Low high-density lipoprotein cholesterol and particle concentrations are associated with greater levels of endothelial activation markers in Multi-Ethnic Study of Atherosclerosis participants

Abstract

Background: High-density lipoproteins (HDL) are well characterized for their role in reverse cholesterol transport but may confer other cardiovascular benefits-specifically, HDL may suppress the endothelial activation cascade in the initiating stages of atherogenesis.

Objective: It was the primary aim of this study to examine the relations of HDL cholesterol (HDL-C), total HDL particle (HDL-P) concentrations, and HDL-P subclasses with circulating levels of endothelial activation markers in a subcohort of Multi-Ethnic Study of Atherosclerosis participants.

Methods: HDL-C was measured by enzymatic assay, and total HDL-P and subclass concentrations were assessed by nuclear magnetic resonance spectroscopy. Concentrations of circulating endothelial activation markers were determined through immunoassay. Multivariable linear regression was used to determine the cross-sectional associations between HDL variables and endothelial markers with statistical adjustment for age, race/ethnicity, sex, education, systolic blood pressure, hypertension medication use, body mass index, smoking status, lipid-lowering medication use, serum creatinine, diabetes, low-density lipoprotein cholesterol, and coronary artery calcium.

Results: HDL-C and HDL-P were found to be inversely associated with soluble vascular cell adhesion molecule-1, soluble vascular intracellular adhesion molecule-1, sL-selectin, and sP-selectin; HDL-P was additionally inversely associated with sE-selectin. Participants with low levels of HDL-C (<40 mg/dL) or HDL-P (<25th percentile) showed 3%-12% higher mean levels of soluble vascular cell adhesion molecule and compared with those above these levels (all P < .01).

Conclusion: Coupled with previous evidence, our findings suggest a modest to moderate relation of HDL and circulating levels of endothelial activation markers in humans. Whether this relationship may have clinical implications in suppressing atherogenesis or coronary heart disease development requires additional research.

Keywords: Cellular adhesion; Endothelial activation; Epidemiology; HDL; Lipoproteins; Nuclear magnetic resonance; Risk factors.