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Effect of Statins on Creatine Kinase Levels Before and After a Marathon Run
Study Questions:
Does statin use increase the risk of exercise-related muscle injury?
Methods:
Serum levels of myoglobin, total creatine kinase (CK), and the CK myocardial (CK-MB), muscle (CK-MM), and brain (CK-BB) isoenzymes were measured in 37 subjects treated with statins and 43 nonstatin-treated controls running the 2011 Boston Marathon. Venous blood samples were obtained the day before (PRE) and within 1 hour (FINISH) and 24 hours after (POST) the race. Hematocrit and hemoglobin values were used to adjust for changes in plasma volume. The CK distribution was normalized before analysis using log transformation.
Results:
The exercise-related increase in CK 24 hours after exercise, adjusted for changes in plasma volume, was greater in the statin users (PRE to POST 133 ± 15 to 1104 ± 150 U/L) than in the controls (PRE to POST 125 ± 12 to 813 ± 137 U/L; p = 0.03 for comparison). The increase in CK-MB 24 hours after exercise was also greater in the statin users (PRE to POST 1.1 ± 3.9 to 8.9 ± 7.0 U/L) than in the controls (PRE to POST 0.0 ± 0.0 to 4.2 ± 5.0 U/L; p < 0.05 for comparison). However, the increases in muscle myoglobin did not differ at any point between the two groups. Increases in CK at both FINISH and POST race measurements were directly related to age in the statin users (r2 = 0.13 and r2 = 0.14, respectively; p < 0.05), but not in the controls (r2 = 0.02 and r2 = 0.00, respectively; p > 0.42), suggesting that susceptibility to exercise-induced muscle injury with statins increases with age.
Conclusions:
The authors concluded that statin use increases exercise-related muscle injury.
Perspective:
Statins can increase resting CK, and at least one statin (lovastatin) has been associated with an increase in CK after vigorous exercise in untrained individuals. Although regular physical exercise protects against exercise-related muscle injury, prolonged physical exercise, including running a marathon, can be associated with dramatic elevation of serum markers of skeletal muscle damage. This observational study compared volunteers with a history of hyperlipidemia receiving one of six statins who ran the Boston Marathon with other volunteers without a diagnosis of hyperlipidemia who ran the same race. Although it could be argued that hyperlipidemia (not statin use) or another unmeasured variable was the actual cause of post-race CK elevation, it seems reasonable enough to implicate statins. However, clinical outcomes in terms of freedom from morbidity and mortality among individuals with hyperlipidemia who use a statin and exercise still might be better than with no statin use or no exercise. As always, therapeutic recommendations should be guided by clinical outcomes, rather than by serum markers.
Keywords: Cyclopentanes, Lovastatin, Oxylipins, Hyperlipidemias, Cardiology, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Exercise, Creatine Kinase, MB Form, Running, Muscular Diseases
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