Antioxidant supplements block the response of HDL to simvastatin-niacin therapy in patients with coronary artery disease and low HDL

One strategy for treating coronary artery disease (CAD) patients with low H DL cholesterol (HDL-C) is to maximally increase. the HDL-C to LDL-C ratio b y combining lifestyle changes with niacin (N) plus a statin. Because HDL ca n 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 niac in (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, 12 7 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 less than or eq ual to0.001) in plasma cholesterol, triglyceride, and LDL-C. However, incre ases 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-H [Lp(A-I)] and t heir 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 response s were blunted by the antioxidants used owing to a striking selective effec t on Lp(A-I). This unexpected adverse interaction between antioxidants and lipid therapy may have important implications for the management of CAD.