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

Ann Med. 2022 Dec;54(1):1036-1046. doi: 10.1080/07853890.2022.2063374.

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 <25th 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP-Binding Cassette Transporters / metabolism
  • Cholesterol
  • Cholesterol, HDL
  • Coronary Artery Disease*
  • Humans
  • Lipoproteins, HDL / metabolism
  • Plaque, Atherosclerotic* / diagnostic imaging
  • Scavenger Receptors, Class B / metabolism

Substances

  • ATP-Binding Cassette Transporters
  • Cholesterol, HDL
  • Lipoproteins, HDL
  • Scavenger Receptors, Class B
  • Cholesterol

Grants and funding

The study is promoted by GISSI Group (ANMCO, Mario Negri Institute and Heart Care Foundation Onlus) which is also the owner of the database. The sponsor of the study is the Heart Care Foundation Onlus, Florence, Italy, a non-profit independent institution. Funding was provided by Telethon Foundation GGP19146 to GDN; PRIN 2017H5F943 to ALC, PRIN 2017K55HLC to GDN, Ministero Della Salute RF-2019-12370896 to ALC and GDN.