Effect of pravastatin on metabolic parameters of apolipoprotein B in patients with mixed hyperlipoproteinemia.
3-Hydroxy-3-methylglutaryl coenzyme A reductase inhibitors reduce plasma cholesterol in different forms of hyperlipoproteinemia. Although an increase in low-density lipoprotein (LDL) receptor activity is the proven mechanism of this therapy in familial hypercholesterolemia, the mechanism remains controversial in mixed hyperlipoproteinemia. A decreased production of apolipoprotein B (apoB) and/or an increased removal of lipoproteins could mediate the hypocholesterolemic effect of these drugs. The effect of pravastatin on the metabolism of apoB was evaluated in a randomized, double blind, placebo controlled, cross-over study in five men with mixed hyperlipoproteinemia. Metabolic parameters for apoB were determined using endogenous labeling with [1-13C]leucine and [15N]glycine and multicompartmental modeling. During pravastatin therapy cholesterol, LDL cholesterol, apoB, and LDL apoB levels were significantly reduced (P < 0.01) by 18%, 20%, 27%, and 29%, respectively, while triglyceride and high-density lipoprotein cholesterol levels remained unchanged. Pravastatin therapy increased the fractional catabolic rate of very low density lipoprotein apoB from 3.9 +/- 0.6 to 5.1 +/- 1.7 per day (P = 0.08) and that of LDL apoB from 0.37 +/- 0.09 to 0.46 +/- 0.10 per day (P < 0.01). The apoB production (placebo 35.2 +/- 11.9 mg/kg per day; pravastatin 25.8 +/- 8.7 mg/kg per day) and conversion of very low density lipoprotein apoB to LDL apoB (placebo 65%, pravastatin 57%) remained stable. Thus, also in mixed hyperlipoproteinemia 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors increase the catabolism of apoB-containing lipoproteins without significantly affecting the production of apoB.
Parhofer
K G
KG
Department of Internal Medicine, Washington University School of Medicine, St. Louis.
Barrett
P H
PH
Dunn
J
J
Schonfeld
G
G
D000328:Adult; D001055:Apolipoproteins B / Q000378:metabolism*; D004311:Double-Blind Method; D006801:Humans; D006954:Hyperlipoproteinemia Type V / Q000097:blood / Q000188:drug therapy*; D007700:Kinetics; D008055:Lipids / Q000097:blood; D008297:Male; D008875:Middle Aged; D017035:Pravastatin / Q000627:therapeutic use*
D001055:Apolipoproteins B; D008055:Lipids; D017035:Pravastatin