Effect of simvastatin on high density lipoprotein subfractions and apolipoproteins in Type IIa hypercholesterolemia

Abstract

Changes in plasma concentrations of high density lipoproteins (HDL) and triglycerides may partly explain the ability of cholesterol-lowering drugs to decrease the incidence of coronary heart disease. We measured the response of fasting plasma lipids, lipoproteins, and apolipoproteins in 46 subjects with Type IIa hypercholesterolemia treated with simvastatin for 3 months. The initial dose of simvastatin (10 mg/day) was subsequently increased up to 40 mg/day if the plasma cholesterol concentration had not fallen below 5.2 mmol/l. Plasma concentrations of HDL cholesterol and of the apolipoproteins AI and AII were increased by simvastatin. The increase in HDL cholesterol (9%) was due to increases in both subfractions (HDL2 17%; HDL3 7%), changes that would be consistent with a beneficial effect on cardiovascular risk. Simvastatin decreased plasma triglyceride concentrations by 25%. Plasma total cholesterol concentrations fell by 35% after 3 months of treatment; this fall was proportional to the initial concentration and was due almost entirely to a 45% fall in low density lipoprotein cholesterol. In contrast, plasma concentrations of lipoprotein Lp(a) were not affected by simvastatin.

Novel Concepts of Statin Therapy for Cardiovascular Risk Reduction in Hypertension

“…Simvastatin therapy (10mg daily optimized to 40mg daily if plasma cholesterol levels did not fall to less than 5.2mmol/l) may increase plasma concentrations of HDL cholesterol by up to 9% [125], and similar results have been reported with fluvastatin [126]. In the Scandinavian Simvastatin Survival Study (4S), the relative risk reduction in the simvastatin group was 35% (95%Cl: in the lowest quartile of baseline low-density-lipoprotein cholesterol and 36% in the highest [127].…”