Change in α ₁ HDL Concentration Predicts Progression in Coronary Artery Stenosis

Abstract

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, simvastatinniacin-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, ␣ 1 and pre␣ 1 , and significantly decreased the 2 smallest particles, pre␤ 1 and ␣ 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 (rϭϪ0.235; PϽ0.01) between the changes in ␣ 1 HDL particle concentration and coronary artery stenosis was noted. Subjects in the third tertile (157% increase in ␣ 1 ) had no progression of stenosis in the 3-year follow-up period, whereas subjects in the first tertile (15% decrease in ␣ 1 ) had an average of 2.1% increase in stenosis. Conclusions-Simvastatin-niacin therapy significantly increased the large apoA-I-containing ␣ 1 HDL particles. This increase was significantly associated with less progression of coronary stenosis even after adjusting for traditional risk factors.

Physical Fitness and Reverse Cholesterol Transport

“…Asztalos et al reported either no difference in pre␤ 1 -HDL between men with or without CAD 24 or a higher pre␤ 1 -HDL/␣ 1 -HDL ratio in subjects with more severe coronary artery stenosis. 25 Miida et al have reported higher pre␤ 1 -HDL values among Japanese men with CAD. 20 The mechanisms responsible for such differences between patients with CAD and healthy subjects have not been studied and may be multiple.…”

HDL Measures, Particle Heterogeneity, Proposed Nomenclature, and Relation to Atherosclerotic Cardiovascular Events

“…CHD patients also often have small discoidal HDL particles and decreased large ␣-1 and ␣-2 HDL particles. Concentrations of these particles are superior to HDL cholesterol concentrations for use in CHD risk prediction (50,51 ).…”

“…Increasing the concentrations of apo AI in ␣-1 HDL to Ͼ200 mg/L (0.52 mmol/L) with a simvastatin/niacin combination has been associated with lack of progression and in some individuals with regression of coronary atherosclerosis (51 ).…”

Laboratory Assessment of HDL Heterogeneity and Function

“…Twodimensional electrophoresis has been used to resolve at least 12 distinct apoA-I-containing HDL subpopulations. A strong negative correlation has also been observed between the large, cholesterol-rich ␣-1 particles and CHD (50 ). In the Framingham Offspring Study (51 ), CHD cases had higher pre-␤-1 and ␣-3 particle and lower ␣-1, pre-␣-3, and pre-␣-1 particle concentrations.…”

“…␣-1 HDL was most significantly associated with CHD, and each milligram per deciliter increase in ␣-1 particle concentration decreased odds of CHD by 26% (P Ͻ 0.0001). Significant negative correlations were also observed in the HDL-Atherosclerosis Treatment study (50 ) and the VA-HIT study (52 ). Conversely, the VA-HIT study demonstrated a significant positive correlation between CHD events and the concentrations of ␣-3 as well as small, lipid-poor pre-␤-1 particles (52 ).…”