Journal of Science and Medicine in Sport 20 (2017) 627632

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Journal of Science and Medicine in Sport

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Original research

Statins for primary prevention in physically active individuals: Do the

risks outweigh the benefits?
a,b,c, d e c
Ishak A. Mansi , Jenny L. English , Michael J. Morris , Song Zhang , Eric
a,b,c b,c
M. Mortensen , Ethan A. Halm
a
Department of Medicine, VA North Texas Health Care System, United States
b c
Departments of Internal Medicine, University of Texas Southwestern Medical Center, United States
Departments of Clinical Sciences, University of Texas Southwestern Medical Center, United States
d
Patient Administration Systems & Biostatistics Activity (PASBA), MEDCOM Head Quarter, JBSA Fort Sam, United States
e
Pulmonary/Critical Care Service, Department of Medicine, San Antonio Military Medical Center, JBSA Fort Sam, United States
article info abstract

Article history: Objectives: There are little data on the potential benefits and adverse events of statins among physically fit individuals. Our
Received 21 September 2016 objective was to examine the associations of statin use with beneficial cardiovascular outcomes and adverse events in active
Received in revised form duty military (a surrogate for high level of physical fitness).
16 November 2016 Accepted 1
Design: This is a retrospective propensity score-matched cohort study of healthy active duty military (fiscal years [FY] 2002
December 2016
2011).
Available online 24 January 2017
Methods: Statin-users received statins during FY 2005 as their only prescription medication. FY 20022004 was used to
describe baseline characteristics; and FY 20062011were used to capture out-comes. Study outcomes included major acute
Keywords:
cardiovascular events (MACE), diabetes mellitus and its complications, kidney diseases, musculoskeletal diseases, obesity,
Physical activity
and malignancy.
Statin
Primary prevention Results: We propensity score matched 837 statin-users to 2488 nonusers. During follow-up, 1.6% statin-users and 1.5%
Diabetes nonusers were diagnosed with MACE (odds ratio [OR] 1.05, 95% confidence interval [CI] 0.551.98), 12.5% of statin-users
Diabetic complications and 5.8% of nonusers were diagnosed with diabetes (OR 2.34, 95% CI 1.793.04), and 1.7% statin- users and 0.7% nonusers
were diagnosed with diabetes with complication (OR 2.47, 95% CI 1.215.04). There were no differences in rates of other
adverse events.
Conclusions: Among healthy physically active individuals, statin use was associated with doubled the odds of diabetes and
diabetic complications without countervailing cardiovascular benefits.
Published by Elsevier Ltd on behalf of Sports Medicine Australia.

1. Introduction primary prevention for individuals who regularly perform intense physical
1
Physical activity and cardiorespiratory fitness (CRF) have strong inverse activity can be different from those who live a sedentary lifestyle. There is no
1 statin primary prevention clinical trial that examined the overall effects of
relationships to cardiovascular (CV) morbidity and mortality. Regardless of
statins in physically active individ-uals who would be expected to benefit less
the anatomical extent of coronary artery disease, patients with good functional from use of statins for primary prevention.
2
capacity (>10 Metabolic Equivalents [METS]) had lower CV mortality.
However, physical activity is not included in CV risk calculators that are In a previous study including enrollees of Tricare (The US Mil-itary
utilized in estimating the necessity of statin therapy for primary prevention of Healthcare System), which included active duty military, Veterans, and their
3
CV disease. families, our group has reported that short-term statin therapy was not
associated with reduction in cardiovascu-lar morbidity but was associated with
Statins effectively lower CV morbidity and mortality but are not without 11
adverse events; specifically, statins are associated with increased risk of increased risk of adverse events. Scarce data exist that exclusively examined
4 5 68 the effects of statins in healthy physically active individuals. The objective of
diabetes, diabetic complications, obesity, and musculoskeletal
9,10 this study is to examine the associations of statin use with short- and long-
diseases, which may inversely affect physical activity. Hence, the overall
term beneficial CV outcomes and adverse effects in a cohort of active duty
impact of prescribing statin therapy for
military. We considered active duty status as a strong proxy for physical
activity with good CRF because of the mandatory biannual military physical
fitness test. The military physical fitness
This study was not posted or presented previously.

Corresponding author.
E-mail address: ishak.mansi@va.gov (I.A. Mansi).

http://dx.doi.org/10.1016/j.jsams.2016.12.075
1440-2440/Published by Elsevier Ltd on behalf of Sports Medicine Australia.
628 I.A. Mansi et al. / Journal of Science and Medicine in Sport 20 (2017) 627632

Table 1
Short-term outcomes of statin-users in comparison to similar nonusers during FY2006 (1st year of follow-up period).

Statin-users N (%) 837 Nonusers N (%) 2488 OR (95% CI) p-value

Major acute cardiovascular events 2 (0.2) 4 (0.2) 1.49 (0.278.14) 0.65
Acute myocardial infarction 1 (0.1) 1 (0.0) n/a
Cardiac arrest and ventricular fibrillation 1 (0.1) 0 (0.0) n/a
Acute cerebrovascular disease 0 (0.0) 3 (0.1) n/a
Peripheral and visceral atherosclerosis 0 (0.0) 1 (0.0) n/a
Diabetes mellitus 8 (1.0) 5 (0.2) 4.79 (1.5614.69) 0.006
Diabetes mellitus with complications 0 (0.0) 2 (0.1) n/a
Acute and unspecified renal failure 1 (0.1) 0 (0.0) n/a
Chronic kidney disease 0 (0.0) 3 (0.1) n/a
Osteoarthritis and arthropathies 65 (7.8) 166 (6.7) 1.18 (0.871.59) 0.28
Dislocation/strain/sprain 38 (4.5) 122 (4.9) 0.92 (0.641.34) 0.67
Malignancy 6 (0.7) 10 (0.4) 1.79 (0.654.94) 0.26

n/a = due to the small number of events in treatment arms calculation of OR was not meaningful.

test includes measured push-ups, sit-ups, and a timed run; hence, it is a good
marker of CRF.
12
2. Methods
The Institutional Review Boards at Brooke Army Medical Cen-ter and the
VA North Texas Health System approved this study. We extracted national
TRICARE data from the Military Health System (MHS) Data Repository
11
(MDR), as detailed in a previous publication. The MDR includes patient
demographic informa-tion, outpatient and inpatient medical encounters within
MHS and outside of MHS, laboratory data performed within MHS, and the
Pharmacy Data Transaction Service (PDTS). PDTS tracks medication
utilization regardless of dispensing pharmacy location or affili-ation.
According to our agreement with TRICARE, all data were de-identified, to
include rounding dates of medical encounters to the nearest quarter of the
year.
The study period comprised the fiscal years (FY) 2002FY2011
(10/1/20019/30/2011). The period from FY 2002 to 2004 was used to
describe baseline characteristics (Baseline period); FY 2005 was used to
identify patients as statin-users or nonusers (exposure period); and the period
from FY 2006 to 2011 was used to capture outcomes (follow-up period).
We included all active duty military at age 35 years or older, who had at
least one medical encounter at baseline and were still enrolled in the system at
FY 2011. To form a healthy cohort, we:
(1) included patients who had a medical encounter in FY 2005 but were not
prescribed any medication during the exposure period (FY 2005) except for
potentially a statin; (2) excluded patients with pre-existing CV diseases at
baseline according to the Agency for Health Research and Quality Clinical
Classifications Software (AHRQ-CCS): coronary artery diseases,
cerebrovascular diseases, and peripheral vascular diseases.
Statin-users initiated statins during FY 2005 and continued to use statins
for a cumulative duration 60 days during FY 2005, but not thereafter. We
restricted statin use to FY 2005 only to min-imize confounding by indication
(as detailed later). Statin-users were considered new users if they did not
receive statins in FY 20022004. We required that statin-users did not receive
other prescription medications in FY 2005 to ensure that no other drugs may
have contributed to the outcomes nor caused drug interactions as shown in
13
previous studies.
Statin nonusers never received a statin throughout the study. We limited
nonusers to those who had medical encounters in the first 6 months of FY
2005 because the number of these patients was very large.
An outcome event was defined as the occurrence of Interna-tional
Classification of Diseases, 9th Revision, Clinical Modification [ICD-9-CM]
codes during the follow-up period. The outcomes were a priori diagnosis
groups as defined by AHRQ-CCS categories
14
: (1) major acute CV events
(MACE), which comprised acute myocardial
infarction, cardiac arrest and ventricular fibrillation, acute cere-brovascular
disease, and peripheral and visceral atherosclerosis;
(2) diabetes mellitus; (3) diabetes mellitus with complication; (4) acute and
unspecified renal failure; (5) chronic kidney disease; (6) osteoarthritis and
arthropathies; (7) dislocation, strain, sprain; and
15
(8) malignancy (Appendix A).
Patients comorbidities were identified using ICD-9-CM codes and their
15
Charlson Comorbidity Index was calculated using Deyos method. Baseline
2
characteristics of groups were compared using for categorical variables and
Students t-test for continuous vari-ables. We created a propensity score to
match statin-users and nonusers at a ratio of 1:3 using 50 variables
comprising: demo-graphics, personal history, comorbidities, occurrence of
14
outcomes of interest at baseline, undergoing procedures, and healthcare
utilization (Supplementary Table S1 in the online version at DOI:
10.1016/j.jsams.2016.12.075). We used logistic regression to create the
propensity score and perform nearest number matching with a caliper of 0.01
11
as previously described.
We captured outcomes at three different intervals: (1) short-term
outcomes: FY 2006 only (Table 1); (2) intermediate-term outcomes: FY 2006
2009 (Supplementary Table S2 in the online version at DOI:
10.1016/j.jsams.2016.12.075); and long-term outcomes: FY 20062011 (Table
2). To increase speci-ficity of chronic diseases diagnoses, we required that
11
they had been diagnosed in 2 separate encounters as previously published ;
however, we accepted 1 encounter in defining acute diseases such as cardiac
arrest or in conditions known to have low sensitivity in identification using
ICD-9-CM codes such as obesity (Appendix B).
To minimize confounding by indication in determining MACE, we
adopted several measures. First, we included healthy popu-lation who
received statins as the only prescription medication. Patients with CV disease
are likely to receive anti-platelet agents, beta-blockers, and other medications.
Second, we included statin-users who used statins in FY 2005 only since
studies have shown that patients who adhered to statins for shorter periods
only were less likely to have diseases that compel long-term statin
16
prescription. Third, we did not include the exposure period (FY2005) in our
outcomes; excluding a time period equivalent to the expected period for a
17
drug to attain efficacy can mitigate the effects of confounding by indication.
Fourth, we counted the inci-dence of undergoing invasive cardiac procedures
during baseline to serve as a measure for our success in minimizing
confounding by indication. If confounding by indication is present, statin-
users were expected to have more invasive procedures.
For primary analysis, we used conditional logistic regression to calculate
odds ratios (OR) and 95% confidence intervals (95% CI) in the propensity
score- matched cohort in each of short-term, intermediate-term, and long-term
follow-up.
For Secondary analyses, we performed several analyses
adjust-ing for variables such as vital signs and laboratory
values measured
 I.A. Mansi et al. / Journal of Science and Medicine in Sport 20 (2017) 627632 629

Table 2
Long-term outcomes of statin-users in comparison to similar nonusers during follow-up FY 2006-2011.
Statin-users N (%) Nonusers N (%) Primary analysis p-value Secondary analysis p-value
N = 837 N = 2488 OR (95% CI) Adjusted OR (95% CI)
Major acute cardiovascular events 13 (1.6) 37 (1.5) 1.05 (0.551.98) 0.89 a 0.17
1.71 (0.803.64)
1.23 (0.493.06)b 0.66
1.16 (0.462.95)c 0.75
Acute myocardial infarction 6 (0.7) 8 (0.3) 2.24 (0.776.47) 0.14
Cardiac arrest and ventricular fibrillation 1 (0.1) 5 (0.2) 0.59 (0.075.09) 0.64
Acute cerebrovascular disease 4 (0.5) 13 (0.5) 0.91 (0.302.81) 0.88
Peripheral and visceral atherosclerosis 2 (0.2) 12 (0.5) 0.49 (0.112.21) 0.36
Diabetes mellitus 105 (12.5) 144 (5.8) 2.34 (1.793.04) <0.001 a <0.001
2.86 (2.053.99)
2.86 (2.063.98)d <0.001
a
Diabetes mellitus with complications 14 (1.7) 17 (0.7) 2.47 (1.215.04) 0.01 2.40 (0.886.55) 0.09
2.59 (0.986.83)d 0.05
Acute and unspecified renal failure 2 (0.2) 19 (0.8) 0.31 (0.071.34) 0.12
Chronic kidney disease 5 (0.6) 17 (0.7) 0.87 (0.322.38) 0.79 0.79 (0.125.17)c 0.80
e
Osteoarthritis and arthropathies 363 (43.4) 1054 (42.4) 1.04 (0.891.22) 0.61 0.98 (0.811.18) 0.80
e
Dislocation/strain/sprain 247 (29.5) 746 (30.0) 0.99 (0.821.16) 0.80 0.85 (0.691.04) 0.11
Malignancy 30 (3.6) 85 (3.4) 1.05 (0.691.61) 0.82 1.21 (0.722.04)
e 0.46
a Adjusted for: Systolic blood pressure, diastolic blood pressure, body mass index at FY 2011, and propensity score; results were available for 2102 patients only.
b Adjusted for: Systolic blood pressure, diastolic blood pressure, body mass index, HDL- Cholesterol, LDL-Cholesterol; results were available for 1103 patients only.
c Adjusted for: Presence of diabetes mellitus during follow-up period, systolic blood pressure, diastolic blood pressure, body mass index, HDL- Cholesterol, LDL-Cholesterol,

and propensity score; results were available for 1103 patients only.
d Adjusted for: body mass index at FY 2011, and propensity score; results were available for 2102 patients only.
e Adjusted for: Presence of diabetes mellitus during follow-up period, systolic blood pressure, diastolic blood pressure, body mass index, and propensity score; results

were available for 2102 patients only.

at end of the follow-up period (FY 2011) to account for any con-founders that Table 3
18 Long-term hazard ratios of outcomes in statin-users in comparison to similar nonusers.
might have been differentially introduced during the follow-up period. For
example, clinicians may have prescribed statins because they noted in those
Hazard ratio (95% CI) p-value
patients (who would be statin-users) a tendency toward sedentary life style or
unhealthy eating habits; therefore, we adjusted for body mass index, blood Major acute cardiovascular events 1.04 (0.56, 1.97) 0.89
Diabetes mellitus 2.26 (1.77, 2.90) <0.001
pres-sure, and other parameters at FY 2011 (Table 2). We also performed Diabetes mellitus with complication 2.46 (1.21, 4.99) 0.01
Cox-proportional hazard regression analysis and determined haz-ard ratios Acute kidney disease 0.31 (0.07, 1.34) 0.12
(HR) of each outcome among statin-users in comparison to nonusers (Table Chronic kidney disease 0.87 (0.32, 2.37) 0.79
3). In each analysis, the outcome was the time interval from the beginning of Osteoarthritis and arthropathies 1.06 (0.94, 1.19) 0.38
the follow-up period until the first occurrence of the outcome of interest. Dislocation/strain/sprain 0.99 (0.86, 1.14) 0.89

intermediate-term outcomes (FY 2006FY 2009). Statin-users in comparison

Statistical significance was defined as two-tailed p-values <0.05.
Statistical analyses were performed using SPSS version 21 (IBM, Armonk,
NY).
3. Results
Cohort assembly is depicted in Fig. S1 of Supplementary mate-rial in the
online version at DOI: 10.1016/j.jsams.2016.12.075. Out of 877 statin-users
and 86,097 nonusers who met study criteria, we successfully matched 837
statin-users and 2488 nonusers (ratio of 1:3) with no statistically significant
differences in all baseline char-acteristics (Supplementary Table S1 in the
online version at DOI: 10.1016/j.jsams.2016.12.075). The cohort was healthy
at baseline with a mean age of 45 year-old and a mean Charlson comorbidity
score of <0.1; 97% were men. Only one patient underwent cardiac
catheterization and none had a revascularization procedure.
Patients were followed-up for 19,443 person-years. Statin-users used
statins for a mean period of 234 days (standard devi-ation [SD] 97 days)
and a median of 270 days; 75% of the prescriptions were for simvastatin, 19%
for atorvastatin, 4% for pravastatin and lovastatin, and 2% for rosuvastatin. At
some point during the study period, 19% used low-intensity statins, 82% used
moderate- intensity statins, and 8% used high-intensity statins. Statin intensity
was defined according to the 2013 Amer-ican College of
Cardiology/American Heart Association (ACC/AHA) cholesterol guidelines
with modification to include simvastatin 80 mg in the high-intensity group as
11
we described in previous publication.
Tables 1 and 2 depict short-term (FY 2006), and long-term outcomes (FY
20062011). Table S2 of Supplementary material in the online version at
DOI: 10.1016/j.jsams.2016.12.075 depicts
to nonusers had increased risk of diabetes that con-sistently continued
throughout follow-up. At FY 2011, 5.8% of nonusers and 12.5% of statin-
users were diagnosed with diabetes (OR 2.34, 95% CI 1.793.04). The risk for
diabetes with complica-tions was also higher among statin-users. In long-term
follow-up, 0.7% of nonusers, 1.7% of statin-users were diagnosed with
diabetes with complication (OR 2.47, 95% CI 1.215.04). There was no dif-
ference in the risk of musculoskeletal diseases, renal diseases, or malignancy
between statin-users and nonusers.
At end of long-term follow-up, only 1.5% of nonusers and 1.6% of statin-
users were diagnosed with MACE (OR 1.05, 95% CI 0.551.98). Overall,
incidence of MACE was low (2.63 events per 1000 person-years in nonusers
and 2.58 in statin-users, p = 0.9).
Secondary analyses showed that the risk of diabetes persisted despite
various adjustments (Table 2). Similarly, adjusting for these variables and lipid
values during the follow-up did not change our findings regarding MACE. Of
note, one patient of the nonusers died during FY2011, but none of the statin-
users.
Time-to-event analyses showed a similar pattern of increased hazard of
diabetes and diabetes complications in statin-users with no difference in
MACE (Table 3 and Supplementary Fig. S2 in the online version at DOI:
10.1016/j.jsams.2016.12.075).
4. Discussion
This study of healthy active duty military, a strong surrogate for physically
active population with good CRF, demonstrated that statin use for primary
prevention was associated with approxi-mately doubled odds of developing
diabetes mellitus and diabetic complications. Both statin-users and nonusers in
this physically active healthy population had very low rates of MACE (2.63
events
630 I.A. Mansi et al. / Journal of Science and Medicine in Sport 20 (2017) 627632

per 1000 person-years in nonusers
and 2.58 in statin- users), in con-
trast to a rate of 3.99 events per
1000 person-years in the general
19
population ; hence, statin
beneficial cardiovascular effects
could not be demonstrated.
Active duty military status is a
strong proxy for physical activity
with good CRF because of the
military requirements for passing a
biannual basic military physical
fitness test. The basic military
physical fitness test provides a
measure of upper and lower body
muscular endurance and overall
20
physical fitness. Whereas the
details of the test may vary with the
branch of the service (Army, Air
Force, or Navy), it generally
consists of timed push-ups and sit-
ups and a timed run that must be
completed within a prespecified
time interval. For example, the
Army Physical Fitness Test must be
completed within 2 h, with a
maximum of 20 min of rest
between its three events of push-
ups, sit-ups, and a 2-mile run,
which have to be performed in this
specific sequence. It has a
maximum score of 300 and
21
minimum passing score of 180. In
order for a 45-year-old male soldier
(mean age of subjects included in
this study) to pass the test, he
should be able to perform at least
30 push-ups in two minutes and 32
sit- ups in two minutes, and
complete a 2 mile-run in <18.43
21
min.
In a previous study from the
same Tricare population using
similar inclusion and exclusion
criteria to this study but included
Veterans and family members not
only active duty military, we
reported that the overall rate of
MACE was higher than the rate
reported in this study
(approximately 2.1% in our
previous study vs. 1.5% in this
11
study). Of note, although the
overall rate of dia-betes was much
higher in the previous study
(12.5%) in comparison to the
current study that included active
duty military only (7.5%), the odds
ratio of diabetes in statin-users in
comparison to nonusers was higher
in the current study (OR 2.34) than
in the previous study that included
general population (OR 1.93).
Similarly, although the overall rate
of diabetes with complication was
higher in the pre-vious study (1.7%)
in comparison to the current study
(0.9%), the odds ratio of diabetes
with complication was higher in
active duty military (OR 2.47) than
11
in the previous study (OR 2.15).
This observational study helps
fill a gap in the literature because
there are no published randomized
trials that examined the long-term
effects of statin use in physically
active individuals. Our findings are
clinically significant because none
of the CV risk score calculators
consider CRF in its calculations,
therefore, some of those healthy and
active individuals will unnecessary
3
receive statins. Additionally, our
study also found that the risks of
adverse events persist long after
statins were discontinued, which
have been also reported in some
studies noting that both statins CV
benefits and adverse events
persisted for 35 years after the
9,11,22
treatment had been stopped.
The increased risk of diabetes
among statin-users is well described
23
in clinical trials, meta- analysis,
5,24
and observational studies. In the
JUPITER trial (the Justification for
the Use of Statins in Prevention: an
Intervention Trial Evaluating
Rosuvas-tatin), higher incidence of
diabetes was noted among statin-
users despite its short median
23
follow-up of 1.9 years. We have
previ-ously reported the association
of statin use with increased risk of
5,11
diabetic complications.
Additionally, several studies
including a prospective
10
observational study, a cross-
6 result in a relative risk reduction of
sectional study, and a clinical
7 32
trial, indicate that statin use is
associated with higher risk of
obesity.
On the other hand, several
studies have shown that struc-tured
aerobic exercise have favorable CV
benefits similar to
1,25,26
medications. A recent study
noted that individuals with high
physical fitness (>10 METS) in
comparison to those with lowest
fitness had lowest risk of mortality
regardless of whether statins were
taken or not indicating that statins
offered little or no bene-fit in those
27
at high CRF. In a meta- analysis
(33 studies including 102,980
participants), each MET unit of
maximal aerobic capacity
shorter periods only. Using ICD-9-
was associated with 13% reduction CM codes may not reflect disease
1
in total mortality ; such a reduc- severity, how-ever, we do not know
tion compare favorably to statins.
25 of any reason for differential bias
In another meta-analysis, there were between statin-users and nonusers.
no detectable differences between Furthermore, adjusting for actual
exercise and drug inter-ventions in values of blood pressure, body mass
the secondary prevention of
28 index, blood glucose, hemoglobin
coronary heart disease. Whereas A1c, and serum lipids at end of
from the perspective of their
follow-up did not significantly
beneficial effects, exercise and
change our results; yet, we only had
statins may be comparable, statins
increase the risk of diabetes and laboratory and vital signs data at the
29
insulin resistance, but exercise end of follow-up for approximately
decreases the risk of diabetes one-third of the study patients.
25
and insulin resistance. Another limitation for the study is
This study suggests that we may that we could not ascertain that all
need to adjust our approach and subjects in the study have
priorities to primary prevention for successfully passed their military
various populations. Recently, the physical fitness test. Whereas it is
incidence of acute coronary events
expected that all active duty mil-
has been declining in devel-oped
30 itary pass the test, exemptions due
countries, whereas the prevalence
to illness, injury, or other causes
of diabetes and obesity had
may exist; the proportions of such
31
soared. For example, the exceptions is not expected to be
estimated prevalence of diabetes high, specifically among this study
mellitus in the US in 20112012 healthy population.
31
was 1214% and the esti-mated
4
relative risk increase of incident
7
diabetes with statin use is 1012%
; this would translate to an absolute
number of additional 1.21.4 5. Conclusion
incident diabetes for every 100
statin-users. Therefore, the benefit-
Short term statin use in a
risk ratio of statin therapy for healthy, physically active population
healthier contemporary pop-ulations
was associated with higher risks of
such as those included in this study
may be very different from those diabetes and diabetic com-plications
demonstrated in older clinical trials without any of the hoped for CV
employing sicker populations. benefits. Our findings raise
Indeed, in this study, the absolute concerns about the risk-benefit ratio
number of MACE events was too of statins among phys-ically active,
small to demonstrate CV benefits. healthy individuals. Future
Even considering that statins would
refinements of CV risk calculators
CV diseases of 25% according to and national guidelines regarding
statins for primary prevention
clinical trials, the absolute
should consider factoring in
number of MACE events would be
too small to demonstrate a physical activity.
statistically significant benefit.
Practical implications
Our study has several - This study examined the risks of
limitations including its major acute cardiovascular
retrospective observational design events, diabetes mellitus and its
that may suffer from unrecognized complications, kidney diseases,
con-founders. It may be tempting to
musculoskeletal diseases, and
surmise that our findings are due to malignancy in a cohort of healthy
unidentified confounders, however, physically active participants of
one would expect to see an increase statin-users and nonusers.
in risk of other diseases such as
kidney diseases, malignancy, and
osteoarthritis, not only those
outcomes that have biological
plausibility and are reported in
recent studies. Although limiting
statin-users to those who used
statins in FY 2005 helps mitigating
confounding by indication, it limits
the generalizabil-ity of our study to
individuals who used statins for
I.A. Mansi et al. / Journal of Science and Medicine in Sport 20 (2017) 627632 631
- Statin-users used statins for primary prevention and statins were their only Appendix B. Number of separate encounters with a diagnosis that
prescription medication. Nonusers received medical care but did not receive are required to define the occurrence of the diagnosis.
any medications.
- We matched statin users and nonusers baseline characteristics on
demographics, personal history, comorbidities, occurrence of outcomes of Disease group (definition) Number of
interest at baseline, undergoing procedures, and healthcare utilization. We, encounters
thereafter, examined the risks of out-comes during the follow-up period. Immunization and infectious disease screening (CCS 10) 1
Thyroid diseases (CCS 48) 2
- Among healthy physically active participants, statin use was associated with Diabetes mellitus without complication (CCS 49) 2
Diabetes mellitus with complication (CCS 50) 2
doubled the odds of diabetes and diabetic com-plications without Gout (CCS 54) 2
countervailing cardiovascular benefits. Deficiency anemia (CCS 59) 2
- Physically active healthy individuals with good cardiorespiratory fitness Headache (CCS 84) 2
may not benefit from statin therapy for primary preven-tion. Further study is Cataract (CCS 86) 2
Valvular heart diseases (CCS 96) 2
urgently needed to examine the benefit-risk ratio of statin therapy in this
Pericarditis, myocarditis, endocarditis (CCS 97) 2
category of population. Additionally, specific cardiovascular risk calculators Hypertension (CCS 98) 2
that incorporate intensive physical activity as one of its substrate need to be Hypertension with complication (CCS 99) 2
developed to guide statin therapy for such population. Acute myocardial infarction (CCS 100) 2
Non-specific chest pain (CCS 102) 2
Cor pulmonale (CCS 103) 2
Nonspecific heart diseases (CCS 104) 2
Funding source Conduction disorders (CCS 105) 2
Cardiac dysrhythmias (CCS 106) 2
No funding was provided for the conduct of this study. This material is the Cardiac arrest and ventricular fibrillation (CCS 107) 1
Acute cerebrovascular disease (CCS 109) 2
result of work supported with resources and the use of facilities at the VA Peripheral and visceral atherosclerosis (CCS 114) 2
North Texas Health Care System and the University of Texas Southwestern. Aortic; peripheral; and visceral artery aneurysms (CCS 115) 2
Drs. Halms effort was funded in part by the AHRQ R24 HS022418 and Chronic obstructive pulmonary disease and bronchiectasis 2
NCATS U54 RFA-TR-12-006, and Dr. Mortensens by AHRQ R24 (CCS 127)
Asthma (CCS 128) 2
HS022418.
Gastroduodenal ulcer (CCS 139) 2
Gastritis and duodenitis (CCS 140) 2
Disclaimer Gastrointestinal hemorrhage (CCS 153) 2
Nephritis and nephrosis (CCS 156) 2
The views expressed herein are those of the authors and do not reflect the Acute and unspecified renal failure (CCS 157) 1
Chronic kidney disease (CCS 158) 2
official policy or position of the Department of the Army, Department of Osteoarthritis and other non-traumatic joint disorders 2
Defense, VA Administration, or the US Government. The authors are (CCS 203 and 204)
employees of the US government. This work was prepared as part of their Spondylosis, intervertebral disc disorders, other back 2
official duties and, as such, there is no copyright to be transferred. problems (CCS 205)
Osteoporosis (CCS 206) 2
Pathological fracture (CCS 207) 2
Trauma-related joint disorders and dislocations; sprains 2
Acknowledgement and strains (CCS 225 and 232)
Syncope (CCS 245) 1
Rehabilitation care, fitting of prostheses, and adjustment 2
This material is the result of work supported with resources and the use of
of devices (CCS 254)
facilities at the VA North Texas Health Care System and the University of Alcohol abuse/dependence (CCS 660) 1
Texas Southwestern. No funding was provided for the conduct of this study; Illicit drugs use (CCS 661) 1
Drs. Halms effort was funded in part by the AHRQ R24 HS022418 and Family history of cardiovascular disease (V171, V1749, 1
NCATS U54 RFA-TR-12-006, and Dr. Mortensens by AHRQ R24 V174, V1741, and V173)
Obesity (ICD-9-CM codes: 2780, 27800, 27801, 27802, 1
HS022418.
27803, 2781, 2788, and 7831)
Smoking (ICD-9-CM codes: 3051 and V1582) 1
Appendix A. Definitions of
outcomes.
Outcome
Diabetes mellitus without
complication
Diabetes mellitus with complication
Major acute cardiovascular events (MACE) comprised of:
Acute myocardial infarction
Cardiac arrest and ventricular
fibrillation
Acute cerebrovascular disease
Peripheral and visceral
atherosclerosis
Acute and unspecified renal failure
Chronic kidney disease
Osteoarthritis and arthropathies
Dislocation/strain/sprain
Malignancy
AHRQ-CCS = the Agency of
Health Research and Quality
17
Clinical Classification Software.
Musculoskeletal procedures (CCS procedural codes categories)
Procedures involving joints, muscles and tendons (149,
151, 155, 156, 159, 160, 162, 163, and 164)
Partial or total hip or knee replacement (152, 153, 154)
Procedures involving spinal vertebrae (3, 5, and 158)
Reduction of fracture and dislocation (ICD- 9-CM codes:
797, 7970, 7971, 7972, 7973, 7974, 7975, 7976, 7977,
7978, 7979, 798, 7980, 7981, 7982, 7983, 7984, 7985,
7986, 7987, 7988, 7989)
Cardiovascular procedures (CCS procedural codes categories)
Electrocardiography (202)
Echocardiography (193)
Stress test (201)
Cardiac catheterization (47)
Percutaneous coronary intervention (45 and 46)
Coronary artery bypass graft surgery (44)
Pacemaker/defibrillator implantation (48)
Peripheral arterial revascularization procedures (51, 55,
and multilevel code 7.18)
CCS = Clinical Classification
Software Category of the Agency of
17
Health Research and Quality.
632 I.A. Mansi et al. / Journal of Science and Medicine in Sport 20 (2017) 627632

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