A comprehensive systematic review and meta-analysis investigating the relationship between cholesterol efflux capacity and cardiovascular risk

Background: HDL is decisive for reverse cholesterol transport, enabling the removal of cholesterol from macrophages in atherosclerotic plaques. Although HDL-C has long been allied to CVS protection, recent evidence suggests that CEC may more accurately reflect HDL’s functional efficacy. However, studies exploring the relationship between CEC and CAD risk have produced inconsistent results. Objectives: The association between CEC and CAD risk was assessed, along with its potential to predict MACE, including cardiac mortality, all-cause mortality, and non-fatal MI, in this systematic review and meta-analysis. Material and methods: A comprehensive search of PubMed, Scopus, Web of Science, and The Cochrane Library was conducted to identify studies published up to January 2025. Observational studies comparing CEC levels between individuals with and without CAD were included. Results: Twenty-three studies met the inclusion criteria. The pooled SMD of – 0.40 (95% CI: -0.53−-0.26), with a p-value < 0.0001, revealed significantly lower CEC levels in CAD patients compared to non-CAD individuals. Higher CEC was strongly allied with a reduced risk of CAD – OR = 0.57; 95% CI: 0.48−0.67, P < 0.00001, and a pooled risk ratio (RR) of 0.64; 95% CI: 0.48−0.86, p = 0.003. Impaired CEC was associated with an increased risk of cardiac mortality – OR = 3.94; 95% CI: 2.63−5.90, p < 0.00001, and all-cause mortality – OR = 2.84; 95% CI: 2.01−4.00, p < 0.00001. However, insignificant association was found between CEC and non-fatal MI (OR = 3.47; 95% CI: 0.41−29.22, p = 0.25). Conclusion: This meta-analysis underscores the probability of CEC as a biomarker for the assessment of CVS risk. Higher CEC levels are linked to a reduced risk of CAD, cardiac mortality, and all-cause mortality, but no significant relationship was observed with non-fatal MI. Future research should prioritize standardizing CEC measurement methods and investigating its therapeutic potential for preventing atherosclerotic CVS disease.