title: Effect of atorvastatin on plasma apoE metabolism in patients with combined hyperlipidemia.
abstract: Atorvastatin, a synthetic HMG-CoA reductase inhibitor used for the treatment of hyperlipidemia and the prevention of coronary artery disease, significantly lowers plasma cholesterol and low-density lipoprotein cholesterol (LDL-C) levels. It also reduces total plasma triglyceride and apoE concentrations. In view of the direct involvement of apoE in the pathogenesis of atherosclerosis, we have investigated the effect of atorvastatin treatment (40 mg/day) on in vivo rates of plasma apoE production and catabolism in six patients with combined hyperlipidemia using a primed constant infusion of deuterated leucine. Atorvastatin treatment resulted in a significant decrease (i.e., 30-37%) in levels of total triglyceride, cholesterol, LDL-C, and apoB in all six patients. Total plasma apoE concentration was reduced from 7.4 +/- 0.9 to 4.3 +/- 0.2 mg/dl (-38 +/- 8%, P < 0.05), predominantly due to a decrease in VLDL apoE (3.4 +/- 0.8 vs. 1.7 +/- 0.2 mg/dl; -42 +/- 11%) and IDL/LDL apoE (1.9 +/- 0.3 vs. 0.8 +/- 0.1 mg/dl; -57 +/- 6%). Total plasma lipoprotein apoE transport (i.e., production) was significantly reduced from 4.67 +/- 0.39 to 3.04 +/- 0.51 mg/kg/day (-34 +/- 10%, P < 0.05) and VLDL apoE transport was reduced from 3.82 +/- 0.67 to 2.26 +/- 0.42 mg/kg/day (-36 +/- 10%, P = 0.057). Plasma and VLDL apoE residence times and HDL apoE kinetic parameters were not significantly affected by drug treatment. Percentage decreases in VLDL apoE concentration and VLDL apoE production were significantly correlated with drug-induced reductions in VLDL triglyceride concentration (r = 0.99, P < 0.001; r = 0.88, P < 0.05, respectively, n = 6). Our results demonstrate that atorvastatin causes a pronounced decrease in total plasma and VLDL apoE concentrations and a significant decrease in plasma and VLDL apoE rates of production in patients with combined hyperlipidemia.
authors.affiliation: Hyperlipidemia and Atherosclerosis Research Group, Montréal, Québec, Canada. cohnj@ircm.qc.ca
authors.forename: Jeffrey S
authors.initials: JS
authors.lastname: Cohn
authors.forename: Michel
authors.initials: M
authors.lastname: Tremblay
authors.forename: Rami
authors.initials: R
authors.lastname: Batal
authors.forename: Hélène
authors.initials: H
authors.lastname: Jacques
authors.forename: Lyne
authors.initials: L
authors.lastname: Veilleux
authors.forename: Claudia
authors.initials: C
authors.lastname: Rodriguez
authors.forename: P Hugh R
authors.initials: PH
authors.lastname: Barrett
authors.forename: Denise
authors.initials: D
authors.lastname: Dubreuil
authors.forename: Madeleine
authors.initials: M
authors.lastname: Roy
authors.forename: Lise
authors.initials: L
authors.lastname: Bernier
authors.forename: Orval
authors.initials: O
authors.lastname: Mamer
authors.forename: Jean
authors.initials: J
authors.lastname: Davignon
mesh_terms: D000328:Adult; D001057:Apolipoproteins E / Q000097:blood* / Q000378:metabolism*; D000069059:Atorvastatin; D006538:Heptanoic Acids / Q000008:administration & dosage / Q000494:pharmacology*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D006950:Hyperlipidemia, Familial Combined / Q000097:blood* / Q000378:metabolism*; D007700:Kinetics; D008079:Lipoproteins, VLDL / Q000097:blood / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D011758:Pyrroles / Q000008:administration & dosage / Q000494:pharmacology*; D013997:Time Factors
chemical_list: D001057:Apolipoproteins E; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008079:Lipoproteins, VLDL; D011758:Pyrroles; D000069059:Atorvastatin