Change in α1 HDL Concentration Predicts Progression in Coronary Artery Stenosis

Objective— We examined the effects of simvastatin-niacin and antioxidant vitamins on changes in high-density lipoprotein (HDL) subpopulations and alterations in coronary artery stenosis, as assessed by angiography. Methods and Results— Lipids, lipoproteins, and HDL particles were measured on and off treatment in 123 subjects of the HDL-Atherosclerosis Treatment Study. Patients were assigned to 4 treatment groups, simvastatin-niacin, simvastatin-niacin-antioxidant vitamins, antioxidant vitamins, and placebo. Subjects were followed for 3 years on treatment and then for 2 months off treatment. Simvastatin-niacin significantly increased the 2 large apoA-I–containing HDL subpopulations, α 1 and preα 1 , and significantly decreased the 2 smallest particles, preβ 1 and α 3 , compared with values obtained from the same patients off treatment. Adding antioxidant vitamins to the lipid-modifying agents blunted these effects (not significant). A significant negative correlation ( r =−0.235; P 1 HDL particle concentration and coronary artery stenosis was noted. Subjects in the third tertile (157% increase in α 1 ) had no progression of stenosis in the 3-year follow-up period, whereas subjects in the first tertile (15% decrease in α 1 ) had an average of 2.1% increase in stenosis. Conclusions— Simvastatin-niacin therapy significantly increased the large apoA-I–containing α 1 HDL particles. This increase was significantly associated with less progression of coronary stenosis even after adjusting for traditional risk factors.