Effect of atorvastatin on apolipoprotein B48 metabolism and low-density lipoprotein receptor activity in normolipidemic patients with coronary artery disease.
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.
Dane-Stewart
Cheryl A
CA
Department of Medicine, University of Western Australia, Bentley, Western Australia 6102.
Watts
Gerald F
GF
Pal
Sebely
S
Chan
Dick
D
Thompson
Peter
P
Hung
Joseph
J
Mamo
John C l
JC
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
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