December 13, 2021Open Access
Cholesterol Efflux Capacity and Its Association With Adverse Cardiovascular Events: A Systematic Review and Meta-Analysis
Key Result
High cholesterol efflux capacity levels were associated with a 37% lower risk of adverse cardiovascular events compared with low levels (RR 0.63).
Study Design
Type
Meta-Analysis (n=25,132)
Structured PICO
Does higher cholesterol efflux capacity reduce the risk of adverse cardiovascular events?
P
Population
25,132 participants from 20 studies with varying cardiovascular risk profiles, followed for 1 to 16 years to evaluate the association between cholesterol efflux capacity and adverse cardiovascular events.
E
Exposure
High cholesterol efflux capacity (CEC) levels
C
Comparator
Low cholesterol efflux capacity (CEC) levels
O
Outcome
Adverse cardiovascular events (inclusive of atherosclerotic cardiovascular disease (ASCVD) or mortality)composite
Higher cholesterol efflux capacity is associated with a lower risk of adverse cardiovascular outcomes, independent of HDL-C levels, suggesting its potential as a biomarker or therapeutic target.
Main Result
Relative Risk: 0.63 (95% CI 0.52–0.76)
p-value: p=<0.00001
Limitations
- Follow-up duration and case definitions for adverse cardiovascular events and ASCVD varied across the included studies.
- Covariates included in the multivariable models were not consistent and may impact the accuracy of the adjusted risk estimates.
- The cutoff value for defining high versus low CEC varied across the included studies, preventing the application of a uniform cutoff value.
Abstract
Background: Serum high-density lipoprotein cholesterol (HDL-C) levels are inversely associated with cardiovascular disease events. Yet, emerging evidence suggests that it is the functional properties of HDL, in particular, reverse cholesterol transport, which is a key protective mechanism mediating cholesterol removal from macrophage cells and reducing plaque lipid content. Cholesterol efflux capacity (CEC) measures the capacity of HDL to perform this function. A systematic review and meta-analysis were conducted to explore the association of CEC and adverse cardiovascular events. Methods: A comprehensive literature review of Embase, PubMed, and Web of Science Core Collection from inception to September 2019 was performed for all studies that examined the association between CEC and cardiovascular outcomes. The primary outcome was adverse cardiovascular events, which were inclusive of atherosclerotic cardiovascular disease (ASCVD) or mortality. Results: A total of 20 trials were included. Compared with low CEC levels, high CEC levels were associated with a 37% lower risk of adverse cardiovascular events (crude RR = 0.63; 95% CI, 0.52–0.76; P 0.00001). Every SD increase of CEC was associated with a 20% lower risk of adverse cardiovascular events (HR = 0.80; 95% CI, 0.66–0.97; P = 0.02). The association remained significant after adjusting for cardiovascular risk factors, medications, and HDL-C levels (HR = 0.76; 95% CI, 0.63–0.91; P = 0.004). A significant CEC-endpoint relationship was observed ( P = 0.024) such that for every 0.1 unit increase in CEC, there was a 5% reduced risk for adverse cardiovascular events (RR = 0.95; 95% CI, 0.91–0.99). Conclusions: Higher CEC is associated with lower adverse cardiovascular outcomes. These findings warrant further research on whether CEC is merely a biomarker or a mechanism that could be targeted as a pharmacologic intervention for improving clinical outcomes. PROSPERO Registration Number: CRD42020146681; https://www.crd.york.ac.uk/prospero/ .