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

Contents lists available at ScienceDirect

Journal of Science and Medicine in Sport


journal homepage:www.elsevier.com/locate/jsams

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 infarction, cardiac arrest and ventricular fibrillation, acute cere-brovascular
marker of CRF.
12 disease, and peripheral and visceral atherosclerosis;
(2) diabetes mellitus; (3) diabetes mellitus with complication; (4) acute and
2. Methods unspecified renal failure; (5) chronic kidney disease; (6) osteoarthritis and
arthropathies; (7) dislocation, strain, sprain; and
The Institutional Review Boards at Brooke Army Medical Cen-ter and the 15
(8) malignancy (Appendix A).
VA North Texas Health System approved this study. We extracted national
Patients comorbidities were identified using ICD-9-CM codes and their
TRICARE data from the Military Health System (MHS) Data Repository 15
11 Charlson Comorbidity Index was calculated using Deyos method. Baseline
(MDR), as detailed in a previous publication. The MDR includes patient 2
demographic informa-tion, outpatient and inpatient medical encounters within characteristics of groups were compared using for categorical variables and
MHS and outside of MHS, laboratory data performed within MHS, and the Students t-test for continuous vari-ables. We created a propensity score to
Pharmacy Data Transaction Service (PDTS). PDTS tracks medication match statin-users and nonusers at a ratio of 1:3 using 50 variables
comprising: demo-graphics, personal history, comorbidities, occurrence of
utilization regardless of dispensing pharmacy location or affili-ation. 14
According to our agreement with TRICARE, all data were de-identified, to outcomes of interest at baseline, undergoing procedures, and healthcare
include rounding dates of medical encounters to the nearest quarter of the utilization (Supplementary Table S1 in the online version at DOI:
year. 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
The study period comprised the fiscal years (FY) 2002FY2011 as previously described.
(10/1/20019/30/2011). The period from FY 2002 to 2004 was used to
We captured outcomes at three different intervals: (1) short-term
describe baseline characteristics (Baseline period); FY 2005 was used to
outcomes: FY 2006 only (Table 1); (2) intermediate-term outcomes: FY 2006
identify patients as statin-users or nonusers (exposure period); and the period
2009 (Supplementary Table S2 in the online version at DOI:
from FY 2006 to 2011 was used to capture outcomes (follow-up period).
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
We included all active duty military at age 35 years or older, who had at 11
least one medical encounter at baseline and were still enrolled in the system at they had been diagnosed in 2 separate encounters as previously published ;
FY 2011. To form a healthy cohort, we: however, we accepted 1 encounter in defining acute diseases such as cardiac
arrest or in conditions known to have low sensitivity in identification using
(1) included patients who had a medical encounter in FY 2005 but were not
ICD-9-CM codes such as obesity (Appendix B).
prescribed any medication during the exposure period (FY 2005) except for
potentially a statin; (2) excluded patients with pre-existing CV diseases at
To minimize confounding by indication in determining MACE, we
baseline according to the Agency for Health Research and Quality Clinical adopted several measures. First, we included healthy popu-lation who
Classifications Software (AHRQ-CCS): coronary artery diseases, received statins as the only prescription medication. Patients with CV disease
cerebrovascular diseases, and peripheral vascular diseases. 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
Statin-users initiated statins during FY 2005 and continued to use statins studies have shown that patients who adhered to statins for shorter periods
for a cumulative duration 60 days during FY 2005, but not thereafter. We only were less likely to have diseases that compel long-term statin
restricted statin use to FY 2005 only to min-imize confounding by indication 16
prescription. Third, we did not include the exposure period (FY2005) in our
(as detailed later). Statin-users were considered new users if they did not
outcomes; excluding a time period equivalent to the expected period for a
receive statins in FY 20022004. We required that statin-users did not receive 17
other prescription medications in FY 2005 to ensure that no other drugs may drug to attain efficacy can mitigate the effects of confounding by indication.
have contributed to the outcomes nor caused drug interactions as shown in Fourth, we counted the inci-dence of undergoing invasive cardiac procedures
13 during baseline to serve as a measure for our success in minimizing
previous studies. confounding by indication. If confounding by indication is present, statin-
users were expected to have more invasive procedures.
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. For primary analysis, we used conditional logistic regression to calculate
odds ratios (OR) and 95% confidence intervals (95% CI) in the propensity
An outcome event was defined as the occurrence of Interna-tional
score- matched cohort in each of short-term, intermediate-term, and long-term
Classification of Diseases, 9th Revision, Clinical Modification [ICD-9-CM]
follow-up.
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
For Secondary analyses, we performed several analyses
(MACE), which comprised acute myocardial 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. to nonusers had increased risk of diabetes that con-sistently continued
Statistical analyses were performed using SPSS version 21 (IBM, Armonk, throughout follow-up. At FY 2011, 5.8% of nonusers and 12.5% of statin-
NY). 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
3. Results 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-
Cohort assembly is depicted in Fig. S1 of Supplementary mate-rial in the ference in the risk of musculoskeletal diseases, renal diseases, or malignancy
online version at DOI: 10.1016/j.jsams.2016.12.075. Out of 877 statin-users between statin-users and nonusers.
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 At end of long-term follow-up, only 1.5% of nonusers and 1.6% of statin-
differences in all baseline char-acteristics (Supplementary Table S1 in the users were diagnosed with MACE (OR 1.05, 95% CI 0.551.98). Overall,
online version at DOI: 10.1016/j.jsams.2016.12.075). The cohort was healthy incidence of MACE was low (2.63 events per 1000 person-years in nonusers
at baseline with a mean age of 45 year-old and a mean Charlson comorbidity and 2.58 in statin-users, p = 0.9).
score of <0.1; 97% were men. Only one patient underwent cardiac Secondary analyses showed that the risk of diabetes persisted despite
catheterization and none had a revascularization procedure. various adjustments (Table 2). Similarly, adjusting for these variables and lipid
values during the follow-up did not change our findings regarding MACE. Of
Patients were followed-up for 19,443 person-years. Statin-users used note, one patient of the nonusers died during FY2011, but none of the statin-
statins for a mean period of 234 days (standard devi-ation [SD] 97 days) users.
and a median of 270 days; 75% of the prescriptions were for simvastatin, 19% Time-to-event analyses showed a similar pattern of increased hazard of
for atorvastatin, 4% for pravastatin and lovastatin, and 2% for rosuvastatin. At diabetes and diabetes complications in statin-users with no difference in
some point during the study period, 19% used low-intensity statins, 82% used MACE (Table 3 and Supplementary Fig. S2 in the online version at DOI:
moderate- intensity statins, and 8% used high-intensity statins. Statin intensity 10.1016/j.jsams.2016.12.075).
was defined according to the 2013 Amer-ican College of
Cardiology/American Heart Association (ACC/AHA) cholesterol guidelines 4. Discussion
with modification to include simvastatin 80 mg in the high-intensity group as
11 This study of healthy active duty military, a strong surrogate for physically
we described in previous publication.
active population with good CRF, demonstrated that statin use for primary
prevention was associated with approxi-mately doubled odds of developing
Tables 1 and 2 depict short-term (FY 2006), and long-term outcomes (FY diabetes mellitus and diabetic complications. Both statin-users and nonusers in
20062011). Table S2 of Supplementary material in the online version at this physically active healthy population had very low rates of MACE (2.63
DOI: 10.1016/j.jsams.2016.12.075 depicts events
630 I.A. Mansi et al. / Journal of Science and Medicine in Sport 20 (2017) 627632
with complication was higher in shorter periods only. Using ICD-9-
per 1000 person-years in nonusers active duty military (OR 2.47) than was associated with 13% reduction CM codes may not reflect disease
11 1
and 2.58 in statin- users), in con- in the previous study (OR 2.15). in total mortality ; such a reduc- severity, how-ever, we do not know
trast to a rate of 3.99 events per tion compare favorably to statins.
25 of any reason for differential bias
1000 person-years in the general In another meta-analysis, there were between statin-users and nonusers.
19 This observational study helps
population ; hence, statin fill a gap in the literature because no detectable differences between Furthermore, adjusting for actual
beneficial cardiovascular effects there are no published randomized exercise and drug inter-ventions in values of blood pressure, body mass
could not be demonstrated. the secondary prevention of
trials that examined the long-term 28 index, blood glucose, hemoglobin
effects of statin use in physically coronary heart disease. Whereas A1c, and serum lipids at end of
Active duty military status is a active individuals. Our findings are from the perspective of their
follow-up did not significantly
strong proxy for physical activity beneficial effects, exercise and
clinically significant because none change our results; yet, we only had
with good CRF because of the statins may be comparable, statins
of the CV risk score calculators increase the risk of diabetes and laboratory and vital signs data at the
military requirements for passing a consider CRF in its calculations, 29
insulin resistance, but exercise end of follow-up for approximately
biannual basic military physical therefore, some of those healthy and
fitness test. The basic military decreases the risk of diabetes one-third of the study patients.
active individuals will unnecessary 25
physical fitness test provides a and insulin resistance. Another limitation for the study is
3
receive statins. Additionally, our This study suggests that we may that we could not ascertain that all
measure of upper and lower body
muscular endurance and overall study also found that the risks of need to adjust our approach and subjects in the study have
20 adverse events persist long after priorities to primary prevention for successfully passed their military
physical fitness. Whereas the statins were discontinued, which various populations. Recently, the physical fitness test. Whereas it is
details of the test may vary with the have been also reported in some incidence of acute coronary events
branch of the service (Army, Air expected that all active duty mil-
studies noting that both statins CV has been declining in devel-oped
Force, or Navy), it generally 30 itary pass the test, exemptions due
benefits and adverse events countries, whereas the prevalence
consists of timed push-ups and sit- to illness, injury, or other causes
persisted for 35 years after the of diabetes and obesity had
ups and a timed run that must be 9,11,22 may exist; the proportions of such
treatment had been stopped. 31
completed within a prespecified soared. For example, the exceptions is not expected to be
time interval. For example, the estimated prevalence of diabetes high, specifically among this study
Army Physical Fitness Test must be The increased risk of diabetes mellitus in the US in 20112012 healthy population.
completed within 2 h, with a among statin-users is well described 31
was 1214% and the esti-mated
23 4
maximum of 20 min of rest in clinical trials, meta- analysis, relative risk increase of incident
between its three events of push- 5,24 7
and observational studies. In the diabetes with statin use is 1012%
ups, sit-ups, and a 2-mile run, JUPITER trial (the Justification for ; this would translate to an absolute
which have to be performed in this the Use of Statins in Prevention: an number of additional 1.21.4 5. Conclusion
specific sequence. It has a Intervention Trial Evaluating incident diabetes for every 100
maximum score of 300 and Rosuvas-tatin), higher incidence of statin-users. Therefore, the benefit-
21
Short term statin use in a
minimum passing score of 180. In diabetes was noted among statin- risk ratio of statin therapy for healthy, physically active population
order for a 45-year-old male soldier users despite its short median healthier contemporary pop-ulations
23 was associated with higher risks of
(mean age of subjects included in follow-up of 1.9 years. We have such as those included in this study
may be very different from those diabetes and diabetic com-plications
this study) to pass the test, he previ-ously reported the association
demonstrated in older clinical trials without any of the hoped for CV
should be able to perform at least of statin use with increased risk of
5,11 employing sicker populations. benefits. Our findings raise
30 push-ups in two minutes and 32 diabetic complications. Indeed, in this study, the absolute concerns about the risk-benefit ratio
sit- ups in two minutes, and Additionally, several studies number of MACE events was too of statins among phys-ically active,
complete a 2 mile-run in <18.43 including a prospective small to demonstrate CV benefits. healthy individuals. Future
21 10
min. observational study, a cross- Even considering that statins would
refinements of CV risk calculators
6 result in a relative risk reduction of
sectional study, and a clinical CV diseases of 25% according to and national guidelines regarding
7 32 statins for primary prevention
In a previous study from the trial, indicate that statin use is clinical trials, the absolute
associated with higher risk of should consider factoring in
same Tricare population using number of MACE events would be
similar inclusion and exclusion obesity. too small to demonstrate a physical activity.
criteria to this study but included statistically significant benefit.
Veterans and family members not On the other hand, several
studies have shown that struc-tured Practical implications
only active duty military, we
aerobic exercise have favorable CV
reported that the overall rate of
benefits similar to Our study has several - This study examined the risks of
MACE was higher than the rate 1,25,26
reported in this study medications. A recent study limitations including its major acute cardiovascular
(approximately 2.1% in our noted that individuals with high retrospective observational design events, diabetes mellitus and its
previous study vs. 1.5% in this physical fitness (>10 METS) in that may suffer from unrecognized complications, kidney diseases,
11 comparison to those with lowest con-founders. It may be tempting to
study). Of note, although the musculoskeletal diseases, and
fitness had lowest risk of mortality surmise that our findings are due to malignancy in a cohort of healthy
overall rate of dia-betes was much regardless of whether statins were
unidentified confounders, however, physically active participants of
higher in the previous study taken or not indicating that statins
(12.5%) in comparison to the offered little or no bene-fit in those one would expect to see an increase statin-users and nonusers.
current study that included active 27 in risk of other diseases such as
at high CRF. In a meta- analysis
duty military only (7.5%), the odds kidney diseases, malignancy, and
(33 studies including 102,980
ratio of diabetes in statin-users in participants), each MET unit of osteoarthritis, not only those
comparison to nonusers was higher maximal aerobic capacity outcomes that have biological
in the current study (OR 2.34) than plausibility and are reported in
in the previous study that included recent studies. Although limiting
general population (OR 1.93). statin-users to those who used
Similarly, although the overall rate statins in FY 2005 helps mitigating
of diabetes with complication was confounding by indication, it limits
higher in the pre-vious study (1.7%) the generalizabil-ity of our study to
in comparison to the current study individuals who used statins for
(0.9%), the odds ratio of diabetes
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
Musculoskeletal procedures (CCS procedural codes categories)
outcomes.
Procedures involving joints, muscles and tendons (149,
151, 155, 156, 159, 160, 162, 163, and 164)
Outcome Partial or total hip or knee replacement (152, 153, 154)
Diabetes mellitus without Procedures involving spinal vertebrae (3, 5, and 158)
Reduction of fracture and dislocation (ICD- 9-CM codes:
complication
797, 7970, 7971, 7972, 7973, 7974, 7975, 7976, 7977,
Diabetes mellitus with complication
7978, 7979, 798, 7980, 7981, 7982, 7983, 7984, 7985,
Major acute cardiovascular events (MACE) comprised of:
7986, 7987, 7988, 7989)
Acute myocardial infarction
Cardiovascular procedures (CCS procedural codes categories)
Cardiac arrest and ventricular
fibrillation Electrocardiography (202)
Acute cerebrovascular disease Echocardiography (193)
Peripheral and visceral Stress test (201)
atherosclerosis Cardiac catheterization (47)
Acute and unspecified renal failure Percutaneous coronary intervention (45 and 46)
Chronic kidney disease Coronary artery bypass graft surgery (44)
Osteoarthritis and arthropathies Pacemaker/defibrillator implantation (48)
Dislocation/strain/sprain Peripheral arterial revascularization procedures (51, 55,
Malignancy and multilevel code 7.18)

CCS = Clinical Classification


AHRQ-CCS = the Agency of Software Category of the Agency of
Health Research and Quality 17
Health Research and Quality.
17
Clinical Classification Software.
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