Predictive value of HDL function in patients with coronary artery disease: relationship with coronary plaque characteristics and clinical events

Abstract

Background: HDL is endowed with several metabolic, vascular, and immunoinflammatory protective functions. Among them, a key property is to promote reverse cholesterol transport from cells back to the liver. The aim of this study was to estimate the association of scavenger receptor class B type I (SR-BI)- and ATP binding cassette transporter A1 (ABCA1)-mediated cholesterol efflux (the two major routes for cholesterol efflux to HDL) with the presence, extent, and severity of coronary artery disease (CAD), vascular wall remodelling processes, coronary plaque characteristics, and the incidence of myocardial infarction in the different subgroups of patients from the CAPIRE study.

Methods: Patients (n = 525) from the CAPIRE study were divided into two groups: low-risk factors (RF), with 0-1 RF (n = 263), and multiple-RF, with ≥2 RFs; within each group, subjects were classified as no-CAD or CAD based on the segment involvement score (SIS) evaluated by coronary computed tomography angiography (SIS = 0 and SIS > 5, respectively). SR-BI- and ABCA1-mediated cholesterol efflux were measured using the plasma of all patients.

Results: SR-BI-mediated cholesterol efflux was significantly reduced in patients with CAD in both the low-RF and multiple-RF groups, whereas ABCA1-mediated cholesterol efflux was similar among all groups. In CAD patients, multivariable analysis showed that SR-BI-mediated cholesterol efflux <25^th percentile predicted cardiovascular outcome (odds ratio 4.1; 95% CI: 1.3-13.7; p = .019), whereas ABCA-1-mediated cholesterol efflux and HDL-C levels significantly did not. Despite this finding, reduced SR-BI-mediated cholesterol efflux was not associated with changes in high-risk plaque features or changes in the prevalence of elevated total, non-calcified, and low-attenuation plaque volume.

Conclusion: SR-BI-mediated cholesterol efflux capacity is lower in patients with diffuse coronary atherosclerosis. In addition, a lower SR-BI-mediated cholesterol efflux capacity is associated with the worst clinical outcomes in patients with CAD, independently of atherosclerotic plaque features. Key MessagesIncreased cholesterol efflux capacity, an estimate of HDL function, is associated with a reduced CVD risk, regardless of HDL-C levels.HDL-C levels are significantly lower in patients with CAD.Lower SR-BI-mediated cholesterol efflux capacity is observed in patients with diffuse coronary atherosclerosis and is associated with the worst clinical outcomes in patients with CAD, independently of atherosclerotic plaque features.

Keywords: Cholesterol efflux capacity; SR-BI; atherosclerotic plaque volume; coronary artery disease.

Figure 1.

HDL-C levels and cholesterol efflux in patient subgroups. Patients from the CAPIRE study were stratified based on the number of risk factors (low-RF and multiple-RF) and the presence or absence of CAD (CAD and no-CAD). HDL-C levels (A), SR-BI-mediated cholesterol efflux (B), and ABCA1-mediated cholesterol efflux (C) were evaluated in each subgroup. **p < .01; ***p < .001 (One-way ANOVA, Tuckey post-hoc). RF: risk factor; CAD: coronary artery disease; HDL-C: high-density lipoprotein cholesterol; SR-BI: scavenger receptor class B type I; ABCA1: ATP binding cassette transporter A1.

Figure 2.

Kaplan-Meier event-free survival curves for death and acute coronary syndrome (ACS) stratified by SR-BI-mediated cholesterol efflux capacity, ABCA1-mediated cholesterol efflux capacity, and HDL-C levels. HDL-C: high density- lipoprotein cholesterol; SR-BI: scavenger receptor class B type I; ABCA1: ATP binding cassette transporter A1.

Figure 3.

Prevalence of death ad ACS according to the interaction between HDL-C and SR-BI-mediated cholesterol efflux capacity. HDL-C: high-density lipoprotein cholesterol; SR-BI: scavenger receptor class B type I; ABCA1: ATP binding cassette transporter A1.