Indicators of the atherogenic lipoprotein phenotype measured with density gradient ultracentrifugation predict changes in carotid intima-media thickness in men and women

Abstract

Objective: Progression of carotid intima-media thickness (CIMT) is a surrogate indicator for the early stages of atherosclerosis.

Methods: The study investigated relationships between baseline lipoprotein cholesterol, triglyceride (TG), and apolipoprotein (Apo) B levels assessed with density gradient ultracentrifugation (DGU) and progression of posterior wall common CIMT in men (45-75 years of age) and women (55-74 years of age) in the control arm of a clinical trial. Participants had baseline posterior wall CIMT 0.7-2.0 mm, without significant stenosis. CIMT was assessed using B-mode ultrasound at baseline, and 12 and ~18 months. A DGU cholesterol panel that assessed the major lipoprotein classes and subclasses, plus triglycerides, lipoprotein (a) cholesterol, low-density lipoprotein (LDL) peak time (inversely related to LDL particle density), and Apo B were performed on fasting baseline samples. Apo B was also measured using an enzyme linked immunosorbent assay.

Results: Baseline CIMT was inversely associated (P < 0.001) with CIMT progression. After adjustment for baseline CIMT, significant predictors of posterior wall CIMT progression in linear regression analyses included LDL peak time (inverse, P = 0.045), total high-density lipoprotein cholesterol (HDL-C) (inverse, P = 0.001), HDL(2)-C (inverse, P = 0.005), HDL(3)-C (inverse, P = 0.003), very low-density lipoprotein (VLDL)-C (P = 0.037), and VLDL(1+2)-C (P = 0.016).

Conclusion: These data indicate that DGU-derived indicators of the "atherogenic lipoprotein phenotype," including increased TG-rich lipoprotein cholesterol, lower HDL-C and HDL-C subfractions, and a greater proportion of LDL-C carried by more dense LDL particles, are associated with CIMT progression in men and women at moderate risk for coronary heart disease.

Keywords: atherosclerosis; carotid intima media thickness; coronary heart disease risk; density gradient ultracentrifugation; lipids; lipoprotein subfractions.