doi: 10.1161/hq1001.096624
© 2001 American Heart Association, Inc.
Atherosclerosis and Lipoproteins |
Niacin, but Not Gemfibrozil, Selectively Increases LP-AI, a Cardioprotective Subfraction of HDL, in Patients With Low HDL Cholesterol
From the Cholesterol Research Center, Department of Veterans Affairs Healthcare System, Long Beach, Calif, and the Department of Medicine, University of California, Irvine.
Correspondence to Moti L. Kashyap, MD, Director, Cholesterol Research Center, Department of Veterans Affairs Healthcare System, Professor of Medicine, University of California, Irvine, 5901 E Seventh St (11/111-I), Long Beach, CA 90822. E-mail moti.kashyap{at}med.va.gov
Abstract—— Evidence indicates that the high density lipoprotein (HDL) subfraction containing apolipoprotein A-I without apolipoprotein AII (LP-AI) is more antiatherogenic than HDL particles containing apolipoprotein A-I and apolipoprotein A-II (LP-AI+AII). This study examined the effect of extended-release niacin (niacin-ER) and gemfibrozil on LP-AI and LP-AI+AII particles in patients with low levels of HDL cholesterol (HDL-C). Mechanisms by which these agents modulate HDL particles were investigated by in vitro studies using human hepatoblastoma (Hep G2) cells. A total of 139 patients with low HDL-C (
40 mg/dL) were randomized to niacin-ER or gemfibrozil in a multicenter double-blind trial. Patients were dose-escalated with once-nightly niacin-ER (1 to 2 g) or gemfibrozil (1.2 g) for 19 weeks. Niacin-ER had a greater effect in raising HDL-C and apolipoprotein A-I levels than did gemfibrozil. Niacin-ER at 1- and 2-g doses increased LP-AI levels by 8.7±4.0% (P=0.033) and 24.0±4.4% (P<0.001), respectively. Gemfibrozil had no consistent effect on LP-AI levels. LP-AI+AII levels increased 5% to 8% by both agents. In vitro studies showed that niacin, but not gemfibrozil, selectively decreased the uptake of 125I-labeled LP-AI holoparticles by Hep G2 cells. The uptake of [3H]cholesterol ester was 
75% greater from LP-AI versus LP-AI+AII particles, but neither niacin nor gemfibrozil affected cholesterol ester uptake. These data indicate that unlike gemfibrozil, niacin selectively increases LP-AI compared with LP-AI+AII particle concentration in patients with low HDL-C levels. The mechanism of action of increased LP-AI concentration appears to be mediated by decreased hepatic removal of LP-AI particles, which are more efficient in reverse cholesterol transport, thus suggesting an additional mechanism by which niacin mediates its antiatherogenic properties.
Key Words: lipoproteins • drugs • atherosclerosis • apolipoproteins
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