title: Antioxidant supplements block the response of HDL to simvastatin-niacin therapy in patients with coronary artery disease and low HDL.
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, beta-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 HDL(2)-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 HDL(2)-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.
authors.affiliation: Division of Metabolism, Endocrinology, and Nutrition, Department of Medicine, School of Medicine, University of Washington, Seattle 98103, USA. mccheung@u.washington.edu
authors.forename: M C
authors.initials: MC
authors.lastname: Cheung
authors.forename: X Q
authors.initials: XQ
authors.lastname: Zhao
authors.forename: A
authors.initials: A
authors.lastname: Chait
authors.forename: J J
authors.initials: JJ
authors.lastname: Albers
authors.forename: B G
authors.initials: BG
authors.lastname: Brown
mesh_terms: D000328:Adult; D000368:Aged; D000975:Antioxidants / Q000494:pharmacology*; D001205:Ascorbic Acid / Q000494:pharmacology; D008076:Cholesterol, HDL / Q000737:chemistry / Q000378:metabolism*; D008078:Cholesterol, LDL / Q000378:metabolism; D003327:Coronary Disease / Q000188:drug therapy* / Q000378:metabolism; D019587:Dietary Supplements; D004347:Drug Interactions; D005260:Female; D006801:Humans; D000960:Hypolipidemic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D009525:Niacin / Q000494:pharmacology* / Q000627:therapeutic use; D010316:Particle Size; D012643:Selenium / Q000494:pharmacology; D019821:Simvastatin / Q000494:pharmacology* / Q000627:therapeutic use; D014810:Vitamin E / Q000494:pharmacology; D019207:beta Carotene / Q000494:pharmacology
chemical_list: D000975:Antioxidants; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D000960:Hypolipidemic Agents; D019207:beta Carotene; D014810:Vitamin E; D009525:Niacin; D019821:Simvastatin; D012643:Selenium; D001205:Ascorbic Acid