ARTICLE IN PRESS

Impact of Multiple Chronic Conditions in Patients Hospitalized

with Stroke and Transient Ischemic Attack

Mohammed Yousufuddin, MD, MSc,* Adam C. Bartley, MS,†

Mouaz Alsawas, MD,‡ Heather L. Sheely, BSN,* Jessica Shultz, BSN,*
Paul Y. Takahashi, MD,§ Nathan P. Young, DO,‖ and M. Hassan Murad, MD‡,¶

Background: The prevalence and clinical impact of chronic conditions (CCs) have
increasingly been recognized as an important public health concern. We evalu-
ated the prevalence of coexisting CCs and their association with 30-day mortality
and readmission in hospitalized patients with stroke and transient ischemic attack
(TIA). Methods: In a retrospective study of patients aged ≥18 years hospitalized
for first-ever stroke and TIA, we assessed the prevalence of coexisting CCs and
their predictive value for subsequent 30-day mortality and readmission. Results:
Study cohort comprised 6771 patients, hospitalized for stroke (n = 4068) and TIA
(n = 2703), 51.4% men, with mean age of 68.2 years (standard deviation: ±15.6),
mean number of CCs of 2.9 (±1.7), 30-day mortality rate of 8.6% (entire cohort),
and 30-day readmission rate of 9.7% (in 2498 patients limited to Olmsted and
surrounding counties). In multivariable models, significant predictors of (1) 30-
day mortality were coexisting heart failure (HF) (odds ratio [OR]: 1.45, 95% confidence
interval [CI]: 1.09-1.92), cardiac arrhythmia (OR: 1.74, 95% CI: 1.40-2.17), coro-
nary artery disease (CAD) (OR: 1.64, 95% CI: 1.29-2.08), cancer (OR: 1.67, 95%
CI: 1.31-2.14), and diabetes (HR: 1.28, 95% CI: 1.01-1.62); and (2) 30-day readmis-
sion (n = 2498) were CAD (OR: 1.50, 95% CI: 1.09-2.07), cancer (OR: 1.46, 95% CI:
1.01-2.10), and arthritis (OR: 1.62, 95% CI: 1.09-2.40). Conclusions: In patients hos-
pitalized with stroke and TIA, CCs are highly prevalent and influence 30-day mortality
and readmission. Optimal therapeutic and lifestyle interventions for CAD, HF,
cardiac arrhythmia, cancer, diabetes, and arthritis may improve early clinical outcome.
Key Words: Trend—stroke—chronic condition—mortality—readmission.
© 2017 National Stroke Association. Published by Elsevier Inc. All rights reserved.

From the *Department of Hospital Internal Medicine, Mayo Clinic
Health System, Austin, Minnesota; †Division of Biomedical Statis-
tics and Informatics, Mayo Clinic, Rochester, Minnesota; ‡Division
of Preventive Medicine, Mayo Clinic, Rochester, Minnesota; §Divi-
sion of Primary Care Internal Medicine, Mayo Clinic, Rochester,
Minnesota; ‖Division of Neurology, Mayo Clinic, Rochester, Min-
nesota; and ¶Center for the Science of Health Care Delivery, Mayo
Clinic, Rochester, Minnesota.
Received September 23, 2016; revision received January 5, 2017;
accepted January 18, 2017.
Address correspondence to Mohammed Yousufuddin, MD, MSc,
Department of Hospital Internal Medicine, Mayo Clinic Health
System, 1000 First Drive NW, Austin, MN 55912. E-mail:
Yousufuddin.mohammed@Mayo.edu.
1052-3057/$ - see front matter
© 2017 National Stroke Association. Published by Elsevier Inc. All
rights reserved.
http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2017.01.015
Stroke and transient ischemic attack (TIA) are the leading
causes of hospitalization, readmission, and excess mor-
tality in the United States1,2 and worldwide.3,4 TIA is a
medical emergency and associated with a high short-
term risk of stroke, cardiovascular events, and death.5 A
third of patients with TIA, indeed, have an acute cere-
bral infarct detected by magnetic resonance imaging.6 TIA
and ischemic stroke represent a continuum of acute isch-
emic cerebrovascular syndrome.1,7 Therefore, it is reasonable
to investigate both TIA and stroke as a combined het-
erogeneous cohort. Increasing prevalence of individual
and multiple chronic conditions (MCC) among U.S. adults
is currently a major public health concern and prompted
a great deal of attention in recent years.8 Data from the
2010 National Health Interview Survey ascertained that

Journal of Stroke and Cerebrovascular Diseases, Vol. ■■, No. ■■ (■■), 2017: pp ■■–■■ 1
 ARTICLE IN PRESS
2 M. YOUSUFUDDIN ET AL.
9
approximately 26% of U.S. adults had MCC. However,
the prevalence and implication for early clinical out-
comes of coexisting individual or MCC in patients with
first-ever stroke and TIA are not well understood. Al-
though numerous population-based studies have focused
on risk factors for initial stroke and TIA, research on sub-
sequent clinical events is limited. Specifically, no study
has reported association between individual or MCC and
short-term clinical outcomes after index hospitalization
for stroke and TIA. Understanding the prevalence of
chronic conditions (CCs) and their impact on clinical
outcome in patients with stroke and TIA provides an op-
portunity to improve patient care.
Therefore, in a broader hospitalized stroke and TIA
patient population, we attempted to evaluate the prev-
alence of simultaneously coexisting single and MCC to
determine whether these conditions have any impact on
30-day all-cause mortality and all-cause readmission after
initial stroke and TIA.
Methods
Study Design and Population
This is a retrospective study of patients aged ≥18 years
hospitalized for first-ever stroke and TIA at Mayo Clinic
Hospital, Rochester, Minnesota, a comprehensive stroke
center, from January 2005 to August 2015. The look-
back period extended to approximately 10 years to ensure
validity of first-ever event. The data were extracted by
dedicated abstraction personnel using the International Clas-
sification of Diseases, Ninth Revision, Clinical Modification
(ICD-9-CM) codes. Previous studies have demonstrated
a high positive predictive value of ICD-9-CM codes for
the discharge diagnoses of stroke and TIA.10,11 Stroke was
subtyped according to Stroke Data Bank scheme12 as (1)
ischemic stroke (cardioembolic and non-cardioembolic isch-
emic stroke), (2) primary intracerebral hemorrhage (PICH),
and (3) subarachnoid hemorrhage (SAH). Spinal cord stroke
and cerebral venous thrombosis-related strokes were ex-
cluded due to rarity. The diagnoses of stroke and TIA
were based on physician provider as documented in clin-
ical notes. Patients who refused participation in clinical
research were excluded. The study was approved by the
Mayo Clinic Institutional Review Board.
Measures of CCs
Chronic condition is defined as a long-term condition
requiring medical attention.13 Twenty CCs specified by
the Office of the Assistant Secretary for Health13 were ini-
tially selected for the present study. Because the cohort
was defined by first-ever stroke, stroke was excluded from
the list of 20 CCs. The presence or absence of the re-
maining 19 conditions was identified using Clinical
Classifications Software codes. These are codes that group
ICD-9-CM codes and are part of the U.S. Healthcare Cost
and Utilization Project (H-Cup) tool. The prevalence of
MCC was estimated by the proportion of patients with
2 or more coexisting CCs. Prevalent CCs were further
categorized into 4 levels based on the number of coex-
isting CCs: <2, 2, 3, and 4+ .
Measures of Outcome
Co-primary outcomes included prevalence of coexist-
ing CCs, estimates of death from any cause within 30
days of a date of hospital admission, and 30-day read-
mission from any cause from date of discharge. Mortality
statistics were performed for the entire cohort, regard-
less of zip codes, whereas readmission rates were calculated
in a targeted patient population restricted to Olmsted and
immediate surrounding counties to minimize underesti-
mation of true rates of subsequent rehospitalizations.
Statistical Analysis
Descriptive data were summarized as mean (stan-
dard deviation) for continuous variables and frequency
(percent) for categorical variables. Men and women and
young (<65 years) and older (≥65 years) participants were
compared by chi-square test for categorical variables, and
2-sample Student t-test for continuous variables. To assess
the effect of CCs on clinical outcomes, we fit logistic re-
gression models that included selected CCs, plus
sociodemographic factors and stroke subtype. In addi-
tion to models that included all CCs, we fit models that
used the number of CCs instead. The results are pre-
sented as odds ratios (OR) and 95% confidence interval
(CI).
Results
The study cohort comprised 6771 patients who were
first hospitalized with a primary discharge diagnosis of
stroke (n = 4068, 60.1%) and TIA (n = 2703, 39.9%); 51.4%
were men and 92.7% were white. Tables 1 and 2 illus-
trate the baseline characteristics by age, sex, and stroke
subtypes for the entire patient population and those re-
stricted to Olmsted and immediate surrounding counties,
respectively. In overall patient population, the mean age
was 68.2 ± 15.6 years and the male-to-female ratio was
1.1:1 (51.4%-48.6%). Of the 19 selected CCs, autism, hep-
atitis, HIV, and schizophrenia were excluded from the
analysis for <1% co-occurrence with stroke and TIA. We
incorporated sociodemographics and 15 distinct coexist-
ing CCs in logistic regression models to assess the risk
for death and readmission from any cause by 30 days
after index hospitalization. Overall 30-day mortality
was 8.6%, lowest for TIA (.6%) and highest for PICH
(28.6%). We ascertained 30-day readmission rate in a
sample of patients restricted to Olmstead and immedi-
ate surrounding counties (n = 2498) because of concern
about underrating true rates of readmission if wider
 IMPACT OF MULTIPLE CHRONIC CONDITIONS IN PATIENTS WITH STROKE AND TIA
Table 1. Overall study population and prevalence of individual chronic conditions and chronic condition cluster by sex, age and stroke subtypes

Sex Age Stroke subtypes

Ischemic Ischemic
Entire cohort Male Female P <65 years ≥65 years P TIA non-embolic embolic PICH SAH P

Entire cohort 6771 3482 3289 – 2539 4232 – 2703 2016 754 825 473 –
Age in years Overall 68.2 ± 15.6 67.6 ± 14.8 68.9 ± 16.5 <.001 – – – 67.2 ± 14.4 70.3 ± 15.8 73.0 ± 15.9 68.9 ± 16.5 56.6 ± 13.8 <.001
Gender Male 3482 (51.4%) – – – 1319 (51.9%) 2163 (51.1%) .504 1444 (53.4%) 1041 (51.6%) 376 (49.9%) 433 (52.5%) 188 (39.7%) <.001

ARTICLE IN PRESS
Female 3289 (48.6%) – – – 1220 (48.1%) 2069 (48.9%) – 1259 (46.6%) 975 (48.4%) 378 (50.1%) 392 (47.5%) 285 (60.3%) –
Race White 6275 (92.7%) 3215 (92.3%) 3060 (93.0%) .266 2257 (88.9%) 4018 (94.9%) <.001 2527 (93.5%) 1866 (92.6%) 716 (95.0%) 740 (89.7%) 426 (90.1%) <.001
African–American 66 (1.0%) 36 (1.0%) 30 (.9%) .610 50 (2.0%) 16 (.4%) <.001 17 (.6%) 13 (.6%) 10 (1.3%) 19 (2.3%) 7 (1.5%) <.001
Other 243 (3.6%) 122 (3.5%) 121 (3.7%) .698 144 (5.7%) 99 (2.3%) <.001 77 (2.8%) 90 (4.5%) 16 (2.1%) 41 (5.0%) 19 (4.0%) .001
Unknown 187 (2.8%) 109 (3.1%) 78 (2.4%) .057 88 (3.5%) 99 (2.3%) .006 82 (3.0%) 47 (2.3%) 12 (1.6%) 25 (3.0%) 21 (4.4%) .025
Prevalence of Dyslipidemia 3780 (55.8%) 2086 (59.9%) 1694 (51.5%) <.001 1127 (44.4%) 2653 (62.7%) <.001 1671 (61.8%) 1258 (62.4%) 415 (55.0%) 313 (37.9%) 123 (26.0%) <.001
individual Hypertension 4969 (73.4%) 2594 (74.5%) 2375 (72.2%) .033 1439 (56.7%) 3530 (83.4%) <.001 1948 (72.1%) 1540 (76.4%) 573 (76.0%) 642 (77.8%) 266 (56.2%) <.001
preselected Depression 782 (11.5%) 273 (7.8%) 509 (15.5%) <.001 352 (13.9%) 430 (10.2%) <.001 269 (10.0%) 266 (13.2%) 86 (11.4%) 100 (12.1%) 61 (12.9%) .01
15 chronic Diabetes 1645 (24.3%) 956 (27.5%) 689 (20.9%) <.001 479 (18.9%) 1166 (27.6%) <.001 611 (22.6%) 607 (30.1%) 196 (26.0%) 168 (20.4%) 63 (13.3%) <.001
conditions Arthritis 605 (8.9%) 253 (7.3%) 352 (10.7%) <.001 98 (3.9%) 507 (12.0%) <.001 224 (8.3%) 203 (10.1%) 94 (12.5%) 64 (7.8%) 20 (4.2%) <.001
Cancer 983 (14.5%) 562 (16.1%) 421 (12.8%) <.001 248 (9.8%) 735 (17.4%) <.001 351 (13.0%) 311 (15.4%) 126 (16.7%) 162 (19.6%) 33 (7.0%) <.001
Arrhythmia 1915 (28.3%) 993 (28.5%) 922 (28.0%) .658 320 (12.6%) 1595 (37.7%) <.001 522 (19.3%) 606 (30.1%) 478 (63.4%) 245 (29.7%) 64 (13.5%) <.001
Asthma 310 (4.6%) 121 (3.5%) 189 (5.7%) <.001 128 (5.0%) 182 (4.3%) .158 137 (5.1%) 89 (4.4%) 37 (4.9%) 29 (3.5%) 18 (3.8%) .333
CAD 1861 (27.5%) 1198 (34.4%) 663 (20.2%) <.001 351 (13.8%) 1510 (35.7%) <.001 898 (33.2%) 529 (26.2%) 235 (31.2%) 167 (20.2%) 32 (6.8%) <.001
Substance use 319 (4.7%) 238 (6.8%) 81 (2.5%) <.001 222 (8.7%) 97 (2.3%) <.001 63 (2.3%) 119 (5.9%) 44 (5.8%) 57 (6.9%) 36 (7.6%) <.001
COPD 552 (8.2%) 302 (8.7%) 250 (7.6%) .107 124 (4.9%) 428 (10.1%) <.001 242 (9.0%) 150 (7.4%) 76 (10.1%) 66 (8.0%) 18 (3.8%) <.001
Osteoporosis 370 (5.5%) 46 (1.3%) 324 (9.9%) <.001 38 (1.5%) 332 (7.8%) <.001 121 (4.5%) 130 (6.4%) 67 (8.9%) 44 (5.3%) 8 (1.7%) <.001
CKD 672 (9.9%) 400 (11.5%) 272 (8.3%) <.001 138 (5.4%) 534 (12.6%) <.001 229 (8.5%) 237 (11.8%) 111 (14.7%) 74 (9.0%) 21 (4.4%) <.001
Heart failure 574 (8.5%) 269 (7.7%) 305 (9.3%) .022 80 (3.2%) 494 (11.7%) <.001 125 (4.6%) 204 (10.1%) 170 (22.5%) 61 (7.4%) 14 (3.0%) <.001
Dementia 395 (5.8%) 160 (4.6%) 235 (7.1%) <.001 26 (1.0%) 369 (8.7%) <.001 70 (2.6%) 165 (8.2%) 88 (11.7%) 66 (8.0%) 6 (1.3%) <.001
Prevalence of Mean number of CC 2.9 ± 1.7 3.0 ± 1.7 2.8 ± 1.8 <.001 2.1 ± 1.6 3.5 ± 1.6 <.001 2.8 ± 1.7 3.2 ± 1.7 3.7 ± 1.9 2.8 ± 1.7 1.7 ± 1.4 <.001
chronic Patients with MCC 5274 (77.9%) 2800 (80.4%) 2474 (75.2%) <.001 1517 (59.7%) 3757 (88.8%) <.001 2052 (75.9%) 1697 (84.2%) 663 (87.9%) 626 (75.9%) 236 (49.9%) <.001
condition Patients with <2 CCs 1497 (22.1%) 682 (19.6%) 815 (24.8%) <.001 1022 (40.3%) 475 (11.2%) <.001 651 (24.1%) 319 (15.8%) 91 (12.1%) 199 (24.1%) 237 (50.1%) <.001
clusters Patients with 2 CCs 1355 (20.0%) 688 (19.8%) 667 (20.3%) .592 618 (24.3%) 737 (17.4%) <.001 535 (19.8%) 394 (19.5%) 103 (13.7%) 212 (25.7%) 111 (23.5%) <.001
Patients with 3 CCs 1500 (22.2%) 807 (23.2%) 693 (21.1%) .037 457 (18.0%) 1043 (24.6%) <.001 636 (23.5%) 470 (23.3%) 158 (21.0%) 159 (19.3%) 77 (16.3%) <.001
Patients with ≥4 CCs 2419 (35.7%) 1305 (37.5%) 1114 (33.9%) .002 442 (17.4%) 1977 (46.7%) <.001 881 (32.6%) 833 (41.3%) 402 (53.3%) 255 (30.9%) 48 (10.1%) <.001

Abbreviations: CAD, coronary artery disease; CC, chronic condition; CKD, chronic kidney disease; COPD, chronic obstructive pulmonary disease; MCC, multiple chronic conditions; PICH, primary intracerebral hemorrhage; SAH,
subarachnoid hemorrhage; TIA, transient ischemic attack.

3
 4
Table 2. Study population limited to Olmsted and surrounding counties and prevalence of multiple chronic conditions by sex, age, and stroke subtype

Sex Age Stroke subtypes

Ischemic Ischemic
Entire cohort Male Female P <65 years ≥65 years P TIA non-embolic embolic PICH SAH P

Entire cohort 2849 1399 1450 – 840 2009 – 816 1129 424 362 118 –
Age in years Overall 72.1 ± 15.3 69.5 ± 15.0 74.6 ± 15.3 <.001 – – – 70.8 ± 14.1 73.1 ± 15.4 75.6 ± 15.4 72.8 ± 15.1 57.2 ± 13.1 <.001
Gender Male 1399 (49%) – – – 484 (57.6%) 915 (45.5) <.001 441 (54.0%) 533 (47.2%) 199 (46.9%) 179 (49.4%) 47 (39.8%) .006

ARTICLE IN PRESS
Female 1450 (51%) – – – 356 (42.4%) 1094 (54.5%) – 375 (46.0%) 596 (52.8%) 225 (53.1%) 183 (50.6%) 71 (60.2%) –
Race White 2677 (94.0%) 1302 (93.1%) 1375 (94.8%) .048 748 (89.0%) 1929 (96.0%) <.001 788 (96.6%) 1056 (93.5%) 405 (95.5%) 321 (88.7%) 107 (90.7%) <.001
African–American 35 (1.2%) 23 (1.6%) 12 (.8%) .048 26 (3.1%) 9 (.4%) <.001 6 (.7%) 10 (.9%) 8 (1.9%) 9 (2.5%) 2 (1.7%) .057
Other 104 (3.7%) 57 (4.1%) 47 (3.2%) .236 53 (6.3%) 51 (2.5%) <.001 17 (2.1%) 52 (4.6%) 6 (1.4%) 25 (6.9%) 4 (3.4%) <.001
Unknown 33 (1.2%) 17 (1.2%) 16 (1.1%) .781 13 (1.5%) 20 (1.0%) .209 5 (.6%) 11 (1.0%) 5 (1.2%) 7 (1.9%) 5 (4.2%) .007
Prevalence of Dyslipidemia 1683 (59.1%) 865 (61.8%) 818 (56.4%) .003 446 (53.1%) 1237 (61.6%) <.001 546 (66.9%) 717 (63.5%) 238 (56.1%) 145 (40.1%) 37 (31.4%) <.001
individual Hypertension 2226 (78.1%) 1069 (76.4%) 1157 (79.8%) .029 517 (61.5%) 1709 (85.1%) <.001 635 (77.8%) 889 (78.7%) 337 (79.5%) 302 (83.4%) 63 (53.4%) <.001
preselected Depression 381 (13.4%) 126 (9.0%) 255 (17.6%) <.001 125 (14.9%) 256 (12.7%) .126 104 (12.7%) 161 (14.3%) 50 (11.8%) 52 (14.4%) 14 (11.9%) .645
15 chronic Diabetes 767 (26.9%) 430 (30.7%) 337 (23.2%) <.001 186 (22.1%) 581 (28.9%) <.001 213 (26.1%) 355 (31.4%) 110 (25.9%) 75 (20.7%) 14 (11.9%) <.001
conditions Arthritis 320 (11.2%) 110 (7.9%) 210 (14.5%) <.001 45 (5.4%) 275 (13.7%) <.001 85 (10.4%) 130 (11.5%) 63 (14.9%) 37 (10.2%) 5 (4.2%) .015
Cancer 411 (14.4%) 209 (14.9%) 202 (13.9%) .444 67 (8.0%) 344 (17.1%) <.001 103 (12.6%) 175 (15.5%) 70 (16.5%) 55 (15.2%) 8 (6.8%) .033
Arrhythmia 998 (35.0%) 466 (33.3%) 532 (36.7%) .059 128 (15.2%) 870 (43.3%) <.001 224 (27.5%) 366 (32.4%) 277 (65.3%) 114 (31.5%) 17 (14.4%) <.001
Asthma 143 (5.0%) 53 (3.8%) 90 (6.2%) .003 47 (5.6%) 96 (4.8%) .363 50 (6.1%) 55 (4.9%) 24 (5.7%) 12 (3.3%) 2 (1.7%) .114
CAD 845 (29.7%) 496 (35.5%) 349 (24.1%) <.001 123 (14.6%) 722 (35.9%) <.001 294 (36.0%) 314 (27.8%) 140 (33.0%) 89 (24.6%) 8 (6.8%) <.001
Substance use 152 (5.3%) 116 (8.3%) 36 (2.5%) <.001 101 (12.0%) 51 (2.5%) <.001 25 (3.1%) 61 (5.4%) 23 (5.4%) 31 (8.6%) 12 (10.2%) <.001
COPD 264 (9.3%) 138 (9.9%) 126 (8.7%) .28 54 (6.4%) 210 (10.5%) <.001 90 (11.0%) 91 (8.1%) 44 (10.4%) 33 (9.1%) 6 (5.1%) .09
Osteoporosis 219 (7.7%) 20 (1.4%) 199 (13.7%) <.001 12 (1.4%) 207 (10.3%) <.001 60 (7.4%) 88 (7.8%) 42 (9.9%) 26 (7.2%) 3 (2.5%) .107
CKD 315 (11.1%) 179 (12.8%) 136 (9.4%) .004 43 (5.1%) 272 (13.5%) <.001 75 (9.2%) 137 (12.1%) 69 (16.3%) 30 (8.3%) 4 (3.4%) <.001
Heart failure 335 (11.8%) 141 (10.1%) 194 (13.4%) .006 34 (4.0%) 301 (15.0%) <.001 65 (8.0%) 123 (10.9%) 112 (26.4%) 32 (8.8%) 3 (2.5%) <.001
Dementia 288 (10.1%) 108 (7.7%) 180 (12.4%) <.001 14 (1.7%) 274 (13.6%) <.001 44 (5.4%) 138 (12.2%) 61 (14.4%) 43 (11.9%) 2 (1.7%) <.001
Prevalence of Mean number of CC 3.3 ± 1.7 3.3 ± 1.7 3.3 ± 1.8 .206 2.3 ± 1.6 3.7 ± 1.7 <.001 3.2 ± 1.7 3.4 ± 1.7 3.9 ± 1.9 3.0 ± 1.8 1.7 ± 1.3 <.001
chronic Patients with MCC 2418 (84.9%) 1178 (84.2%) 1240 (85.5%) .328 1848 (92.0%) 1848 (92.0%) <.001 695 (85.2%) 979 (86.7%) 386 (91.0%) 293 (80.9%) 65 (55.1%) <.001
condition Patients with <2 CCs 431 (15.1%) 221 (15.8%) 210 (14.5%) .328 161 (8.0%) 161 (8.0%) <.001 121 (14.8%) 150 (13.3%) 38 (9.0%) 69 (19.1%) 53 (44.9%) <.001

M. YOUSUFUDDIN ET AL.
clusters Patients with 2 CCs 539 (18.9%) 273 (19.5%) 266 (18.3%) .426 323 (16.1%) 323 (16.1%) <.001 147 (18.0%) 208 (18.4%) 60 (14.2%) 92 (25.4%) 32 (27.1%) <.001
Patients with 3 CCs 627 (22.0%) 302 (21.6%) 325 (22.4%) .594 462 (23.0%) 462 (23.0%) .049 208 (25.5%) 245 (21.7%) 84 (19.8%) 69 (19.1%) 21 (17.8%) .039
Patients with ≥4 CCs 1252 (43.9%) 649 (44.8%) 649 (44.8%) .373 1063 (52.9%) 1063 (52.9%) <.001 340 (41.7%) 526 (46.6%) 242 (57.1%) 132 (36.5%) 12 (10.2%) <.001

Abbreviations: CAD, coronary artery disease; CC, chronic condition; CKD, chronic kidney disease; COPD, chronic obstructive pulmonary disease; MCC, multiple chronic conditions; PICH, primary intracerebral hemorrhage; SAH,
subarachnoid hemorrhage; TIA, transient ischemic attack.
 ARTICLE IN PRESS
IMPACT OF MULTIPLE CHRONIC CONDITIONS IN PATIENTS WITH STROKE AND TIA 5

Figure 1. Percentage of patients hospitalized for

first-ever stroke and transient ischemic attack with
the 15 preselected chronic conditions. Data pre-
sented as percentage of patients with stroke and
transient ischemic attack who also had a chronic
condition. The 15 selected chronic conditions are
displayed in ranking order from top to bottom. Ab-
breviations: CKD, chronic kidney disease; COPD,
chronic obstructive pulmonary disease.

geographic area is included. The 30-day readmission rate
was 9.7%, lowest for SAH (7.9%) and highest for embolic
ischemic stroke (11.9%).
Comorbid CCs were highly prevalent in hospitalized
stroke and TIA patient population. The 5 most common
simultaneously coexisting CCs were hypertension (73.4%),
dyslipidemia (55.8%), cardiac arrhythmia (28.3%), coro-
nary artery disease (CAD) (27.5%), and diabetes (24.3%)
in overall patient population. The distribution of indi-
vidual CCs and chronic condition cluster are represented
in Figures 1 and 2. Approximately 80% of patients had
≥2 and 35.7% had ≥4 CCs. The adjusted OR and 95% CI
were calculated for each of the 15 CCs and are repre-
sented in Figure 3. After adjustments to age, gender, race,
source of admission, stroke subtype, year of admission,
and discharge destination, multivariable models identi-
fied underlying cancer (OR: 1.67, 95% CI: 1.31-2.14), CAD
(OR: 1.64, 95% CI: 1.29-2.08), cardiac arrhythmia (pri-
marily atrial fibrillation) (OR: 1.74, 95% CI: 1.40-2.17),
diabetes (OR: 1.28, 95% CI: 1.01-1.62), and heart failure
(OR: 1.45, 95% CI: 1.09-1.92) as independent predictors
for increased risk of 30-day mortality. In contrast, arthri-
tis (OR: .57, 95% CI: .39-0.82), depression (OR: .70, 95%
CI: .51-0.97), dyslipidemia (OR: .53, 95% CI: .42-0.65), hy-
pertension (OR: .71, 95% CI: .55-0.91), and substance use
(OR: .46, 95% CI: .25-0.85) were all associated with a lower

Ischemic stroke, embolic Ischemic stroke, non-embolic

SA PICH TIA Entire
60
53.3

50.1
50

41.3

40
35.7
Figure 2. Chronic condition clusters. Abbrevia- 32.6
tions: PICH, primary intracerebral hemorrhage; SAH, 30.9

subarachnoid hemorrhage; TIA, transient isch- % 30

25.7
emic attack. 24.1 24.1 23.5 23.3 23.5
22.1 22.2
21.0
19.5 19.8 20.0 19.3
20
15.8 16.3
13.7
12.1
10.1
10

0
<2 2 3 ≥4
Chronic condition clusters
 ARTICLE IN PRESS
6 M. YOUSUFUDDIN ET AL.

Figure 3. Forest plots, adjusted to variables shown in the plots, show impact of sociodemographic variables, single chronic condition, multiple chronic
conditions on 30-day mortality from admission (left, n = 6771), and 30-day readmission from discharge date (right, n = 2498). Boxes and horizontal line
represent odds ratio and 95% confidence interval for each variable. Abbreviations: CHF, congestive heart failure; CI confidence interval; CKD, chronic
kidney disease; COPD, chronic obstructive pulmonary disease; ED, emergency department; HHC, home health care.

risk of death at 30 days after initial hospitalization. Fur-
thermore, our multivariable model identified coexisting
CAD (OR: 1.50, 95% CI: 1.09-2.07), cancer (OR: 1.46, 95%
CI: 1.01-2.10), and arthritis (OR: 1.62, 95% CI: 1.09-2.40)
as independent predictors of 30-day readmission. We found
no statistical difference in the odds of death or readmis-
sion at 30 days across levels of MCC of up to 4 or more
compared with MCC of <2.
Discussion
To our knowledge, this is the first study to describe
the prevalence of 15 CCs (from the list of 20 CCs created
by the Office of the Assistant Secretary for Health) in pa-
tients hospitalized with first-ever stroke and TIA, and to
ascertain the impact of individual as well as MCC on
30-day mortality and readmission. Analysis of our data
supports 3 key conclusions. (1) Patients with initial stroke
and TIA have a high prevalence of MCC, defined as the
presence of 2 or more CCs.13 (2) Of the 15 selected CCs,
the presence of coexisting CAD, heart failure, cancer, cardiac
arrhythmia, and diabetes was associated with increased
risk of 30-day all-cause mortality following hospitaliza-
tion for stroke and TIA. (3) Similarly, the presence of
coexisting CAD, cancer, and arthritis was associated with
30-day readmission from any cause.
The prevalence rates of ≥2 CCs and ≥4 CCs were 21.1%
and 4.9%, respectively, in U.S. adults aged ≥18 years.14
In a representative sample of >1.2 million unselected Medi-
care beneficiaries, the point prevalence of ≥4 CCs was
24.1%.15 By comparison, our results in patients with stroke
and TIA showed that 80% had coexisting MCC and 36%
had ≥4 CCs. The 5 most common simultaneously co-
occurring CCs with a prevalence rate of >20% were
hypertension, dyslipidemia, cardiac arrhythmia, CAD, and
diabetes in overall patient population. We ascertained that
the prevalence of selected CCs, with the exception of de-
pression, arthritis, and asthma, was higher in our study
cohort than those previously reported in non-stroke
population,1,16-23 but comparable with stroke population
as previously reported.24-27 However, Arnett et al re-
ported the rates of prevalence of many individual CCs
in patients with stroke aged ≥65 years greater than those
observed in the current study.28 We confirmed that co-
existing MCCs in patients with stroke and TIA were almost
ubiquitous in adults aged ≥65 years, where 89% of the
 ARTICLE IN PRESS
IMPACT OF MULTIPLE CHRONIC CONDITIONS IN PATIENTS WITH STROKE AND TIA
patients had ≥2 CCs compared with the younger cohort
aged <65 years (60%). These findings were broadly in
agreement with a number of previous reports of increas-
ing prevalence of MCC with age in primary care
population and in Medicare beneficiaries.29-34 The occur-
rence of MCC in the current study was lower in women
(75%) than in men (80%), contradictory to the data from
the National Health Interview Survey14 and unselected
Medicare beneficiaries, both of which showed a higher
prevalence in women than in men for each level (2 or 3
or more) of MCC.9 These gender-related variations in the
prevalence of MCC between published studies and our
data are likely related to differences in demographics, pop-
ulation of interest (stroke and TIA), and population mix,
especially the inclusion of patients with SAH who had
lower rates of comorbidity and who were predomi-
nantly women. Furthermore, we observed striking
differences in the rates of distribution of individual CCs
by gender. Men were more likely than women to have
coexisting hypertension, dyslipidemia, diabetes, cancer,
CAD, chronic obstructive pulmonary disease, substance
abuse, and chronic kidney disease; the vast majority of
these conditions were at least partly amenable to life-
style interventions for optimization of overall clinical care.
On the other hand, depression, arthritis, asthma, osteo-
porosis, heart failure, and dementia were all relatively
more common in women than in men. The information
related to patterns of distribution of individual CCs has
important clinical implications in determining prevalent
MCC combinations and help clinicians develop strate-
gies tailored to individual patient. The mechanism(s) for
occurrence of MCC in patients with stroke and TIA, rel-
ative to general population, is not fully understood.
Increased life expectancy with rapid growth of elderly
segment of population, advances in public health and treat-
ment of acute conditions with decrease in case fatality
rates (http://www.cdc.gov/nchs/data/nvsr/nvsr65/nvsr65
_04.pdf), high prevalence of shared risk factors, enhance-
ments in administrative data management, and effective
tracking of diagnoses over time are likely contributing
to increased prevalence of CCs among patients with stroke
and TIA.35-41
We found that increased 30-day mortality was inde-
pendently associated with 5 of the 15 selected underlying
CCs: CAD, cancer, cardiac arrhythmia (primarily atrial
fibrillation), diabetes, and heart failure (Fig 3). These find-
ings are more or less in concordance with previously
published reports on stroke mortality and other adverse
clinical events.42-46 However, in the most published lit-
erature, the follow-up was longer and the focus was on
rates of stroke or TIA recurrence and death at multiple
time points. In our study population, CAD (the fourth
most common CC) and cancer (the sixth most common
CC) were associated with increased risk of both read-
mission and death at 30 days after index hospitalization;
these findings are in agreement with a number of pub-
7
27,46-54
lished studies. Previously published data showed that
active cancer, regardless of type, was associated with in-
creased risk of acute stroke and subsequent stroke-
related morbidity.55,56 We broadly reproduced these findings
in our cohort as compared with large epidemiologic studies
in cancer patients.57,58 Diabetes is a major risk factor for
initial stroke59 and has a multiplicative effect on subse-
quent stroke-related mortality.48,60
Not all CCs are equal in how they influence 30-day
clinical outcome. Counterintuitively, many conditions
among our hospitalized stroke and TIA patient popula-
tion have little impact on 30-day clinical outcome as
reported by some previous investigations.51,61 We ob-
served that concomitant presence of dyslipidemia,
depression, hypertension, arthritis, and substance abuse
in patients with stroke and TIA was associated with
favorable 30-day mortality, with adjusted OR signifi-
cantly <1.00. A number of previous studies mostly on
non-stroke and non-TIA patient population have dem-
onstrated a paradox of inverse relationship between
several risk factors and mortality.42,62,63 Although hyper-
tension, the most common (73%) coexisting CC in our
cohort, is the single most important risk factor for
initial stroke and TIA,64-67 its impact on subsequent
clinical events was less well defined, with published
studies providing contradictory findings.57,58,68 Depres-
sion is also a risk factor for incident stroke, but has no
significant influence on early clinical outcome.69,70 On
the other hand, the role of dyslipidemia on initial
stroke and subsequent clinical events is not fully under-
stood with conflicting published data.71-73 Ironically, higher
levels of low-density lipoprotein cholesterol were shown
to reduce the risk of PICH.74
We found that comorbid CAD, cancer, or arthritis was
independently associated with higher odds for 30-day re-
admission in comparison with other comorbid CCs. Patients
with stroke and TIA, who survive to hospital dis-
charge, are most likely to experience cardiovascular events
in the longer term; therefore, underlying CAD increases
the risk of readmission.27 Cancer was the sixth most
common comorbid CC afflicting 14.5% of our study cohort,
a prevalence much greater than the data from previous
health survey75 likely related to the demography of our
study population. Cancer conferred a higher mortality
and readmission risk in our cohort, in accordance with
several lines of evidence that suggested a poorer clini-
cal outcome after stroke among patients with underlying
cancer.55,56 A large community-based study in general patient
population demonstrated that non-institutionalized Medi-
care beneficiaries with ≥4 coexisting CCs had a 99-fold
increased odds of incident hospitalization in compari-
son with those with no comorbidity.15 On the contrary,
we did not find an association with levels of multiple
CCs and 30-day event rates, potentially from the vari-
able mix of coexisting CCs with a wide range of
moderating influences.
 ARTICLE IN PRESS
8 M. YOUSUFUDDIN ET AL.
Our study has several limitations, which include limi-
tations inherent to retrospective analysis, reliance on ICD-
9-CM codes to identify study cohort, and the use of CCs
to ascertain coexisting CCs. However, our methods conform
to the regulatory practices by the Centers of Medicare
and Medicaid Services and H-Cup 11 (https://
www.cms.gov/Medicare/Quality-Initiatives-Patient
-Assessment-Instruments/HospitalQualityInits/Measure
-Methodology.html). We examined a limited number of
variables due to database constraints. We were unable
to incorporate important information known to influ-
ence early clinical outcomes, including the National
Institutes of Health Stroke Scale score and several phys-
iological indicators.42,76 The hospital-based patients as
examined in the present study were likely to have a greater
frequency of CCs than community-based stroke and TIA
population, potentially from referral, hospitalization, and
health insurance coverage bias.77 Despite these limita-
tions, the strengths of our study include its large, hospital-
based cohort and well-characterized patient population
with regard to primary diagnosis of TIA and stroke and
secondary diagnosis of multiple underlying CCs. Pa-
tients were overwhelmingly cared for by stroke neurologists
as the primary provider or as consulting physician. Our
medical record system is efficient with a high level of
case ascertainment for incident stroke and TIA and prompt
mortality updates.78 The reported cumulative, all-cause
30-day mortality after stroke varied by stroke subtypes,
from 10.9%-26% among patients with all stroke sub-
types combined24,26,46,79-82 to as high as 46.5% in hemorrhagic
stroke.83 A relatively lower mortality rate in the present
study is potentially explained by greater heterogeneity
in our study population, including inclusion of those with
TIA.
In this large, broader hospitalized stroke and TIA patient
population, comorbid CCs are highly prevalent and many
of the CCs significantly influence 30-day mortality and
readmission. Optimal therapeutic and lifestyle interven-
tions for CAD, heart failure, cardiac arrhythmia, cancer,
diabetes, and arthritis may improve early clinical outcome.
Several lines of evidence suggest that lifestyle modifica-
tion and behavioral therapy directly or indirectly benefit
a number of CCs associated with poor prognosis, in-
cluding heart failure, CAD, cardiac arrhythmia, cancer,
diabetes, and arthritis, and therefore has potential to
improve early adverse clinical outcomes following initial
stroke and TIA. Identifying patients hospitalized for stroke
and TIA, who are at high risk for death and readmis-
sion at 30 days, has significant potential for acute care
delivery and post-discharge follow-up patterns.
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