May 23rd, 2013
Small Study Suggests Statins May Blunt Benefits of Exercise
A small study is raising big questions about whether statins may blunt the beneficial effects of exercise. The study has been published online in the Journal of the American College of Cardiology and is the subject of a New York Times blog.
Some 37 previously sedentary, overweight or obese adults with at least two other risk factors underwent 12 weeks of aerobic exercising training; 19 were randomized to also receive a statin (simvastatin 40 mg/day). At the end of the study, cardiorespiratory fitness, as measured by maximal oxygen uptake, had increased significantly by 10% in the control group but only by 1.5% in the simvastatin group. The control group also had a significant 13% increase in skeletal muscle citrate synthase activity, a measure of mitochondrial activity in muscles, compared with a 4.5% decrease in the simvastatin group. The authors, led by John Thyfault at the University of Missouri, say their results “suggest that simvastatin may mitigate improvements in fitness in response to exercise training by impairing increases in skeletal muscle mitochondrial content and function.”
The authors conclude: “Given the strong independent cardio-protective effects of increasing cardiorespiratory fitness or lowering LDL, the benefits and risks of each should be carefully considered when choosing treatment modalities.”
The study raises troubling questions about the interactions of statins and exercise, but its small size, along with other limitations, may hinder its immediate impact. In an accompanying editorial, Paul Thompson and Beth Parker take note of several of these limitations. For one, because the control group did not take a placebo pill, participants were not blinded to their treatment. They cite evidence that people on statins are likely to overestimate the skeletal muscle side effects of statins.
They also note that the researchers did not report whether the two groups achieved similar levels of exercise intensity:
We have observed a reduction in spontaneous physical activity levels in individuals over age 55 years treated with atorvastatin. Knowing whether or not the statin-treated subjects exercise-trained less intensely…would indicate if statins reduced the training stimulus itself or if they reduced the physiological response to a similar training stimulus.
Thompson and Parker also cite a recent analysis published in the Lancet that found that both statins and increased physical fitness were independently associated with low mortality but that “the combination of statin treatment and increased fitness resulted in substantially lower mortality risk than either alone.” This suggests that the short-term changes in surrogate endpoints seen in the JACC study, even if found to be true, may not result in important long-term differences in health.
Robert Eckel, speaking on behalf of the American Heart Association, raised several other questions about the study. “The bottom line,” he said, is that the simvastatin 40 mg regimen used in the study “may impact on your training,” but that the results would need to be validated for lower doses of simvastatin and for other statins. In addition, he said, the results of a study in a population that does not have established cardiovascular disease should not be extrapolated to people with established disease, in whom the benefits of statins have been conclusively demonstrated.