Independent associations between plasma lipoprotein subfraction levels and the course of coronary artery disease in the St. Thomas' Atherosclerosis Regression Study (STARS)

Abstract

Associations between plasma lipoprotein subfractions and changes in coronary artery disease (CAD) were examined in 74 men who completed the St. Thomas' Atherosclerosis Regression Study (STARS). Plasma lipoproteins were isolated by stepwise, preparative ultracentrifugation at repeated intervals during the 38-month trial. Paired coronary angiograms were quantitatively analyzed by a computerized method. In univariate linear regression analysis, changes in mean absolute width (ΔMAWS) and minimum absolute width (ΔMinAWS) of coronary segments were significantly correlated with in-trial concentrations of cholesterol in intermediate-density lipoprotein ([IDL] d = 1.006 to 1.019 kg/L), low-density lipoprotein ([LDL 2] d = 1.019 to 1.040 kg/L; LDL 3, d = 1.040 to 1.063 kg/L), and high-density lipoprotein ([HDL 3] d = 1.125 to 1.210 kg/L) subfractions; no significant associations were found with other lipoproteins. IDL, LDL 3, and HDL 3 cholesterol were then selected for multiple linear regression analysis because these variables were not co-correlated and because they attained a significance of P less than or equal to .1 in univariate regression. In this analysis, only LDL 3 cholesterol level was a significant negative predictor ( P < .05) of both ΔMAWS and ΔMinAWS; a positive association between ΔMinAWS and HDL 3 cholesterol level just failed to reach conventional statistical significance ( P = .066). Correlations between changes in coronary luminal dimensions and LDL 3 cholesterol level were independent of age, smoking, weight, and blood pressure. Most patients showing regression of coronary atherosclerosis had an LDL 3 cholesterol level of less than 1.8 mmol/L. The findings suggest that LDL 3 is the plasma lipoprotein subfraction that exerts the single most powerful effect on the course of CAD in middle-aged men with hypercholesterolemia.