HDL cholesterol efflux capacity and incident cardiovascular events
Open accessAbstract
BACKGROUND: It is unclear whether high-density lipoprotein (HDL) cholesterol concentration plays a causal role in atherosclerosis. A more important factor may be HDL cholesterol efflux capacity, the ability of HDL to accept cholesterol from macrophages, which is a key step in reverse cholesterol transport. We investigated the epidemiology of cholesterol efflux capacity and its association with incident atherosclerotic cardiovascular disease outcomes in a large, multiethnic population cohort. METHODS: We measured HDL cholesterol level, HDL particle concentration, and cholesterol efflux capacity at baseline in 2924 adults free from cardiovascular disease who were participants in the Dallas Heart Study, a probability-based population sample. The primary end point was atherosclerotic cardiovascular disease, defined as a first nonfatal myocardial infarction, nonfatal stroke, or coronary revascularization or death from cardiovascular causes. The median follow-up period was 9.4 years. RESULTS: In contrast to HDL cholesterol level, which was associated with multiple traditional risk factors and metabolic variables, cholesterol efflux capacity had minimal association with these factors. Baseline HDL cholesterol level was not associated with cardiovascular events in an adjusted analysis (hazard ratio, 1.08; 95% confidence interval [CI], 0.59 to 1.99). In a fully adjusted model that included traditional risk factors, HDL cholesterol level, and HDL particle concentration, there was a 67% reduction in cardiovascular risk in the highest quartile of cholesterol efflux capacity versus the lowest quartile (hazard ratio, 0.33; 95% CI, 0.19 to 0.55). Adding cholesterol efflux capacity to traditional risk factors was associated with improvement in discrimination and reclassification indexes. CONCLUSIONS: Cholesterol efflux capacity, a new biomarker that characterizes a key step in reverse cholesterol transport, was inversely associated with the incidence of cardiovascular events in a population-based cohort. (Funded by the Donald W. Reynolds Foundation and others.).
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Recent studies suggest HDL has a complex role in atherogenesis and dysfunctional HDL may be more relevant to atherosclerosis than the HDL-C level.
“Recent studies suggest that HDL has a complex role in atherogenesis and that the presence of dysfunctional HDL may be more relevant to the development of atherosclerosis than the HDL-C level. 93-95”
From 2016 ESC/EAS Guidelines for the Management of Dyslipidaemias (2016) · cites this paper as [95]
The rate of cholesterol efflux has been associated with cardiovascular events and deaths.
“The rate of cholesterol efflux has been associated with the prevalence of CHD, independent of the HDL-C concentration [24], with cardiovascular events and deaths (Fig. 4) [25, 26].”
From HDL cholesterol: reappraisal of its clinical relevance (2017) · cites this paper as [25]
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Self-citation
- Authors
- Rohatgi, A., Khera, A., Berry, J. D., Givens, E. G., Ayers, C. R., Wedin, K. E., Neeland, I. J., Yuhanna, I. S., Rader, D. R., de Lemos, J. A., & Shaul, P. W.
- Affiliations
- Emory University (US)
- The University of Texas Southwestern Medical Center (US)
- Venue
- New England Journal of Medicine
- Publisher
- Massachusetts Medical Society
- Published
- 2014-12-18
- Volume
- 371
- Issue
- 25
- Pages
- 2383-2393
- ISSN
- 0028-4793 (ISSN-L)
- 1533-4406
- PMC
- PMC4308988
- OpenAlex
- W2109429564
- Cited by
- 1,390
- References
- 29
- Citations by year
- 2026: 67 · 2025: 76 · 2024: 102 · 2023: 76 · 2022: 104 · 2021: 146 · 2020: 112 · 2019: 137 · 2018: 142 · 2017: 139 · 2016: 157 · 2015: 123 · 2014: 4 · 2013: 2
- FWCI
- 139.91
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- New England Journal of Medicine (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- American Heart Association
- National Institutes of Health (UL1TR001105)
- National Heart, Lung, and Blood Institute (K08HL1813, K08HL118131)
- National Center for Advancing Translational Sciences
- Topics
- Health Sciences › Medicine › Surgery › Cholesterol and Lipid Metabolism
- Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Paraoxonase enzyme and polymorphisms
- Keywords
- HDL cholesterol efflux capacity, HDL cholesterol, reverse cholesterol transport, atherosclerotic cardiovascular disease, cardiovascular risk, cardiovascular biomarkers, myocardial infarction, stroke, coronary revascularization, cardiovascular mortality, risk reclassification
- MeSH terms
- Adult, Biological Transport, Cardiovascular Diseases, Female, Follow-Up Studies, Humans, Lipoproteins, HDL, Cholesterol, LDL, Male, Middle Aged, Risk Factors, Biomarkers, Incidence, Atherosclerosis
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