The effect of statins on RyR and RyR-associated disease

Abstract

We sought to review the effects of statins on the ryanodine receptor (RyR) and on RyR-associated diseases, with an emphasis on catecholaminergic polymorphic ventricular tachycardia (CPVT). Statins can affect skeletal muscle and produce statin-associated muscle symptoms (SAMS) but have no adverse effects on cardiac muscle. These contrasting effects may be due to differences in how statins affect the skeletal (RyR1) and cardiac (RyR2) RyR. We searched PubMed to identify English language articles reporting the pathophysiology of the RyR, the effect of statins on RyR function, and on RyR-associated genetic diseases. We selected 150 articles for abstract review, 96 of which provided sufficient information to be included and were reviewed in detail. Fifteen articles highlighted the interaction of statins with the RyR. Nine identified the interaction of statins with RyR1, six addressed the interaction of statins with RyR2, 13 suggested that statins reduce ventricular arrhythmias (VA), and seven suggested that statins increase the risk of malignant hyperthermia (MH). In general, statins increase RyR1 and decrease RyR2 activity. We identified no articles examining the effect of statins on CPVT, a condition often caused by defects in RyR2. Statins appear to increase the risk of MH and decrease the risk of ventricular arrhythmia. The effect of statins on CPVT has not been directly examined, but statins’ reduction in RyR2 function and their apparent reduction in VA suggest that they may be beneficial in this condition.