Statins may impair exercise capacity in males but not females
Statins demonstrate sex-specific effects on cardiopulmonary exercise capacity, such that current use is associated with impaired exercise capacity in males but not females, according to a study.
Researchers analysed cross-sectional data from two independent cohorts of the Study of Health in Pomerania, involving 3,500 adults (50 percent male). Oxygen consumption (VO2) at peak exercise (VO2peak) and anaerobic threshold (VO2@AT) was assessed during symptom-limited cardiopulmonary exercise testing.
A linear regression model adjusting for potential confounders (age, sex, previous myocardial infarction and physical inactivity) revealed an association between statin use and reduced VO2peak (2,090 ml/min for users vs 2,336 for nonusers; p<0.0001) and VO2@AT (1,111 ml/min for users vs 1,172 ml/min for nonusers; p=0.0061) in males but not in females (VO2peak: 1,503 ml/min for users vs 1,467 ml/min for nonusers; VO2@AT: 864 ml/min for users vs 854 ml/min for nonusers). These observations persisted despite further adjustments for body mass index, smoking, hypertension, diabetes and estimated glomerular filtration rate.
Statins and exercise both have systemic pleiotropic effects that increase endothelial nitric oxide bioavailability and improve endothelial function, in addition to decreasing the overall inflammatory burden and vascular resistance. [Acta Physiol (Oxf) 2010;199:441–450; Nat Rev Immunol 2011;11:607–615; Vascul Pharmacol 2007;46:1–9]
The sex-specific effect of statins on exercise capacity may be attributed to the risk of skeletal muscle myopathy associated with the drug. This particular side effect is said to mainly affect the glycolytic type II muscle and not oxidative type I fibres, and women particularly have more type I fibres than men. [Neuromuscular Disorders 2011;21:744–745; Am J Cardiovasc Drugs 2008;8:373–418]
Another explanation for the sex-specific effect of statin is that lipophilic statins (eg, lovastatin, simvastatin, fluvastatin, atorvastatin and pivastatin) are metabolized in first-pass in the liver through the hepatic cytochrome enzyme system, with women having higher concentrations of CYP3A4 may thus be able to metabolize statins more quickly. [Clin Interv Aging 2013;8:47–59]
Additional studies using a randomized design are warranted to test whether the present observations can be confirmed and to assess whether exercise and not drug usage is more suitable as a first frontier in primary disease prevention, researchers said. Such studies should provide data on whether individuals in primary cardiovascular prevention aiming to increase their cardiopulmonary exercise capacity should take statins.