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), HDL₂-C (inverse, P = 0.005), HDL₃-C (inverse, P = 0.003), very low-density lipoprotein (VLDL)-C (P = 0.037), and VLDL₁₊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:

• carotid intima media thickness
• density gradient ultracentrifugation
• coronary heart disease risk
• lipids
• atherosclerosis
• lipoprotein subfractions

Acknowledgments

This study was funded by Roll International Corporation, Los Angeles, CA and Atherotech, Birmingham, AL.

Disclosure

KC Maki, MR Dicklin, and MH Davidson received a research grant from Roll International Corporation to conduct the original study in which the blood samples were collected and the CIMT was measured, and received funding from Atherotech to write this manuscript. MH Davidson is on the Medical Advisory Board of Atherotech. PD Mize and KR Kulkarni are employees of Atherotech.