Reduced Activity Raises Cautions in Older Men Using Statins

June 10, 2014

CHICAGO, IL — Physical-activity levels were "modestly" lower among statin users compared with nonusers independently of other cardiac medications and of medical history, but activity wasn't further inhibited over time, in a prospective community-based cohort of men aged >65 followed for about seven years[1].

Whereas activity levels declined similarly in prevalent statin users and statin nonusers, "new statin use was associated with a more rapid decline in physical activity than nonuse," according to the authors of the new analysis, led by Dr David SH Lee (Oregon State University, Portland).

The observational study suggests that in men like those in the cohort, "statins are associated with less physical activity for as long as statins are used." It wasn't possible to discern a cause-and-effect relationship, but "possible reasons for lower physical-activity levels in statin users may be general muscle pain caused by statins (a well-known adverse effect), exercise-endured myopathy, or muscular fatigue."

The group's report, based on participants in the Osteoporotic Fractures in Men Study (MrOS) enrolling from 2000 to 2002, was published June 9, 2014 in JAMA Internal Medicine.

The men self-reported activity levels at baseline and at two follow-up visits using the Physical Activity Scale for the Elderly (PASE). The second follow-up also included accelerometer-based measurements of metabolic equivalents (METs) and minutes of moderate activity, vigorous activity, or sedentary behavior.

Among the 4137 persons in the baseline analysis, 24% were statin users and 76% were statin nonusers. Statin users scored a mean of 5.8 points lower than nonusers (p=0.03) on the PASE assessment controlled for age, clinical site, MI, stroke, hypertension, diabetes, perceived health, body-mass index, and total-cholesterol levels.

Of the 3039 patients in the longitudinal analyses, 24% were already on statins, 48% did not take statins, and 28% initiated statins during follow-up. PASE scores fell an average of 2.5 per year in statin nonusers and 2.8 per year for the prevalent users, not a significant difference. They dropped a significant 0.9 points further for new users than for nonusers, according to the group. However, the overall adjusted difference in PASE score changes across the three groups wasn't significant (p=0.07).

Of note, statin users achieved a mean of 0.03 kcal/kg/h fewer METS (p<0.001), engaged in significantly less moderate and vigorous activity, and were more often sedentary compared with nonusers.

Statin User-to-Nonuser Ratios for Three Median Physical-Activity Levels* (minutes per day) by Accelerometer in an MrOS Cohort

Activity Level Ratio p
Moderate physical activity 0.91 0.003
Vigorous physical activity 0.92 0.01
Sedentary behavior 1.006 0.003
*Controlled for clinical site and season of the year, age, body-mass index, beta-blockers, ACE inhibitors or angiotensin-receptor blockers, total cholesterol, MI, stroke, hypertension, diabetes, and perceived health

The group proposed "two possible reasons" that prevalent statin use didn't seem to cause a more rapid fall in physical activity, as hypothesized: those most susceptible to muscle symptoms may have stopped their use during the study, or they may have gone off the drugs after a decline in health, they write. Indeed, 11% of statin users had gone off the drugs before the second follow-up visit.

"Some might imagine that reduced activity in new statin users should be managed by urging statin users to exercise more, but this approach is not without hazard," writes DrBeatrice Alexandra Golomb (University of California San Diego, La Jolla) in an accompanying editorial[2]. "Statins compromise muscle in part by marring cell energy (by mitochondrial and oxidative mechanisms). Adding exercise aggravates risk of energy shortfall relative to demand."

Activity and fitness have salutary effects on overall health, including but not limited to cardiovascular, metabolic, cognitive, functional, sleep-related, and healing-related benefits, she notes. In this light, statin-related activity reduction is "a reminder that all medications bear risks, and prescribing them involves trade-offs. When considering statin use in a given patient, effects on function and the spectrum of outcomes, not merely cause-specific ones, should be considered."

Golomb also pointed out that the current analysis is limited in not including women, "who have shown more statin-related muscle problems compared with men," and people with metabolic syndrome "or other risk factors for statin-related muscle problems."

The analysis was funded by a grant from the Medical Research Foundation of Oregon; neither Lee nor the other authors had disclosures, nor did Golomb.


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