DETERMINANTS OF LDL SUBFRACTION DISTRIBUTION AND CONCENTRATIONS IN YOUNG NORMOLIPIDEMIC SUBJECTS

Human low-density lipoproteins (LDLs) comprise a spectrum of particles that vary in size, density, chemical composition, metabolic behavior, and atherogenicity. To identify determinants of this heterogeneity, w e measured the percent distribution and plasma concentration of the th ree major LDL subfractions in 34 young healthy subjects. These paramet ers were correlated in univariate and multivariate analyses with vario us body and lifestyle factors; plasma lipids and lipoprotein; and the activities of cholesteryl ester transfer protein, lipoprotein lipase, and hepatic lipase (HL). Women (n=15) had significantly more large, bu oyant LDL (LDL-I; density, 1.025 to 1.034 g/mL) and high-density lipop rotein, (HDL(2)) than men (n=19). Both the percentage and concentratio n of LDL-I were correlated negatively with very-low-density lipoprotei n triglycerides (VLDL-TG) and HL; they were correlated positively with HDL-cholesterol (HDL-C) and HDL(2). In addition, percent LDL-I was ne gatively correlated with plasma triglycerides, VLDL-C, LDL-C, and apol ipoprotein (ape) B concentrations. The concentrations of intermediate and small, dense LDL (LDL-II and LDL-III; density, 1.034 to 1.044 and 1.044 to 1.060 g/L, respectively) were positively correlated with LDL- C. LDL-III concentrations were also related to plasma cholesterol and apoB concentrations and HL activity. On multivariate analyses, approxi mately one third of the variability in LDL-I was explained by HL and p lasma triglycerides. More than 80% of the variation in LDL-II was acco unted for by a model that combined LDL-C and plasma apoB with body mas s index and VLDL-TG. Plasma apoB concentrations also featured in multi variate models of LDL-III and together with HL and lipoprotein(a) expl ained approximately one third of its variability. The activity of HL a ccounted for the differences in LDL-I between men and women, the recip rocal relation between LDL-I and LDL-III, and the close association of LDL-I with HDL(2). These data confirm that HL is a major determinant of LDL subfraction distribution and indicate, through coordinate regul ation of LDL-I and HDL(2), that these two subfractions should not be c onsidered as independent predictors of coronary risk.