Arteriosclerosis, Thrombosis, and Vascular Biology. 2001;21:1320-1326
doi: 10.1161/hq0801.095151
doi: 10.1161/hq0801.095151
© 2001 American Heart Association, Inc.
Atherosclerosis and Lipoproteins |
Antioxidant Supplements Block the Response of HDL to Simvastatin-Niacin Therapy in Patients With Coronary Artery Disease and Low HDL
From the Division of Metabolism, Endocrinology, and Nutrition (M.C.C., A.C., J.J.A.), and the Division of Cardiology (X.-Q.Z., B.G.B.), Department of Medicine, School of Medicine, University of Washington, Seattle.
Correspondence to Marian C. Cheung, PhD, University of Washington, 2121 N 35th St, Seattle, WA 98103. E-mail: mccheung{at}u.washington.edu
Abstract—— One strategy for treating coronary artery disease (CAD) patients with low HDL cholesterol (HDL-C) is to maximally increase the HDL-C to LDL-C ratio by combining lifestyle changes with niacin (N) plus a statin. Because HDL can prevent LDL oxidation, the low-HDL state also may benefit clinically from supplemental antioxidants. Lipoprotein changes over 12 months were studied in 153 CAD subjects with low HDL-C randomized to take simvastatin and niacin (S-N), antioxidants (vitamins E and C, ß-carotene, and selenium), S-N plus antioxidants (S-N+A), or placebo. Mean baseline plasma cholesterol, triglyceride, LDL-C, and HDL-C levels of the 153 subjects were 196, 207, 127, and 32 mg/dL, respectively. Without S-N, lipid changes were minor. The S-N and S-N+A groups had comparably significant reductions (P
0.001) in plasma cholesterol, triglyceride, and LDL-C. However, increases in HDL-C, especially HDL2-C, were consistently higher in the S-N group than in the S-N+A group (25% vs 18% and 42% vs 0%, respectively). With S-N, but not with S-N+A, there was a selective increase in apolipoprotein (apo) A-I (64%) in HDL particles containing apo A-I but not A-II [Lp(A-I)] and their particle size. Thus, in CAD patients with low HDL-C, S-N substantially increased HDL2-C, Lp(A-I), and HDL particle size. These favorable responses were blunted by the antioxidants used owing to a striking selective effect on Lp(A-I). This unexpected adverse interaction between antioxidants and lipid therapy may have important implications for the management of CAD.
Key Words: coronary artery disease • low HDL • antioxidant vitamins • lipoproteins • HDL particles
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