cases, as reviewed
relative to medical therapy), but LVAD either for elsewhere.76,80,81 The considerable variability in the
bridge to transplantation (12.3 years at $226 000 penetrance and pathogenicity of specific muta-
per QALY) or as destination therapy (4.4 years at tions makes clinical interpretation of sequence
$202 000 per QALY) was not cost-effective.72 data particularly challenging.

• Missense and truncating variants in the Titin gene CVD have HF, whereas only 10% have CAD.93
CLINICAL STATEMENTS
have been linked to autosomal dominant cardio- Common causes include nonischemic cardio-
AND GUIDELINES
myopathy,82 as well as to DCM, with incomplete myopathies, rheumatic HD, congenital HD,
penetrance in the general population.83 Analysis hypertensive HD, and endomyocardial fibrosis;
of sequence data in 7855 cardiomyopathy case IHD remains relatively uncommon. HF strikes
subjects and >60 000 control subjects revealed individuals in sub-Saharan Africa at a much
the variance in penetrance of putative disease younger age than in the United States and
variants, which further highlights the challenges Europe.94
in clinical interpretation of variation in mendelian • The prevalence estimates for HF across Asia range
disease genes.74 from 1.26% to 6.7%. Rheumatic HD is a major
• Several GWAS have been conducted to identify contributor to HF in certain parts of South Asia,
common variation associated with cardiomyopathy such as India, but recently, trends toward an isch-
and HF in the general population, albeit with modest emic cause for HF have been observed in Asia,
results,81,84 highlighting a small number of putative such as in China and Japan.95
loci, including HSPB7.85–87 Given the heterogeneous • Ischemic HF prevalence in 2010 was highest
multifactorial nature of common HF, identification (>5 per 1000) in high-income North America,
of causal genetic loci remains a challenge. Oceania, and Eastern Europe. In particular, HF
• Genetic variation within subjects with HF may prevalence in 2010 was highest in Oceania
determine outcomes, with a locus on chro- (4.53 [95% CI, 3.19–6.29] per 1000 in females;
mosome 5q22 associated with mortality in HF 5.22 [95% CI, 3.84–7.08] per 1000 in males),
patients.88 A large meta-analysis of >73 000 sub- followed by high-income North America and
jects identified 52 loci associated with myocardial North Africa/Middle East. HF prevalence was
mass.89 The clinical utility of genetic testing for lowest in west sub-Saharan Africa (0.74; 95%
variants associated with common HF and related CI, 0.58–0.98 per 1000 in males and 0.57; 96%
phenotypes remains unclear. CI, 0.44–0.76 per 1000 in females).96 HF made
• HCM is a monogenic disorder with primarily auto- the largest contribution to age-standardized
somal dominant inheritance and is caused by one years lived with disability among males in high-
of hundreds of mutations in up to 18 genes that income North America, Oceania, Eastern and
primarily encode components of the sarcomere, Western Europe, southern Latin America, and
with mutations in MYH7 and cardiac myosin- Central Asia.96

binding protein C (MYBPC3) being the most com- • HF risk factors vary substantially across world
mon, with each having 40 HCM cases attributed regions, with hypertension being highly asso-
to it.91 A mutation is identifiable in 50% to 75% ciated with HF in all regions but most com-
of familial HCM cases. monly in Latin America, the Caribbean, Eastern
• Clinical genetic testing is recommended for Europe, and sub-Saharan Africa, and with
patients with DCM with significant conduction a minimal association of IHD with HF in sub-
system disease or a family history of SCD, as well Saharan Africa.97 IHD prevalence among HF
as in patients with a strong clinical index of suspi- patients is highest in Europe and North America
cion for HCM. It can be considered in other forms but rare in sub-Saharan Africa, whereas hyper-
of dilated and restrictive cardiomyopathy and in tension prevalence among HF patients was
LV noncompaction.92 highest in Eastern Europe and sub-Saharan
• Genetic testing is also recommended in family Africa; valvular and rheumatic HD prevalence
members of patients with DCM, HCM, restrictive among HF patients was highest in East Asia and
cardiomyopathy, and LV noncompaction.92 Asia-Pacific countries.97 Follow-up from a mul-
tiethnic cohort composed of individuals from
low- to middle-income countries in Africa, Asia,
Global Burden of HF the Middle East, and South America will provide
• HF is common throughout sub-Saharan Africa. additional data regarding the global burden
Forty-four percent of patients with newly diagnosed of HF.98

Table 19-1. Heart Failure

CLINICAL STATEMENTS
Prevalence, 2011–2014, Incidence, 2014, Mortality, 2015, Hospital Discharge,

AND GUIDELINES
Population Group Age ≥20 y Age ≥55 y All Ages* 2014, All Ages Cost, 2012†
Both sexes 6 500 000 (2.5%) 1 000 000 75 251 900 000 $30.7 billion
Males 2 900 000 (2.4%) 495 000 33 667 (44.7%)‡ 462 000 …
Females 3 600 000 (2.6%) 505 000 41 584 (55.3%)‡ 438 000 …
NH white males 2.4% 430 000§ 27 783 … …
NH white females 2.5% 425 000§ 34 866 … …
NH black males 2.6% 65 000§ 3603 … …
NH black females 3.9% 80 000§ 4169 … …
Hispanic males 2.0% … 1523 … …
Hispanic females 2.4% … 1716 … …
NH Asian males 1.3% … 528‖ … …
NH Asian females 0.3% … 596‖ … …
NH American Indian or
… … 286 … …
Alaska Native
Heart failure includes people who answered “yes” to the question of ever having congestive heart failure. Ellipses (…) indicate data not available;
and NH, non-Hispanic.
*Mortality data for Hispanic, NH American Indian or Alaska Native, and NH Asian and Pacific Islander people should be interpreted with caution
because of inconsistencies in reporting Hispanic origin or race on the death certificate compared with censuses, surveys, and birth certificates. Studies
have shown underreporting on death certificates of American Indian or Alaska Native, Asian and Pacific Islander, and Hispanic decedents, as well as
undercounts of these groups in censuses.
†Cost data are from Heidenreich et al.14
‡These percentages represent the portion of total mortality attributable to heart failure that is for males vs females.
§Estimates for whites include other nonblack races.
‖Includes Chinese, Filipino, Hawaiian, Japanese, and Other Asian or Pacific Islander.
Sources: Prevalence: National Health and Nutrition Examination Survey 2011 to 2014 (National Center for Health Statistics) and National Heart,
Lung, and Blood Institute. Percentages are age adjusted for Americans ≥20 years of age. Age-specific percentages are extrapolated to the 2014 US
population estimates. These data are based on self-reports. Incidence: Atherosclerosis Risk in Communities Study Community Surveillance, 2005 to
2014 from the National Heart, Lung, and Blood Institute. Mortality: Centers for Disease Control and Prevention/National Center for Health Statistics,
2015 Mortality Multiple Cause-of-Death–United States. Mortality for NH Asians includes Pacific Islanders. Hospital discharges: Healthcare Cost and
Utilization Project, Hospital Discharges, 2014 (data include those inpatients discharged alive, dead, or status unknown).

CLINICAL STATEMENTS
AND GUIDELINES
Chart 19-1. Incidence of peripartum cardiomyopathy.
Adapted from Blauwet et al by permission from BMJ Publishing Group Ltd.13 Copyright © 2011, BMJ Publishing Group Ltd and
the British Cardiovascular Society.
Chart 19-2. Age-standardized global mortality rates of cardiomyopathy and myocarditis per 100 000, both sexes, 2015.
Chart 19-3. Age-standardized global prevalence rates of cardiomyopathy and myocarditis per 100 000, both sexes, 2015.

CLINICAL STATEMENTS
16
AND GUIDELINES
14.1
14 13.4
12
6.2
6 5.7
1.9
2 1.4
0.3 0.5
0
20-39 40-59 60-79 ≥80
Age (Years)
Males Females
Chart 19-4. Prevalence of heart failure for adults ≥20 years by sex and age (NHANES: 2011–2014).
Chart 19-5. First acute decompensated heart failure annual event rates per 1000 from ARIC Community
Surveillance (2005–2014).
ARIC indicates Atherosclerosis Risk in Communities Study.
Source: ARIC and National Heart, Lung, and Blood Institute.

CLINICAL STATEMENTS
AND GUIDELINES
Chart 19-6. Hospital discharges for heart failure by sex (United States: 1997–2014).
Hospital discharges include people discharged alive, dead, and status unknown.
Source: National Hospital Discharge Survey/National Center for Health Statistics and National Heart, Lung, and Blood Institute.
3000
2506
2500 2423
2278
2000 1920
Number of Patients
1652
1500
1010
1000
740
500 338
98
0
2006 2007 2008 2009 2010 2011 2012 2013 2014
Year
Chart 19-7. Number of patients receiving left ventricular assist devices in the United States, 2006 to 2014.
Adapted from Kirklin et al68 with permission from the International Society for Heart and Lung Transplantation. Copyright ©
2015, International Society for Heart and Lung Transplantation.

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92. Ackerman MJ, Priori SG, Willems S, Berul C, Brugada R, Calkins H, Camm 95. Sakata Y, Shimokawa H. Epidemiology of heart failure in Asia. Circ J.
AJ, Ellinor PT, Gollob M, Hamilton R, Hershberger RE, Judge DP, Le Marec 2013;77:2209–2217.
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20. VALVULAR DISEASES Abbreviations Used in Chapter 20 Continued

CLINICAL STATEMENTS
REMEDY Global Rheumatic Heart Disease Registry

AND GUIDELINES
RR relative risk
through 20-5 RV right ventricular
SAVR surgical aortic valve replacement
Click here to return to the Table of Contents SD standard deviation
SNP single-nucleotide polymorphism
Mortality and any-mention mortality in this section STS Society of Thoracic Surgeons
TA transapical
are for 2015. “Mortality” is the number of deaths in
TAVR transcatheter aortic valve replacement
2015 for the given underlying cause based on ICD-10. TF transfemoral
Prevalence data are for 2006. Hospital discharge data TIA transient ischemic attack
are from HCUP, NIS, 2014; data included for inpatients TOF tetralogy of Fallot
discharged alive, dead, or status unknown. Hospital dis-
charge data for 2014 are based on ICD-9 codes. Valvular Heart Disease
(See Table 20-1)
ICD-9 424; ICD-10 I34 to I38.
AF atrial fibrillation 2015: Mortality—25 700. Any-mention mortality—
AGES Age, Gene/Environment Susceptibility 52 305. 2014: Hospital discharges—105 000.
APAC Asia-Pacific Prevalence
ARIC Atherosclerosis Risk in Communities study • A large population-based epidemiological study
BMI body mass index with systematic use of echocardiography on
CAD coronary artery disease 16 501 participants from Olmsted County, MN,
CALA Caribbean and Latin America
showed an overall age-adjusted prevalence of
clinically diagnosed (moderate or greater) valvular
CHS Cardiovascular Health Study HD of 1.8%.1
CI confidence interval • Prevalence of any valve disease increased with
DCM dilated cardiomyopathy age (Ptrend <0.0001)2:
DM Diabetes mellitus — 18 to 44 years: 0.3% (95% CI, 0.2%–0.3%)
— 45 to 54 years: 0.7% (95% CI, 0.6%–0.9%)
EVEREST Efficacy of Vasopressin Antagonism in Heart Failure
Outcome Study With Tolvaptan — 55 to 64 years: 1.6% (95% CI, 1.4%–1.9%)
EVEREST II HRS Endovascular Valve Edge-to-Edge Repair High-Risk Study — 65 to 74 years: 4.4% (95% CI, 3.9%–4.9%)
FDA Food and Drug Administration — ≥75 years: 11.7% (95% CI, 11.0%–12.5%)
FHS Framingham Heart Study • Pooled echocardiographic data from 11 911 par-
ticipants from CARDIA (4351), ARIC (2435), and
GWAS genome-wide association study
CHS (5125) demonstrated a similar increase in
HD heart disease prevalence with advancing age (Ptrend <0.0001;
HF heart failure Table 20-1)2:
HR hazard ratio — 18 to 44 years: 0.7% (95% CI, 0.5%–1.0%)
ICD International Classification of Diseases — 45 to 54 years: 0.4% (95% CI, 0.1%–1.3%)
— 55 to 64 years: 1.9% (95% CI, 1.2%–2.8%)
ICE-PCS International Collaboration on Endocarditis–Prospective
— 65 to 74 years: 8.5% (95% CI, 7.6%–9.4%)
Cohort Study — ≥75 years: 13.2% (95% CI, 11.7%–15.0%)
ICE-PLUS International Collaboration on Endocarditis–PLUS • Adjusted to the entire 2000 US adult popula-
IE infective endocarditis tion, these data suggest that the prevalence of
any valve disease is 2.5% (95% CI, 2.2%–2.7%),
with no difference between males (2.4%; 95%
LV left ventricular CI, 2.1%–2.8%) and females (2.5%; 95% CI,
LVEF left ventricular ejection fraction 2.1%–2.9%).2
MR mitral regurgitation
NH non-Hispanic Aortic Valve Disorders
NHLBI National Heart, Lung, and Blood Institute (See Table 20-1 and Chart 20-1)
OR odds ratio
ICD-9 424.1; ICD-10 I35.
QALY quality-adjusted life-year 2015: Mortality—17 320. Any-mention mortality—
(Continued ) 34 824. 2014: Hospital discharges—77 000.

Prevalence and Incidence CI, 1.015–1.016; P<0.001) for nonrheumatic aor-
CLINICAL STATEMENTS
• Based on the CARDIA, ARIC, and CHS studies, tic valve disease.8
AND GUIDELINES
the authors estimated an age- and sex-adjusted • A recent retrospective analysis of 3 different
(2000 US adult population) prevalence of cohorts of consecutive patients with echocardio-
0.4% (95% CI, 0.3%–0.5%) for aortic steno- graphic diagnosis of bicuspid aortic valve included
sis and 0.5% (95% CI, 0.3%–0.6%) for aortic the following: (1) a community cohort of 416
regurgitation.2 patients with bicuspid aortic valve diagnosed for
• The prevalence of moderate or severe calcific the first time (aged 35±21 years, follow-up 16±7
aortic stenosis in patients ≥75 years old is 2.8% years); (2) a tertiary care cohort of 2824 adults
(95% CI, 2.1%–3.7%) based on pooled echo- with bicuspid aortic valve (aged 51±16 years,
cardiographic data from US cohorts including follow-up 9±6 years); and (3) a cohort of 2242
CARDIA, ARIC, and CHS (Table 20-1).2 adults with bicuspid aortic valve referred for aortic
• Prevalence of aortic stenosis by echocardiogra- valve replacement (aged 62±14 years, follow-up
phy is higher (4.3%) among individuals aged ≥ 6±5 years).9 In the community, morbidity related
70 years in the Icelandic AGES-Reykjavik cohort. to bicuspid aortic valve was higher in males than
In the Norwegian Tromsø study, the incidence in females, with a total combined risk of aortic
of new aortic stenosis was 5 per 1000 per year, regurgitation, surgery, and IE of 52±4% ver-
with the initial mean age of participants being 60 sus 35±6% in females (P=0.01).9 Nevertheless,
years.3 females had a significantly higher RR of death
• In younger age groups, the most prevalent cause in tertiary and surgical referral cohorts, with an
of aortic stenosis is bicuspid aortic valve, the most age-adjusted relative death risk of 1.63 (95%
common form of congenital HD. In an Italian CI, 1.40–1.89) for females versus 1.34 (95% CI,
study of 817 primary school students, the preva- 1.22–1.47) for males (P=0.026).9 The risk of death
lence of bicuspid aortic valves was 0.5% (95% CI, was independently associated with aortic regurgi-
0.13%-1.2%.4 tation (P≤0.04).
• Nationally representative data from Sweden dem-
Complications
onstrate a lower age-adjusted incidence of aortic
• In a cohort of 416 community-based participants
stenosis, from 15.0 to 11.4 per 100 000 males and
from Olmsted County, MN, with bicuspid aor-
from 9.8 to 7.1 per 100 000 females, between
tic valves followed up for a mean (SD) of 16 (7)

the years 1989 to 1991 and 2007 to 2009.5
years, the incidence of aortic dissection in individ-
• The prevalence of moderate or severe aortic
uals ≥50 years of age at baseline was 17.4 (95%
regurgitation in patients ≥75 years is 2.0% (95%
CI, 2.9–53.6) cases per 10 000 patient-years. For
CI, 1.4%–2.7%) based on pooled CARDIA, ARIC,
patients aged ≥50 years with a bicuspid valve
and CHS data (Table 20-1).2
and a baseline aortic aneurysm, the incidence of
Lifetime Risk and Cumulative Risk aortic dissection was 44.9 (95% CI, 7.5–138.5)
• The number of elderly patients with calcific aortic cases per 10 000 patient-years. In the remaining
stenosis is projected to more than double by 2050 participants without baseline aortic aneurysm,
in both the United States and Europe based on a the incidence of aneurysm was 84.9 (95% CI,
simulation model in 7 decision analysis studies.6 63.3–110.9) cases per 10 000 patient-years, for
In the Icelandic AGES-Reykjavik study alone, pro- an age-adjusted RR of 86.2 (95% CI, 65.1–114)
jections suggest a doubling in prevalence among compared with the general population.10
those with severe aortic stenosis aged ≥70 years
Risk Factors
by 2040 and a tripling by 2060.7
• Several prospective and retrospective series have
Mortality attempted to identify risk factors for progression
• Based on ICD-10 (with data coded from 1999 to of aortic stenosis.11–15 Among the highlighted
2009), there were 146 304 deaths in the aortic factors were baseline valve area, degree of valve
valve disease category in the United States. Of calcification, CAD, older age, male sex, bicuspid
these, 82.7% were attributed to aortic stenosis, versus tricuspid involvement, mitral annular calci-
4.0% to aortic insufficiency, and 0.6% to aortic fication, hypercholesterolemia, higher BMI, renal
stenosis with insufficiency, whereas 11.9% were insufficiency, hypercalcemia, smoking, metabolic
unspecified or coded as attributed to other aortic syndrome, and DM.16,17
valve disease and 0.7% to congenital aortic valve • In a retrospective analysis of predictors of cardiac
disease (assumed to be predominantly bicuspid outcomes in 227 ambulatory adults with bicuspid
aortic valve). The change in annual age- and sex- aortic valve, independent predictors of the com-
adjusted mortality rate over time was 1.016 (95% posite endpoint (need for surgery, death, aortic

dissection, endocarditis, HF, arrhythmias, or IHD) CI, 5.27–9.30), and pacemaker implantation (RR,
CLINICAL STATEMENTS
were baseline moderate to severe aortic valve dys- 2.02; 95% CI, 1.51–2.68). TAVR demonstrated
AND GUIDELINES
function (HR, 3.19; 95% CI, 1.35–7.54; P<0.01) significantly lower stroke risk than surgical aortic
and aortic valve leaflet calcification (HR, 4.72; valve replacement in high-risk patients (RR, 1.49;
95% CI, 1.91–11.64; P<0.005).18 95% CI, 1.06–2.10); no differences in pacemaker
implantation were observed in intermediate-risk
Genetics/Family History
patients (RR, 1.68; 95% CI, 0.94–3.00).26
• Multiple SNPs that encode for LDL-C have been
combined to form a genetic risk score that has Cost
been associated with prevalent aortic valve calcifi- • Initial length of stay was an average of 4.4 days
cation (OR, 1.38; 95% CI, 1.09–1.74 per genetic shorter for patients treated with TAVR than for
risk score increment) and incident aortic valve ste- those who underwent surgical valve replace-
nosis (HR, 2.78; 95% CI, 1.22–6.37 per genetic ment. TAVR also reduced the need for rehabilita-
risk score increment) by use of a mendelian ran- tion services at discharge and was associated with
domization design.19 improved 1-month quality of life. TAVR had higher
• The heritability of bicuspid aortic valve has been index admission and projected lifetime costs than
estimated at 89% (0.89±0.06; P<0.001), which surgical aortic valve replacement (differences of
suggests that most cases are familial.20 Bicuspid $11 260 and $17 849 per patient, respectively).
aortic valve has been linked to mutations of However, TAVR was estimated to provide a life-
NOTCH1, as well as GATA5.21,22 time gain of 0.32 QALYs (0.41) with 3% discount-
ing. Lifetime incremental cost-effectiveness ratios
were $55 090 per QALY gained and $43 114 per
• Before US FDA approval of TAVR in 2011, ≈50% of
life-year gained. Based on sensitivity analyses, a
patients with severe aortic stenosis were referred
reduction in the initial cost of TAVR by ≈$1650
for cardiothoracic surgery, and ≈40% underwent
was expected to lead to an incremental cost-effec-
aortic valve replacement according to data from
tiveness ratio of <$50 000 per QALY gained.27
10 US centers of various sizes and geographic dis-
tribution. Reasons for not undergoing aortic valve
replacement included high perioperative risk, age, Mitral Valve Disorders
ICD-9 424.0; ICD-10 I34.
lack of symptoms, and patient or family refusal.23

• From 2011 through 2014, the STS/ACC
Transcatheter Valve Therapy Registry recorded
2014: Hospital discharges—26 000.
26 414 TAVR procedures performed at 348 cen-
ters in 48 US states.24 Sixty-eight percent of Prevalence
patients were ≥80 years of age, and preopera- (See Table 20-1)
tive risk was high; in 2014, median STS risk was • In pooled data from CARDIA, ARIC, and CHS,
6.7%, and 95% of patients were deemed to be mitral valve disease was the most common val-
at extreme or high risk. vular lesion. At least moderate MR occurred at a
• In Germany, the number of TAVR procedures frequency of 1.7% as adjusted to the US adult
increased from 144 in 2007 to 9147 in 2013. population in 2000, increasing from 0.5% in par-
In the same study, the number of surgical aortic ticipants aged 18 to 44 years to 9.3% in partici-
valve replacement procedures decreased from pants aged ≥75 years.2 In the same pooled sample,
8622 to 7048 (Chart 20-1).25 mitral stenosis (commonly related to rheumatic
• A recent meta-analysis identified 50 studies enroll- involvement) was rare, with a frequency of 0.1%
ing 44 247 patients with a mean follow-up of (Table 20-1).
21.4 months that compared TAVR to surgical aor- • A systematic review by de Marchena and col-
tic valve replacement. No difference was found in leagues28 found that in the US population, the
intermediate-term (mean follow-up 21.4 months) prevalence of MR according to the Carpentier
all-cause mortality (RR, 1.06; 95% CI, 0.91–1.22). functional classification system was as follows:
There was a significant difference favoring TAVR in — Type I (congenital MR [<10 per million] and
the incidence of stroke (RR, 0.82; 95% CI, 0.71– endocarditis [3–7 per million]): <20 per
0.94), AF (RR, 0.43; 95% CI, 0.33–0.54), acute 1 million
kidney injury (RR, 0.70; 95% CI, 0.53–0.92), and — Type II (myxomatous MR): 15 170.5 per
major bleeding (RR, 0.57; 95% CI, 0.40–0.81). 1 million
TAVR resulted in a significantly higher incidence — Type IIIa (rheumatic HD, systemic lupus ery-
of vascular complications (RR, 2.90; 95% CI, thematosus, antiphospholipid syndrome,
1.87–4.49), aortic regurgitation (RR, 7.00; 95% and rare diseases): 10 520 per 1 million

— Type IIIb (ischemic MR, LV dysfunction, DCM): left atrial enlargement, MR, presence of a flail
CLINICAL STATEMENTS
16 250 per 1 million leaflet, and prevalent AF at the time of the base-
AND GUIDELINES
— Unclassified: 9530 per 1 million line echocardiogram.31
• In a retrospective investigation of 134 874 individ-
Subclinical Disease
uals in China, 42.44%, 1.63%, and 1.44% had
• Milder, nondiagnostic forms of mitral valve pro-
mild, moderate, and severe MR, respectively.29
lapse, first described in the familial context, are
The prevalence of MR increased with advancing
also present in the community and are associated
age. In individuals with severely reduced systolic
with higher likelihood of mitral valve prolapse in
function (LVEF <30%), the prevalence of severe
offspring (OR, 2.52; 95% CI, 1.25–5.10; P=0.01).
MR was 22.14%, whereas in individuals with
Up to 80% of nondiagnostic morphologies can
LVEF that was moderately depressed (LVEF 30%–
progress to diagnostic mitral valve prolapse.33–35
44%), the prevalence was 13.0%. Similarly, the
prevalence of severe MR was higher with higher Genetics/Family History
mean LV end-systolic diameter: 15.74% at 50 to • Among 3679 Generation 3 participants in the FHS
59 mm and 27.28% at ≥60 mm. The authors (53% female; mean age 40±9 years) with available
reported the cause of severe MR in 1948 individu- parental data, 49 (1%) had mitral valve prolapse.
als. About half had secondary MR (N=976), and Parental mitral valve prolapse was associated with
half had primary causes, including 55 with rheu- a higher prevalence of mitral valve prolapse in off-
matic HD, 96 with IE, 141 with papillary muscle spring (10/186 [5.4%]) compared with no parental
dysfunction, and 608 with mitral valve prolapse. mitral valve prolapse (39/3493 [1.1%]; adjusted
OR, 4.51; 95% CI, 2.13–9.54; P<0.0001).36 A
Lifetime Risk and Cumulative Risk
number of genetic variants have been identified
• Because of the associations between MR and
for the rare X-linked valvular dystrophy and the
advancing age and between functional MR and
most common form of autosomal dominant mitral
HF, an increase in prevalence of MR is expected
valve prolapse through pedigree investigations and
over the coming decades, although no popula-
GWAS. Genes implicated in mitral valve prolapse
tion-based lifetime risk estimations of MR are
include FLNA (encoding for the filamin A protein),
available in the literature.30
DCHS1, TNS1, and LMCD1.37–39
Complications
• In the Olmsted County, MN, population, charac-
(See Chart 20-2)
terized by a mixed spectrum of community-dwell-
• The treatment of mitral valve prolapse remains
ing and referred patients, females were diagnosed
largely surgical and based on valve repair.
with mitral valve prolapse more often than males
Nevertheless, percutaneous mitral valve repair
and at a younger age31; however, females had
techniques are becoming a common treatment
fewer complications (flail leaflet occurred in 2%
option for high-risk patients not deemed candi-
versus 8% in men and severe regurgitation in
dates for surgical repair. Data from the STS/ACC
10% versus 23%; all P<0.001). At 15 years of
Transcatheter Valve Therapy Registry on patients
follow-up, females with no or mild MR had better
commercially treated with the MitraClip percuta-
survival than males (87% versus 77%; adjusted
neous mitral valve repair device showed the fol-
RR, 0.82; 95% CI, 0.76–0.89). In contrast, in indi-
lowing: of 564 patients (56% male, median age
viduals with severe MR, females had worse sur-
83 years), 473 (86%) were severely symptom-
vival than males (60% versus 68%; adjusted RR,
atic. The median STS predicted risk of mortality
1.13; 95% CI, 1.01–1.26). Survival 10 years after
scores for mitral valve repair and replacement
surgery was similar in females and males (77%
were 7.9% (IQR, 4.7%−12.2%) and 10% (IQR,
versus 79%; P=0.14).32
6.3%−14.5%), respectively.40 Most of the trans-
Risk Factors catheter mitral valve repair patients (90.8%) had
• In a community-based study of 833 individuals degenerative disease, and the procedure was suc-
diagnosed with asymptomatic mitral valve pro- cessful in reducing the MR to moderate levels in
lapse and followed up longitudinally in Olmsted 93% of cases. In-hospital mortality was 2.3%, and
County, MN, cardiac mortality was best predicted 30-day mortality was 5.8%. Events occurring in
by the presence of MR and LV systolic dysfunction the first 30 days included stroke (1.8%), bleeding
at the time of diagnosis. Risk factors for cardio- (2.6%), and device-related complications (1.4%).
vascular morbidity (defined as the occurrence of Most patients (84%) were discharged to home
HF, thromboembolic events, endocarditis, AF, or after a 3-day median hospital length (IQR, 1−6
need for cardiac surgery) included age ≥50 years, days). The authors reported a procedural success

rate of 91%. However, based on the EVEREST II prosthetic valve.50 Surgical pulmonary valve replace-
CLINICAL STATEMENTS
trial, mitral valve dysfunction is more common ment is preferred for native pulmonic valve regurgi-
AND GUIDELINES
with percutaneous mitral valve repair than with tation (caused by endocarditis, carcinoid, etc) and
surgical repair (20% versus 2%).41 is associated with <1% periprocedural mortality
• Worldwide, the number of MitraClip procedures and excellent long-term outcome, with >60%
has increased progressively since 2008, especially freedom from reoperation at 10 years.51
in Western Europe. In the United States, the com-
mercial use of the MitraClip started in 2014, with Tricuspid Valve Disorders
a steadily growing number of procedures per-
ICD-9 424.2; ICD-10 I36.
formed (Chart 20-2).42
Cost Tricuspid valve stenosis is an uncommon valvular
• Lifetime costs, life-years, QALYs, and incremen- abnormality usually seen in patients with rheumatic
tal cost per life-year and QALY gained were esti- HD.52
mated for patients receiving MitraClip therapy • Abnormal degrees of tricuspid regurgitation in
compared with standard of care.43 The EVEREST adults are largely functional (ie, related to tri-
II HRS provided data on treatment-specific overall cuspid annular dilation or leaflet tethering in the
survival, risk of clinical events, quality of life, and setting of RV pressure or volume overload) and
resource utilization. The published literature was much less often caused by primary disorders of
reviewed to obtain health utility and unit costs the valve apparatus (endocarditis, Ebstein anom-
(Canadian 2013 dollars). The incremental cost aly, rheumatic, carcinoid, prolapse, or direct valve
per QALY gained was $23 433. Based on sensitiv- injury from a permanent pacemaker or implant-
ity analysis, MitraClip therapy had a 92% chance able cardioverter-defibrillator lead placement).52
of being cost-effective compared with standard • The frequency of tricuspid regurgitation and val-
of care at a $50 000 per QALY willingness-to-pay vular pathology was evaluated in a study of 5223
threshold. adults (predominantly males, with a mean age of
67 years) who underwent echocardiography at
Pulmonary Valve Disorders 3 Veterans Affairs medical centers.53 Moderate
ICD-9 424.3; ICD-10 I37. to severe tricuspid regurgitation was present in
819 (16%), but only 8% had primary tricuspid

valve pathology. In the same study, moderate
• Pulmonic valve stenosis is a relatively common
or greater tricuspid regurgitation was associated
congenital defect, occurring in ≈10% of children
with increased mortality regardless of pulmonary
with congenital HD.44 It is slightly more prevalent in
artery systolic pressure (HR, 1.31; 95% CI, 1.16–
females, and familial occurrence has been reported
1.49 for pulmonary artery systolic pressure >40
in 2% of cases.45 Pulmonic stenosis is usually asso-
mm Hg; HR, 1.32, 95% CI, 1.05–1.62 for pulmo-
ciated with a benign clinical course. In severe cases,
nary artery systolic pressure ≤40 mm Hg) and LVEF
percutaneous balloon valvotomy is the preferred
(HR, 1.49; 95% CI, 1.34–1.66 for EF <50%; HR,
treatment (Chapter 14). In a 2-center consecu-
1.54; 95% CI, 1.37–1.71 for EF ≥50%).53
tive series of 85 children and adolescents followed
• Tricuspid valve surgery is recommended for
up for up to 10 years, reintervention occurred in
patients with severe tricuspid regurgitation
11% who received repeat balloon dilation and 5%
undergoing surgery for left-sided valve disease. A
who required surgical intervention for subvalvular
weaker recommendation for tricuspid valve sur-
or supravalvular stenosis.46 Although residual pul-
gery exists for patients with severe primary tricus-
monary regurgitation was noted in the majority of
pid regurgitation with symptoms unresponsive to
patients, it was predominantly mild.
medical therapy.54
• Trivial or mild pulmonic valve regurgitation is com-
monly found in normal hearts on color Doppler
echocardiography.47 The most common cause of Rheumatic Fever/Rheumatic Heart Disease
severe pulmonic regurgitation is iatrogenic, caused (See Table 20-2 and Charts 20-3 to 20-5)
by surgical valvotomy/valvectomy or balloon pulmo- ICD-9 390 to 398; ICD-10 I00 to I09.
nary valvuloplasty performed for RV outflow tract
obstruction as part of TOF repair.48,49 Percutaneous
2014: Hospital discharges—26 000.
pulmonic valve implantation of either a Melody or
a SAPIEN valve is an option in patients with pros- Prevalence
thetic pulmonic valve regurgitation, including those • Rheumatic HD is uncommon in high-income
with a pulmonary artery conduit with regurgitant countries such as the United States but remains

endemic in some low- and middle-income children with definite rheumatic HD may progress
CLINICAL STATEMENTS
countries.55 to severe disease that requires valve surgery over
AND GUIDELINES
a median follow-up of 7.5 years65; however, many
Mortality
with borderline disease will remain stable, and
• In the United States in 2015, mortality attribut-
30% to 50% will regress to normal over 2 to 5
able to rheumatic fever/rheumatic HD was 3372
years of follow-up.66,67
for all ages (2253 females and 119 males; Table
20-2). Awareness, Treatment, and Control
• In the United States, the 2015 overall age-adjusted • The REMEDY study highlighted consistently poor
death rate for rheumatic fever or rheumatic HD access to recommended therapies among peo-
was 0.9 per 100 000. Death rates varied across ple living with rheumatic HD: only 55% were
racial/ethnic groups but were generally low: NH taking penicillin prophylaxis, and only 3.6% of
white, 0.9 per 100 000; NH black or African females of childbearing age were using contra-
American, 0.7 per 100 000; NH Asian or Pacific ception. Although 70% of those with indications
Islander, 0.6 per 100 000; NH American Indian or (mechanical valve, AF, or severe mitral steno-
Alaska Native, 1.1 per 100 000; and Hispanic or sis) were appropriately prescribed anticoagulant
Latino-origin individuals, 0.6 per 100 000.9,56 drugs, only a quarter of these had therapeutic
• In 1950, ≈15 000 Americans (adjusted for changes international normalized ratios.57
in ICD codes) died of rheumatic fever/rheumatic • Underrecognition of acute rheumatic fever can
HD compared with ≈3400 annually in the present contribute to delayed presentation of disease and
era (NCHS/NHLBI) (Table 20-2). poor outcomes. Of the REMEDY participants from
low-income countries, only 22% reported a his-
Complications tory of prior acute rheumatic fever.57
• People living with rheumatic HD experience high
rates of morbid complications. In REMEDY, 33% Global Burden of Rheumatic HD
had HF, 22% had AF, 7% had prior stroke, and (See Charts 20-3 and 20-5)
4% had prior endocarditis at baseline.57 After 2 • The REMEDY study is a prospective registry of
years of follow-up, the incidence of new events 3343 patients with rheumatic HD from 25 hospi-
was 38 per 1000 patient-years for HF, 8.5 per tals in 12 African countries, India, and Yemen. The
1000 patient-years for stroke or TIA, and 3.7 per age and sex distribution of the subjects is shown
1000 patient-years for endocarditis.55 Rates may in Chart 20-3.55 Rheumatic HD was twice as com-
be even higher in lower-income countries of sub- mon among females, a finding consistent with
Saharan Africa such as Uganda, where patients prior studies across a variety of populations.57
tend to present with advanced disease.58 • Mortality attributable to rheumatic HD remains
• Prognosis after development of complications is exceptionally high in endemic settings. In a study
also worse for people living with rheumatic HD. from Fiji of 2619 people followed up during 2008
In Thailand, patients with rheumatic mitral valve to 2012, the age-standardized death rate was 9.9
disease who had ischemic stroke had a higher (95% CI, 9.8–10.0) per 100 000, or more than
risk of cardiac arrest (OR, 2.1), shock (OR, 2.1), twice the GBD estimates.68 Prognosis is exception-
arrhythmias (OR, 1.7), respiratory failure (OR, ally poor in sub-Saharan Africa, as highlighted by
2.1), pneumonia (OR, 2.0), and sepsis (OR, 1.4) a follow-up study of REMEDY, which had a mor-
after controlling for age, sex, and other comorbid tality rate of 116 per 1000 patient-years in the
chronic diseases.59 first year and 65 per 1000 patient-years in the
second year.55
Subclinical Disease • In GBD 2015, 319 400 (95% CI, 297 300–
• The prevalence of subclinical or latent rheumatic 337 300) people died of rheumatic HD globally.
HD among children has been estimated by echo- The age-standardized death rate was 4.8 (95%
cardiography using published guidelines60 and CI, 4.5–5.1; similar for males and females), which
can be classified as definite or borderline. The represents a 48% decline since 1990.69
prevalence of combined definite and borderline • The 2015 GBD study estimates that 33 million
disease ranges between 10 and 45 per 1000 in people (19 million females and 14 million males)
recent studies61–63 from endemic countries (eg, are living with rheumatic HD globally.70
Nepal, Brazil, and Uganda) compared with <8 per • The GBD 2015 Study used statistical models and
1000 in low-risk populations.64 data on incidence, prevalence, case fatality, excess
• The natural history of latent rheumatic HD mortality, and cause-specific mortality to estimate
detected by echocardiography is not clear. disease burden for 315 diseases and injuries in
Emerging data suggest that up to 20% of 195 countries and territories.70

— Age-standardized mortality attributable to pediatric endocarditis. Using 2003 to 2010 data

CLINICAL STATEMENTS
rheumatic HD is high in India, Pakistan, and from 37 centers in the Pediatric Health Information
AND GUIDELINES
the Pacific Islands (Chart 20-4). Systems Database, Pasquali and colleagues74 did
— Rheumatic HD prevalence is highest in cen- not demonstrate a significant difference in the
tral sub-Saharan Africa, South Asia, and the number of IE hospitalizations after the guidelines
Pacific Island countries (Chart 20-5). were implemented in 2007 (1.6% difference after
versus before guideline implementation; 95% CI,
−6.4% to 10.3%; P=0.7).
Infective Endocarditis • A systematic review that included 160 studies
(See Table 20-3) and 27 083 patients from 1960 to 2011 dem-
ICD-9 421.0; ICD-10 I33.0. onstrated that in hospital-based studies (142
2015: Mortality—1283. Any-mention mortality—2776. studies; 23 606 patients), staphylococcal endo-
2014: Hospital discharges—11 000, primary plus sec- carditis has increased over time (coagulase-neg-
ondary diagnoses. ative Staphylococcus 2% to 10%, P<0.001),
with recent increases in S aureus (21% to 30%,
Prevalence and Incidence P<0.05) and enterococcal IE (6.8% to 10.5%,
• In 2011, there were 47 134 cases of IE and valve P<0.001) over the past decade and a correspond-
replacement in the United States (Table 20-3). ing decrease in streptococcal endocarditis (32%
• According to the 2015 GBD study, the age-stan- to 17%) over the same time period.75
dardized death rate attributable to IE in 2015 was
Complications
1.3 per 100 000.69
• Among 162 cases of left-sided native-valve S
• Although the absolute risk for acquiring IE from
aureus IE retrospectively identified among 1254
a dental procedure is impossible to measure pre-
patients hospitalized between 1990 and 2010 for
cisely, the best available estimates are as follows:
IE, Staphylococcus represented 18% of all IE cases
If dental treatment causes 1% of all cases of viri-
and 23% of native-valve IE cases. HF occurred in
dans group streptococcal IE annually in the United
45% of IE cases, acute renal failure in 23%, sep-
States, the overall risk in the general population
sis in 29%, neurological events in 36%, systemic
is estimated to be as low as 1 case of IE per 14
embolic events in 55%, and in-hospital mortal-
million dental procedures. The estimated absolute
ity in 25%. The risk of in-hospital mortality was

risk rates for acquiring IE from a dental procedure
higher in patients with HF (OR, 2.5; P=0.04) and
in patients with underlying cardiac conditions are
sepsis (OR, 5.3; P=0.001). Long-term 5-year sur-
as follows71:
vival was 49.6±4.9%. There was higher long-term
— Mitral valve prolapse: 1 per 1.1 million
risk of death among individuals with HF (OR, 1.7;
procedures
P=0.03), sepsis (OR, 3.0; P=0.0001), and delayed
— CHD: 1 per 475 000
surgery (OR, 0.43; P=0.003). When the authors
— Rheumatic HD: 1 per 142 000
compared 2 study periods, 1990 to 2000 and
— Presence of a prosthetic cardiac valve: 1 per
2001 to 2010, there was a significant increase in
114 000
bivalvular involvement, valvular insufficiency, and
— Previous IE: 1 per 95 000 dental procedures
acute renal failure from 2001 to 2010. In-hospital
• Data collected between 2004 and 2010 from the
mortality rates and long-term 5-year survival were
Pediatric Health Information System database
not significantly different between the 2 study
from 37 centers that included 1033 cases of IE
periods (28.1% versus 23.5%; P=0.58).76
demonstrated a mortality rate of 6.7% (N=45)
and 3.5% (N=13) among children (0–19 years old) Risk Factors
with and without congenital HD, respectively.72 • The 15-year cohort risk (through 2006) of IE after
• Data from the NIS (2000–2011)73 suggested no diagnosis of mitral valve prolapse (between 1989
change in temporal trends in the incidence of IE to 1998) among Olmsted County, MN, residents
before and after publication of the 2007 AHA was 1.1±0.4% (incidence, 86.6 cases per 100 000
guideline for antibiotic prophylaxis before dental person-years; 95% CI, 43.3–173.2 cases per
procedures.71 These findings from referral centers 100 000 person-years); there was a higher age-
were corroborated by a community-based review and sex-adjusted risk of IE in patients with mitral
of adults in Olmsted County, MN.1 In the Olmsted valve prolapse (RR, 8.1; 95% CI, 3.6–18.0) com-
County, MN, study, age- and sex-adjusted inci- pared with the general population of Olmsted
dence of IE was 7.4 (95% CI, 5.3–9.4) cases per County (P<.001). No IE cases were identified
100 000 person-years. In addition, these guideline among patients without previously diagnosed
changes do not appear to have altered rates of MR. Conversely, there was a higher incidence of IE

in patients with mitral valve prolapse and moder- 95% CI, 0.53–0.87), even in propensity-adjusted
CLINICAL STATEMENTS
ate, moderate-severe, or severe MR (289.5 cases analyses (HR, 0.57; 95% CI, 0.49–0.67).79
AND GUIDELINES
per 100 000 person-years; 95% CI, 108.7–771.2
cases per 100 000 person-years; P=0.02 com-
• Surgery was performed in 47% of cases of defi-
pared with trivial, mild, or mild-moderate MR)
nite left-sided, non–cardiac device-related IE in
and in patients with a flail mitral leaflet (715.5
the ICE-PLUS registry of 1296 patients from 16
cases per 100 000 person-years; 95% CI, 178.9–
countries.80
2861.0 cases per 100 000 person-years; P=0.02
compared with no flail mitral leaflet).77
• Cardiac device IE appears to be present in 6.4% Endocarditis, Valve Unspecified
(95% CI, 5.5%–7.4%) of patients with definite ICD-9 424.9; ICD-10 I38.
IE, according to data from ICE-PCS (2000–2006). 2015: Mortality—5678. Any-mention mortality—11 779.
Nearly half (45.8%; 95% CI, 38.3%–53.4%) of
such cases were related to healthcare-associated
infection. In-hospital and 1-year mortality rates for Heart Valve Procedures
these patients were 14.7% (26 of 177; 95% CI, • In 2013, for heart valve procedures81:
9.8%–20.8%) and 23.2% (41 of 177; 95% CI, — The mean inflation-adjusted cost per hospi-
17.2%–30.1%), respectively. Although not based talization in 2013 dollars was $51 415, com-
on randomized data, compared with individu- pared with $53 711 in 2005 and $43 829 in
als without initial hospitalization device removal, 2000.
there appeared to be a 1-year survival benefit in — The number of discharges for which heart
individuals undergoing device explanation dur- valve surgery was the principal operating
ing the index hospitalization (HR, 0.42; 95% CI, room procedure was 102 425, which was an
0.22–0.82).78 increase from 93 802 in 2005 and 79 719 in
• Prosthetic valve IE continues to be associated with 2000.
high in-hospital and 1-year mortality, although • Total inflation-adjusted national costs in 2013
early surgery is associated with improved out- dollars (in millions) was $5264, which was an
comes compared with medical therapy alone increase from the mean cost (in millions) of $5058
(1-year mortality 22% versus 27%; HR, 0.68; in 2005 and $3488 in 2000.81
Table 20-1. Pooled Prevalence of Valvular Heart Disease From CARDIA, ARIC, and CHS Cohorts
Age, y
P Value for Frequency Adjusted to
18–44 45–54 55–64 65–74 ≥75 Trend 2000 US Adult Population
Participants, n 4351 696 1240 3879 1745 … 209 128 094
Male 1959 (45) 258 (37) 415 (33) 1586 (41) 826 (47) … 100 994 367 (48)
Mitral regurgitation (n=449) 23 (0.5) 1 (0.1) 12 (1.0) 250 (6.4) 163 (9.3) <0.0001 1.7% (95% CI, 1.5%–1.9%)
Mitral stenosis (n=15) 0 (0) 1 (0.1) 3 (0.2) 7 (0.2) 4 (0.2) 0.006 0.1% (95% CI, 0.02%–0.2%)
Aortic regurgitation (n=90) 10 (0.2) 1 (0.1) 8 (0.7) 37 (1.0) 34 (2.0) <0.0001 0.5% (95% CI, 0.3%–0.6%)
Aortic stenosis (n=102) 1 (0.02) 1 (0.1) 2 (0.2) 50 (1.3) 48 (2.8) <0.0001 0.4% (95% CI, 0.3%–0.5%)
Any valve disease … … … … … … …
Overall (n=615) 31 (0.7) 3 (0.4) 23 (1.9) 328 (8.5) 230 (13.2) <0.0001 2.5% (95% CI, 2.2%–2.7%)
Female (n=356) 19 (0.8) 1 (0.2) 13 (1.6) 208 (9.1) 115 (12.6) <0.0001 2.4% (95% CI, 2.1%–2.8%)
Male (n=259) 12 (0.6) 2 (0.8) 10 (2.4) 120 (7.6) 115 (14.0) <0.0001 2.5% (95% CI, 2.1%–2.9%)
Values are n (%) unless otherwise indicated. ARIC indicates Atherosclerosis Risk in Communities study; CARDIA, Coronary Artery Risk Development in Young
Adults; CHS, Cardiovascular Health Study; CI, confidence interval; and ellipses (…), not applicable.
Reprinted from The Lancet (Nkomo et al2), with permission from Elsevier. Copyright © 2006, Elsevier Ltd.

Table 20-2. Rheumatic Fever/Rheumatic Heart Disease Table 20-3. Incidence of IE and Valve Replacement
CLINICAL STATEMENTS
From 2000 to 2011

Hospital
AND GUIDELINES
Mortality, 2015: Discharges, 2014: Valve

Population Group All Ages* All Ages Total IE IE Incidence Replacement per
Both sexes 3372 26 000 Year Cases per 100 000 1000 IE Cases
Males 1119 (33.2%)† 12 000 2000 29 820 11 14
Females 2253 (66.8%)† 14 000 2001 31 526 11 16
NH white males 915 … 2002 32 229 11 19
NH white females 1863 … 2003 35 190 12 18
NH black males 94 … 2004 36 660 13 19
NH black females 149 … 2005 37 508 13 23
Hispanic males 65 … 2006 40 573 14 23
Hispanic females 148 … 2007 38 207 12 30
NH Asian or Pacific 2008 41 143 14 19

34‡ …
Islander males 2009 43 502 14 27
NH Asian or Pacific 2010 43 560 14 27
77‡ …
Islander females
2011 47 134 15 26
NH American Indian
15 …
or Alaska Native IE indicates infective endocarditis.
Reprinted from Pant et al73 with permission from The American College
Ellipses (…) indicate data not available; and NH, non-Hispanic. of Cardiology Foundation. Copyright © 2015, The American College of
*Mortality for American Indian or Alaska Native and Asian and Pacific Cardiology Foundation.
Islander people should be interpreted with caution because of inconsistencies
in reporting race on the death certificate compared with censuses, surveys,
and birth certificates. Studies have shown underreporting on death certificates
of American Indian or Alaska Native, Asian and Pacific Islander, and Hispanic
decedents, as well as undercounts of these groups in censuses.
†These percentages represent the portion of total mortality that is for males
vs females.
‡Includes Chinese, Filipino, Hawaiian, Japanese, and Other Asian or Pacific
Islander.
Sources: Mortality: Centers for Disease Control and Prevention/National

Center for Health Statistics, 2015 Mortality Multiple Cause-of-Death–United
States; data represent underlying cause of death only. Hospital discharges:
Healthcare Cost and Utilization Project, Hospital Discharges, 2014; data include
those inpatients discharged alive, dead, or of unknown status.

CLINICAL STATEMENTS
AND GUIDELINES
Chart 20-1. Number of TAVR and SAVR procedures performed according to type of procedure and age group,
2007 to 2013.
SAVR indicates surgical aortic valve replacement; TA, transapical; TAVR, transcatheter aortic valve replacement; and TF, transfemoral.
Reprinted from Reinöhl et al25 with permission from the Massachusetts Medical Society. Copyright © 2015, Massachusetts
Medical Society.

CLINICAL STATEMENTS
AND GUIDELINES
Chart 20-2. Worldwide experience with the MitraClip procedure from September 2008 until April 2015.
APAC indicates Asia-Pacific; and CALA, Caribbean and Latin America.
Reprinted from Deuschl et al.42 Figure courtesy of Abbott Laboratories.
Chart 20-3. Age and sex distribution of 3343 subjects with rheumatic heart disease participating in the REMEDY study.
REMEDY indicates Global Rheumatic Heart Disease Registry.
Reprinted from Zühlke et al57 by permission of Oxford University Press. Copyright © 2014, The Authors.

Chart 20-4. Age-standardized global mortality rates of rheumatic heart disease per 100 000, both sexes, 2015.
CLINICAL STATEMENTS
AND GUIDELINES
Chart 20-5. Age-standardized global prevalence rates of rheumatic heart disease per 100 000, both sexes, 2015.
Please click here to view the chart and its legend
17. Capoulade R, Clavel MA, Dumesnil JG, Chan KL, Teo KK, Tam JW, Côté
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21. VENOUS THROMBOEMBOLISM HCUP NIS (Charts 21-1 and 21-2) show increas-
CLINICAL STATEMENTS
ing rates of hospitalization cases for both PE from

(DEEP VEIN THROMBOSIS AND
AND GUIDELINES
1996 to 2014 and DVT from 2005 to 2014, with

PULMONARY EMBOLISM), CHRONIC DVT trending down since 2012.1 These trends
VENOUS INSUFFICIENCY, PULMONARY should be considered slightly in light of secular
HYPERTENSION trends, including advances in PE imaging, which
See Charts 21-1 and 21-2 enable the detection of smaller PEs; increased use
of full leg ultrasound, which detects distal DVT;
the advent of treating DVT in the outpatient set-
ting; and the co-occurrence of codes for DVT and
PE in the same patient. On the basis of these data,
Pulmonary Embolism
if we assume 30% of DVTs were treated in the
ICD-9 415.1; ICD-10 I26. outpatient setting in 2014, we estimate 676 000
Mortality—8676. Any-mention mortality—33 499 DVTs occurred in 2014.
(2015 NHLBI tabulation). Hospital discharges—178 000 • The estimated annual incidence of VTE events is
(principal diagnosis), 339 000 (all-listed diagnoses) 300 000 to 600 000; however, these estimates are
(2014 HCUP). ≥10 years old.2–4 These numbers are likely under-
estimates; because there is no comprehensive
Deep Vein Thrombosis surveillance, VTE can be missed or misdiagnosed,
and fatal PEs may not be ascertained because of
ICD-9 451.1, 451.2, 451.81, 451.9, 453.0, low autopsy rates.
453.1 453.2, 453.3, 453.4, 453.5, 453.9; • A modeling study estimated VTE incidence in 6
ICD-10 I80.1, I80.2, I80.3, I80.9, I82.0, countries in Europe (total population 310.4 mil-
I82.1, I82.2, I82.3, I82.4, I82.5, I82.9. lion), accounting for factors such as missed diag-
Mortality—3059. Any-mention mortality—16 017 nosis related to either lack of routine autopsy,
(2015 NHLBI tabulation). Hospital discharges—114 000 misdiagnosis, or underdiagnosis because of lack
(principal diagnosis), 473 000 (all-listed diagnoses) of symptom recognition.5 The authors estimated
(2014 HCUP). annually 465 715 (404 664–538 189) cases of
DVT, 295 982 (242 450–360 363) cases of PE, and

Incidence 370 012 (300 193–483 108) VTE-related deaths.
(Charts 21-1 and 21-2) Of these deaths, only 7% were diagnosed ante-
• Information on VTE incidence in the United States mortem; 34% were sudden fatal PE, and 59%
is limited. New data for this update from the followed undiagnosed PE.
• Using administrative data in the United States, the
Abbreviations Used in Chapter 21 estimated admissions for PE increased from 23 per
100 000 in 1993 to 65 per 100 000 in 2012.6 Trends
BMI body mass index
in DVT incidence were not reported. This pattern
CT computed tomography was also seen in the Tromsø Study in Norway, a
CVI chronic venous insufficiency longitudinal cohort of adults aged 25 to 97 years.
DM diabetes mellitus From the period 1996 to 1997 to the period 2010
DVT deep vein thrombosis
to 2011, the VTE incidence rate increased from 158
per 100 000 to 201 per 100 000. PE rates over the
HD heart disease same time period increased from 45 per 100 000
HIV human immunodeficiency virus (95% CI, 23–67) to 113 per 100 000 (95% CI,
ICD-9 International Classification of Diseases, 9th Revision 82–144). The rate of DVT without PE decreased
(from 112 per 100 000 [95% CI, 77–146] to 88
per 100 000 [95% CI, 61–115]).7
NIS Nationwide Inpatient Sample • In a US cohort of 30 239 black and white adults
PE pulmonary embolism ≥45 years old recruited from 2003 to 2007 and
PH pulmonary hypertension followed up for ≈2 years, age-standardized inci-
REVEAL Registry to Evaluate Early and Long-term PAH Disease
dence rates of VTE were 1.4 to 2.2 per 1000
Management
RR relative risk person-years.8
RV right ventricular • VTE incidence is similar or higher among African
VTE venous thromboembolism Americans and lower among Asian Americans
WHO World Health Organization and Native Americans than among whites.9

• Incidence rates for PE and DVT increase expo- venous ulcer after proximal lower-extremity DVT
CLINICAL STATEMENTS
nentially with advancing age for both males and is 30% and 3.7%, respectively.17
AND GUIDELINES
females.2,10,11 VTE is more serious at older ages • Chronic thromboembolic PH affects ≈4% of
because PE accounts for an increasing proportion patients with PE within 2 years of their initial PE
of VTE as people age. event.18
• Approximately 35% of patients with DVT are
Costs
treated as outpatients, whereas outpatient PE
• A literature review estimated incremental direct
treatment is rare.12,13
medical costs (2014 US dollars) per case among
Lifetime Risk 1-year survivors of acute VTE at $12 000 to
• In 2 US cohorts including 19 599 males and $15 000 and the cost of complications, including
females aged 45 to 99 years at baseline and fol- recurrent VTE, postthrombotic syndrome, chronic
lowed up for 288 535 person-years, the remain- thromboembolic PH, and anticoagulation-related
ing lifetime risk of VTE at age 45 years was 8.1% adverse events, at $18 000 to $23 000 per case.
(95% CI, 7.1%–8.7%) overall, 11.5% in African Assuming 375 000 to 425 000 new cases annu-
Americans, 10.9% in those with obesity, 17.1% ally, overall cost was estimated at $7 to 10 billion
in individuals with the factor V Leiden genetic annually.19
mutation, and 18.2% in people with sickle cell
Risk Factors
trait or disease.14
• Approximately 50% of VTEs are provoked
Mortality because of immobilization, trauma, surgery, or
• Using administrative data for first-time VTE in hospitalization in the antecedent 3 months; 20%
Quebec in 2000 to 2009, 30-day case fatality are associated with cancer; and 10% to 20% are
was 10.6%, and 1-year mortality was 23.0%. unprovoked.10,20–24
The 1-year survival rate was 47% (95% CI, 46%– • Independent VTE risk factors include increasing
48%) for cases with VTE and cancer, 93% (95% age, family history or personal history of throm-
CI, 93%–94%) for cases with unprovoked VTE, bosis, obesity, surgery, trauma/fracture, hospi-
and 84% (95% CI, 83%–84%) with provoked talization, prolonged immobility, nursing home
VTE.15 residence, active cancer, central venous cath-
• Data from a Worcester, MA, surveillance study eter or transvenous pacemaker, prior superficial
from 1999 to 2009 suggested a decline in 3-year vein thrombosis, infection, inherited or acquired
mortality after VTE (from 41% to 26%).15a thrombophilia, kidney disease, neurological dis-
ease with leg paresis, sickle cell anemia and
Recurrence
sickle cell trait, long-distance travel, and among
• VTE is a chronic disease with episodic recurrence;
females, use of estrogen-based contraceptives or
in the absence of long-term anticoagulation,
hormone therapy and during pregnancy and the
≈30% of patients develop recurrence within the
postpartum period.9,25–27
next 10 years.9
• Among patients hospitalized for acute medical
• Data from a Worcester, MA, surveillance study
illness, independent risk factors for VTE include
from 1999 to 2009 suggested a declining
prior VTE, thrombophilia, cancer, age >60 years,
rate of recurrent VTE (from 17% to 9%), per-
leg paralysis, immobilization for 7 days, and
haps attributable to increased use of long-term
admission to an ICU or coronary care unit.28
anticoagulation.15a
• Pregnancy-associated VTE has an incidence of
• Independent predictors of early (within 180 days)
≈1 to 2 per 1000 female-years; compared with
recurrence include active cancer and inadequate
nonpregnant females of childbearing age, the RR
anticoagulation. Two-week case-fatality rates
for VTE is increased 4-fold. In pregnancy, 80% of
for recurrent DVT alone and recurrent PE with or
events are DVT and 20% are PE.29–31 VTE risk is
without DVT are 2% and 11%, respectively.16
higher for pregnancies after in vitro fertilization
Complications than for natural pregnancies,32 as well as in asso-
• Because of the use of anticoagulant therapy to ciation with the usual VTE risk factors and with
treat VTE, bleeding is a major potential compli- multiple gestation, cesarean delivery, or other
cation. Data from a Worcester, MA, surveillance pregnancy complications.33
study from 1999 to 2009 suggested a declining • VTE risk during the postpartum period is ≈5-fold
3-year rate of major bleeding after a VTE (from higher than during pregnancy. Among females
12% to 6%).15a who are pregnant or postpartum, approximately
• The 20-year cumulative incidence of postthrom- one third of the DVT events and one half of the
botic syndrome/venous stasis syndrome and PE events occur after delivery,34 with the RR being

21- to 84-fold increased within 6 weeks postpar- (RR, 2–6), obesity (RR, 2), more extensive DVT
CLINICAL STATEMENTS
tum compared with females who are not preg- (RR, 2), poor quality of initial anticoagulation (RR,
AND GUIDELINES
nant or postpartum.35 2), ongoing symptoms or signs of DVT 1 month

• VTE is highly heritable,36,37 and a variety of coagu- after diagnosis (RR, 4), and elevated D-dimer at 1
lation genes have been implicated. Some muta- month (RR, 4.6–9.9).45,46
tions are rare (eg, deficiencies in antithrombin • Varicose veins are more likely to occur in the set-
III, protein S, and protein C), whereas others are ting of a positive family history, consistent with
relatively common (eg, factor V Leiden mutation, a heritable component. Although a number of
non-O blood group, prothrombin 20210A, and genes are implicated, the genetic factors predis-
sickle cell disease and trait).38 posing to varicose veins have not been definitively
identified.47
Chronic Venous Insufficiency

ICD-10 I87.2. Pulmonary Hypertension
ICD-10 I27.0, I27.2.
Mortality—44. Any-mention mortality—452 (2015
NHLBI tabulation). Mortality—6928. Any-mention mortality—21
701
(2015 NHLBI tabulation).
Prevalence
• Varicose veins are a common manifestation of Prevalence and Incidence
CVI, affecting 25 million US adults. More severe • In the United States, between 2001 and 2010,
venous disease affects 6 million adults.39 hospitalization rates for PH increased signifi-
cantly, and among those aged ≥85 years, hos-
Incidence pitalization rates nearly doubled.48 In 2010, the
• The FHS reported an annual incidence of varicose age-adjusted rate of hospitalization associated
veins of 2.6% in females and 1.9% in males.40 with PH was 131 per 100 000 discharges over-
all, and 1527 per 100 000 for those aged ≥85
Complications years. There is also evidence of increasing mortal-
• More severe venous disease often includes mani- ity rates in both males and females; in 2010, the
festations such as hyperpigmentation, venous death rate for PH as any contributing cause of
eczema, lipodermatosclerosis, atrophie blanche, death was 6.5 per 100 000.48

and healed or active venous ulcers.41 • The prevalence of WHO group 1 PH (idiopathic,
• Analysis of NIS data for black and white Americans heritable, drug/toxin induced, or associated with
demonstrated declines in ulcer debridement, vein other factors including connective tissue disease,
stripping, and sclerotherapy procedures from infections [HIV, schistosomiasis], portal hyperten-
1998 to 2011. Blacks presented at younger ages sion, and congenital HD) is estimated at 6.6 to
and more often had ulcer debridement and his- 26.0 per million adults and the incidence at 1.1 to
tory of DVT than whites.42 7.6 per million adults annually.49
Cost • WHO group 2 PH is attributable to left-sided HD.
• Estimated cost in the United States to treat venous Estimates of the incidence and prevalence are dif-
ulcers is $1 billion annually.41 ficult to ascertain but most likely would track with
HF prevalence rates.49
Risk Factors • The prevalence and incidence of WHO group 3
• The prevalence of moderate CVI increases PH (attributable to lung disease or hypoxia) is dif-
with advancing age, family history, hernia sur- ficult to estimate but likely would track with lung
gery, obesity, number of births, and presence disease prevalence.49
of flat feet in females and is less likely in those • The prevalence of WHO group 4 PH (chronic
with hypertension; risk factors for more severe thromboembolic PH and other pulmonary
CVI include smoking in males and leg injury obstructions) ranges from 1.0% to 8.8% among
in females.43 Blood coagulation disorders and those with PE.36 The incidence is 6.5 per million
inflammatory biomarkers that are related to DVT person-years; ≈1400 incident cases occur annu-
risk are also associated with an increased risk ally among US whites.50
of CVI, consistent with the hypothesis that DVT • WHO group 5 PH has multifactorial mechanisms.
predisposes to CVI.10,44 When it accompanies sickle cell disease, the prev-
• Postthrombotic syndrome, a subset of CVI, has alence is 6% to 10% and increases with advanc-
specific risk factors that can be identified at the ing age. When it accompanies thalassemia, the
time of or after DVT: recurrent ipsilateral DVT prevalence is 2.1%.49,51

Mortality cancer were associated with mortality regardless
CLINICAL STATEMENTS
Mortality of PH depends on the cause and treatment. of surgery.
AND GUIDELINES
• In the US-based REVEAL registry of patients with
Risk Factors
group I pulmonary arterial hypertension enrolled
• Risk factors are implicit in the WHO disease clas-
from 2006 to 2009, 5-year survival was 61.2%
sification of the 5 mechanistic subtypes of PH
to 65.4%. Lower 5-year survival was strongly and
described above. The most common risk factors
directly associated with worse functional class at
are left-sided HD and lung disease.
presentation.52
• In a study of 772 consecutive PE patients without
• A German single-center registry study observed
major comorbidity such as cancer, the risk factors for
a 65.3%, 50.9%, 74.5%, and 18.7% 5-year
chronic thromboembolic PH were unprovoked PE,
survival for patients with idiopathic pulmonary
hypothyroidism, symptom onset >2 weeks before
arterial hypertension, PH associated with con-
PE diagnosis, RV dysfunction on CT or echocardiog-
nective tissue disease, PH caused by congenital
raphy, DM, and thrombolytic therapy or embolec-
HD, and pulmonary venous occlusive disease,
tomy; a risk prediction score including these factors
respectively.53
was able to predict a group with a chronic throm-
• A French registry of 190 patients with idiopathic,
boembolic PH incidence of 10% (95% CI, 6.5%–
familial, or anorexigen-associated PH had 1-
15%).40 Higher BMI also has been associated with
and 3-year survival rates of 82.9% and 58.2%,
chronic thromboembolic PH risk after PE.57
respectively.54
• In sickle cell disease–related PH, the 5-year sur- Global Burden
vival rate in 1 study was 63% with and 83% with- • 80% of patients with PH live in developing coun-
out PH.55 tries, and the cause of their PH is HD and lung dis-
• An international prospective registry that included ease, but schistosomiasis, rheumatic HD, HIV, and
679 patients with chronic thromboembolic PH sickle cell disease remain prominent compared
estimated 3-year survival was 89% with and 70% with developed countries. In these countries,
without pulmonary thromboendarterectomy.56 younger people are more often affected (average
Among the patients with chronic thromboem- age of onset <40 years).49
bolic PH, treatments for PH did not affect survival. • In high-income countries, rates of chronic throm-
High New York Heart Association functional class, boembolic PH are believed to be lower in Japan
increased right atrial pressure, and history of than in the United States and Europe.58
Chart 21-1. Trend in hospitalized pulmonary embolism, 1996 to 2014.

Source: Weighted national estimates from Healthcare Cost and Utilization Project National (Nationwide) Inpatient Sample,
Agency for Healthcare Research and Quality, based on data collected by individual states.1

CLINICAL STATEMENTS
AND GUIDELINES
Chart 21-2. Trend in hospitalized deep vein thrombosis, 2005 to 2014.

Source: Weighted national estimates from Healthcare Cost and Utilization Project National (Nationwide) Inpatient Sample,
Agency for Healthcare Research and Quality, based on data collected by individual states.1
12. Stein PD, Matta F, Hughes PG, Hourmouzis ZN, Hourmouzis NP, White RM,
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CLINICAL STATEMENTS
bolism: burden, mechanisms, and management. Thromb Haemost. for peripheral venous disease resemble those for venous thrombosis: the
AND GUIDELINES
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10.1016/j.amepre.2010.01.010. of the American Heart Association Council on Peripheral Vascular
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Naik R, Pankow JS, Grove ML, Basu S, Key NS, Cushman M. Prospective and Stroke Nursing. The postthrombotic syndrome: evidence-based
study of sickle cell trait and venous thromboembolism incidence. J Thromb prevention, diagnosis, and treatment strategies: a scientific statement
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EE, Meijer K, Sang Y, Matsushita K, Hallan SI, Hammerstrøm J, Cannegieter 10.1161/CIR.0000000000000130.
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30. Bates SM, Middeldorp S, Rodger M, James AH, Greer I. Guidance for the Abstract P2927.
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ment. Hematology Am Soc Hematol Educ Program. 2012;2012:203–207. tors for pulmonary arterial hypertension in a large group of β-thalassemia
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22. PERIPHERAL ARTERY DISEASE AND • The highest prevalence of low ABI (<0.9) has been
CLINICAL STATEMENTS
observed among older adults (22.7% among

AORTIC DISEASES
AND GUIDELINES
individuals aged ≥80 years versus 1.6% among

ICD-9 440.20 to 440.24, 440.30 to 440.32, 440.4, those aged 40–49 years) and NH blacks (≈11.6%
440.9, 443.9, 445.02; ICD-10 I70.2, I70.9, I73.9, in NH blacks versus ≈5.5% in whites).2 The preva-
I74.3, I74.4. See Table 22-1 and Charts 22-1 lence of low ABI (<0.9) is similar between females
through 22-8 (5.9%) and males (5.0%).
• Only ≈10% of people with PAD have the clas-
Click here to return to the Table of Contents sic symptom of intermittent claudication.
Approximately 40% do not complain of leg
Peripheral Artery Disease pain, whereas the remaining 50% have a vari-
Prevalence and Incidence ety of leg symptoms different from classic clau-
(See Table 22-1 and Charts 22-1 and 22-2) dication (ie, exertional pain that either did not
• On the basis of data from several US cohorts dur- stop the individual from walking or did stop
ing the 1970s to 2000s and the 2000 US Census, the individual from walking but did not involve
6.5 million Americans aged ≥40 years (5.5%) are the calves or did not resolve within 10 minutes
estimated to have low ABI (<0.9).1 Of these, one of rest).3,4
fourth have severe PAD (ABI <0.7).1 • On the basis of ICD codes in nationwide claims
• Further accounting for PAD cases with ABI data from large employers’ health plans and
>0.9 (after revascularization or false-negative from Medicare and Medicaid programs between
results with ABI), in 2000, PAD was estimated 2003 and 2008, among adults aged >40 years,
to affect ≈8.5 million Americans aged ≥40 years the annual incidence and prevalence of PAD
(7.2%).2 were 2.69% and 12.02%, respectively.5 The cor-
• Estimates of PAD prevalence in males and females responding estimates for critical limb ischemia,
by age and ethnicity are shown in Charts 22-1 the most severe form of PAD, were 0.35% and
and 22-2.2 1.33%, respectively.
• Data from the NIS demonstrate that admission
Abbreviations Used in Chapter 22 rates because of critical limb ischemia remained
AAA abdominal aortic aneurysm

constant from 2003 to 2011.6
ABI ankle-brachial index
Mortality
AHA American Heart Association (See Table 22-1 and Chart 22-3)
Amer. American • In 2015, the overall any-mention age-adjusted
CHD coronary heart disease death rate for PAD was 15.5 per 100 000. Any-
CI confidence interval mention death rates in males were 18.9 for NH
whites, 23.6 for NH blacks, 8.0 for NH Asians or
Pacific Islanders, 20.0 for NH American Indians or
Alaska Natives, and 14.8 for Hispanic males. In
GBD Global Burden of Disease females, rates were 13.4 for NH whites, 16.3 for
HCUP Healthcare Cost and Utilization Project NH blacks, 5.9 for NH Asians or Pacific Islanders,
HF heart failure 15.3 for NH American Indians or Alaska Natives,
HR hazard ratio and 9.9 for Hispanic females.7
ICD International Classification of Diseases
• In 2015, PAD was the underlying cause in 13 341
deaths. The number of any-mention deaths
IRAD International Registry of Acute Aortic Dissection
attributable to PAD was 58 675 in 2015 (NHLBI
MI myocardial infarction tabulation).
NAMCS National Ambulatory Medical Care Survey • A 2008 meta-analysis of 24 955 males and 23 339
NH non-Hispanic females from 16 cohorts demonstrated a reverse-
NHAMCS National Hospital Ambulatory Medical Care Survey J-shaped association between ABI and mortality
in which participants with an ABI of 1.11 to 1.40
OR odds ratio
were at lowest risk for mortality (Chart 22-3). In
OVER Open Versus Endovascular Repair males, low ABI (≤0.9) carried a 3-fold (RR, 3.33;
PA physical activity 95% CI, 2.74–4.06) risk of all-cause death com-
PAD peripheral artery disease pared with a normal ABI (1.11–1.40), and a
REACH Reduction of Atherothrombosis for Continued Health similar risk was observed in females (RR, 2.71;
RR relative risk 95% CI, 2.03–3.62).8 A similar reverse-J-shaped

association between ABI also was observed for amputations per 100 000 patients with PAD in the
CLINICAL STATEMENTS
cardiovascular mortality. Mountain region. After adjustment for clustering
AND GUIDELINES
• In-hospital mortality was higher in females than at the US Census Bureau level, geographic varia-
males, regardless of disease severity or procedure tion in lower-extremity amputations remained.
performed, even after adjustment for age and Lower-extremity amputation was performed more
baseline comorbidities: 0.5% versus 0.2% after often in the East South Central region (adjusted
percutaneous transluminal angioplasty or stent- OR, 1.152; 95% CI, 1.131–1.174; P<0.001) and
ing for intermittent claudication; 1.0% versus West South Central region (adjusted OR, 1.115;
0.7% after open surgery for intermittent clau- 95% CI, 1.097–1.133; P<0.001) and less often in
dication; 2.3% versus 1.6% after percutaneous the Middle Atlantic region (OR, 0.833; 95% CI,
transluminal angioplasty or stenting for critical 0.820–0.847; P<0.001) versus the South Atlantic
limb ischemia; and 2.7% versus 2.2% after open reference region.17
surgery for critical limb ischemia (P<0.01 for all • Among 186 338 older Medicare PAD patients
comparisons).9 undergoing major lower-extremity amputation,
• Progression of PAD as measured by a decline mortality was found to be 48.3% at 1 year.18
in ABI also carries prognostic value beyond sin- • A study of Medicare beneficiaries reported that
gle measurements.10 Among 508 patients (449 between 2006 and 2011, 39 339 required revas-
males) identified from 2 vascular laboratories in cularization for PAD, and the annual rate of
San Diego, CA, a decline in ABI of >0.15 within a peripheral vascular intervention increased slightly
10-year period was associated with a subsequent from 401.4 to 419.6 per 100 000 people.19
increased risk of all-cause mortality (RR, 2.4; 95% • People with PAD have impaired function and
CI, 1.2–4.8) and CVD mortality (RR, 2.8; 95% CI, quality of life, regardless of whether or not they
1.3–6.0) at 3 years’ follow-up.10 report leg symptoms. Furthermore, patients
• Among 400 patients with PAD confirmed with with PAD, including those who are asymptom-
digital subtraction angiography, aortoiliac (proxi- atic, experience a significant decline in lower-
mal) disease was associated with an increased risk extremity function over time.20–22 A few recent
of mortality or cardiovascular events compared studies have demonstrated that even individuals
with infrailiac (distal) disease (adjusted HR, 3.28; with low-normal ABI (0.91–0.99) have reduced
95% CI, 1.87–5.75).11 Compared with infrailiac physical function compared with those with
PAD, aortoiliac PAD was associated with younger normal ABI.23

age, male sex, and smoking. • Among patients with established PAD, higher PA
levels during daily life are associated with better
Complications
overall survival rate, a lower risk of death because
• PAD is a marker for systemic atherosclerotic dis-
of CVD, and slower rates of functional decline.24,25
ease, and thus, people with PAD are more likely
In addition, better 6-minute walk performance
to have atherosclerosis in other vascular beds (eg,
and faster walking speed are associated with
coronary, carotid, and renal arteries and abdomi-
lower rates of all-cause mortality, cardiovascular
nal aorta).12–15
mortality, and mobility loss.26,27
• Pooled data from 11 studies in 6 countries found
that the pooled age-, sex-, risk factor–, and CVD- Interventions
adjusted RRs in people with PAD (defined by ABI • A 2011 systematic review evaluated lower-
<0.9) versus those without were 1.45 (95% CI, extremity aerobic exercise against usual care and
1.08–1.93) for CHD and 1.35 (95% CI, 1.10– demonstrated a range of benefits, including the
1.65) for stroke.16 following28:
• From 2000 to 2008, the overall rate of lower- — Increased time to claudication by 71 seconds
extremity amputation decreased significantly (79%) to 918 seconds (422%)
during the study period, from 7258 to 5790 per — Increased distance before claudication by 15
100 000 Medicare beneficiaries with PAD. Patients m (5.6%) to 232 m (200%)
with PAD who underwent major lower-extremity — Increased walking distance/time by 67% to
amputation were more likely to have DM (60.3% 101% after 40 minutes of walking 2 to 3
versus 35.7% with PAD without amputation; times per week
P<0.001). There was significant geographic varia- • Observational studies have found that the risk of
tion in the rate of lower-extremity amputation, death,29 MI,30 and amputation29 are substantially
from 8400 amputations per 100 000 patients greater in individuals with PAD who continue to
with PAD in the East South Central region to 5500 smoke than in those who stopped smoking.

• The “2016 AHA/ACC Guideline on the countries, respectively, important risk factors for
CLINICAL STATEMENTS
Management of Patients With Lower Extremity PAD included cigarette smoking (OR, 2.72 versus
AND GUIDELINES
Peripheral Artery Disease” noted that several 1.42), DM (OR, 1.88 versus 1.47), hypertension
randomized and observational studies dem- (OR, 1.55 versus 1.36), and hypercholesterolemia
onstrate that statins reduced the risk of major (OR, 1.19 versus 1.14).39
adverse cardiovascular events and amputation • A study of 3.3 million people 40 to 99 years of
among people with PAD.31 age primarily self-referring for vascular screening
• A meta-analysis of 42 trials demonstrated that tests in the United States showed that risk fac-
antiplatelet therapy reduces the odds of vascular tor burden was associated with increased preva-
events by 26% among patients with PAD.32,33 lence of PAD, and there was a graded association
• Data from the REACH registry of 8273 PAD par- between the number of traditional risk factors
ticipants suggest that only 70% of PAD patients and the prevalence of PAD.40
receive lipid-lowering therapy and only 82% • Other risk factors for PAD include sedentary life-
receive antiplatelet therapy for secondary CVD style, elevated inflammation markers, hyperten-
prevention.34 sion in pregnancy, and CKD.40–43
• In a study that randomized patients with PAD to 3 • A secondary analysis of a randomized feeding
groups (optimal medical care, supervised exercise trial showed reduced risk of incident PAD with
training, and iliac artery stent placement), super- the Mediterranean diet compared with a control
vised exercise resulted in superior treadmill walk- diet.44
ing distance compared with stenting. Results in
the exercise group and stent group were superior Awareness
to optimal medical care alone.35 • A cross-sectional, population-based telephone
• Endovascular therapies for critical limb ischemia survey of >2500 adults ≥50 years of age, with
are being used with greater frequency in the oversampling of blacks and Hispanics, found that
United States. From 2003 to 2011, there was a 26% expressed familiarity with PAD in contrast
significant increase in endovascular treatment to >65% for CHD, stroke, and HF. Of these, half
of critical limb ischemia (from 5.1% to 11.0%), were not aware that DM and smoking increase
which was accompanied by lower rates of in-hos- the risk of PAD. One in 4 knew that PAD is asso-
pital mortality and major amputation, as well as ciated with increased risk of MI and stroke, and
shorter length of stay.6 only 14% were aware that PAD could lead to
amputation. All knowledge domains were lower
Hospital Discharges and Ambulatory Care Visits in individuals with lower income and education
(See Table 22-1) levels.3
• Principal diagnosis discharges for PAD slightly • In data concerning people aged ≥70 years or
decreased from 2004 to 2014, with first-listed those aged 50 to 69 years with a history of DM
discharges of 140 000 and 115 000, respectively or smoking, as well as their physicians, 83% of
(NHLBI tabulation). patients with a prior diagnosis of PAD were aware
• In 2014, there were 1 097 000 physician office of the diagnosis, but only half of their physicians
visits and 36 000 ED visits with a primary had recognized the diagnosis.3
diagnosis of PAD (NAMCS/NHAMCS, NHLBI
tabulation). Global Burden of PAD
(See Charts 22-4 and 22-5)
Risk Factors • A systematic study of 34 studies reported that
• The risk factors for PAD are similar but not iden- globally, 202 million people were living with PAD,
tical to those for CHD. Cigarette smoking is a and during the preceding decade, the number of
stronger risk factor for PAD than for CHD.37 Age- people with PAD increased by 28.7% in low- to
and sex-adjusted OR for heavy smoking was 3.94 middle-income countries and by 13.1% in high-
for symptomatic PAD and 1.66 for CHD.37 income countries (Chart 22-4).39
• Among males in the Health Professionals • The GBD 2015 Study used statistical models and
Follow-up Study, smoking, type 2 DM, hyperten- data on incidence, prevalence, case fatality, excess
sion, and hypercholesterolemia accounted for mortality, and cause-specific mortality to estimate
75% (95% CI, 64%–87%) of risk associated with disease burden for 315 diseases and injuries in
development of clinical PAD.38 195 countries and territories. PAD prevalence
• In a meta-analysis of 34 studies from high- is high in southern and sub-Saharan Africa and
income countries and low- to middle-income tropical Latin America (Chart 22-5).45

Aortic Diseases a nationwide screening program targeting
CLINICAL STATEMENTS
ICD-9 440, 441, 444, and 447; ICD-10 I70, 65-year-old males.51
AND GUIDELINES
• Data from IRAD demonstrated that the rate of
I71, I74, I77, and I79.
mesenteric malperfusion in 1809 patients with
Aortic Aneurysm and Acute Aortic Dissection type A acute dissections was 3.7%, with a higher
(See Charts 22-6 through 22-8) mortality rate than for patients without malperfu-
ICD-9 441; ICD-10 I71. sion (63.2% versus 23.8%, P<0.001).52
Prevalence and Incidence • Data from IRAD demonstrated that patients with
• The prevalence of AAAs that are 2.9 to 4.9 cm acute type B aortic dissection have heterogeneous
in diameter ranges from 1.3% in males 45 to 54 in-hospital outcomes. In-hospital mortality in
years of age to 12.5% in males 75 to 84 years patients with and without complications (such as
of age. For females, the prevalence ranges from mesenteric ischemia, renal failure, limb ischemia,
0% in the youngest to 5.2% in the oldest age or refractory pain) was 20.0% and 6.1%, respec-
groups.46 tively. In patients with complications, in-hospital
• A meta-analysis of 15 475 individuals from 18 mortality associated with surgical and endovas-
studies on small AAAs (3.0–5.4 cm) demonstrated cular repair was 28.6% and 10.1% (P=0.006),
that mean aneurysm growth rate was 2.21 mm respectively.53
per year and did not significantly vary by age and Hospital Discharges
sex. Growth rates were higher in smokers (by
0.35 mm/y) and lower in patients with DM (by • In 2014, there were 69 000 hospital discharges
0.51 mm/y).47 with aortic aneurysm as principal diagnoses,
• A study from Olmsted County, MN,48 demon- of which 50 000 were males and 19 000 were
strated annual age- and sex-adjusted incidences females (HCUP, NHLBI tabulation).
per 100 000 people of 3.5 (95% CI, 2.2–4.9) for
Interventions
thoracic aortic aneurysm rupture and 3.5 (95%
• Results from 4 trials (N=3314 participants) evalu-
CI, 2.4–4.6) for acute aortic dissection.
ating the effect of open or endovascular repair of
Mortality small AAAs (4.0–5.5 cm) did not demonstrate an
advantage to earlier intervention compared with
2015: Mortality—9988. Any-mention mortality—

16 522. routine ultrasound surveillance.54
• According to the 2013 GBD study, the age- • Data from 23 838 patients with ruptured AAAs
standardized death rate attributable to aortic collected through the NIS (2005–2010) demon-
aneurysm in 2013 was 2.7 per 100 000 (95% strated in-hospital mortality of 53.1% (95% CI,
CI, 2.6–2.8), which represents a 10% median 51.3%–54.9%), with 80.4% (95% CI, 79.0%–
decrease since 1990.49 However, because of 81.9%) undergoing intervention for repair. Of
population growth and aging, the number of individuals who underwent repair, 20.9% (95%
deaths attributable to AAAs increased by 78.5% CI, 18.6%–23.2%) underwent endovascular
from 1990 to 2015.45 repair, with a 26.8% (95% CI, 23.7%–30.0%)
postintervention mortality rate, and 79.1% (95%
Complications CI, 76.8%–81.4%) underwent open repair, with
• Rates of small AAA (3.0–5.4 cm in diameter) a 45.6% (95% CI, 43.6%–47.5%) postinterven-
rupture range from 0.71 to 11.03 per 1000 tion mortality rate.55
person-years, with higher rupture rates in smok- • Data from the NIS suggest that the use of endo-
ers (pooled HR, 2.02; 95% CI, 1.33–3.06) and vascular repair of AAAs rose substantially between
females (pooled HR, 3.76; 95% CI, 2.58–5.47; 2000 and 2010 (5% versus 74% of all AAA
P<0.001).47 repairs, respectively), whereas the overall num-
• A 2015 systematic review that included 4 ran- ber of AAAs (≈45 000 per year) remained stable.
domized trials of ultrasound screening dem- In-hospital mortality and length of stay declined
onstrated lower AAA-associated mortality, during this period, but costs rose.56
emergency operations, and rupture with screen- • At least for the first 3 years after elective repair
ing, but with higher AAA-associated elective of an AAA, individuals who have endovascular
repair rates; however, there was no effect on repair may have better outcomes than those who
all-cause mortality (Chart 22-7).50 Similar results undergo open repair. After multivariable adjust-
were reported in a systematic review report ment, Medicare patients who underwent open
prepared for the US Preventive Services Task AAA repair had a higher risk of all-cause mortal-
Force45 and in a 2016 Swedish study evaluating ity (HR, 1.24; 95% CI, 1.05–1.47), AAA-related

mortality (HR, 4.37; 95% CI, 2.51–7.66), and were similar for endovascular repair (8% versus
CLINICAL STATEMENTS
complications at 1 year than patients who under- 9%, P=0.56).63 On the basis of data from the
AND GUIDELINES
went endovascular repair.57 However, after 8 years NIS (N=1400), weekend repair for thoracic aortic
of follow-up, survival in the open repair group was aneurysm rupture (n=322) was associated with
similar to that in the endovascular repair group. Of higher mortality than weekday repair (n=1078;
note, individuals in the endovascular repair group OR, 2.55; 95% CI, 1.77–3.68), likely because of
had a higher rate of eventual aneurysm rupture delays in surgical intervention.64
(5.4%) than patients who underwent open repair • Seventeen-year trends in the IRAD database
(1.4%).58 Similar findings were observed in the (1996–2013) demonstrate an increase in sur-
OVER Veterans Affairs Cooperative trial, which gical repair of type A thoracic dissections
compared open AAA repair to endovascular repair (79%–90%) and a significant decrease in in-
in 881 patients and demonstrated reductions in hospital and surgical mortality for type A dis-
mortality from endovascular repair at 2 years (HR, sections (31%–22% [P<0.001] and 25%–18%
0.63; 95% CI, 0.40–0.98) and 3 years (HR, 0.72; [P=0.003], respectively). Type B dissections were
95% CI, 0.51–1.00).59 However, there was no sur- more likely to be treated with endovascular
vival difference between open and endovascular therapies, but no significant changes in mortal-
repair in individuals followed up for up to 9 years ity were observed.65
(mean, 5 years; HR, 0.97; 95% CI, 0.77–1.22).59
Risk Factors
• In comparisons of the United States and the
• Many risk factors for atherosclerosis are also asso-
United Kingdom, the United States demonstrated
ciated with increased risk for AAAs.66 Of these,
a higher rate of AAA repair, smaller AAA diameter
smoking is the most important modifiable risk
at the time of repair, and lower rates of AAA rup-
factor for AAAs.67
ture and AAA-related death.60
• A 2014 systematic review of 17 community-based
• In ruptured AAAs, implementation of a contem-
observational studies demonstrated a consistent,
porary endovascular-first protocol was associated
inverse association between DM and prevalent
with decreased perioperative morbidity and mor-
AAAs (OR, 0.80; 95% CI, 0.70–0.90).68
tality, a higher likelihood of discharge to home,
• On the basis of nationally representative data
and improved long-term survival in a retrospective
from the United Kingdom, giant cell arteritis has
analysis of 88 consecutive patients seen at an aca-
been demonstrated to be associated with a 2-fold

demic medical center.61
higher risk (sub-HR, 1.92; 95% CI, 1.52–2.41)
• The data for surgery in thoracic aortic aneurysms
after adjustment for competing risks for devel-
are more mixed between open and endovascular
oping an AAA. These data also demonstrate an
repair. A sample of 12 573 and 2732 Medicare
inverse association between DM and AAAs.69
patients who underwent open thoracic aortic
aneurysm and endovascular repair from 1998 Global Burden of Aortic Aneurysm
to 2007 demonstrated higher perioperative (See Chart 22-8)
mortality for open repair in both intact (7.1% • The GBD 2015 Study used statistical models
versus 6.1%, P=0.07) and ruptured (46% ver- and data on incidence, prevalence, case fatal-
sus 28%, P<0.01) thoracic aortic aneurysms ity, excess mortality, and cause-specific mortal-
but higher 1-year (87% versus 82%, P=0.001) ity to estimate disease burden for 315 diseases
and 5-year (72% versus 62%, P=0.001) survival and injuries in 195 countries and territories. The
rates.62 Perioperative mortality rates for open highest age-standardized mortality rates attribut-
thoracic aortic aneurysms were higher for NH able to aortic aneurysm are reported in northern
black Medicare patients than for white Medicare Europe and southern and tropical Latin America
patients (18% versus 10%, P<0.001), but rates (Chart 22-8).45

Table 22-1. Peripheral Artery Disease
CLINICAL STATEMENTS
Hospital
AND GUIDELINES
Prevalence, Mortality, Discharges,
Population Group Age ≥40 y 2015, All Ages* 2014, All Ages
Both sexes ≥6.8 Million 13 341 115 000
Males … 5900 (44.2%)† 69 000
Females … 7441 (55.8%)† 46 000
NH white males … 4751 …
NH white females … 6099 …
NH black males … 701 …
NH black females … 850 …
Hispanic males … 296 …
Hispanic females … 307 …
NH Asian or Pacific … 89‡ …
Islander males
NH Asian or Pacific … 116‡ …
Islander females
NH American Indian/ … 71 …
Alaska Native

*Mortality for Hispanic, American Indian or Alaska Native, and Asian and Pacific
Islander people should be interpreted with caution because of inconsistencies in
reporting Hispanic origin or race on the death certificate compared with censuses,
surveys, and birth certificates. Studies have shown underreporting on death
certificates of American Indian or Alaska Native, Asian and Pacific Islander, and
Hispanic decedents, as well as undercounts of these groups in censuses.
†These percentages represent the portion of total mortality attributable to
peripheral artery disease that is for males vs females.
‡Includes Chinese, Filipino, Hawaiian, Japanese, and Other Asian or Pacific
Islander.
Sources: Prevalence: Data derived from Allison et al.2 Prevalence of

peripheral artery disease is based on an ankle-brachial index <0.9 or a previous
revascularization for peripheral artery disease. Mortality: Centers for Disease
Control and Prevention/National Center for Health Statistics, 2015 Mortality
Multiple Cause-of-Death–United States.
70
59.0
60
50
40
Prevalence (%)
30 28.7
24.4 22.5
22.6 21.5
20
13.2
11.7
9.2 9.6 9.8
10
5.4 6.1
5.0 4.5 4.3 3.5
2.6 3.4
1.4 1.2 1.9
0.2 1.2 0.9
0
40-49 50-59 60-69 70-79 ≥80
Age (Years)
NH White African American Hispanic Asian Amer. Indian
Chart 22-1. Estimates of prevalence of peripheral artery disease in males by age and ethnicity.
Amer. indicates American; and NH, non-Hispanic.
Data derived from Allison et al.2

CLINICAL STATEMENTS
40
AND GUIDELINES
35.1
35 33.8
30
25
Prevalence (%)
20.0 18.2
20 18.2 18.2
14.7
15
10 8.9 8.6
7.9 7.9
6.9
5.1
5 4.3 3.9
3.0 3.2 3.4 3.1
1.9 1.4
0.3 0.0 0.4 0.7
0
40-49 50-59 60-69 70-79 ≥80
Age (Years)
NH White African American Hispanic Asian Amer. Indian
Chart 22-2. Estimates of prevalence of peripheral artery disease in females by age and ethnicity.
Amer. indicates American; and NH, non-Hispanic.
Data derived from Allison et al.2
Chart 22-3. Hazard ratios of cardiovascular mortality with 95% confidence interval by ankle-brachial index
categories.
Data derived from Fowkes et al.8

CLINICAL STATEMENTS
AND GUIDELINES
Chart 22-4. Prevalence of peripheral artery disease by age in males and females in high-income countries and low-
income or middle-income countries.
Adapted from The Lancet (Fowkes et al39), with permission from Elsevier. Copyright © 2013, Elsevier Ltd.
Chart 22-5. Age-standardized global prevalence rates of peripheral artery disease per 100 000, both sexes, 2015.
60
50 50
40 40
Rupture Risk/year (%)
30 30
20 20 20
15
10 10
5
3
0 0 0.5
<4 cm 4 to 5 cm 5 to 6 cm 6 to 7 cm 7 to 8 cm >8 cm
Chart 22-6. Association between the diameter and the minimum and maximum risk of abdominal aortic aneurysm
rupture per year.
Data derived from Brewster et al.70

CLINICAL STATEMENTS
900
AND GUIDELINES
800 770
700 667
Number needed to screen

600
500
400 370
333
300
238
208
200 181 175
100
0
3-5 years 6-7 years 10-11 years 13-15 years
AAA associated mortality Ruptured AAAs
Chart 22-7. Numbers needed to screen to avoid an AAA-associated death and a ruptured AAA.
AAA indicates abdominal aortic aneurysm.
Data derived from Eckstein et al.50
Chart 22-8. Age-standardized global mortality rates of aortic aneurysm per 100 000, both sexes, 2015.
McDermott MM, Stoffers HE, Hooi JD, Knottnerus JA, Ogren M, Hedblad
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Di Bartolomeo R, Folesani G, Pyeritz RE, Braverman AC, Montgomery DG, Surg. 2014;60:318–324. doi: 10.1016/j.jvs.2014.02.052.
Isselbacher EM, Nienaber CA, Eagle KA, Fattori R. Clinical presentation, 65. Pape LA, Awais M, Woznicki EM, Suzuki T, Trimarchi S, Evangelista A,
management, and short-term outcome of patients with type A acute dis- Myrmel T, Larsen M, Harris KM, Greason K, Di Eusanio M, Bossone
section complicated by mesenteric malperfusion: observations from the E, Montgomery DG, Eagle KA, Nienaber CA, Isselbacher EM, O’Gara
International Registry of Acute Aortic Dissection. J Thorac Cardiovasc P. Presentation, diagnosis, and outcomes of acute aortic dissec-
Surg. 2013;145:385–390 e1. tion: 17-year trends from the International Registry of Acute Aortic
53. Trimarchi S, Tolenaar JL, Tsai TT, Froehlich J, Pegorer M, Upchurch GR, Dissection. J Am Coll Cardiol. 2015;66:350–358. doi: 10.1016/j.jacc.
Fattori R, Sundt TM 3rd, Isselbacher EM, Nienaber CA, Rampoldi V, 2015.05.029.
Eagle KA. Influence of clinical presentation on the outcome of acute 66. Singh K, Bønaa KH, Jacobsen BK, Bjørk L, Solberg S. Prevalence of and risk
B aortic dissection: evidences from IRAD. J Cardiovasc Surg (Torino). factors for abdominal aortic aneurysms in a population-based study: the
2012;53:161–168. Tromsø Study. Am J Epidemiol. 2001;154:236–244.
54. Filardo G, Powell JT, Martinez MAM, Ballard DJ. Surgery for small asymp- 67. Lederle FA. In the clinic: abdominal aortic aneurysm. Ann Intern Med.
tomatic abdominal aortic aneurysms. Cochrane Database Syst Rev. 2009;150:ITC5–ITC1. doi: 10.7326/0003-4819-150-9-200905050-01005.
2015;(2):CD001835. 68. De Rango P, Farchioni L, Fiorucci B, Lenti M. Diabetes and abdominal aortic
55. Karthikesalingam A, Holt PJ, Vidal-Diez A, Ozdemir BA, Poloniecki aneurysms. Eur J Vasc Endovasc Surg. 2014;47:243–261. doi: 10.1016/j.
JD, Hinchliffe RJ, Thompson MM. Mortality from ruptured abdomi- ejvs.2013.12.007.
nal aortic aneurysms: clinical lessons from a comparison of outcomes 69. Robson JC, Kiran A, Maskell J, Hutchings A, Arden N, Dasgupta B,
in England and the USA. Lancet. 2014;383:963–969. doi: 10.1016/ Hamilton W, Emin A, Culliford D, Luqmani RA. The relative risk of aortic
S0140-6736(14)60109-4. aneurysm in patients with giant cell arteritis compared with the general
56. Dua A, Kuy S, Lee CJ, Upchurch GR Jr, Desai SS. Epidemiology of aortic population of the UK. Ann Rheum Dis. 2015;74:129–135. doi: 10.1136/
aneurysm repair in the United States from 2000 to 2010. J Vasc Surg. annrheumdis-2013-204113.
2014;59:1512–1517. doi: 10.1016/j.jvs.2014.01.007. 70. Brewster DC, Cronenwett JL, Hallett JW Jr, Johnston KW, Krupski WC,
57. Jackson RS, Chang DC, Freischlag JA. Comparison of long-term sur- Matsumura JS; Joint Council of the American Association for Vascular
vival after open vs endovascular repair of intact abdominal aortic aneu- Surgery and Society for Vascular Surgery. Guidelines for the treatment
rysm among Medicare beneficiaries. JAMA. 2012;307:1621–1628. doi: of abdominal aortic aneurysms: report of a subcommittee of the Joint
10.1001/jama.2012.453. Council of the American Association for Vascular Surgery and Society
58. Schermerhorn ML, Buck DB, O’Malley AJ, Curran T, McCallum JC, Darling for Vascular Surgery. J Vasc Surg. 2003;37:1106–1117. doi: 10.1067/
J, Landon BE. Long-term outcomes of abdominal aortic aneurysm in the mva.2003.363.

23. QUALITY OF CARE Abbreviations Used in Chapter 23 Continued
CLINICAL STATEMENTS
See Tables 23-1 through 23-11 and
AND GUIDELINES
N/A not available or not applicable
Chart 23-1 NM not measured
NSTEMI non–ST-segment–elevation myocardial infarction
Click here to return to the Table of Contents OHCA out-of-hospital cardiac arrest
OR odds ratio
The Institute of Medicine has defined quality of care as PA physical activity
“the degree to which health services for individuals and
PINNACLE Registry Practice Innovation and Clinical Excellence
populations increase the likelihood of desired health Registry
outcomes and are consistent with current professional PPO preferred provider organization
knowledge.”1 The Institute of Medicine has defined 6 ROC Resuscitation Outcomes Consortium
RR relative risk
Abbreviations Used in Chapter 23 SBP systolic blood pressure
ACEI angiotensin-converting enzyme inhibitor
SF-12 12-item Short Form
ACS acute coronary syndrome
STEMI ST-segment–elevation myocardial infarction
ACTION Registry- Acute Coronary Treatment and Intervention TAVR transcatheter aortic valve replacement
GWTG Outcomes Network Registry–Get With the
TIA transient ischemic stroke
Guidelines (now known as ACTION Registry)
tPA tissue-type plasminogen activator
AED automated external defibrillator
UFH unfractionated heparin
VT/VF ventricular tachycardia/ventricular fibrillation
YLL years of life lost
ARB angiotensin receptor blocker
specific domains for improving health care, including
BMI body mass index
BP blood pressure
care that is safe, effective, patient centered, timely, effi-
CAD coronary artery disease cient, and equitable.
CHD coronary heart disease In the following sections, data on quality of care will
CHF congestive heart failure be presented across these 6 domains to highlight cur-
CI confidence interval rent care and to stimulate efforts to improve the qual-
COURAGE Clinical Outcomes Utilizing Revascularization and ity of cardiovascular care nationally. Where possible,
Aggressive Drug Evaluation
CPR cardiopulmonary resuscitation
data are reported from recently published literature or
CVD cardiovascular disease as standardized quality indicators drawn from quality-
D2B door-to-balloon improvement registries whose methods are consistent
DM diabetes mellitus with performance measures endorsed by the ACC and
DNR do not resuscitate the AHA.2 Additional data related to quality of care,
DVT deep vein thrombosis such as adherence to ACC/AHA clinical practice guide-
ECG electrocardiogram
lines, are also included to provide a spectrum of quality-
of-care data. The data selected are meant to provide
EMS emergency medical services current examples of quality of care and are not meant
ETco2 end-tidal carbon dioxide to be comprehensive given the sheer number of publi-
GBD Global Burden of Disease cations yearly.
HbA1c hemoglobin A1c (glycosylated hemoglobin)
HF heart failure Safety
HMO health maintenance organization
The safety domain has been defined as avoiding injuries
HR hazard ratio
IHCA in-hospital cardiac arrest
to patients from the care that is intended to help them.
IHD ischemic heart disease The following publications have focused on safety
IQR interquartile range issues related to cardiac care:
IV intravenous • Using the CathPCI Registry, Tsai et al3 found that
KCCQ Kansas City Cardiomyopathy Questionnaire almost one fourth of dialysis patients undergo-
ing PCI (N=22 778) received a contraindicated
LV left ventricular
LVEF left ventricular ejection fraction
antithrombotic agent, specifically enoxaparin,
LVSD left ventricular systolic dysfunction eptifibatide, or both. Patients who received a
MD medical doctor contraindicated antithrombotic agent had an
MET metabolic equivalent increased risk of in-hospital bleeding (OR, 1.63;
(Continued ) 95% CI, 1.35–1.98).

• Using data from the PINNACLE Registry, Hira and aspirin was prescribed to 73% of patients treated
CLINICAL STATEMENTS
colleagues4 showed that among 27 533 patients with PCI and 44.6% of patients managed medi-
AND GUIDELINES
receiving prasugrel, 13.9% (N=3824) had a con- cally; 56.7% of patients with an in-hospital bleed-
traindication to prasugrel use (ie, history of TIA ing event were also discharged on high-dose
or stroke). This was considered inappropriate pra- aspirin. Among 9075 patients discharged on aspi-
sugrel use. A further 4.4% of patients (N=1210) rin, thienopyridine, and warfarin, 44.0% were
were receiving it for a nonrecommended indi- prescribed high-dose aspirin therapy.
cation (age >75 years without history of DM or
MI or weight <60 kg). Both inappropriate and Effectiveness
nonrecommended prasugrel use showed wide
practice-level variation (median rate ratio of 2.89
(See Tables 23-1 through 23-7
[95% CI, 2.75–3.03] and 2.29 [95% CI, 2.05– and Chart 23-1)
2.51], respectively). Effective care has been defined as providing services
• In a random sample of adult medical and surgical based on scientific knowledge to all who could ben-
care patients (not specifically patients with CVD) efit and refraining from providing services to those not
in Massachusetts hospitals, López et al5 assessed likely to benefit from them. It also encompasses moni-
the association between disclosure of an adverse toring results of the care provided and using them to
event and patients’ perception of quality of care. improve care for all patients.1
Overall, only 40% of adverse events were dis- • Using data from the ACTION Registry-GWTG,
closed. Higher quality ratings were associated among 202 213 patients discharged after AMI
with disclosure of an adverse event. Conversely, from 526 US participating sites between January
lower patient perception of quality of care was 2007 and March 2011, Rao and colleagues9
associated with events that were preventable and showed that only 14.5% of the eligible patients
with events that caused discomfort. without a documented contraindication received
• In an analysis from the PINNACLE Registry, Hira aldosterone antagonists. Fewer than 2% of the
and colleagues6 showed that among 68 808 participating sites used aldosterone antagonists in
patients receiving aspirin therapy for primary pre- ≥50% of eligible patients.
vention, roughly 11.6% (7972 of 68 808) were • Data from the PINNACLE Registry showed that
receiving inappropriate aspirin therapy (10-year
among 156 145 CAD patients in 58 practices, just

risk of CVD <6%). There was significant practice- over two thirds (N=103 830, 66.5%) of patients
level variation in inappropriate aspirin use (range, were prescribed the optimal combination of
0%–71.8%; median, 10.1%; IQR, 6.4%) for medications (β-blockers, ACEIs/ARBs, statins) for
practices with an adjusted median rate ratio of which they were eligible. After adjustment for
1.63 (95% CI, 1.47–1.77).6 patient factors, the practice median rate ratio for
• Using Medicare Patient Safety Monitoring System prescription was 1.25 (95% CI, 1.20–1.32), which
data abstracted from medical records on 21 indicates a 25% likelihood that any 2 practices
specific adverse events in 4 categories (adverse would differ in treating identical CAD patients.10
drug events, general events, hospital-acquired Another study from the PINNACLE Registry
infection, and postprocedural events) for 61 523 showed that among 215 193 patients with DM
patients hospitalized between 2005 and 2011 without concomitant CVD, statins were pre-
for AMI, CHF, pneumonia, or conditions requiring scribed in only 61.6% of the patients. The median
surgery, Wang et al7 reported that among patients practice statin prescription rate was 62.3% (IQR,
with AMI, the rate of occurrence of adverse events 55.7%–68.1%). The adjusted median rate ratio
declined from 5.0% to 3.7% (difference, 1.3%; was 1.57 (95% CI, 1.52–1.61), which suggests
95% CI, 0.7%–1.9%). Among patients with CHF, a 57% practice-level variation in statin use for 2
the rate of occurrence of adverse events declined similar patients.11
from 3.7% to 2.7% (difference, 1.0%; 95% CI, • A study from a national cohort of 972 532 CVD
0.5%–1.4%). Patients with pneumonia and those patients in the Veterans Health Administration
with conditions requiring surgery had no signifi- showed that females with CVD (N=13 371) were
cant declines in adverse event rates. less likely than males to receive statins (57.6%
• Using aspirin dosing data from 221 199 patients versus 64.8%; P<0.0001) or high-intensity statins
with MI enrolled in the ACTION Registry-GWTG, (21.1% versus 23.6%; P<0.0001) as recom-
Hall and colleagues8 showed a 25-fold variation mended in the 2013 ACC/AHA cholesterol man-
in the use of high-dose aspirin (325 mg/d) across agement guideline. In adjusted models, female
participating centers. Overall, 60.9% of patients sex was independently associated with a lower
were discharged on high-dose aspirin. High-dose likelihood of receiving statins (OR, 0.68; 95% CI,

0.66–0.71) or high-intensity statins (OR, 0.76; (90.0% versus 91.1%, P=0.47). The composite
CLINICAL STATEMENTS
95% CI, 0.73–0.80). The authors concluded 1-year outcome of death or all-cause readmission
AND GUIDELINES
that although females with CVD are less likely to rates was also not different between the 2 groups
receive evidence-based statin and high-intensity (median 62.9% versus 65.3%; P=0.10). The high
statins than males, use of statins remains low in HF excess readmission ratio group had higher
both sexes.12 1-year all-cause readmission rates (median 59.1%
• Stub et al13 reported a post hoc secondary analy- versus 54.7%; P=0.01); however, 1-year mortal-
sis of a large, partial factorial trial of interventions ity rates were lower among the high versus low
for patients with OHCA. The quality of hospital- group, with a trend toward statistical significance
based postresuscitation care given to each patient (median 28.2% versus 31.7%; P=0.07). The
was assigned an evidence-based quality score authors concluded that the quality of care and
that considered (1) initiation of temperature man- clinical outcomes were comparable among hospi-
agement; (2) achievement of target temperature tals with high versus low risk-adjusted 30-day HF
32°C to 34°C; (3) continuation of temperature readmission rates.15
management for >12 hours; (4) performance of • In a comparative effectiveness study of single-
coronary angiography within 24 hours; and (5) versus dual-chamber implantable cardioverter-
no withdrawal of life-sustaining treatment before defibrillators using data from the Implantable
day 3. These were aggregated as hospital-level Cardioverter Defibrillator Registry, Peterson and
composite performance scores, which varied colleagues16 found that among patients receiv-
widely (median [IQR] scores from lowest to high- ing an implantable cardioverter-defibrillator for
est hospital quartiles, 21% [20%–25%] versus primary prevention without indications for pac-
59% [55%–64%]). Adjusted survival to discharge ing, the use of a dual-chamber device compared
increased with each quartile of composite per- with a single-chamber device was associated with
formance score (from lowest to highest: 16.2%, a higher risk of device-related complications and
20.8%, 28.5%, and 34.8%; P<0.01). Adjusted similar 1-year mortality and hospitalization out-
rates of favorable neurological outcome also comes. In a propensity-matched cohort, rates
increased (from lowest quartile to highest: 8.3%, of complications were lower for single-chamber
13.8%, 22.2%, and 25.9%; P<0.01). Hospital devices (3.51% versus 4.72%; P<0.001; risk dif-
score was significantly associated with outcome ference, −1.20 [95% CI, −1.72 to −0.69]), but
after risk adjustment for established baseline fac- device type was not significantly associated with
tors (highest versus lowest adherence quartile: 1-year mortality (unadjusted rate, 9.85% versus
adjusted OR of survival, 1.64; 95% CI, 1.13–2.38). 9.77%; HR, 0.99 [95% CI, 0.91–1.07]; P=0.79),
• Ong et al14 reported results of the effectiveness of 1-year all-cause hospitalization (unadjusted rate,
a combined health coaching telephone call and 43.86% versus 44.83%; HR, 1.00 [95% CI, 0.97–
telemonitoring intervention after discharge of 1.04]; P=0.82), or hospitalization for HF (unad-
patients after hospitalization for HF (715 patients justed rate, 14.73% versus 15.38%; HR, 1.05
randomized to the intervention arm and 722 to [95% CI, 0.99–1.12]; P=0.19).
the usual care arm). The intervention was not • In 2013, investigators from the GBD 2010 study
associated with the primary outcome (readmis- described their findings from a systematic analy-
sion for any cause) within 180 days after dis- sis of disease burden, injuries, and leading risk
charge. The primary outcome occurred in 50.8% factors in the United States and compared them
of patients in the intervention arm and 49.2% of with those of 34 countries in the Organization for
the patients in the usual care arm (HR, 1.03; 95% Economic Co-operation and Development. They
CI, 0.88–1.20).14 reported that the US life expectancy for both
• Pandey et al reported results from the GWTG-HF sexes combined increased from 75.2 years in
registry evaluating the association between the HF 1990 to 78.2 years in 2010. During the same time
excess readmission ratio and performance mea- period, healthy life expectancy (ie, the number of
sures, in-hospital, and 1-year clinical outcomes. years that a person at a given age can expect to
They stratified participating centers into groups live in good health, taking into account mortality
with low (HF excess readmission ratio ≤1) versus and disability) increased from 65.8 to 68.1 years
high (HF excess readmission ratio >1) risk-adjusted in the United States. Despite declines in the YLLs
readmission rates. There were no differences because of premature mortality secondary to IHD
between the low and high risk-adjusted 30-day and stroke, 15.9% of YLLs were related to IHD
readmission groups in median adherence rate to and 4.3% of YLLs were related to stroke in the
all performance measures (95.7% versus 96.5%, United States in 2010, which highlights the con-
P=0.37) or median percentage of defect-free care tinued dominance of CVD in causing premature

death. Despite these absolute improvements, the — The median (IQR) risk-standardized 30-day
CLINICAL STATEMENTS
US rank among 34 countries in the Organization readmission rate was 16.4% (16.1%, 16.7%)
AND GUIDELINES
for Economic Co-operation and Development for AMI, 21.7% (21.1%, 22.4%) for HF, and
changed from 18th to 27th for the age-stan- 12.3% (12.0%, 12.7%) for ischemic stroke.
dardized death rate, from 20th to 27th for life • Inpatient ACS, HF, and stroke quality-of-care
expectancy at birth, from 14th to 26th for healthy measures data, including trends in care data,
life expectancy, and from 23rd to 28th for the where available from national registries, are given
age-standardized YLL. These results indicate that in Tables 23-1 through 23-4.
improvements in population health in the United • Selected outpatient quality-of-care measures from
States have not kept pace with advances in popu- the National Committee for Quality Assurance
lation health in other wealthy nations.17 Health Plan Employed Data and Information Set
• A randomized study that evaluated the utility Measures of Care for 2015 appear in Table 23-5.
of lifestyle-focused text messaging intervention • Quality-of-care measures for patients who had
(352 patients in the intervention group and 358 OHCA and were enrolled in the ROC cardiac
patients in the control group) among patients arrest registry in 2014 (ROC Investigators, unpub-
with CHD showed at 6 months of follow-up that lished data, November 23, 2014) are given in
there were statistically significant reductions in Table 23-6. Longitudinal measures are also avail-
LDL-C levels (mean difference, −5 mg/dL; 95% able (Chart 23-1).
CI, −9 to 0), SBP (−7.6 mm Hg; 95% CI, −9.8 to • Quality-of-care measures for patients who had
−5.4), BMI (−1.3 kg/m2; 95% CI, −1.6 to −0.9]), IHCA and were enrolled in the AHA’s GWTG-
and smoking (RR, 0.61; 95% CI, 0.48–0.76) and Resuscitation quality improvement project in
a statistically significant increase in PA (345 MET 2016 are given in Table 23-7.
min/week; 95% CI, 195–495).18
• Bucholz and colleagues19 showed that patients
admitted to high-performing hospitals after AMI Patient-Centered Care
had longer life expectancies than patients treated Patient-centered care has been defined as the provi-
at low-performing hospitals. This survival benefit sion of care that is respectful of and responsive to indi-
appeared in the first 30 days and persisted over vidual patient preferences, needs, and values and that
17 years of follow-up. The study sample included ensures that patient values guide all clinical decisions.
119 735 patients with AMI who were admitted Dimensions of patient-centered care include the follow-
to 1824 hospitals. On average, patients treated ing: (1) respect for patients’ values, preferences, and
at high-performing hospitals lived between 0.74 expressed needs; (2) coordination and integration of
and 1.14 years longer than patients treated at care; (3) information, communication, and education;
low-performing hospitals. (4) physical comfort; (5) emotional support; and (6)
• In a longitudinal cohort study of 48 million hos- involvement of family and friends. Studies that focused
pitalizations among 20 million Medicare fee-for- on some of these aspects of patient-centered care are
service patients across 3497 hospitals, Desai and highlighted below.
colleagues20 showed patients at hospitals sub- • Okunrintemi et al22 reported results from a nation-
ject to penalties under the Hospital Readmission ally representative survey of 6810 patients with
Reduction Program had greater reductions in ASCVD representing 18.3 million US adults. They
readmission rates than those at nonpenalized assessed whether consumer-reported patient-pro-
hospitals. Reductions in readmission rates were vider communication, as assessed by Consumer
greater for target versus nontarget conditions for Assessment of Health Plans Surveys, was associ-
patients at the penalized hospitals but not at non- ated with evidence-based medication use, health-
penalized hospitals. care resource utilization, and cost. ASCVD patients
• Outcome measures of 30-day mortality and who reported poor versus optimal patient-pro-
30-day readmission after hospitalization for AMI, vider communication scores were 52% and 26%
HF, or ischemic stroke have been developed that more likely to report that they were not taking
adjust for patient mix (eg, comorbidities) so that a statin or aspirin, respectively; had significantly
comparisons can be made across hospitals.21 greater utilization of health resources (OR for ≥2
According to national Medicare data from July ED visits, 1.41 [95% CI, 1.09–1.81]; OR for ≥2
2014 through June 2015: hospitalizations, 1.36 [95% CI, 1.04–1.79]); and
— The median (IQR) hospital risk-standardized had an estimated $1243 ($127-$2359) higher
mortality rate was 13.9% (13.3%, 14.5%) annual healthcare expenditure.
for AMI, 12.1% (11.3%, 12.9%) for HF, and • The COURAGE trial, which investigated a strat-
14.7% (14.0%, 15.6%) for ischemic stroke. egy of PCI plus optimal medical therapy versus

optimal medical therapy alone, demonstrated communication (regression coefficient −0.85) or
CLINICAL STATEMENTS
that both groups had significant improvement physician communication (regression coefficient
AND GUIDELINES
in health status during follow-up. By 3 months, −0.87) were significantly associated with lower
health status scores had increased in the PCI risk-adjusted HF 30-day readmissions. The authors
group compared with the medical therapy group, concluded that these associations support contin-
to 76±24 versus 72±23 for physical limitation ued reevaluation of these measures and increased
(P=0.004), 77±28 versus 73±27 for angina sta- emphasis on patient experience and outcomes, as
bility (P=0.002), 85±22 versus 80±23 for angina planned for the Value-Based Purchasing program
frequency (P<0.001), 92±12 versus 90±14 for of the Centers for Medicare & Medicaid Services.
treatment satisfaction (P<0.001), and 73±22 ver- • McClellan et al26 reported the association between
sus 68±23 for quality of life (P<0.001). The PCI patient-initiated electronic messaging (e-messag-
plus optimal medical therapy group had a small ing) and quality of care for patients with hyper-
but significant incremental benefit compared tension and DM in a fee-for-service setting. They
with the optimal medical therapy group early on, compared the quality of care among patients
but this benefit disappeared by 36 months.23 using e-messaging (before and after program ini-
• A randomized trial tested a multifaceted interven- tiation) relative to nonmessaging patients. Their
tion to improve adherence to 4 cardioprotective results showed that although patient initiated
medications (clopidogrel, statins, ACEIs/ARBs, e-messaging was associated with a small (1%–
and β-blockers) after ACS. A total of 253 patients 7%) but statistically significant increased prob-
were randomized to either a multifaceted inter- ability of completing recommended tests (HbA1c
vention (including pharmacist-led medication or LDL-C measurement and BP measurement), no
reconciliation and tailoring; patient education; consistent associations were found between ini-
collaborative care between a pharmacist and a tiating e-messages and test values (mean HbA1c,
patient’s primary care provider and/or cardiologist; mean SBP, mean LDL-C) or whether test values
and 2 types of voice messaging for patient educa- were controlled (HbA1c ≤8%, LDL-C ≤100 mg/dL,
tion and medication refill reminder) or to usual BP ≤140/90 mm Hg). The authors concluded that
care. After a 1-year period, 89.3% of the patients patient-initiated e-messaging could increase the
in the intervention group were adherent to the likelihood of completing recommended tests but
4 cardioprotective medications (mean proportion might not be sufficient to improve clinical out-
of days covered >0.8) compared with 73.9% in comes for most patients with DM or hypertension
the usual care group (P=0.003). A greater propor- without additional interventions.26
tion of patients in the intervention arm than in • Reynolds et al27 reported results on health-related
the usual care group were adherent to clopidogrel quality of life after TAVR in inoperable patients
(86.8% versus 70.7%; P=0.03), statins (93.2% with severe aortic stenosis compared with those
versus 71.3%; P<0.001), and ACEIs/ARBs (93.1% receiving standard therapy. Health-related qual-
versus 81.7%; P=0.03) but not β-blockers (88.1% ity of life was assessed at baseline and at 1, 6,
versus 84.8%; P=0.59). There were no statisti- and 12 months with the KCCQ and the 12-item
cally significant differences in the proportion of SF-12 Health Survey. Although the KCCQ sum-
patients who achieved BP or LDL-C level goals.24 mary scores improved in both groups, the extent
• Dy et al25 reported results of a cross-sectional of improvement was greater in the TAVR group
study of 895 US hospitals in the Press Ganey data- than in the standard care group at 1 month
base from July 2008 to June 2011. They evalu- (mean between-group difference, 13 points;
ated the outcome of the Centers for Medicare 95% CI, 8–19 points), with larger benefits at 6
& Medicaid Services Hospital Compare website’s months (mean difference, 21 points; 95% CI,
hospital-level risk-adjusted 30-day HF mortality 15–27 points) and 12 months (mean difference,
and readmission with HF processes of care and 26 points; 95% CI, 19–33 points). At 12 months,
patient-reported perspective (Hospital Consumer TAVR patients also reported higher physical and
Assessment of Healthcare Providers and Systems mental health scores on the 12-item SF-12 Health
domains for HF). Results showed no significant Survey, with a mean difference of 5.7 and 6.4
association between process measures and lower points, respectively (P<0.001 for both compari-
mortality or readmissions in adjusted analyses; sons) compared with standard care.
however, higher ratings on Hospital Consumer • In a qualitative study of shared decision making,
Assessment of Healthcare Providers and Systems Rothberg and colleagues28 showed that in conver-
patient perspectives of care were significantly sations between cardiologists and patients with
correlated with lower readmissions in adjusted stable angina, informed decision making was
analyses. For example, a higher rating on nurse often incomplete. Of 59 conversations conducted

by 23 cardiologists, 2 (3%) included all 7 elements P<0.0001). By contrast, risk-adjusted in-hospital

CLINICAL STATEMENTS
of informed decision making, whereas 8 (14%) and 6-month mortality at the population level,
AND GUIDELINES
met a more limited definition of procedure, alter- independent of patient-specific D2B times, rose in
natives, and risks. Neither the presence of angina the growing and changing population of patients
nor severity of symptoms was associated with undergoing primary PCI during the study period.
choosing angiography and possible PCI. These authors concluded that the absence of an
association of annual D2B time and changes in
mortality at the population level should not be
Timely Care interpreted as an indication of its individual-level
(See Table 23-8) relation in patients with STEMI undergoing pri-
The timely care domain relates to reducing waits and mary PCI.
sometimes harmful delays for both those who receive • A study of 204 591 patients with ischemic and
and those who give care. Timeliness is an important hemorrhagic strokes admitted to 1563 GTWG-
characteristic of any service and is a legitimate and Stroke participating hospitals between April 1,
valued focus of improvement in health care and other 2003, and June 30, 2010, showed that 63.7% of
industries. the patients arrived at the hospital by EMS. Older
• Among patients who underwent primary PCI for patients, those with Medicaid and Medicare, and
STEMI and were enrolled in the CathPCI Registry those with severe strokes were more likely to
(N=96 738) in a period that coincided with activate EMS. Conversely, minority race/ethnicity
national efforts to reduce D2B times, median D2B (black, Hispanic, Asian) and living in rural com-
times declined from 83 minutes in the 12 months munities were associated with a lower likelihood
from July 2005 to June 2006 to 67 minutes in of EMS use. EMS transport was independently
the 12 months from July 2008 to June 2009. associated with an onset-to-door time ≤3 hours,
This improvement in processes of care was not a higher proportion of patients meeting door-
associated with improved outcome (risk-adjusted to-imaging time of ≤25 minutes, more patients
in-hospital mortality 5.0% in 2005–2006 versus meeting a door-to-needle time of ≤60 minutes,
4.7% in 2008–2009; P=0.34).29 and more eligible patients being treated with tPA
• Glickman et al30 showed that a year-long imple- if onset of symptoms was ≤2 hours. The authors
mentation of standardized protocols as part of a concluded that although EMS use was associated
statewide regionalization program was associated with rapid evaluation and treatment of stroke,
with a significant improvement in median door- more than one third of stroke patients fail to use
in–door-out times among 436 STEMI patients EMS.32
who presented at non-PCI hospitals who required • Data on time to reperfusion for STEMI or ischemic
transfer (before intervention: 97 minutes [IQR, stroke are provided from national registries in
56–160 minutes]; after intervention: 58 minutes Table 23-8.
[IQR, 35–90 minutes]; P<0.0001).
• Nallamothu et al31 evaluated the association
between D2B times and mortality after primary Efficiency
PCI over time at both the hospital and the individ- Efficiency has been defined as avoiding waste, in par-
ual patient level among 150 116 STEMI patients ticular waste of equipment, supplies, ideas, and energy.
from 423 hospitals who underwent primary PCI In an efficient healthcare system, resources are used to
between January 1, 2005, and December 31, get the best value for the money spent.
2011, in the CathPCI Registry. Annual D2B times • A study of 35 191 CHD patients from the US
decreased significantly from a median of 86 min- Department of Veterans Affairs healthcare system
utes (IQR, 65–109 minutes) in 2005 to 63 min- showed that among 27 947 patients with LDL-C
utes (IQR, 47–80 minutes) in 2011 (P<0.0001), levels <100 mg/dL, 9200 (32.9%) received addi-
with a concurrent rise in risk-adjusted in-hospi- tional lipid assessments without any treatment
tal mortality (from 4.7% to 5.3%; P=0.06) and intensification during the 11 months from the
risk-adjusted 6-month mortality (from 12.9% to index lipid panel. Even among 13 114 patients
14.4%; P=0.001). In multilevel models, shorter with LDL-C <70 mg/dL, repeat lipid testing was
patient-specific D2B times were consistently asso- performed in 8177 patients (62.4%) during 11
ciated at the individual level with lower in-hos- months of follow-up. These results show that
pital mortality (adjusted OR for each 10-minute redundant lipid testing is common in patients
decrease, 0.92; 95% CI, 0.91–0.93; P<0.0001) with CHD.33
and 6-month mortality (adjusted OR for each • In a recent study from the PINNACLE Registry, the
10-minute decrease, 0.94; 95% CI, 0.93–0.95; authors compared the quality of care delivered

by physicians and advanced practice providers patients undergoing PCI for nonacute indications
CLINICAL STATEMENTS
(nurse practitioners and physicians assistants) for (28.9% of the cohort), 50.4% of the procedures
AND GUIDELINES
459 669 patients with CAD, HF, or AF. Compliance were classified as appropriate, 38% as uncertain,
with most CAD, HF, and AF measures was com- and 11.6% as inappropriate. There was also sub-
parable, except for a higher rate of smoking ces- stantial variation for inappropriate nonacute PCI
sation screening and intervention (adjusted rate across hospitals (median hospital rate, 10.8%;
ratio, 1.14; 95% CI, 1.03–1.26) and cardiac reha- IQR, 6.0%–16.7%).
bilitation referral (rate ratio, 1.40; 95% CI, 1.16–
1.70) among CAD patients receiving care from
advanced practice providers. Compliance with all
Equitable Care
eligible CAD measures was low for both (12.1% (See Tables 23-9 through 23-11)
and 12.2% for advanced practice providers and Equitable care means the provision of care that does
physicians, respectively), with no significant dif- not vary in quality because of personal characteristics
ference. The authors concluded that apart from such as sex, ethnicity, geographic location, and SES sta-
minor differences, a collaborative care delivery tus. The aim of equity is to secure the benefits of quality
model using both physicians and advanced prac- health care for all the people of the United States. With
tice providers could deliver an overall comparable regard to equity in caregiving, all individuals rightly
quality of outpatient cardiovascular care com- expect to be treated fairly by local institutions, includ-
pared with a physician-only model.34 ing healthcare organizations.
• Himmelstein et al35 analyzed whether more- • Data on the quality of care by race/ethnicity and
computerized hospitals had lower costs of care sex in the ACTION Registry-GWTG (2014) are pro-
or administration or better quality, to address a vided in Table 23-9. Data on the quality of care by
common belief that computerization improves race/ethnicity and sex in the GWTG-HF Program
healthcare quality, reduces costs, and increases (2016) are provided in Table 23-10. Data on the
administrative efficiency. They found that hos- quality of care by race/ethnicity and sex in the
pitals that increased computerization faster GWTG-Stroke Program (2016) are provided in
had more rapid administrative cost increases Table 23-11.
(P=0.0001); however, higher overall computer- • Chan et al38 demonstrated that rates of survival to
ization scores correlated weakly with better qual-
discharge were lower for black patients (25.2%)

ity scores for AMI (r=0.07, P=0.003) but not for than for white patients (37.4%) after IHCA.
HF, pneumonia, or the 3 conditions combined. In Lower rates of survival to discharge for blacks
multivariate analyses, more-computerized hospi- reflected lower rates of both successful resuscita-
tals had slightly better quality. For example, the tion (55.8% versus 67.4%) and postresuscitation
overall computerization score was associated with survival (45.2% versus 55.5%). Adjustment for
a modes effect on better composite quality score the hospital site at which patients received care
(parameter estimate=2.36; P=0.013) The authors explained a substantial portion of the racial dif-
concluded that hospital computing might mod- ferences in successful resuscitation (adjusted RR,
estly improve process measures of quality but 0.92; 95% CI, 0.88–0.96; P<0.001) and elimi-
does not reduce administrative or overall costs. nated the racial differences in postresuscitation
• Makam and Nguyen36 showed cardiac biomarker survival (adjusted RR, 0.99; 95% CI, 0.92–1.06;
testing in the ED is common even among those P=0.68). The authors concluded that much of the
without symptoms suggestive of ACS. Biomarker racial difference was associated with the hospital
testing occurred in 8.2% of visits in the absence center in which black patients received care.
of symptoms related to ACS, representing 8.5 • Cohen et al39 demonstrated that among hos-
million visits. Among individuals who were sub- pitals engaged in a national quality monitor-
sequently hospitalized, cardiac biomarkers were ing and improvement program, evidence-based
tested in 47% of all visits. Biomarkers were care for AMI appeared to improve over time for
tested in 35.4% of visits in this group despite the patients irrespective of race/ethnicity, and differ-
absence of ACS-related symptoms. ences in care by race/ethnicity care were reduced
• In a multicenter study of patients undergoing PCI, or eliminated. They analyzed 142 593 patients
Chan et al37 reported results of the appropriate- with AMI (121 528 whites, 10 882 blacks, and
ness of PCI for both acute and nonacute indica- 10 183 Hispanics) at 443 hospitals participating
tions. Among patients undergoing PCI for acute in the GWTG-CAD program. Overall, defect-free
indications (71.1% of the cohort), 98.5% of the care was 80.9% for whites, 79.5% for Hispanics
procedures were classified as appropriate, 0.3% (adjusted OR versus whites, 1.00; 95% CI, 0.94–
as uncertain, and 1.1% as inappropriate. Among 1.06; P=0.94), and 77.7% for blacks (adjusted OR

versus whites, 0.93; 95% CI, 0.87–0.98; P=0.01). rates but not mortality. An increase of 1 IQR of
CLINICAL STATEMENTS
A significant gap in defect-free care was observed median county consumer price index–adjusted
AND GUIDELINES
for blacks during the first half of the study but income was associated with a decline of 46 and
was no longer present during the remainder of 37 AMI hospitalizations per 100 000 person-years
the study. Overall, progressive improvements for 1999 and 2013, respectively.
in defect-free care were observed regardless of • Al-Khatib et al42 analyzed implantable cardioverter-
racial/ethnic groups. defibrillator use for primary prevention among
• Thomas et al40 analyzed data among hospitals that 11 880 patients with a history of HF, LVEF <35%,
voluntarily participated in the AHA’s GWTG-HF and age >65 years enrolled in the GWTG-HF reg-
program from January 2005 through December istry from January 2005 through December 2009.
2008. Relative to white patients, Hispanic and From 2005 to 2007, overall implantable cardio-
black patients hospitalized with HF were signifi- verter-defibrillator use increased from 30.2% to
cantly younger (median age 78, 63, and 64 years, 42.4% and then remained unchanged in 2008 to
respectively) but had lower EFs (mean EF 41.1%, 2009. After adjustment for confounders, implant-
38.8%, and 35.7%, respectively) with a higher able cardioverter-defibrillator use increased sig-
prevalence of DM (40.2%, 55.7%, and 43.8%, nificantly in the overall study population during
respectively) and hypertension (70.6%, 78.4%, 2005 to 2007 (OR, 1.28; 95% CI, 1.11–1.48 per
and 82.8%, respectively). The provision of guide- year; P=0.0008) and in black females (OR, 1.82;
line-based care was comparable for white, black, 95% CI, 1.28–2.58 per year; P=0.0008), white
and Hispanic patients. Black (1.7%) and Hispanic females (OR, 1.30; 95% CI, 1.06–1.59 per year;
(2.4%) patients had lower in-hospital mortality P=0.010), black males (OR, 1.54; 95% CI, 1.19–
than white patients (3.5%). Improvement in adher- 1.99 per year; P=0.0009), and white males (OR,
ence to all-or-none HF measures increased annually 1.25; 95% CI, 1.06–1.48 per year; P=0.0072).
from year 1 to year 3 for all 3 racial/ethnic groups. The increase in implantable cardioverter-defibril-
• In an observational study, Spatz and colleagues41 lator use was greatest among blacks. They con-
showed the rate of decline in AMI hospitalizations cluded that although previously described racial
from January 1, 1999, to December 31, 2013 for disparities in the use of implantable cardioverter-
low-income counties lagged behind high-income defibrillators were no longer present in their study
counties by 4.3 years (95% CI, 3.1–5.9 years). by the end of the study period, a sex difference in
Income was associated with AMI hospitalization their use persisted.
Table 23-1. AMI Quality-of-Care Measures, 2016

ACTION Registry- ACTION Registry-
Quality-of-Care Measure GWTG STEMI* GWTG NSTEMI*
Aspirin within 24 h of admission† 98.4 97.8
Aspirin at discharge‡ 99.2 98.4
β-Blockers at discharge 98.2 97.0
Lipid-lowering medication at discharge§ 99.6 99.2

ARB/ACEI at discharge for patients with LVEF <40% 92.5 89.8
ACEI at discharge for AMI patients 64.8 52.0
ARB at discharge for AMI patients 12.9 17.0
Adult smoking cessation advice/counseling 98.1 98.1
Cardiac rehabilitation referral for AMI patients 83.4 75.2
Values are percentages. ACEI indicates angiotensin-converting enzyme inhibitor; ACTION Registry-GWTG,
Acute Coronary Treatment and Intervention Outcomes Network Registry–Get With the Guidelines; AMI, acute
myocardial infarction; ARB, angiotensin receptor blocker; LVEF, left ventricular ejection fraction; NSTEMI, non–
ST-segment–elevation myocardial infarction; and STEMI, ST-segment–elevation myocardial infarction.
*ACTION Registry-GWTG: STEMI and NSTEMI patients are reported separately. Patients must be admitted
with acute ischemic symptoms within the previous 24 hours, typically reflected by a primary diagnosis of
STEMI or NSTEMI. Patients who are admitted for any other clinical condition are not eligible. Data reported
include data from the first quarter of 2016 to the fourth quarter of 2016.
†Effective January 1, 2015, this measure was updated in the ACTION Registry-GWTG to exclude patients
who are taking dabigatran, rivaroxaban, or apixaban (novel oral anticoagulant medications) at home.
‡Effective January 1, 2015, this measure was updated in the ACTION Registry-GWTG to exclude patients
who were prescribed dabigatran, rivaroxaban, or apixaban (novel oral anticoagulant medications) at discharge.
§Denotes statin use at discharge. Use of nonstatin lipid-lowering agent was 3.9% for STEMI patients and
6.2% for NSTEMI patients in the ACTION Registry-GWTG.

Table 23-2. HF Quality-of-Care Measures, 2016
CLINICAL STATEMENTS
Quality-of-Care Measure AHA GWTG-HF
AND GUIDELINES
LVEF assessment 98.94
ARB/ACEI at discharge for patients with LVSD 93.66
Complete discharge instructions 94.06
β-Blockers at discharge for patients with LVSD, no 97.81

contraindications
Anticoagulation for AF or atrial flutter, no 85.48
contraindications
Values are percentages. ACEI indicates angiotensin-converting enzyme

inhibitor; AF, atrial fibrillation; AHA, American Heart Association; ARB,
angiotensin receptor blocker; GWTG-HF, Get With the Guidelines–Heart
Failure; HF, heart failure; LVEF, left ventricular ejection fraction; and LVSD, left
ventricular systolic dysfunction.
Table 23-3. Time Trends in ACTION Registry-GWTG CAD Quality-of-Care Measures, 2010 to 2016
Quality-of-Care Measure 2010 2011 2012 2013 2014 2015 2016
Aspirin within 24 h of admission* 97 97.6 97.8 95.4 98.1 98.6 98.5
Aspirin at discharge† 98 98.3 98.4 98.4 98.7 98.7 98.7
β-Blockers at discharge 96 96.7 97.1 97.1 97.6 97.5 97.5
Statin use at discharge 92 98.4 98.8 98.8 99.1 99.2 99.4

ARB/ACEI at discharge for patients with LVEF <40% 86 87.8 89.7 90.0 91.2 90.2 91.0
Adult smoking cessation advice/counseling 98 98.4 98.4 98.4 98.6 98.0 98.1
Cardiac rehabilitation referral for AMI patients 75 76.5 77.3 77.2 79.4 77.8 78.6
Values are percentages. ACEI indicates angiotensin-converting enzyme inhibitor; ACTION Registry-GWTG, Acute Coronary Treatment and
Intervention Outcomes Network Registry–Get With the Guidelines; AMI, acute myocardial infarction; ARB, angiotensin receptor blocker; CAD,
coronary artery disease; and LVEF, left ventricular ejection fraction.
*Effective January 1, 2015, this measure was updated in the ACTION Registry-GWTG to exclude patients taking dabigatran, rivaroxaban, or
apixaban (novel oral anticoagulant medications) at home.
†Effective January 1, 2015, this measure was updated in the ACTION Registry-GWTG to exclude patients who were prescribed dabigatran,
rivaroxaban, or apixaban (novel oral anticoagulant medications) at discharge.
Table 23-4. Additional ACTION Registry-GWTG Quality-of-Care Metrics for AMI

Care, 2016
Quality Metrics Overall STEMI NSTEMI
ECG within 10 min of arrival 68.1 77.0 64.2
Aspirin within 24 h of arrival 98.5 98.4 97.8
Any anticoagulant use* 95.0 96.7 93.8
Dosing errors
UFH dose 49.4 46.9 49.6
Enoxaparin dose 9.0 6.3 9.1
Glycoprotein IIb/IIIa inhibitor dose 5.0 5.2 4.5
Aspirin at discharge 98.7 99.2 98.4
Prescribed statins on discharge 99.4 99.6 99.2
Adult smoking cessation advice/counseling 98.1 98.1 98.1
Cardiac rehabilitation referral 78.6 83.4 75.2
In-hospital mortality† (95% CI) 4.17 (4.01–4.41) 6.17 (5.90–6.64) 2.92 (2.79–3.17)
Values are percentages. Data reported include data from the first quarter of 2015 to the fourth quarter of 2015. ACTION
Registry-GWTG indicates Acute Coronary Treatment and Intervention Outcomes Network Registry–Get With the Guidelines;
AMI, acute myocardial infarction; CI, confidence interval; NSTEMI, non–ST-segment–elevation myocardial infarction; STEMI,
ST-segment–elevation myocardial infarction; and UFH, unfractionated heparin.
*Includes UFH, low-molecular-weight heparin, or direct thrombin inhibitor use.
†Includes all patients.

Table 23-5. National Committee for Quality Assurance Health Plan Employer Data and Information Set Measures
CLINICAL STATEMENTS
of Care, 2015
AND GUIDELINES
Commercial Medicare Medicaid

HMO PPO HMO PPO HMO
AMI
β-Blocker persistence* 84.8 82.0 90.9 90.8 80.5
BP control† 60.5 53.4 67.9 65.6 54.7

DM
HbA1c testing 90.1 88.8 93.2 92.7 86.0
HbA1c >9.0% 33.8 44.3 27.4 26.5 45.4
Eye examination performed 53.7 47.1 68.8 68.4 52.7
Monitoring nephropathy 90.4 87.4 95.5 94.7 90
BP <140/90 mm Hg 60.2 49.7 61.9 55.2 59.0
Advising smokers and tobacco users to quit 75.9 72.1 N/A N/A 75.9
BMI percentile assessment in children and adolescents (3–17 y of age) 61.4 46.0 N/A N/A 64.4
Nutrition counseling (children and adolescents [3–17 y of age]) 58.9 46.6 N/A N/A 60.2
Counseling for physical activity (children and adolescents [3–17 y of age]) 54.8 42.4 N/A N/A 53.4
BMI assessment for adults 18–74 y of age 75.2 56.7 93.3 89.3 80.8
Physical activity discussion in older adults (≥65 y of age) N/A 53.5 55.3 N/A
Physical activity advice in older adults (≥65 y of age) N/A 50.5 49.9 N/A
Values are percentages. AMI indicates acute myocardial infarction; BMI, body mass index; BP, blood pressure; DM, diabetes mellitus; HbA1c, hemoglobin A1c; HMO,
health maintenance organization; N/A, not available or not applicable; and PPO, preferred provider organization.
*β-Blocker persistence: received persistent β-blocker treatment for 6 months after AMI hospital discharge.
†Adults 18 to 59 years of age with BP <140/90 mm Hg, adults aged 60 to 85 years with a diagnosis of DM and BP <140/90 mm Hg, and adults aged 60 to 85
years without a diagnosis of DM and BP <150/90 mm Hg.
Table 23-6. Quality of Care for Patients With Out-of-Hospital Cardiac Arrest at US ROC Sites (January 1,
2014 to December 31, 2014)
Overall Adults Children
Bystander and EMS care*
Bystander CPR, % 46.1 (45.0–47.3) 45.7 (44.6–46.9) 61.4 (54.9–67.9)
Shocked by AED before EMS, % 2.0 (1.7–2.4) 2.1 (1.7–2.4) 1.4 (0.0–3.0)
Chest compression fraction during first 5 min of CPR, % 0.85 (0.12) 0.85 (0.12) 0.83 (0.13)
Compression depth, mm 48.1 (10.7) 48.1 (10.7) 47.2 (9.5)
Preshock pause duration, s 10.8 (11.0) 10.8 (10.9) 16.2 (16.4)
Time to first EMS defibrillator applied, min 8.8 (4.5) 8.8 (4.5) 8.7 (4.2)
Hospital-based metrics†
Hypothermia induced after initial VT/VF, %‡ 66.3 (62.3–70.3) 66.2 (62.1–70.2) 100 (100–100)
No order for withdrawal/DNR during first 72 h, %§ 45.0 (42.1–48.0) 44.8 (41.9–47.8) 100 (100–100)
Implantable cardioverter-defibrillator assessment, initial VT/ 30.3 (24.8–35.8) 30.0 (24.5–35.6) 100 (100–100)
VF, no AMI per MD notes or final ECG interpretation, %‖
Values are mean (95% confidence interval) or mean (SD). Because age is missing for some cases, these cases are not included in either adults or
children, thus explaining why overall rates equal the adult rates when rates for children are not available. AED indicates automated external defibrillator;
AMI, acute myocardial infarction; CPR, cardiopulmonary resuscitation; DNR, do not resuscitate; EMS, emergency medical services; MD, medical doctor;
ROC, Resuscitation Outcomes Consortium; and VT/VF, ventricular tachycardia/ventricular fibrillation.
*Data are from EMS-treated cases.
†During 2014, there was 1 pediatric case with initial rhythm VT/VF admitted to the hospital.
‡Denominator is all cases with initial rhythm VT/VF and admitted to the hospital.
§Denominator is all cases admitted to the hospital.
‖Denominator is all cases with initial rhythm VT/VF, no indication of AMI, no percutaneous coronary intervention, no bypass, and admitted to the
hospital.

Table 23-7. Quality of Care of Patients With In-Hospital
CLINICAL STATEMENTS
Cardiac Arrest Among GWTG-Resuscitation Hospitals,
AND GUIDELINES
2016
Adults Children
Event outside critical care setting 46.3 12.5
All objective CPR data collected 98.7 99.1
ETco2 used during arrest 6.9 33.2
Induced hypothermia after resuscitation
7.6 10.7
from shockable rhythm
Values are mean percentages. CPR indicates cardiopulmonary resuscitation;

ETco2, end-tidal CO2; and GWTG, Get With the Guidelines.
Source: GWTG-Resuscitation Investigators, June 2017.
Table 23-8. Timely Reperfusion for AMI and Stroke, 2016

ACTION-
GWTG-Stroke Registry
Quality-of-Care Measure (for Stroke) GWTG STEMI
STEMI
Thrombolytic agents within 30 min NA 52.0
PCI within 90 min* NA 95.9
Stroke
IV tPA in patients who arrived <2 h 86.74 N/A
after symptom onset, treated ≤3 h
IV tPA in patients who arrived <3.5 h 47.06† N/A
after symptom onset, treated ≤4.5 h
IV tPA door-to-needle time ≤60 min 79.87 N/A
Values are percentages. ACTION Registry-GWTG, Acute Coronary Treatment

and Intervention Outcomes Network Registry; AMI, acute myocardial infarction;

GWTG, Get With the Guidelines; IV, intravenous; N/A, not applicable; PCI,
percutaneous coronary intervention; STEMI, ST-segment–elevation myocardial
infarction; tPA, tissue-type plasminogen activator.
*Excludes transfers.
†IV tPA in patients who arrived <3.5 hours after symptom onset, treated
≤4.5 hours measure was changed in 2016 to include in-hospital strokes in the
denominator.
Table 23-9. Quality of Care by Race/Ethnicity and Sex in the ACTION Registry, 2014
Race/Ethnicity Sex
Quality-of-Care Measure White Black Other Males Females
Aspirin at admission 98.1 98.2 98.3 98.4 97.7
Aspirin at discharge 98.8 98.0 98.8 98.9 98.2
β-Blockers at discharge 97.6 97.2 97.5 97.9 97.0
Time to PCI ≤90 min for STEMI patients 96.1 94.3 96.0 96.2 95.2
ARB/ACEI at discharge for patients with LVEF <40% 91.2 91.7 88.5 91.5 90.5
Statins at discharge 99.1 98.9 99.4 99.3 98.8
Values are percentages. Data reported include data from first quarter of 2015 to fourth quarter of 2015. ACEI indicates
angiotensin-converting enzyme inhibitor; ACTION, Acute Coronary Treatment and Intervention Outcomes Network; ARB, angiotensin
receptor blocker; LVEF, left ventricular ejection fraction; PCI, percutaneous coronary intervention; and STEMI, ST-segment–elevation
myocardial infarction.

Table 23-10. Quality of Care by Race/Ethnicity and Sex in the GWTG-HF Program, 2016
CLINICAL STATEMENTS
Race/Ethnicity Sex
AND GUIDELINES
Quality-of-Care Measure White Black Hispanic Males Females

Postdischarge appointment* 78.35 79.18 70.65 77.64 77.62
Complete set of discharge instructions 93.60 95.21 95.17 94.63 93.37
Measure of LV function* 99.07 99.29 97.01 99.06 98.81
ACEI or ARB at discharge for patients with LVSD, no
93.45 94.83 92.14 93.68 93.83
contraindications*
Smoking cessation counseling, current smokers 92.10 93.96 93.79 93.15 92.49
Evidence-based specific β-blockers* 91.88 94.69 91.52 92.88 92.25
β-Blockers at discharge for patients with LVSD, no

97.82 98.16 96.93 97.95 97.59
contraindications
Hydralazine/nitrates at discharge for patients with LVSD, no
… 31.53 20.00 33.30 28.07
contraindications†
Anticoagulation for AF or atrial flutter, no contraindications 86.11 84.23 83.14 86.10 84.73
Composite quality-of-care measure (using discharge instructions
96.46 96.99 95.79 96.65 96.35
and β-blocker at discharge)
Values are percentages. ACEI indicates angiotensin-converting enzyme inhibitor; AF, atrial fibrillation; ARB, angiotensin receptor blocker; ellipses, data not
available; GWTG-HF, Get With the Guidelines−Heart Failure; LV, left ventricular; and LVSD, left ventricular systolic dysfunction.
*Indicates the 4 key achievement measures targeted in GWTG-HF.
†For black patients only.
Table 23-11. Quality of Care by Race/Ethnicity and Sex in the GWTG-Stroke Program, 2016
Race/Ethnicity Sex
Quality-of-Care Measure White Black Hispanic Males Females
IV tPA in patients who arrived ≤2 h after symptom onset, treated ≤3 h* 86.37 87.38 87.03 87.25 86.23
IV tPA in patients who arrived <3.5 h after symptom onset, treated ≤4.5 h† 45.83 49.24 50.97 47.54 46.58
IV tPA door-to-needle time ≤60 min 79.51 80.11 80.79 81.31 78.37
Thrombolytic complications: IV tPA and life-threatening, serious systemic
10.62 10.77 7.46 10.70 11.00
hemorrhage
Antithrombotic agents <48 h after admission* 97.40 97.08 96.53 97.41 97.10
DVT prophylaxis by second hospital day* 99.24 99.19 99.04 99.21 99.23
Antithrombotic agents at discharge* 98.82 98.40 97.95 98.72 98.46
Anticoagulation for atrial fibrillation at discharge* 96.16 95.63 96.09 96.33 95.94
Therapy at discharge if LDL-C >100 mg/dL or LDL-C not measured or on
98.01 98.33 97.51 98.43 97.68
therapy at admission*
Counseling for smoking cessation* 97.48 97.40 97.11 97.49 97.39
Lifestyle changes recommended for BMI >25 kg/m 2
52.86 54.45 54.37 53.20 53.29
Composite quality-of-care measure 97.89 97.76 97.37 97.95 97.61
Values are percentages. BMI indicates body mass index; DVT, deep vein thrombosis; GWTG, Get With the Guidelines; IV, intravenous; LDL-C, low-density lipoprotein
cholesterol; and tPA, tissue-type plasminogen activator.
*Indicates the 7 key achievement measures targeted in GWTG–Stroke.
†This measure was changed in 2016 to include in-hospital strokes in the denominator.

CLINICAL STATEMENTS
50
AND GUIDELINES
45
40
35
30
Percentage
25
20
15
10
0
2006 2007 2008 2009 2010 2011 2012 2013 2014
Survival EMS Treated Survival First Rhythm Shockable

First Rhythm Shockable Bystander CPR
Lay Use of AED
Chart 23-1. Survival rates after out-of-hospital cardiac arrest in US sites of the Resuscitation Outcomes
Consortium, 2006 to 2014.
AED indicates automated external defibrillator; CPR, cardiopulmonary resuscitation; and EMS, emergency medical services.
Data Registry Acute Coronary Treatment and Intervention Outcomes

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Nallamothu BK, Peterson ED, Rumsfeld JS; National Cardiovascular Data 12. Virani SS, Woodard LD, Ramsey DJ, Urech TH, Akeroyd JM, Shah T, Deswal
Registry. Contraindicated medication use in dialysis patients undergoing A, Bozkurt B, Ballantyne CM, Petersen LA. Gender disparities in evidence-
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10.1001/jama.2009.1800. 2015;115:21–26. doi: 10.1016/j.amjcard.2014.09.041.
4. Hira RS, Kennedy K, Jneid H, Alam M, Basra SS, Petersen LA, Ballantyne 13. Stub D, Schmicker RH, Anderson ML, Callaway CW, Daya MR, Sayre MR,
CM, Nambi V, Chan PS, Virani SS. Frequency and practice-level variation in Elmer J, Grunau BE, Aufderheide TP, Lin S, Buick JE, Zive D, Peterson ED,
inappropriate and nonrecommended prasugrel prescribing: insights from Nichol G; ROC Investigators. Association between hospital post-resuscita-
the NCDR PINNACLE registry. J Am Coll Cardiol. 2014;63(pt A):2876– tive performance and clinical outcomes after out-of-hospital cardiac arrest.
2877. doi: 10.1016/j.jacc.2014.04.011. Resuscitation. 2015;92:45–52. doi: 10.1016/j.resuscitation.2015.04.015.
5. López L, Weissman JS, Schneider EC, Weingart SN, Cohen AP, Epstein AM. 14. Ong MK, Romano PS, Edgington S, Aronow HU, Auerbach AD, Black JT,
Disclosure of hospital adverse events and its association with patients’ rat- De Marco T, Escarce JJ, Evangelista LS, Hanna B, Ganiats TG, Greenberg
ings of the quality of care. Arch Intern Med. 2009;169:1888–1894. doi: BH, Greenfield S, Kaplan SH, Kimchi A, Liu H, Lombardo D, Mangione CM,
10.1001/archinternmed.2009.387. Sadeghi B, Sadeghi B, Sarrafzadeh M, Tong K, Fonarow GC; for the Better
6. Hira RS, Kennedy K, Nambi V, Jneid H, Alam M, Basra SS, Ho PM, Deswal Effectiveness After Transition–Heart Failure (BEAT-HF) Research Group.
A, Ballantyne CM, Petersen LA, Virani SS. Frequency and practice-level Effectiveness of remote patient monitoring after discharge of hospitalized
variation in inappropriate aspirin use for the primary prevention of car- patients with heart failure: the Better Effectiveness After Transition – Heart
diovascular disease: insights from the National Cardiovascular Disease Failure (BEAT-HF) randomized clinical trial [published correction appears
Registry’s Practice Innovation and Clinical Excellence registry. J Am Coll in JAMA Intern Med. 2016;176:568]. JAMA Intern Med. 2016;176:310–
Cardiol. 2015;65:111–121. doi: 10.1016/j.jacc.2014.10.035. 318. doi: 10.1001/jamainternmed.2015.7712.
7. Wang Y, Eldridge N, Metersky ML, Verzier NR, Meehan TP, Pandolfi 15. Pandey A, Golwala H, Xu H, DeVore AD, Matsouaka R, Pencina M,
MM, Foody JM, Ho SY, Galusha D, Kliman RE, Sonnenfeld N, Krumholz Kumbhani DJ, Hernandez AF, Bhatt DL, Heidenreich PA, Yancy CW, de
HM, Battles J. National trends in patient safety for four common con- Lemos JA, Fonarow GC. Association of 30-day readmission metric for
ditions, 2005-2011. N Engl J Med. 2014;370:341–351. doi: 10.1056/ heart failure under the hospital readmissions reduction program with
NEJMsa1300991. quality of care and outcomes. JACC Heart Fail. 2016;4:935–946. doi:
8. Hall HM, de Lemos JA, Enriquez JR, McGuire DK, Peng SA, Alexander 10.1016/j.jchf.2016.07.003.
KP, Roe MT, Desai N, Wiviott SD, Das SR. Contemporary patterns of 16. Peterson PN, Varosy PD, Heidenreich PA, Wang Y, Dewland TA, Curtis JP,
discharge aspirin dosing after acute myocardial infarction in the United Go AS, Greenlee RT, Magid DJ, Normand SL, Masoudi FA. Association of
States: results from the National Cardiovascular Data Registry (NCDR). single- vs dual-chamber ICDs with mortality, readmissions, and compli-
Circ Cardiovasc Qual Outcomes. 2014;7:701–707. doi: 10.1161/ cations among patients receiving an ICD for primary prevention. JAMA.
CIRCOUTCOMES.113.000822. 2013;309:2025–2034. doi: 10.1001/jama.2013.4982.
9. Rao KK, Enriquez JR, de Lemos JA, Alexander KP, Chen AY, McGuire 17. US Burden of Disease Collaborators. The state of US health, 1990–2010:
DK, Fonarow GC, Das SR. Use of aldosterone antagonists at discharge burden of diseases, injuries, and risk factors. JAMA. 2013;310:591–606.
after myocardial infarction: results from the National Cardiovascular doi: 10.1001/jama.2013.13805.

18. Chow CK, Redfern J, Hillis GS, Thakkar J, Santo K, Hackett ML, Jan 30. Glickman SW, Lytle BL, Ou FS, Mears G, O’Brien S, Cairns CB, Garvey
CLINICAL STATEMENTS
S, Graves N, de Keizer L, Barry T, Bompoint S, Stepien S, Whittaker R, JL, Bohle DJ, Peterson ED, Jollis JG, Granger CB. Care processes associ-
AND GUIDELINES
Rodgers A, Thiagalingam A. Effect of lifestyle-focused text messag- ated with quicker door-in-door-out times for patients with ST-elevation-
ing on risk factor modification in patients with coronary heart disease: myocardial infarction requiring transfer: results from a statewide
a randomized clinical trial. JAMA. 2015;314:1255–1263. doi: 10.1001/ regionalization program. Circ Cardiovasc Qual Outcomes. 2011;4:382–
jama.2015.10945. 388. doi: 10.1161/CIRCOUTCOMES.110.959643.
19. Bucholz EM, Butala NM, Ma S, Normand ST, Krumholz HM. Life expec- 31. Nallamothu BK, Normand SL, Wang Y, Hofer TP, Brush JE Jr, Messenger
tancy after myocardial infarction, according to hospital performance. N JC, Bradley EH, Rumsfeld JS, Krumholz HM. Relation between door-to-
Engl J Med. 2016;375:1332–1342. doi: 10.1056/NEJMoa1513223. balloon times and mortality after primary percutaneous coronary interven-
20. Desai NR, Ross JS, Kwon JY, Herrin J, Dharmarajan K, Bernheim SM, tion over time: a retrospective study. Lancet. 2015;385:1114–1122. doi:
Krumholz HM, Horwitz LI. Association between hospital penalty status 10.1016/S0140-6736(14)61932-2.
under the hospital readmission reduction program and readmission rates 32. Ekundayo OJ, Saver JL, Fonarow GC, Schwamm LH, Xian Y, Zhao X,
for target and nontarget conditions. JAMA. 2016;316:2647–2656. doi: Hernandez AF, Peterson ED, Cheng EM. Patterns of emergency medical
10.1001/jama.2016.18533. services use and its association with timely stroke treatment: findings
21. Centers for Medicare & Medicaid Services. Medicare Hospital Quality from Get With the Guidelines–Stroke. Circ Cardiovasc Qual Outcomes.
2016 Chartbook: Performance Report on Outcome Measures. https://www. 2013;6:262–269. doi: 10.1161/CIRCOUTCOMES.113.000089.
cms.gov/Medicare/Quality-Initiatives-Patient-Assessment-Instruments/ 33. Virani SS, Woodard LD, Wang D, Chitwood SS, Landrum CR, Urech
HospitalQualityInits/OutcomeMeasures.html. Accessed September 6, TH, Pietz K, Chen GJ, Hertz B, Murawsky J, Ballantyne CM, Petersen
2016. LA. Correlates of repeat lipid testing in patients with coronary heart
22. Okunrintemi V, Spatz ES, Di Capua P, Salami JA, Valero-Elizondo J, Warraich disease. JAMA Intern Med. 2013;173:1439–1444. doi: 10.1001/
H, Virani SS, Blaha MJ, Blankstein R, Butt AA, Borden WB, Dharmarajan jamainternmed.2013.8198.
K, Ting H, Krumholz HM, Nasir K. Patient-provider communication and 34. Virani SS, Maddox TM, Chan PS, Tang F, Akeroyd JM, Risch SA, Oetgen
health outcomes among individuals with atherosclerotic cardiovascular WJ, Deswal A, Bozkurt B, Ballantyne CM, Petersen LA. Provider type
disease in the United States: Medical Expenditure Panel Survey 2010 to and quality of outpatient cardiovascular disease care: insights from the
2013. Circ Cardiovasc Qual Outcomes. 2017;10:e003635. doi: 10.1161/ NCDR PINNACLE Registry. J Am Coll Cardiol. 2015;66:1803–1812. doi:
CIRCOUTCOMES.117.003635. 10.1016/j.jacc.2015.08.017.
23. Weintraub WS, Spertus JA, Kolm P, Maron DJ, Zhang Z, Jurkovitz C, Zhang 35. Himmelstein DU, Wright A, Woolhandler S. Hospital computing and the
W, Hartigan PM, Lewis C, Veledar E, Bowen J, Dunbar SB, Deaton C, costs and quality of care: a national study. Am J Med. 2010;123:40–46.
Kaufman S, O’Rourke RA, Goeree R, Barnett PG, Teo KK, Boden WE, doi: 10.1016/j.amjmed.2009.09.004.
Mancini GB; COURAGE Trial Research Group. Effect of PCI on quality of 36. Makam AN, Nguyen OK. Use of cardiac biomarker testing in the emer-
life in patients with stable coronary disease. N Engl J Med. 2008;359:677– gency department. JAMA Intern Med. 2015;175:67–75. doi: 10.1001/
687. doi: 10.1056/NEJMoa072771. jamainternmed.2014.5830.
24. Ho PM, Lambert-Kerzner A, Carey EP, Fahdi IE, Bryson CL, Melnyk SD, 37. Chan PS, Patel MR, Klein LW, Krone RJ, Dehmer GJ, Kennedy K,
Bosworth HB, Radcliff T, Davis R, Mun H, Weaver J, Barnett C, Barón A, Nallamothu BK, Weaver WD, Masoudi FA, Rumsfeld JS, Brindis RG,
Del Giacco EJ. Multifaceted intervention to improve medication adher- Spertus JA. Appropriateness of percutaneous coronary intervention.
ence and secondary prevention measures after acute coronary syn- JAMA. 2011;306:53–61. doi: 10.1001/jama.2011.916.
drome hospital discharge: a randomized clinical trial. JAMA Intern Med. 38. Chan PS, Nichol G, Krumholz HM, Spertus JA, Jones PG, Peterson ED,
2014;174:186–193. doi: 10.1001/jamainternmed.2013.12944. Rathore SS, Nallamothu BK; for the American Heart Association National
25. Dy SM, Chan KS, Chang HY, Zhang A, Zhu J, Mylod D. Patient perspec- Registry of Cardiopulmonary Resuscitation (NRCPR) Investigators.
tives of care and process and outcome quality measures for heart fail- Racial differences in survival after in-hospital cardiac arrest. JAMA.
ure admissions in US hospitals: how are they related in the era of public 2009;302:1195–1201. doi: 10.1001/jama.2009.1340.
reporting? Int J Qual Health Care. 2016;28:522–528. doi: 10.1093/intqhc/ 39. Cohen MG, Fonarow GC, Peterson ED, Moscucci M, Dai D, Hernandez
mzw063. AF, Bonow RO, Smith SC Jr. Racial and ethnic differences in the treat-
26. McClellan SR, Panattoni L, Chan AS, Tai-Seale M. Patient-initiated electronic ment of acute myocardial infarction: findings from the Get With the
messages and quality of care for patients with diabetes and hypertension Guidelines–Coronary Artery Disease program. Circulation. 2010;121:2294–
in a large fee-for-service medical group: results from a natural experiment. 2301. doi: 10.1161/CIRCULATIONAHA.109.922286.
Med Care. 2016;54:287–295. doi: 10.1097/MLR.0000000000000483. 40. Thomas KL, Hernandez AF, Dai D, Heidenreich P, Fonarow GC, Peterson
27. Reynolds MR, Magnuson EA, Lei Y, Leon MB, Smith CR, Svensson LG, ED, Yancy CW. Association of race/ethnicity with clinical risk fac-
Webb JG, Babaliaros VC, Bowers BS, Fearon WF, Herrmann HC, Kapadia S, tors, quality of care, and acute outcomes in patients hospitalized with
Kodali SK, Makkar RR, Pichard AD, Cohen DJ; for the Placement of Aortic heart failure. Am Heart J. 2011;161:746–754. doi: 10.1016/j.ahj.2011.
Transcatheter Valves (PARTNER) Investigators. Health-related quality of life 01.012.
after transcatheter aortic valve replacement in inoperable patients with 41. Spatz ES, Beckman AL, Wang Y, Desai NR, Krumholz HM. Geographic
severe aortic stenosis. Circulation. 2011;124:1964–1972. doi: 10.1161/ variation in trends and disparities in acute myocardial infarction hospi-
CIRCULATIONAHA.111.040022. talization and mortality by income levels, 1999-2013. JAMA Cardiol.
28. Rothberg MB, Sivalingam SK, Kleppel R, Schweiger M, Hu B, Sepucha 2016;1:255–265. doi: 10.1001/jamacardio.2016.0382.
KR. Informed decision making for percutaneous coronary intervention for 42. Al-Khatib SM, Hellkamp AS, Hernandez AF, Fonarow GC, Thomas KL,
stable coronary disease. JAMA Intern Med. 2015;175:1199–1206. doi: Al-Khalidi HR, Heidenreich PA, Hammill S, Yancy C, Peterson ED; for the
10.1001/jamainternmed.2015.1657. Get With the Guidelines Steering Committee and Hospitals. Trends in use
29. Menees DS, Peterson ED, Wang Y, Curtis JP, Messenger JC, Rumsfeld JS, of implantable cardioverter-defibrillator therapy among patients hospital-
Gurm HS. Door-to-balloon time and mortality among patients under- ized for heart failure: have the previously observed sex and racial dispari-
going primary PCI. N Engl J Med. 2013;369:901–909. doi: 10.1056/ ties changed over time? Circulation. 2012;125:1094–1101. doi: 10.1161/
NEJMoa1208200. CIRCULATIONAHA.111.066605.

24. MEDICAL PROCEDURES Cardiac Catheterization and PCI
CLINICAL STATEMENTS
See Tables 24-1 and 24-2 and Charts 24-1 (See Tables 24-1 and 24-2)
AND GUIDELINES
through 24-4 • PCI inpatient discharges decreased from 359 000 for
males and 190 000 for females in 1997 to 325 000
Click here to return to the Table of Contents and 155 000, respectively, by 2014 (Chart 24-1).
• Data on Medicare beneficiaries undergoing a cor-
Trends in Operations and Procedures onary revascularization procedure between 2008
and 2012 indicate that the rapid growth in non-
(See Tables 24-1 and 24-2 and Charts 24-1
admission PCIs (from 60 405 to 106 495) has been
through 24-2) more than offset by the decrease in PCI admis-
• The mean hospital charges for cardiovascular pro- sions (from 363 384 to 295 434).2
cedures in 2014 ranged from $43 484 for carotid • In 2014, the mean hospital charge for PCI was
endarterectomy to $808 770 for heart transplants $84 813 (Table 24-1).
(Table 24-1). • From 2004 to 2014, the number of cardiac cathe-
• The trends in the numbers of 5 common cardio- terizations decreased from 1 486 000 to 1 016 000
vascular procedures in the United States from annually (HCUP, NHLBI tabulation; Chart 24-1).
1993 to 2014 are presented in Chart 24-1. Of • In 2014, an estimated 480 000 PCI (previously
the 5 procedures, cardiac catheterization was the referred to as percutaneous transluminal coronary
most common procedure for all years presented angioplasty, or PTCA) procedures were performed
(Chart 24-1). in the United States (HCUP, NHLBI tabulation;
• Of the 10 leading diagnostic groups in the United Chart 24-1).
States, the greatest number of surgical proce- • In 2014, ≈68% of PCI procedures were performed
dures were cardiovascular and obstetrical proce- on males, and ≈50% were performed on people
dures (Chart 24-2). ≥65 years of age (HCUP, NHLBI tabulation; Table
• The total number of inpatient cardiovascular 24-2).
operations and procedures decreased 6%, from • Inpatient hospital deaths for PCI increased from
8 461 000 in 2004 to 7 971 000 in 2014 (NHLBI 0.8% in 2004 to 2.1% in 2014 (HCUP, NHLBI tabula-
tabulation of HCUP data; Table 24-2). tion). In 2014, ≈82% of stents implanted during PCI
• Data from the HCUP were examined for trends were drug-eluting stents compared with 18% that
from 1997 to 2014 for use of PCI and CABG.1 were bare-metal stents (HCUP, NHLBI tabulation).
• In a study of nontransferred patients with STEMI
treated with primary PCI from July 2006 to
Coronary Artery Bypass Grafting March 2008, there was significant improvement
• The number of inpatient discharges for CABG over time in the percentage of patients receiv-
decreased from 683 000 in 1997 to 371 000 in ing PCI within 90 minutes, from 54.1% from
2014 (Chart 24-1). July to September 2006 to 74.1% from January
• In 1997, the number of inpatient discharges for to March 2008, among hospitals participating in
CABG was 484 000 for males and 199 000 for the GWTG-CAD program. This improvement was
females; these declined to 277 000 and 94 000, seen whether or not hospitals joined the Door-to-
respectively, in 2014. Balloon Alliance during that period.3
• The rate of any cardiac stent procedure per 10 000
Abbreviations Used in Chapter 24 population rose by 61% from 1999 to 2006, then
ASD atrial septal defect
declined by 27% between 2006 and 2009.4
AV atrioventricular
CABG coronary artery bypass graft
GWTG-CAD Get With the Guidelines–Coronary Artery Disease
Cardiac Open Heart Surgery
HCUP Healthcare Cost and Utilization Project • Data from the STS Adult Cardiac Surgery
HLHS hypoplastic left heart syndrome Database, which voluntarily collects data from
ICD-9-CM International Classification of Diseases, 9th Revision, ≈80% of all hospitals that perform CABG in the
Clinical Modification
United States, indicate that a total of 151 474
PCI percutaneous coronary intervention procedures involved isolated CABG in 2015.5
PTCA percutaneous transluminal coronary angioplasty • Among other major procedures, there were
STEMI ST-segment–elevation myocardial infarction 29 462 isolated aortic valve replacements and 7027
STS Society of Thoracic Surgeons isolated mitral valve replacements; 17 570 proce-
VSD ventricular septal defect dures involved both aortic valve replacement and

CABG, whereas 2681 procedures involved both • In 2016, 3191 heart transplantations were per-
CLINICAL STATEMENTS
mitral valve replacement and CABG.5 formed in the United States (Chart 24-3). There
AND GUIDELINES
are 253 transplant hospitals in the United States,

134 of which performed heart transplantations in
Congenital Heart Surgery, 2012 to 2015 2016.
According to data from the STS Congenital Heart • Of the recipients in 2016, 71.6% were male, and
Surgery Database6: 61.4% were white; 22.0% were black, whereas
• There were 120 391 procedures performed from 11.4% were Hispanic. Heart transplantations by
January 2012 to December 2015. The in-hospital recipient age are shown in Chart 24-4.
mortality rate was 3.1% during that time period. • For transplants that occurred between 2012 and
The 5 most common diagnoses were HLHS 2015, the 1-year survival rate was 90.5% for
(6.3%), type 2 VSD (6.2%), patent ductus arte- males and 91.1% for females; the 5-year sur-
riosus (5.1%), secundum ASD (4.0%), and other vival rates based on 2008 to 2011 transplants
cardiac (4.5%).6 were 78.3% for males and 77.7% for females.
• The 5 most common primary procedures were The 1- and 5-year survival rates for white car-
delayed sternal closure (7.6%), patch VSD repair diac transplant patients were 90.7% and 79.0%,
(6.4%), mediastinal exploration (3.6%), patch respectively. For black patients, they were 90.7%
ASD repair (3.2%), and complete AV canal (AV and 74.1%, respectively. For Hispanic patients,
septal defect) repair (2.8%).6 they were 90.1% and 79.9%, respectively. For
Asian patients, they were 91.3% and 80.0%,
respectively.
Heart Transplantations • As of April 12, 2017, 3957 patients were on
(See Charts 24-3 and 24-4) the transplant waiting list for a heart transplant,
According to data from the Organ Procurement and and 43 patients were on the list for a heart/lung
Transplantation Network (as of March 1, 2017): transplant.
Table 24-1. 2014 National HCUP Statistics: Mean Hospital Charges, In-Hospital Death
Rates, and Mean Length of Stay for Various Cardiovascular Procedures

Mean Hospital In-Hospital Mean Length
Procedure Charges, $ Death Rate, % of Stay, d ICD-9-CM Procedure Codes
Total vascular and cardiac surgery 35–39, 00.50–00.51,
90 215 3.34 6.3
and procedures 00.53–00.55, 00.61–00.66
Cardiac revascularization (bypass) 168 541 1.78 9.3 36.1–36.3
PCI 84 813 2.07 3.5 00.66, 17.55, 36.01, 36.02, 36.05
Cardiac catheterization 57 494 1.42 4.2 37.21–37.23
Pacemakers 83 521 1.46 5.1 37.7–37.8, 00.50, 00.53
Implantable defibrillators 171 476 0.69 6.3 37.94–37.99, 00.51, 00.54
Carotid endarterectomy 43 484 0.27 2.6 38.12
Heart valves 35.00–35.14, 35.20–35.28,
201 557 3.36 9.7
35.96, 35.97, 35.99
Heart transplantations 808 770 7.84 45.4 37.51
Principal procedure only. HCUP indicates Healthcare Cost and Utilization Project; ICD-9-CM, International Classification of
Diseases, Clinical Modification, 9th Revision; and PCI, percutaneous coronary intervention.
Data derived from the Agency for Healthcare Research and Quality.

Table 24-2. Estimated* Inpatient Cardiovascular Operations, Procedures, and Patient Data by Sex and Age: United
CLINICAL STATEMENTS
States, 2014 (in Thousands)
AND GUIDELINES
Sex Age, y
Operation/Procedure/
Patients ICD-9-CM Procedure Codes All Male Female 18–44 45–64 64–84 ≥85
Heart valves 35.00–35.14, 35.20–35.28, 35.96,
156 92 63 11 40 83 16
35.97, 35.99
PCI 00.66, 17.55, 36.01, 36.02, 36.05 480 325 155 26 213 212 28
PCI with stents 36.06, 36.07 434 294 140 24 194 191 25
Coronary artery bypass graft 36.1–36.3 371 276 94 10 148 204 9
Cardiac catheterization 37.21–37.23 1016 625 391 68 432 455 54
Pacemakers 37.7, 37.8, 00.50, 00.53 351 185 166 9 57 197 85
Pacemaker devices 37.8, 00.53 141 72 69 3 19 80 38
Pacemaker leads 37.7, 00.50 210 114 97 7 38 117 47
Implantable defibrillators 37.94–37.99, 00.51, 00.54 60 43 17 4 21 30 3
Carotid endarterectomy 38.12 86 51 35 0 20 60 6
Total vascular and cardiac 35–39, 00.50–00.51, 00.53– 00.55,
7971 4602 3368 777 2860 3402 558
surgery and procedures†‡ 00.61–00.66
These data do not reflect any procedures performed on an outpatient basis. Many more procedures are being performed on an outpatient basis. Some of the
lower numbers in this table compared with 2006 probably reflect this trend. Data include procedures performed on newborn infants. Ellipses (…) indicate data not
available; ICD-9-CM, International Classification of Diseases, Clinical Modification, 9th Revision; and PCI, percutaneous coronary intervention.
*Breakdowns are not available for some procedures, so entries for some categories do not add to totals. These data include codes for which the estimated number
of procedures is <5000. Categories with such small numbers are considered unreliable by the National Center for Health Statistics and in some cases may have been
omitted.
†Totals include procedures not shown here.
‡This estimate includes angioplasty and stent insertions for noncoronary arteries.
Data derived from Healthcare Cost and Utilization Project National Inpatient Sample, 2014, Agency for Healthcare Research and Quality.
Chart 24-1. Trends in cardiovascular procedures, United States: 1993 to 2014; inpatient procedures only.
Data derived from Healthcare Cost and Utilization Project, National (Nationwide) Inpatient Sample, Agency for Healthcare
Research.

CLINICAL STATEMENTS
AND GUIDELINES
7.4
7.4
5.7
5.4
1.4
1.4
1.3
1.1
0.4
Chart 24-2. Number of surgical procedures in the 10 leading diagnostic groups, United States, 2014.
Data derived from Healthcare Cost and Utilization Project, National (Nationwide) Inpatient Sample, Agency for Healthcare
Research.
Chart 24-3. Trends in heart transplantations, 1975 to 2016.

Data derived from Organ Procurement and Transplantation Network as of March 1, 2017.

CLINICAL STATEMENTS
AND GUIDELINES
Chart 24-4. Heart transplantations in the United States by recipient age, 2016.
Data derived from Organ Procurement and Transplantation Network.7
4. Auerbach D, Maeda J, Steiner C. Hospital Stays With Cardiac Stents,

REFERENCES 2009. Rockville, MD: US Agency for Healthcare Research and Quality;
1. Healthcare Cost and Utilization Project (HCUP). HCUPnet website. https:// April 2012. HCUP Statistical Brief No. 128.
hcupnet-archive.ahrq.gov/. Accessed May 1, 2017. 5. Adult Cardiac Surgery Database: Executive Summary: 10 Years: STS
2. Culler SD, Kugelmass AD, Brown PP, Reynolds MR, Simon AW. Trends Period Ending 12/31/2015. Society of Thoracic Surgeons website.
in coronary revascularization procedures among Medicare beneficiaries https://www.sts.org/sites/default/files/documents/ACSD_2016Harvest1_
between 2008 and 2012. Circulation. 2015;131:362–370. doi: 10.1161/ ExecutiveSummary.pdf. Accessed March 1, 2017.
CIRCULATIONAHA.114.012485. 6. STS Congenital Heart Surgery Database. Society of Thoracic Surgeons web-
3. Nallamothu BK, Krumholz HM, Peterson ED, Pan W, Bradley E, Stern AF, site. https://www.sts.org/registries-research-center/sts-national-database/
Masoudi FA, Janicke DM, Hernandez AF, Cannon CP. Door-to-balloon times congenital-heart-surgery-database. Accessed November 13, 2017.
in hospitals within the Get-With-the-Guidelines Registry after initiation of 7. Organ Procurement and Transplantation Network. https://optn.transplant.
the Door-to-Balloon (D2B) Alliance. Am J Cardiol. 2009;103:1051–1055. hrsa.gov/data/. Accessed November 13, 2017.

25. ECONOMIC COST OF to CVD and stroke illness during 2013 to 2014 among
CLINICAL STATEMENTS
workers, people keeping house, people in institutions,

CARDIOVASCULAR DISEASE
AND GUIDELINES
and people unable to work. Those morbidity costs were

See Tables 25-1 and 25-2 and Charts 25-1 substantial in very old studies, but an adequate update
through 25-6 could not be made.

Most Costly Diseases
Using data from MEPS, the annual direct and indirect (See Tables 25-1 through 25-2 and Chart
cost of CVD and stroke in the United States is an esti- 25-2)
mated $329.7 billion (Table 25-1 and Chart 25-1). This CVD and stroke accounted for 14% of total health
figure includes $199.2 billion in expenditures (direct expenditures in 2013 to 2014, more than any major
costs, which include the cost of physicians and other diagnostic group.1 By way of comparison, CVD total
professionals, hospital services, prescribed medication, direct costs shown in Table 25-1 are higher than the
and home health care, but not the cost of nursing 2013 to 2014 AHRQ estimates for cancer, which were
home care) and $130.5 billion in lost future productiv- $81.3 billion (51% for outpatient or doctor office vis-
ity attributed to premature CVD and stroke mortality in its, 33% for inpatient care, and 12% for prescription
2013 to 2014 (indirect costs). drugs).1
The direct costs for CVD and stroke are the health- Table 25-2 shows direct and indirect costs for CVD
care expenditures for 2013 to 2014 (average annual) by sex and by 2 broad age groups. Chart 25-2 shows
available on the website of the nationally representa- total direct costs for the 22 leading chronic diseases in
tive MEPS of the AHRQ.1 Details on the advantages or the MEPS list. HD is the most costly condition.1
disadvantages of using MEPS data are provided in the The estimated direct costs of CVD and stroke in
“Heart Disease and Stroke Statistics–2011 Update.”2 the United States increased from $105.7 billion in
Indirect mortality costs are estimated for 2013 to 2014 1997 to 1998 to $199.1 billion in 2013 to 2014
(average annual) by multiplying the number of deaths (Chart 25-3).
for those years attributable to CVD and strokes, in age
and sex groups, by estimates of the present value of
lifetime earnings for those age and sex groups as of
Projections
2013 to 2014. Mortality data are from the National Vital (See Charts 25-3 through 25-6)
Statistics System of the NCHS.3 The present values of • The AHA developed methodology to project
lifetime earnings are unpublished estimates furnished future costs of care for HBP, CHD, HF, stroke, and
by the Institute for Health and Aging, University of all other CVD.6
California, San Francisco, by Wendy Max, PhD, on April • By 2035, 45.1% of the US population is projected
29, 2015. Those estimates have a 3% discount rate, to have some form of CVD.7
which is the recommended percentage.4 The discount • Between 2015 and 2035, total direct medical
rate removes the effect of inflation in income over the costs of CVD are projected to increase from $318
lifetime of earnings. The estimate is for 2013, inflated billion to $749 billion (2015 $ in billions). Of this
to 2014 to account for the 2013 to 2014 change in total in 2035, 55.5% is attributable to hospital
hourly worker compensation in the business sector costs, 15.3% to medications, 15.0% to physi-
reported by the US Bureau of Labor Statistics.5 The indi- cians, 7.2% to nursing home care, 5.5% to home
rect costs exclude lost productivity costs attributable health care, and 1.5% to other costs.7
• Indirect costs (attributable to lost productivity) for
Abbreviations Used in Chapter 25 all CVDs are estimated to increase from $237 bil-
AHA American Heart Association lion in 2015 to $368 billion in 2035 (2015 $ in
AHRQ Agency for Healthcare Research and Quality billions), an increase of 55%.7
CHD coronary heart disease • Between 2015 and 2035, the total costs are
CHF congestive heart failure expected to increase for total CVD, HBP and HBP
COPD chronic obstructive pulmonary disease as a risk factor, CHD, CHF, stroke, and other CVDs
(Chart 25-4).
GI gastrointestinal (tract)
• Between 2015 and 2035, the projected total
HBP high blood pressure (direct and indirect) costs of total CVD are esti-
HD heart disease mated to remain relatively stable for 18- to
HF heart failure 44-year-olds, increase slightly for 45- to 64-year-
MEPS Medical Expenditure Panel Survey olds, and increase sharply for 65- to 79-year-olds
NCHS National Center for Health Statistics and adults aged ≥80 years (Chart 25-5).

• Whereas the direct costs of CVD for home health to more than double in this same time frame
CLINICAL STATEMENTS
care, nursing homes, physicians, and medications (Chart 25-6).
AND GUIDELINES
are estimated to rise steadily between 2015 and • These data indicate that CVD prevalence and
2035, the projected hospital costs are estimated costs are projected to increase substantially.
Table 25-1. Estimated Direct and Indirect Costs (in Billions of Dollars) of CVD and Stroke: United
States, Average Annual, 2013 to 2014
Other
Heart Hypertensive Circulatory
Disease* Stroke Disease† Conditions Total CVD
Direct costs‡
Hospital inpatient stays 55.0 13.8 7.5 14.0 90.3
Hospital ED visits 6.3 1.1 1.9 1.3 10.6
Hospital outpatient or office-based provider visits 22.7 2.7 13.4 7.5 46.3
Home health care 7.3 5.1 6.1 1.1 19.6
Prescribed medicines 9.6 0.9 20.0 1.8 32.3
Total expenditures 100.9 23.6 48.9 25.7 199.2
Indirect costs§
Lost productivity/mortality 103.9 16.5 4.3 5.8 130.5
Grand totals 204.8 40.1 53.2 31.5 329.7
Numbers do not add to total because of rounding. CVD indicates cardiovascular disease; and ED, emergency department.
*This category includes coronary heart disease, heart failure, part of hypertensive disease, cardiac dysrhythmias, rheumatic heart disease,
cardiomyopathy, pulmonary heart disease, and other or ill-defined heart diseases.
†Costs attributable to hypertensive disease are limited to hypertension without heart disease.
‡Medical Expenditure Panel Survey healthcare expenditures are estimates of direct payments for care of a patient with the given disease
provided during the year, including out-of-pocket payments and payments by private insurance, Medicaid, Medicare, and other sources.
Payments for over-the-counter drugs are not included. These estimates of direct costs do not include payments attributed to comorbidities.
Total CVD costs are the sum of costs for the 4 diseases but with some duplication.
§The Statistics Committee agreed to suspend presenting estimates of lost productivity attributable to morbidity until a better estimating
method can be developed. Lost future earnings of people who died in 2013 to 2014, discounted at 3%.
Sources: Estimates from the Household Component of the Medical Expenditure Panel Survey of the Agency for Healthcare Research and
Quality for direct costs (average annual 2013 to 2014).1 Indirect mortality costs are based on 2013 to 2014 counts of deaths by the National
Center for Health Statistics and an estimated present value of lifetime earnings furnished for 2013 by Wendy Max (Institute for Health and
Aging, University of California, San Francisco, April 29, 2015) and inflated to 2014 from change in worker compensation reported by the US
Bureau of Labor Statistics. All estimates prepared by Michael Mussolino, National Heart, Lung, and Blood Institute.
Table 25-2. Costs of Total CVD and Stroke in Billions

of Dollars by Age and Sex: United States, Average
Annual, 2013 to 2014
Age Age
Total Males Females <65 y ≥65 y
Direct 199.2 109.6 89.6 87.5 111.7
Indirect mortality 130.5 97.1 33.4 110.8 19.7
Total 329.7 206.7 123.0 198.3 131.4
Numbers may not add to total because of rounding. CVD indicates

cardiovascular disease.
Source: Medical Expenditure Panel Survey, average annual 2013 to 2014
(direct costs) and mortality data from the National Center for Health Statistics
and present value of lifetime earnings from the Institute for Health and Aging,
University of California, San Francisco (indirect costs).1
All estimates prepared by Michael Mussolino, National Heart, Lung, and
Blood Institute.

CLINICAL STATEMENTS
AND GUIDELINES
Chart 25-1. Direct and indirect costs of CVD and stroke (in billions of dollars), United States, average annual, 2013
to 2014.
Source: Prepared by the National Heart, Lung, and Blood Institute.1–4
Chart 25-2. The 22 leading diagnoses for direct health expenditures, United States, average annual 2013 to 2014
(in billions of dollars).
COPD indicates chronic obstructive pulmonary disease; and GI, gastrointestinal (tract).
Source: National Heart, Lung, and Blood Institute; estimates are from the Medical Expenditure Panel Survey, Agency for
Healthcare Research and Quality, and exclude nursing home costs.1

CLINICAL STATEMENTS
AND GUIDELINES
Chart 25-3. Estimated direct cost (in billions of dollars) of CVD and stroke: United States, average annual (1997–
1998 to 2013–2014).
Sources: Estimates from the Household Component of the Medical Expenditure Panel Survey of the Agency for Healthcare
Research and Quality for direct costs (average annual 1997–1998 to 2013–2014).1
Chart 25-4. Projected total costs of CVD, 2015 to 2035 (2015 dollars in billions) in the United States.
CHD indicates coronary heart disease; CHF, congestive heart failure; CVD, cardiovascular disease; and HBP, high blood pressure.
Data from RTI International.7 Copyright © 2016, American Heart Association, Inc.

CLINICAL STATEMENTS
AND GUIDELINES
Chart 25-5. Projected total (direct and indirect) costs of total cardiovascular disease by age from 2015 to 2035
(2015 dollars in billions).
Chart 25-6. Projected direct costs of total cardiovascular disease by type of cost from 2015 to 2035 (2015 dollars in
billions).

REFERENCES 4. Gold MR, Siegel JE, Russell LB, Weinstein MC, eds. Cost-Effectiveness in
CLINICAL STATEMENTS
Health and Medicine. New York, NY: Oxford University Press; 1996.
1. Agency for Healthcare Research and Quality. Medical Expenditure Panel
AND GUIDELINES
5. US Bureau of Labor Statistics, Office of Compensation Levels and Trends.
Survey: household component summary tables. Table 7: Total expenses Employment Cost Index, Historical Listing - Volume V: Continuous
and percent distribution for selected conditions by type of service: Occupational and Industry Series: September 1975-September 2016. Table
United States, average annual 2013–2014. Agency for Healthcare 4: employment cost index for total compensation, for civilian workers, by
Research and Quality website. https://meps.ahrq.gov/mepsweb/data_ occupation and industry: continuous occupational and industry series.
stats/tables_compendia_hh_interactive.jsp?_SERVICE=MEPSSocket0&_ https://www.bls.gov/web/eci/ecicois.pdf. Accessed October 31, 2016.
PROGRAM=MEPSPGM.TC.SAS&File=HC2Y2014&Table=HC2Y2014%5F 6. Heidenreich PA, Trogdon JG, Khavjou OA, Butler J, Dracup K, Ezekowitz
CNDXP%5FC&_Debug=. Accessed February 27, 2017. MD, Finkelstein EA, Hong Y, Johnston SC, Khera A, Lloyd-Jones DM,
2. Roger VL, Go AS, Lloyd-Jones DM, Adams RJ, Berry JD, Brown TM, Nelson SA, Nichol G, Orenstein D, Wilson PW, Woo YJ; on behalf of
Carnethon MR, Dai S, de Simone G, Ford ES, Fox CS, Fullerton HJ, the American Heart Association Advocacy Coordinating Committee;
Gillespie C, Greenlund KJ, Hailpern SM, Heit JA, Ho PM, Howard VJ, Stroke Council; Council on Cardiovascular Radiology and Intervention;
Kissela BM, Kittner SJ, Lackland DT, Lichtman JH, Lisabeth LD, Makuc Council on Clinical Cardiology; Council on Epidemiology and Prevention;
DM, Marcus GM, Marelli A, Matchar DB, McDermott MM, Meigs JB, Council on Arteriosclerosis; Thrombosis and Vascular Biology; Council on
Moy CS, Mozaffarian D, Mussolino ME, Nichol G, Paynter NP, Rosamond Cardiopulmonary; Critical Care; Perioperative and Resuscitation; Council
WD, Sorlie PD, Stafford RS, Turan TN, Turner MB, Wong ND, Wylie-Rosett on Cardiovascular Nursing; Council on the Kidney in Cardiovascular
J; on behalf of the American Heart Association Statistics Committee Disease; Council on Cardiovascular Surgery and Anesthesia, and
and Stroke Statistics Subcommittee. Heart disease and stroke statis- Interdisciplinary Council on Quality of Care and Outcomes Research.
tics–2011 update: a report from the American Heart Association [pub- Forecasting the future of cardiovascular disease in the United States:
lished corrections appear in Circulation. 2011;124:e426 and Circulation. a policy statement from the American Heart Association. Circulation.
2011;123:e240]. Circulation. 2011;123:e18–e209. doi: 10.1161/ 2011;123:933–944. doi: 10.1161/CIR.0b013e31820a55f5.
CIR.0b013e3182009701. 7. Projections of Cardiovascular Disease Prevalence and Costs: 2015–2035.
3. National Center for Health Statistics. Mortality multiple cause micro-data Technical Report [report prepared for the American Heart Association].
files, 2014: public-use data file and documentation: NHLBI tabulations. Research Triangle Park, NC: RTI International; November 2016. http://www.
http://www.cdc.gov/nchs/data_access/Vitalstatsonline.htm#Mortality_ heart.org/idc/groups/heart-public/@wcm/@adv/documents/downloadable/
Multiple. Accessed February 27, 2017. ucm_491513.pdf. Accessed November 13, 2017.

26. AT-A-GLANCE SUMMARY TABLES • Blood cholesterol—Table 7-1

CLINICAL STATEMENTS
• High blood pressure—Table 8-1

See Tables 26-1 through 26-3
AND GUIDELINES
• Diabetes mellitus—Table 9-1

Click here to return to the Table of Contents • Total cardiovascular diseases—Table 12-1
• Stroke—Table 13-1
Sources: See the following summary tables and charts • Congenital cardiovascular defects—Table 14-1
for complete details: • Coronary heart disease—Table 18-1; Table 18-2
• Overweight/obesity—Table 6-1 • Heart failure—Table 19-1
Table 26-1. Males and CVD: At-a-Glance Table

NH American
NH White NH Black Hispanic NH Asian Indian/Alaska
Diseases and Risk Factors Both Sexes Total Males Males Males Males Males Native*
Overweight and obesity
Prevalence, 2011–2014
Overweight and obesity, BMI >25.0 kg/m2† 157.2 M (69.4%) 78.8 M (72.5%) 73.0% 69.1% 79.6% 46.6% …
Obesity, BMI >30.0 kg/m2† 82.2 M (36.3%) 37.3 M (34.3%) 33.6% 37.5% 39.0% 11.2% …
Blood cholesterol
Total cholesterol >200 mg/dL† 94.6M (39.7%) 42.3 M (37.0%) 37.0% 32.6% 43.1% 39.9% …
Total cholesterol >240 mg/dL† 28.5 M (11.9%) 12.1 M (10.6%) 10.8% 7.3% 13.6% 10.8% …
LDL-C >130 mg/dL† 71.3 M (30.3%) 34.0 M (30.0%) 29.3% 29.9% 36.6% 29.2% …
HDL-C <40 mg/dL† 44.0 M (18.7%) 32.1 M (27.9%) 28.4% 20.7% 30.7% 25.0% …
HBP
Prevalence, 2011–2014† 85.7 M (34.0%) 40.8 M (34.5%) 34.5% 45.0% 28.9% 28.8% 26.4%
Mortality, 2015‡§ 78 862 37 099 (47.0%) 24 801 7835 2874 1057‖ 485
DM
Physician-diagnosed DM† 23.4 M (9.1%) 11.4 M (9.4%) 8.0% 14.1% 12.6% 11.8% …
Undiagnosed DM† 7.6 M (3.1%) 4.5 M (3.8%) 3.6% 2.8% 6.3% 5.7% …
Prediabetes† 81.6 M (33.9%) 46.2 M (40.2%) 39.6% 32.8% 45.9% 42.0% …
Incidence, diagnosed DM†¶ 1.7 M … … … … … …
Mortality, 2015‡§ 79 535 43 123 (54.2%) 29 813 6806 4426 1322 1034
Total CVD
Prevalence, 2011–2014† 92.1 M (36.6%) 44.3 M (37.4%) 37.7% 46.0% 31.3% 31.0% …
Mortality, 2015‡§# 836 546 422 355 (50.5%) 329 397 51 053 26 739 10 584‖ 4300
Stroke
Prevalence, 2014† 7.2 M (2.7%) 3.1 M (2.4%) 2.2% 3.9% 2.0% 1.0% 3.0%**
New and recurrent strokes‡ 795.0 K 370.0 K (46.5%) 325.0 K†† 45.0 K†† … … …
Mortality, 2015‡§ 140 323 58 288 (41.7%) 43 100 7962 4544 2153‖ 646
CHD
Prevalence, CHD, 2011–2014† 16.5 M (6.3%) 9.1 M (7.4%) 7.7% 7.1% 5.9% 5.0% 9.3%
Prevalence, MI, 2011–2014† 7.9 M (3.0%) 4.7 M (3.8%) 4.0% 3.3% 2.9% 2.6% …
Prevalence, AP, 2011–2014† 8.7 M (3.4%) 4.2 M (3.5%) 3.7% 3.5% 2.7% 2.0% …
New and recurrent MI and Fatal CHD‡‡ 1.05 M 610.0 K 520.0 K†† 90.0K†† … … …
New and recurrent MI‡‡ 805.0 K 470.0 K … … … … …
Incidence, Stable AP§§ 565.0 K 370.0 K … … … … …
(Continued )

CLINICAL STATEMENTS
NH American
AND GUIDELINES
Diseases and Risk Factors Both Sexes Total Males Males Males Males Males Native*
Mortality, 2015, CHD‡§ 366 801 209 298 (57.1%) 167 236 21 006 13 416 5154 2044
Mortality, 2015, MI‡§ 114 023 65 211 (57.2%) 52 393 6400 4246 1516‖ 624
HF
Prevalence, 2011–2014† 6.5 M (2.5%) 2.9 M (2.4%) 2.4% 2.6% 2.0% 1.3% …
Incidence, 2014‖‖ 1.0 M 495.0 K 430.0 K†† 65.0 K†† … … …
Mortality, 2015‡§ 75 251 33 667 (44.7%) 27 783 3603 1523 528‖ 286
AP indicates angina pectoris (chest pain); BMI, body mass index; CHD, coronary heart disease (includes heart attack, AP chest pain, or both); CVD, cardiovascular
disease; DM, diabetes mellitus; ellipses (…), data not available; HBP, high blood pressure; HDL-C, high-density lipoprotein cholesterol; HF, heart failure; K, thousands;
LDL-C, low-density lipoprotein cholesterol; M, millions; MI, myocardial infarction (heart attack); and NH, non-Hispanic.
*Both sexes.
†Age ≥20 years.
‡All ages.
§Mortality for Hispanic, NH American Indian or Alaska Native, and NH Asian and Pacific Islander people should be interpreted with caution because of
inconsistencies in reporting.
‖Includes Chinese, Filipino, Hawaiian, Japanese, and other Asian or Pacific Islander.
¶Centers for Disease Control and Prevention, National Diabetes Statistics Report, 2014.
#Total CVD mortality includes deaths of congenital heart disease.
**National Health Interview Survey (2014), ≥18 years of age.
††Estimates include Hispanics and non-Hispanics. Estimates for whites include other nonblack races.
‡‡Age ≥35 years.
§§Age ≥45 years.
‖‖Age ≥55 years.
Table 26-2. Females and CVD: At-a-Glance Table

NH American
Diseases and Risk Factors Both Sexes Total Females Females Females Females Females Native*

Prevalence, 2011 - 2014
Overweight and obesity, BMI ≥25.0 kg/m2† 157.2 M (69.4%) 78.2 M (66.4%) 63.7% 82.2% 77.1% 34.6% …
Obesity, BMI ≥30.0 kg/m † 2

82.2 M (36.3%) 45.1 M (38.3%) 35.5% 56.9% 45.7% 11.9% …
Blood cholesterol
Prevalence, 2011 - 2014
Total cholesterol ≥200 mg/dL† 94.6M (39.7%) 52.3 M (42.0%) 43.4% 36.1% 41.2% 40.5% …
Total cholesterol ≥240 mg/dL† 28.5 M (11.9%) 16.4 M (13.0%) 13.8% 9.6% 12.5% 11.2% …
LDL-C ≥130 mg/dL† 71.3 M (30.3%) 37.3 M (30.4%) 32.1% 27.9% 28.7% 25.0% …
HDL-C <40 mg/dL† 44.0 M (18.7%) 11.9 M (10.0%) 10.3% 8.0% 11.8% 6.7% …
HBP
Prevalence, 2011–2014† 85.7 M (34.0%) 44.9 M (33.4%) 32.3% 46.3% 30.7% 25.7% 26.4%
Mortality, 2015 ‡§ 78 862 41 763 (53.0%) 29 850 7651 2702 1176‖ 485
DM
Physician-diagnosed DM† 23.4 M (9.1%) 12.0 M (8.9%) 7.4% 13.6% 12.7% 9.1% …
Undiagnosed DM† 7.6 M (3.1%) 3.1 M (2.3%) 1.5% 3.5% 4.4% 4.3% …
Prediabetes† 81.6 M (33.9%) 35.4 M (27.8%) 29.2% 24.1% 25.0% 25.5% …
Incidence, diagnosed DM†¶ 1.7 M … … … … … …
Mortality, 2015‡§ 79 535 36 412 (45.8%) 23 777 6887 3852 1277 1034
Total CVD
Prevalence, 2011–2014† 92.1 M (36.6%) 47.8 M (35.9%) 35.1% 47.7% 33.3% 27.0% …
Mortality, 2015‡§# 836 546 414 191(49.5%) 327 279 50 231 23 350 9969‖ 4300
(Continued )

CLINICAL STATEMENTS
NH American
AND GUIDELINES

Diseases and Risk Factors Both Sexes Total Females Females Females Females Females Native*
Stroke
Prevalence, 2014† 7.2 M (2.7%) 4.1 M (2.9%) 2.8% 4.0% 2.6% 2.5% 3.0%**
New and recurrent strokes‡ 795.0 K 425.0 K (53.5%) 365.0 K†† 60.0 K†† … … …
Mortality, 2015‡§ 140 323 82 035 (58.3%) 63 730 9798 5251 2645‖ 646
CHD
Prevalence, CHD, 2011–2014† 16.5 M (6.3%) 7.4 M (5.3%) 5.3% 5.7% 6.1% 2.6% 9.3%
Prevalence, MI, 2011–2014† 7.9 M (3.0%) 3.2 M (2.3%) 2.4% 2.2% 2.1% 0.7% …
Prevalence, AP, 2011–2014† 8.7 M (3.4%) 4.5 M (3.3%) 3.3% 3.3% 3.8% 1.3% …
New and recurrent MI and fatal CHD‡‡ 1.05 M 445.0 K 370.0 K†† 75.0 K†† … … …
New and recurrent MI‡‡ 805.0 K 335.0 K … … … … …
Incidence, stable AP§§ 565.0 K 195.0 K … … … … …
Mortality, 2015, CHD‡§ 366 801 157 503 (42.9%) 124 614 18 048 9639 3767 2044
Mortality, 2015, MI‡§ 114 023 48 812 (42.8%) 38 407 5723 3106 1167‖ 624
HF
Prevalence, 2011–2014† 6.5 M (2.5%) 3.6 M (2.6%) 2.5% 3.9% 2.4% 0.3% …
Incidence, 2014‖‖ 1.0 M 505.0K 425.0 K†† 80.0 K†† … … …

Mortality, 2015‡§ 75 251 41 584 (55.3%) 34 866 4169 1716 596‖ 286
AP indicates angina pectoris (chest pain); BMI, body mass index; CHD, coronary heart disease (includes heart attack, AP chest pain, or both); CVD, cardiovascular
disease; DM, diabetes mellitus; ellipses (…), data not available; HBP, high blood pressure; HDL-C, high-density lipoprotein cholesterol; HF, heart failure; K, thousands;
LDL-C, low-density lipoprotein cholesterol; M, millions; MI, myocardial infarction (heart attack); and NH, non-Hispanic.
*Both sexes.
†Age ≥20 years.
‡All ages.
§Mortality for Hispanic, American Indian or Alaska Native, and Asian and Pacific Islander people should be interpreted with caution because of inconsistencies in
reporting.
‖Includes Chinese, Filipino, Hawaiian, Japanese, and other Asian or Pacific Islander.
¶Centers for Disease Control and Prevention, National Diabetes Statistics Report, 2014.
#Total CVD mortality includes deaths of congenital heart disease.
**National Health Interview Survey (2014), ≥18 years of age.
††Estimates include Hispanics and non-Hispanics. Estimates for whites include other nonblack races.
‡‡Age ≥35 years.
§§Age ≥45 years.
‖‖Age ≥55 years.

Table 26-3. Children, Youth, and CVD: At-a-Glance Table
CLINICAL STATEMENTS
NH Whites NH Blacks Hispanic NH Asian
AND GUIDELINES
Both Total Total
Diseases and Risk Factors Sexes Males Females Males Females Males Females Males Females Males Females
Prevalence, 2011–2014*
Children and 24.0 M 12.3 M 11.7 M 29.3% 28.0% 32.8% 37.6% 40.4% 39.8% 24.9% 15.0%
adolescents, ages 2–19 (32.1%) (32.3%) (32.0%)
y, overweight or obese
Children and 12.3 M 6.2 M 6.1 M 14.0% 14.7% 17.5% 20.0% 21.7% 21.0% 11.4% 5.3%
adolescents, ages 2–19 (16.5%) (16.3%) (16.7%)
y, obese
Blood cholesterol, mg/dL, 2011–2014
Mean total cholesterol
Ages 6–11 y 158.9 158.5 159.3 156.5 159.6 162.1 162.2 159.5 156.9 161.9 167.6
Ages 12–19 y 156.7 152.3 161.3 151.7 162.0 152.3 159.5 154.7 160.5 158.1 166.7
Mean HDL-C
Ages 6–11 y 54.3 55.6 52.9 55.1 52.8 60.0 56.3 54.3 51.3 55.8 54.5
Ages 12–19 y 51.0 49.1 52.9 48.3 52.0 52.4 55.7 48.8 52.8 52.0 57.1
Mean LDL-C
Ages 12–19 y 87.7 85.7 89.8 86.5 89.9 86.6 90.9 85.9 87.8 84.5 96.9
Congenital cardiovascular defects (all age group)§
Mortality, 2015†‡ 3128 1751 (56%) 1377 (44%) 1035 812 328 229 295 257 63 55§
“Overweight and obesity” indicates a body mass index (BMI) at or above the 85th percentile of the Centers for Disease Control (CDC) and Prevention 2000 growth
chart. Obesity is based on BMI at or above the 95th percentile of the CDC growth charts. CVD indicates cardiovascular disease; HDL-C, high-density lipoprotein
cholesterol; LDL-C, low-density lipoprotein cholesterol; M, millions; and NH, non-Hispanic.
*NHANES 2011 to 2014 (ages 2–19 years) from Ogden CL, Carroll MD, Fryar CD, Flegal KM. Prevalence of obesity among adults and youth: United States,
2011–2014. NCHS Data Brief. 2015;(219):1–8.
†All ages.
‡Mortality for Hispanic, American Indian or Alaska Native, and Asian and Pacific Islander people should be interpreted with caution because of inconsistencies
in reporting.
§NH American Indian/Alaska Native. Mortality: 38.

27. GLOSSARY — National Health and Nutrition Examination

CLINICAL STATEMENTS
Survey III (NHANES III; 1988–1994)

AND GUIDELINES
Click here to return to the Table of Contents — National Health and Nutrition Examination
Survey (NHANES; 1999 to …) (ongoing)
— National Health Interview Survey (NHIS;
• Age-adjusted rates—Used mainly to compare the
ongoing)
rates of ≥2 communities or population groups or
— National Hospital Discharge Survey (NHDS;
the nation as a whole over time. The American
1965–2010)
Heart Association (AHA) uses a standard popu-
— National Ambulatory Medical Care Survey
lation (2000), so these rates are not affected by
(NAMCS; ongoing)
changes or differences in the age composition of
— National Hospital Ambulatory Medical Care
the population. Unless otherwise noted, all death
Survey (NHAMCS; ongoing)
rates in this publication are age adjusted per — National Nursing Home Survey (periodic)
100 000 population and are based on underlying — National Home and Hospice Care Survey
cause of death. (periodic)
• Agency for Healthcare Research and Quality — National Vital Statistics System (ongoing)
(AHRQ)—A part of the US Department of Health • Centers for Medicare & Medicaid Services—The
and Human Services, this is the lead agency federal agency that administers the Medicare,
charged with supporting research designed to Medicaid, and Child Health Insurance programs.
improve the quality of health care, reduce the cost • Comparability ratio—Provided by the NCHS to
of health care, improve patient safety, decrease allow time-trend analysis from one International
the number of medical errors, and broaden Classification of Diseases (ICD) revision to another.
access to essential services. The AHRQ sponsors It compensates for the “shifting” of deaths from
and conducts research that provides evidence- one causal code number to another. Its applica-
based information on healthcare outcomes, qual- tion to mortality based on one ICD revision means
ity, cost, use, and access. The information helps that mortality is “comparability modified” to be
healthcare decision makers (patients, clinicians, more comparable to mortality coded to the other
health system leaders, and policy makers) make ICD revision.
more informed decisions and improve the qual- • Coronary heart disease (CHD) (ICD-10 codes I20–
ity of healthcare services. The AHRQ conducts I25)—This category includes acute myocardial
the Medical Expenditure Panel Survey (MEPS; infarction (I21–I22), other acute ischemic (coro-
ongoing). nary) heart disease (I24), angina pectoris (I20),
• Bacterial endocarditis—An infection of the heart’s atherosclerotic cardiovascular disease (I25.0), and
inner lining (endocardium) or of the heart valves. all other forms of chronic ischemic (coronary)
The bacteria that most often cause endocarditis heart disease (I25.1–I25.9).
are streptococci, staphylococci, and enterococci. • Death rate—The relative frequency with which
• Body mass index (BMI)—A mathematical formula death occurs within some specified interval of
to assess body weight relative to height. The mea- time in a population. National death rates are
sure correlates highly with body fat. It is calcu- computed per 100 000 population. Dividing the
lated as weight in kilograms divided by the square total number of deaths by the total population
of the height in meters (kg/m2). gives a crude death rate for the total population.
• Centers for Disease Control and Prevention/ Rates calculated within specific subgroups, such
National Center for Health Statistics (CDC/NCHS)— as age-specific or sex-specific rates, are often
CDC is an agency within the US Department of more meaningful and informative. They allow
Health and Human Services. The CDC conducts well-defined subgroups of the total population to
the Behavioral Risk Factor Surveillance System be examined. Unless otherwise stated, all death
(BRFSS), an ongoing survey. The CDC/NCHS con- rates in this publication are age adjusted and are
ducts or has conducted these surveys (among per 100 000 population.
others): • Diseases of the circulatory system (ICD codes
— National Health Examination Survey (NHES I, I00–I99)—Included as part of what the AHA calls
1960–1962; NHES II, 1963–1965; NHES III, “cardiovascular disease” (“Total cardiovascular
1966–1970) disease” in this Glossary).
— National Health and Nutrition Examination • Diseases of the heart—Classification the NCHS
Survey I (NHANES I; 1971–1975) uses in compiling the leading causes of death.
— National Health and Nutrition Examination Includes acute rheumatic fever/chronic rheu-
Survey II (NHANES II; 1976–1980) matic heart diseases (I00–I09), hypertensive heart

disease (I11), hypertensive heart and renal disease “major cardiovascular diseases” for any calcula-
CLINICAL STATEMENTS
(I13), CHD (I20–I25), pulmonary heart disease and tions. See “Total cardiovascular disease” in this
AND GUIDELINES
diseases of pulmonary circulation (I26–I28), heart Glossary.
failure (I50), and other forms of heart disease • Metabolic syndrome—Metabolic syndrome is
(I29–I49, I50.1–I51). “Diseases of the heart” are defined* as the presence of any 3 of the fol-
not equivalent to “total cardiovascular disease,” lowing 5 diagnostic measures: elevated waist
which the AHA prefers to use to describe the circumference (≥102 cm in males or ≥88 cm in
leading causes of death. females), elevated triglycerides (≥150 mg/dL [1.7
• Hispanic origin—In US government statistics, mmol/L] or drug treatment for elevated triglyc-
“Hispanic” includes people who trace their erides), reduced high-density lipoprotein choles-
ancestry to Mexico, Puerto Rico, Cuba, Spain, terol (<40 mg/dL [0.9 mmol/L] in males, <50 mg/
the Spanish-speaking countries of Central or dL [1.1 mmol/L] in females, or drug treatment for
South America, the Dominican Republic, or other reduced high-density lipoprotein cholesterol), ele-
Spanish cultures, regardless of race. It does not vated blood pressure (≥130 mm Hg systolic blood
include people from Brazil, Guyana, Suriname, pressure, ≥85 mm Hg diastolic blood pressure, or
Trinidad, Belize, or Portugal, because Spanish is drug treatment for hypertension), and elevated
not the first language in those countries. Most of fasting glucose (≥100 mg/dL or drug treatment
the data in this update are for Mexican Americans for elevated glucose).
or Mexicans, as reported by government agen- • Morbidity—Incidence and prevalence rates are
cies or specific studies. In many cases, data for all both measures of morbidity (ie, measures of vari-
Hispanics are more difficult to obtain. ous effects of disease on a population).
• Hospital discharges—The number of inpatients • Mortality—Mortality data for states can be
(including newborn infants) discharged from obtained from the NCHS website (http://cdc.
short-stay hospitals for whom some type of dis- gov/nchs/), by direct communication with the
ease was the first-listed diagnosis. Discharges CDC/NCHS, or from the AHA on request. The
include those discharged alive, dead, or “status total number of deaths attributable to a given
unknown.” disease in a population during a specific interval
• International Classification of Diseases (ICD) of time, usually 1 year, are reported. These data
codes—A classification system in standard use are compiled from death certificates and sent
in the United States. The ICD is published by by state health agencies to the NCHS. The pro-
the World Health Organization. This system is cess of verifying and tabulating the data takes
reviewed and revised approximately every 10 to ≈2 years.
20 years to ensure its continued flexibility and • National Heart, Lung, and Blood Institute
feasibility. The 10th revision (ICD-10) began with (NHLBI)—An institute in the National Institutes
the release of 1999 final mortality data. The ICD of Health in the US Department of Health and
revisions can cause considerable change in the Human Services. The NHLBI conducts such studies
number of deaths reported for a given disease. as the following:
The NCHS provides “comparability ratios” to — Framingham Heart Study (FHS; 1948 to …)
compensate for the “shifting” of deaths from (ongoing)
one ICD code to another. To compare the num- — Honolulu Heart Program (HHP; 1965–1997)
ber or rate of deaths with that of an earlier year, — Cardiovascular Health Study (CHS; 1988 to
the “comparability-modified” number or rate …) (ongoing)
is used. — Atherosclerosis Risk in Communities (ARIC)
• Incidence—An estimate of the number of new study (1985 to …) (ongoing)
cases of a disease that develop in a population, — Strong Heart Study (SHS; 1989–1992,
usually in a 1-year period. For some statistics, new 1991–1998)
and recurrent attacks, or cases, are combined. — The NHLBI also published reports of the
The incidence of a specific disease is estimated by Joint National Committee on Prevention,
multiplying the incidence rates reported in com- Detection, Evaluation, and Treatment of
munity- or hospital-based studies by the US popu- High Blood Pressure and the Third Report of
lation. The rates in this report change only when the Expert Panel on Detection, Evaluation,
new data are available; they are not computed and Treatment of High Blood Cholesterol in
annually. Adults (Adult Treatment Panel III).
• Major cardiovascular diseases—Disease classifi-
cation commonly reported by the NCHS; repre- *According to criteria established by the AHA/NHLBI and published in
sents ICD codes I00 to I78. The AHA does not use Circulation (Circulation. 2005;112:2735–2752).

• National Institute of Neurological Disorders and in the totals for whites, blacks, American Indians
CLINICAL STATEMENTS
Stroke (NINDS)—An institute in the National or Alaska Natives, and Asian or Pacific Islanders
AND GUIDELINES
Institutes of Health of the US Department of according to the race listed on the decedent’s
Health and Human Services. The NINDS sponsors death certificate. Data for Hispanic people include
and conducts research studies such as these: all people of Hispanic origin of any race. See
— Greater Cincinnati/Northern Kentucky Stroke “Hispanic origin” in this Glossary.
Study (GCNKSS) • Stroke (ICD-10 codes I60–I69)—This category
— Rochester (Minnesota) Stroke Epidemiology includes subarachnoid hemorrhage (I60); intra-
Project cerebral hemorrhage (I61); other nontraumatic
— Northern Manhattan Study (NOMAS) intracranial hemorrhage (I62); cerebral infarc-
— Brain Attack Surveillance in Corpus Christi tion (I63); stroke, not specified as hemorrhage or
(BASIC) Project infarction (I64); occlusion and stenosis of prece-
• Physical activity—Any bodily movement pro- rebral arteries not resulting in cerebral infarction
duced by the contraction of skeletal muscle that (I65); occlusion and stenosis of cerebral arteries
increases energy expenditure above a basal level. not resulting in cerebral infarction (I66); other
• Physical fitness—The ability to perform daily tasks cerebrovascular diseases (I67); cerebrovascular
with vigor and alertness, without undue fatigue, disorders in diseases classified elsewhere (I68);
and with ample energy to enjoy leisure-time pur- and sequelae of cerebrovascular disease (I69).
suits and respond to emergencies. Physical fitness • Total cardiovascular disease (ICD-10 codes I00–
includes a number of components consisting of I99, Q20–Q28)—This category includes rheumatic
cardiorespiratory endurance (aerobic power), skel- fever/rheumatic heart disease (I00–I09); hyperten-
etal muscle endurance, skeletal muscle strength, sive diseases (I10–I15); ischemic (coronary) heart
skeletal muscle power, flexibility, balance, speed of disease (I20–I25); pulmonary heart disease and
movement, reaction time, and body composition. diseases of pulmonary circulation (I26–I28); other
• Prevalence—An estimate of the total number of forms of heart disease (I30–I52); cerebrovascular
cases of a disease existing in a population dur- disease (stroke) (I60–I69); atherosclerosis (I70);
ing a specified period. Prevalence is sometimes other diseases of arteries, arterioles, and capillaries
expressed as a percentage of population. Rates (I71–I79); diseases of veins, lymphatics, and lymph
for specific diseases are calculated from periodic nodes not classified elsewhere (I80–I89); and other
health examination surveys that government and unspecified disorders of the circulatory system
agencies conduct. Annual changes in preva- (I95–I99). When data are available, we include
lence as reported in this Statistical Update reflect congenital cardiovascular defects (Q20–Q28).
changes in the population size. Changes in rates • Underlying cause of death or any-mention cause
can be evaluated only by comparing prevalence of death—These terms are used by the NCHS
rates estimated from surveys conducted in dif- when defining mortality. Underlying cause of
ferent years. Note: In the data tables, which death is defined by the World Health Organization
are located in the different disease and risk fac- as “the disease or injury which initiated the chain
tor chapters, if the percentages shown are age of events leading directly to death, or the circum-
adjusted, they will not add to the total. stances of the accident or violence which pro-
• Race and Hispanic origin—Race and Hispanic ori- duced the fatal injury.” Any-mention cause of
gin are reported separately on death certificates. death includes the underlying cause of death and
In this publication, unless otherwise specified, up to 20 additional multiple causes listed on the
deaths of people of Hispanic origin are included death certificate.

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Circulation

AHA STATISTICAL UPDATE

Heart Disease and Stroke Statistics—

WRITING GROUP MEMBERS Each chapter listed in the Table of

Monik C. Jiménez, ScD, SM Connie W. Tsao, MD, MPH

Key Words: AHA Scientific

© 2018 American Heart Association, Inc.

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TABLE OF CONTENTS administrators, researchers, health advocates, and oth-

ers seeking the best available data on these factors and

21. Venous Thromboembolism (Deep Vein

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and treatment. (mean age 60 years, 50% males) reported a nearly

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34% increase in hospitalizations for DVT and a

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On behalf of the American Heart Association Council on

Medical Procedures (Chapter 24) ARTICLE INFORMATION

year’s worth of effort by dedicated volunteer physicians

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Writing Group Disclosures Continued

Other Speakers’ Consultant/

Writing Group Research Bureau/ Expert Ownership Advisory

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Writing Group Disclosures Continued

infective endocarditis: guidelines from the American Heart Association:

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1. ABOUT THESE STATISTICS • NAMCS—physician office visits

• National Vital Statistics System—national and

Click here to return to the Table of Contents state mortality data

CDC Centers for Disease Control and Prevention

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Incidence and Recurrent Attacks Population Estimates

tal outpatient departments and EDs. Ambulatory care

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to the European standard.7 Unless otherwise stated, all Race/Ethnicity

death rates in this publication are age adjusted and are

deaths per 100 000 population.

National Center for Health Statistics; 2015. http://www.cdc.gov/nchs/

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2. CARDIOVASCULAR HEALTH health can also be represented as being “ideal,” “inter-

goals and areas that require greater attention to meet

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and heritage.10 strated a stepwise association between cardiovas-

0.24 (95% CI, 0.13–0.47) for CVD mortality, and

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centage of those with poor levels while increasing adults.

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Poor Intermediate Ideal

Adults ≥20 y of age Yes Former ≥12 mo Never or quit >12 mo

Adults ≥20 y of age ≥30 kg/m2 25–29.9 kg/m2 <25 kg/m2

Children 2–19 y of age >95th percentile 85th–95th percentile <85th percentile

Adults ≥20 y of age <2 (0–39) 2–3 (40–79) 4–5 (80–100)

Children 5–19 y of age <2 (0–39) 2–3 (40–79) 4–5 (80–100)

Adults ≥20 y of age ≥240 200–239 or treated to goal <200

Children 6–19 y of age ≥200 170–199 <170

Adults ≥20 y of age ≥126 100–125 or treated to goal <100

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Adults ≥20 y of age Yes Former ≥12 mo Never or quit >12 mo

Adults ≥20 y of age ≥30 kg/m2 25–29.9 kg/m2 <25 kg/m2

Children 2–19 y of age >95th percentile 85th–95th percentile <85th percentile

Adults ≥20 y of age <2 (0–39) 2–3 (40–79) 4–5 (80–100)

Children 5–19 y of age <2 (0–39) 2–3 (40–79) 4–5 (80–100)

Adults ≥20 y of age ≥240 200–239 or treated to goal <200

Children 6–19 y of age ≥200 170–199 <170

Adults ≥20 y of age ≥126 100–125 or treated to goal <100

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