Pravastatin投与による血清CoQ<sub>10</sub>濃度の変化と心機能への影響について

Abstract

Pravastatin, which is clinically employed in the treatment of patients with hypercholesterolemia successfully lowers cholesterol levels. The mechanism of the action of pravastatin is inhibition of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, the key enzyme in the biosynthesis of cholesterol from acetyl-CoA. Inhibition of this enzyme may also inhibit the intrinsic biosynthesis of coenzyme Q10 (CoQ10), and consequently attenuate cardiac function. In fact, it has been reported that lovastatin, an HMG-CoA reductase inhibitor, decreases CoQ10 levels and cardiac function, according to evaluation by impedance cardiography (ICG).In order to determine the effects of pravastatin on serum CoQ10 and cardiac function in 12 hypercholesterolemic patients whose cardiac status was class I (NYHA), we measured serum CoQ10 and lipid levels and evaluated cardiac function before and after the administration of pravastatin 10mg/day over 4 weeks.CoQ10 levels were determined by HPLC. Total cholesterol and triglyceride levels were determined by the enzymatic method. HDL cholesterol was determined by the heparin/manganese chloride precipitation method. LDL cholesterol was calculated according to Friedewald's equation. Cardiac function was evaluated by ICG and echocardiography. The Heather, Weissler and Acceleration Indices were measured by ICG and the %FS, EF and CO were measured by echocardiography.After four weeks of pravastatin administration, the serum total and the LDL cholesterol level had decreased significantly, and the HDL cholesterol level had increased significantly. At the same time, the serum CoQ10 concentration had decreased (p<0.005) significantly. However, there were no significant changes in cardiac function, as evaluated by ICG and echocardiography.These results indicate that pravastatin decreases CoQ10 levels, but does not affect cardiac function in hypercholesterolemic patients whose cardiac status is class I.