EFFECTS OF SIMVASTATIN ON PLASMA-LIPOPROTEIN SUBFRACTIONS, CHOLESTEROL ESTERIFICATION RATE, AND CHOLESTERYL ESTER TRANSFER PROTEIN IN TYPE-II HYPERLIPOPROTEINEMIA

We investigated the effects of simvastatin on plasma levels of lipopro tein subfractions, cholesterol esterification rates and activities of cholesteryl ester transfer protein in 28 patients with type II hyperli poproteinemia (i.e., nonfamilial hyperlipoproteinemia type IIa and typ e IIb, and heterozygous familial hypercholesterolemia (FH)). Plasma le vels of VLDL-cholesterol (C) and VLDL-triglyceride (TG) were significa ntly reduced overall by 12.9 +/- 58.0% (mean +/- S.D.; P < 0.05) and 4 .2 +/- 54.2% (P < 0.05) respectively, but not in FH. Plasma levels of IDL-C and IDLT-G were decreased overall by 23.2 +/- 47.5% (P < 0.001) and 12.3 +/- 49.7% (P < 0.05), respectively, again mainly due to decre ases seen in nonfamilial type II hyperlipoproteinemia. Plasma levels o f LDL1 (1.019 < d < 1.045)-C and LDL1-TG were significantly reduced by 33.1 +/- 12.9% (P < 0.001) and 23.3 +/- 24.7%(P < 0.001), respectivel y. Plasma levels of LDL2 (1.045 < d < 1.063)-C were significantly redu ced by 22.9 +/- 18.1% (P < 0.001) overall but not in FH. Gradient PAGE showed no consistant changes in the distribution of LDL particles. Th us, plasma levels of all apo B-containing lipoprotein subfractions wer e reduced by simvastatin, but its effects varied among the three subgr oups. Cholesterol esterification rates were suppressed by 9.3 +/- 19.7 % (P < 0.01) and activities of cholesteryl ester transfer protein were reduced by 30.6 +/- 21.5% (P < 0.001). Changes in CETP activity and i n plasma levels of cholesterol in lipoprotein subfractions were not co rrelated Thus, the changes in distribution of lipoprotein subfractions were not due mainly to CETP suppression.