Change in α ₁ 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, alpha1 and prealpha1, and significantly decreased the 2 smallest particles, prebeta1 and alpha3, 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<0.01) between the changes in alpha1 HDL particle concentration and coronary artery stenosis was noted. Subjects in the third tertile (157% increase in alpha1) had no progression of stenosis in the 3-year follow-up period, whereas subjects in the first tertile (15% decrease in alpha1) had an average of 2.1% increase in stenosis. CONCLUSIONS: Simvastatin-niacin therapy significantly increased the large apoA-I-containing alpha1 HDL particles. This increase was significantly associated with less progression of coronary stenosis even after adjusting for traditional risk factors.