Mechanisms
Atorvastatin cuts CETP activity by up to 26.4% while reshaping apolipoprotein distribution in hypertriglyceridemia (Metabolism 2000)
Original title: Lipid and apolipoprotein levels and distribution in patients with hypertriglyceridemia: effect of triglyceride reductions with atorvastatin
Twenty-seven patients with primary hypertriglyceridemia (triglycerides above 350 mg/dL) were treated with atorvastatin 20 mg/d (n=16) or 80 mg/d (n=11) for 4 weeks. Beyond dose-dependent cholesterol and triglyceride reductions, apoE fell 37% and 49%, apoC-II fell 28% and 42%, and apoC-III fell 18% and 30% at the low and high dose. CETP activity, measured as the percentage of 3H-cholesteryl oleate transferred from HDL to LDL, fell in a dose-dependent manner by 10.3% and 26.4% with the low and high dose. Fast protein liquid chromatography showed a 2-fold rise in the cholesterol-to-apoB ratio across VLDL-to-LDL subfractions and a reduced VLDL-associated apoB fraction (30.5% versus 26.8%), consistent with atorvastatin reducing the pool of triglyceride-rich lipoproteins partly through lowered CETP-mediated transfer.
Original abstract
Atorvastatin is a new hepatic hydroxymethyl glutaryl coenzyme A (HMG-CoA) reductase inhibitor that has been demonstrated to be efficacious in reducing both triglyceride (TG) and cholesterol (CHOL) levels in humans. Twenty-seven (N = 27) patients with primary hypertriglyceridemia (TG > 350 mg/dL) were studied before and after 4 weeks on atorvastatin treatment at a dosage of either 20 (n = 16) or 80 (n = 11) mg/d. The present report examines changes in the plasma levels of several apolipoproteins, including apolipoprotein C-II (apoC-II), apoC-III, and apoE, after atorvastatin. Dose-dependent reductions in both CHOL (20.3% v 43.1%) and TG (26.5% v 45.8%) for the low and high dose, respectively, have been reported in these individuals. In addition to the reductions in apoB commonly associated with the use of HMG-CoA reductase inhibitors, significant reductions in apoE (37% and 49%), apoC-II (28% and 42%), and apoC-III (18% and 30%) were observed with this agent at the 20- and 80-mg/d dosage, respectively. Using fast protein liquid chromatography (FPLC) to fractionate whole plasma according to particle size, the effect of atorvastatin on lipid and apolipoprotein distribution in 20 lipoprotein fractions was also determined. Our results indicate that after 4 weeks on atorvastatin, (1) there was a 2-fold increase in the CHOL content as assessed by the CHOL/apoB ratio for 13 subfractions from very-low-density lipoprotein (VLDL) to small low-density lipoprotein (LDL); (2) there was a statistically significant reduction in the percentage of plasma apoB associated with VLDL-sized particles (30.5% v 26.8%); (3) there was a preferential reduction in plasma apoE from non-apoB-containing lipoproteins with treatment; (4) the losses of apoC-II and apoC-III, on the other hand, were comparable for all lipoprotein fractions; and (5) the fraction of plasma TG associated with HDL was increased after treatment. These changes in lipids and apolipoproteins did not depend on the dose of atorvastatin. There was, on the other hand, a dose-dependent reduction in cholesteryl ester transfer protein (CETP) activity, defined as the percentage of 3H-cholesteryl oleate transferred from high-density lipoprotein (HDL) to LDL. CETP activity was reduced by 10.3% and 26.4% with the low and high dose of atorvastatin. Together, these composition data would be consistent with a net reduction in the number of TG-rich lipoproteins that may be explained by (1) a reduction in VLDL synthesis, (2) a preferential removal of VLDL without conversion to LDL, and (3) a preferential accelerated removal of a subpopulation of LDL.
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 18 August 2026. Methods.