LDL particle size distribution is associated with carotid intima-media thickness in healthy 50-year-old men

Results of cross-sectional and prospective studies have suggested that smal l, dense low-density lipoprotein (LDL) particles predispose to coronary hea rt disease. We investigated the relationships between plasma concentrations of LDL subfractions and intima-media thickness (IMT) of the common carotid artery (CCA), quantified by B-mode ultrasound, in 94 healthy, 50-year-old men, all of whom were homozygous for the apolipoprotein E3 allele. A novel 3% to 7.5% polyacrylamide gradient gel was developed to provide separation of LDL subfractions with high resolution, as was a procedure to quantify pl asma concentrations of these LDL subspecies. The LDL particle size distribu tion pattern obtained by the gradient gel electrophoresis procedure was in good agreement with the one obtained by a well-established, single-spin den sity gradient ultracentrifugation technique. LDL-II (particle size, 23.5 to 25.0 nm) was the most abundant subfraction, and its plasma concentration c orrelated closely with the total LDL cholesterol concentration (r=0.61, P<0 .001) but not with CCA IMT (r=-0.13, NS). In contrast, the plasma concentra tion of the predominant small, dense LDL particle subfraction (LDL-III; par ticle size, 22.5 to 23.5 nm) correlated strongly with CCA IMT (r=0.42, P<0. 001). In multivariate analysis, the plasma concentration of the LDL-III sub fraction contributed significantly to the variation in CCA IMT (R-2=0.19). When plasma triglycerides and LDL cholesterol were forced into the multivar iate model, 10% of the variation in CCA IMT was still accounted for by the LDL-TIT subfraction. In summary, use of a novel and sensitive gradient gel electrophoresis method for evaluation of LDL heterogeneity provided the bas is for demonstrating an independent relation between the plasma concentrati on of small LDL and IMT of the CCA in healthy, middle-aged men.