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