Abstract 15652: Cholesterol Uptake Capacity, a Novel Measure of High Density Lipoprotein Functionality for Coronary Risk Stratification
Introduction: Recent studies have shown that the capacity of high-density lipoprotein (HDL) to stimulate cholesterol efflux from lipid-laden macrophages is a better predictor of cardiovascular disease status than overall HDL cholesterol (HDL-C) concentration. However, conventional procedures for measuring cholesterol efflux capacity involve radiolabeled cholesterol and cultured cells. Thus a simpler method to measure HDL functionality is needed for clinical application.
Methods: In this study, we hypothesized that the efficiency of HDL-induced cholesterol efflux from macrophages is dependent mainly on the capacity of HDL to accept cholesterol, which we named cholesterol “uptake capacity”. In order to test the hypothesis, apoB-depleted serum was incubated with a fluorescently labeled cholesterol, followed by its capture by an immobilized anti-apolipoprotein A1 antibody, and then fluorescence signals were detected from the labeled cholesterol incorporated into HDL. We quantified cholesterol uptake capacity of serum samples from 210 patients with coronary artery disease who had previously undergone revascularization.
Results: The assay system had high reproducibility (CV<10%) with short processing time (<6 hours). Cholesterol uptake capacity declined with myeloperoxidase-mediated oxidation of HDL or in the presence of an inhibitor lecithin-cholesterol acyltransferase. Cholesterol uptake capacity significantly correlated with cholesterol efflux capacity (r=0.82, P<0.0001, n=29). Furthermore, cholesterol uptake capacity correlated inversely with requirement of revascularization (P=0.023). In patients with optimal control of low-density lipoprotein cholesterol, multivariable analysis adjusted for traditional coronary risk factors including HDL-C showed that only cholesterol uptake capacity remained significant (odds ratio 0.30, 95% CI 0.13-0.65, P=0.0025, n=131).
Conclusion: Cholesterol uptake capacity is an alternative measure of HDL functionality and may provide a substitute for cholesterol efflux capacity. The assay system could be applicable for assessing CVD risk in the clinical setting.
Author Disclosures: A. Harada: Employment; Significant; Sysmex Corporation. R. Toh: Research Grant; Modest; Sysmex Corporation. K. Murakami: Employment; Significant; Sysmex Corporation. M. Kiriyama: Employment; Significant; Sysmex Corporation. K. Yoshikawa: Employment; Significant; Sysmex Corporation. T. Kubo: Employment; Significant; Sysmex Corporation. K. Miwa: Employment; Significant; Sysmex Corporation. Y. Irino: Research Grant; Modest; Sysmex Corporation. K. Mori: None. N. Tanaka: None. T. Ishida: None. K. Hirata: Research Grant; Modest; Sysmex Corporation.
- © 2016 by American Heart Association, Inc.