LDL and apoB
Simvastatin lowers CETP mass and activity by 16 percent in type IIb hyperlipidemia without changing CETP specific activity (Atherosclerosis 1999)
Original title: Plasma lipoprotein distribution and lipid transfer activities in patients with type IIb hyperlipidemia treated with simvastatin
In a double-blind, randomized 8-week trial, 12 type IIb hyperlipidemic patients received simvastatin 20 mg/day and 12 received placebo, with detailed LDL and HDL subfraction analysis and endogenous lipoprotein-dependent and independent CETP and PLTP activity assays. Simvastatin reduced lipid and apolipoprotein B content of the major LDL subfractions without changing overall LDL/HDL size distribution, significantly increased PLTP activity in the lipoprotein-dependent assay (P<0.01), and significantly decreased plasma CETP activity in the lipoprotein-dependent assay (P<0.01), explained by a 16% drop in CETP mass concentration (P<0.01). CETP specific activity was unaffected by simvastatin, reflecting the lack of change in triglyceride-rich lipoprotein acceptors. Changes in plasma CETP mass correlated positively with changes in CETP activity (r=0.483, P=0.0561), total cholesterol (r=0.769, P<0.01), and LDL cholesterol (r=0.736, P<0.01), though neither CETP nor PLTP activity emerged as a main determinant of the LDL and HDL distribution profiles.
Original abstract
The aim of the present study was to search in type IIb hyperlipidemic patients for putative concomitant effects of simvastatin on the physicochemical characteristics of low density lipoproteins (LDL) and high density lipoproteins (HDL), as well as on the activities of the cholesteryl ester transfer protein (CETP) and the phospholipid transfer protein (PLTP) that were determined in both endogenous lipoprotein-dependent and endogenous lipoprotein-independent assays. In a double-blind, randomized trial, patients received either placebo (one tablet/day; n = 12) or simvastatin (20 mg/day; n = 12) for a period of 8 weeks after a 5-week run-in period. Simvastatin, unlike placebo, reduced the lipid and apolipoprotein B contents of the most abundant LDL-1, LDL-2, and LDL-3 subfractions without inducing significant changes in the overall size distribution of LDL and HDL. Whereas simvastatin significantly increased PLTP activity in an endogenous lipoprotein-dependent assay (P < 0.01), no variation was observed in a lipoprotein-independent assay. Simvastatin significantly decreased plasma CETP activity in an endogenous lipoprotein-dependent assay (P < 0.01), and the reduction in plasma cholesteryl ester transfer rates was explained by a 16% drop in CETP mass concentration (P < 0.01). In contrast, the specific activity of CETP was unaffected by the simvastatin treatment reflecting at least in part the lack of significant alteration in plasma triglyceride-rich lipoprotein acceptors. The simvastatin-induced changes in plasma CETP mass levels correlated positively with changes in plasma CETP activity (r = 0.483, P = 0.0561), in total cholesterol levels (r = 0.769; P < 0.01), and in LDL-cholesterol levels (r = 0.736; P < 0.01). Whereas the observations suggest that simvastatin might exert concomitant beneficial effects on plasma CETP and LDL levels, neither plasma cholesteryl ester transfer activity nor plasma phospholipid transfer activity appeared as the main determinants of the LDL and HDL distribution profiles in type IIb hyperlipidemic patients.
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 19 August 2026. Methods.