Exercise Doesn't Worsen Statin Muscle Symptoms

Muscle pain from moderate physical activity wasn't any worse for statin users than nonusers, even for those who reported preexisting statin-associated muscle symptoms (SAMS), a prospective study showed.

Individuals who entered a program of walking 30 to 50 km (about 19 to 31 miles) daily for 4 days started and ended up with the same amount of exercise-induced muscle injury as measured by lactate dehydrogenase, creatine kinase (CK), myoglobin, cardiac troponin I, and NT-proBNP levels -- whether they were statin users with or without muscle symptoms or not on a statin at all.

Symptomatic statin users reported worse muscle pain and fatigue at baseline, but did not have disproportionate increases in these symptoms after moderate exercise compared with the other groups, according to researchers led by Neeltje Allard, MD, of Radboud University Medical Center in Nijmegen, the Netherlands.

Only muscle relaxation time increased more in symptomatic statin users than in the non-user control arm of the study reported in the April 11 issue of the Journal of the American College of Cardiology.

"These results demonstrate that prolonged moderate-intensity exercise is safe for statin users and can be performed by statin users to maintain a physically active lifestyle and to derive its cardiovascular health benefits," Allard's group concluded.

Statins are a cornerstone cardiovascular prevention therapy that have the potential downside of causing muscle symptoms in a small proportion of patients, perhaps through CoQ10 depletion.

"Often, patients reporting SAMS limit their activity owing to pain, weakness, and concerns that exercise will exacerbate muscle injury. Therefore, exercise, a foundation of improving and maintaining cardiometabolic health, is often avoided or limited," wrote Robert Rosenson, MD, cardiologist and lipids specialist at the Icahn School of Medicine at Mount Sinai in New York City, in an accompanying editorial.

Indeed, vigorous exercise had been shown to raise CK levels to a larger extent in statin users compared with nonstatin users, suggesting that statins exacerbate exercise-induced skeletal muscle injury.

However, the new findings suggested that moderate-intensity exercise might improve muscle performance in statin users without worsening their muscle symptoms.

"In summary, many patients who develop SAMS may engage in a moderately intensive walking program without concern for worsened muscle biomarkers or performance," Rosenson agreed.

"Exercise is an essential component of restoring fitness for maintaining health and fitness in all patients at increased risk for an atherosclerotic cardiovascular disease event, particularly those with a disabling event, such as myocardial infarction, and treatment of major cardiovascular risk factors, such as hypertension, prediabetes, or diabetes and dyslipidemia," he said.

For the present study, Allard and colleagues recruited adults for the Nijmegen Four Days Marches project and had their muscle injury markers, muscle performance, and muscle symptoms assessed at baseline and after exercise.

Participants were 35 symptomatic statin users, 34 asymptomatic statin users, and 31 control subjects who walked 30, 40, or 50 km daily at an unspecified pace for 4 consecutive days. Age was in the 60s on average. The statins most frequently used were simvastatin and atorvastatin.

Statin users had any symptoms characterized by the presence, localization, and onset of muscle cramps, pain, and/or weakness, using the statin myalgia clinical index score. Patients with primary myopathic disorders and secondary causes of nonstatin muscle weakness were excluded.

Leukocyte CoQ10 measured at baseline did not differ among study groups. Nor did CoQ10 have any relationship with muscle injury, fatigue resistance, or reported muscle symptoms after exercise.

"We did not obtain muscle biopsy specimens so we could not directly assess skeletal muscle mitochondrial function and muscular CoQ10 levels, although [near-infrared spectroscopy] and leukocyte CoQ10 levels are accepted surrogates for muscle mitochondrial function and intramuscular CoQ10 levels, respectively," study investigators acknowledged.

Rosenson pointed out that the study was also limited by the selection bias in that all participants were capable of walking the specified amount for the intervention. The short-term assessments also precluded evaluation of a longer-term walking program and training effect.

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