title: Effect of atorvastatin on apolipoprotein B48 metabolism and low-density lipoprotein receptor activity in normolipidemic patients with coronary artery disease.
abstract: We aimed to examine postprandial dyslipidemia in normolipidemic patients with coronary artery disease (CAD) and the effects of treatment with an hydroxymethyl glutaryl coenzyme A (HMG-CoA) reductase inhibitor (atorvastatin). Subjects with angiographicaly established CAD were randomized to treatment for 12 weeks with 80 mg/d atorvastatin or placebo and the effects on markers of postprandial lipoproteins and low-density lipoprotein (LDL)-receptor binding determined. LDL-receptor binding was determined in mononuclear cells, as a surrogate for hepatic activity. Fasting levels of cholesterol (P <.001), LDL-cholesterol (P <.001), apolipoprotein (apo)B(48) (P =.019), remnant-like particle-cholesterol (RLP-C) (P =.032), and total postprandial apoB(48) area under the curve (AUC) (P =.013) significantly decreased with atorvastatin compared with placebo. Atorvastatin also significantly increased LDL-receptor binding activity (P <.001), and this was correlated with changes in fasting apoB(48) (r =.80, P =.01). We report that aberrations in chylomicron metabolism in normolipidemic CAD subjects are correctable with atorvastatin by a mechanism involving increased LDL-receptor activity. This effect may, in part, explain the cardiovascular benefit of statins used in clinical trials of CAD patients with normal lipid levels.
authors.affiliation: Department of Medicine, University of Western Australia, Bentley, Western Australia 6102.
authors.forename: Cheryl A
authors.initials: CA
authors.lastname: Dane-Stewart
authors.forename: Gerald F
authors.initials: GF
authors.lastname: Watts
authors.forename: Sebely
authors.initials: S
authors.lastname: Pal
authors.forename: Dick
authors.initials: D
authors.lastname: Chan
authors.forename: Peter
authors.initials: P
authors.lastname: Thompson
authors.forename: Joseph
authors.initials: J
authors.lastname: Hung
authors.forename: John C l
authors.initials: JC
authors.lastname: Mamo
mesh_terms: D000328:Adult; D000368:Aged; D000924:Anticholesteremic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D053283:Apolipoprotein B-48; D001055:Apolipoproteins B / Q000097:blood*; D019540:Area Under Curve; D000069059:Atorvastatin; D002914:Chylomicrons / Q000097:blood; D003327:Coronary Disease / Q000097:blood* / Q000188:drug therapy*; D005215:Fasting; D005260:Female; D006538:Heptanoic Acids / Q000008:administration & dosage / Q000494:pharmacology*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D019518:Postprandial Period; D011758:Pyrroles / Q000008:administration & dosage / Q000494:pharmacology*; D011973:Receptors, LDL / Q000097:blood*; D016896:Treatment Outcome; D014280:Triglycerides / Q000097:blood
chemical_list: D000924:Anticholesteremic Agents; D053283:Apolipoprotein B-48; D001055:Apolipoproteins B; D002914:Chylomicrons; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011758:Pyrroles; D011973:Receptors, LDL; D014280:Triglycerides; D000069059:Atorvastatin