Association of Cholesterol Efflux Capacity with Adverse Cardiovascular Outcomes: A Meta-Analysis†

Abstract

<h3>Lead Author's Financial Disclosures</h3> Nothing to disclose. <h3>Study Funding</h3> CSL Behring. <h3>Background/Synopsis</h3> Reverse cholesterol transport is the primary mechanism of cholesterol elimination from atherosclerotic plaque by macrophages. <h3>Objective/Purpose</h3> To explore the association of cholesterol efflux capacity (CEC), a measure of high-density lipoprotein (HDL) function, with adverse cardiovascular (CV) outcomes, a systematic literature review and meta-analysis was conducted. <h3>Methods</h3> A literature review was performed to collect studies examining the association between CEC and CV outcomes. The primary outcome was adverse CV events, a composite of incident atherosclerotic CV disease (acute coronary syndrome, stroke/transient ischemic attack, revascularization or new atherosclerotic plaque) or all-cause mortality. <h3>Results</h3> A total of 25,132 subjects from 20 studies were included. Compared with low CEC levels, high CEC levels were associated with a 37% lower risk of the primary outcome (RR=0.63; 95% CI, 0.52-0.76; P<0.00001; Figure A). Every SD increase in CEC was associated with a 20% lower risk of adverse CV events (HR=0.80; 95% CI, 0.66-0.97; P=0.02). The association remained significant after adjusting for CV risk factors, medications, and HDL concentration (HR=0.76; 95% CI, 0.63-0.91; P=0.004). For every 0.1 unit increase in CEC, there was a 5% risk reduction in adverse CV events (RR=0.95; 95% CI, 0.91-0.99; Figure B). <h3>Conclusions</h3> Higher CEC is associated with lower adverse CV outcomes. These findings warrant further investigation of CEC as a potential therapeutic target to improve clinical outcomes.