Cholesterol Efflux Capacity, High-Density Lipoprotein Function, and Atherosclerosis

By A. Khera, M. Cuchel, M. de la Llera-Moya, Amrith Rodrigues, Megan F. Burke, K. Jafri, B. French, J. A. Phillips, Megan L Mucksavage, R. Wilensky and 3 more. New England Journal of Medicine, 2011

1,863 citations recorded by the source corpus.

BACKGROUND High-density lipoprotein (HDL) may provide cardiovascular protection by promoting reverse cholesterol transport from macrophages. We hypothesized that the capacity of HDL to accept cholesterol from macrophages would serve as a predictor of atherosclerotic burden. METHODS We measured cholesterol efflux capacity in 203 healthy volunteers who underwent assessment of carotid artery intima–media thickness, 442 patients with angiographically confirmed coronary artery disease, and 351 patients without such angiographically confirmed disease. We quantified efflux capacity by using a validated ex vivo system that involved incubation of macrophages with apolipoprotein B–depleted serum from the study participants. RESULTS The levels of HDL cholesterol and apolipoprotein A-I were significant determinants of cholesterol efflux capacity but accounted for less than 40% of the observed variation. An inverse relationship was noted between efflux capacity and carotid intima–media thickness both before and after adjustment for the HDL cholesterol level. Furthermore, efflux capacity was a strong inverse predictor of coronary disease status (adjusted odds ratio for coronary disease per 1-SD increase in efflux capacity, 0.70; 95% confidence interval [CI], 0.59 to 0.83; P<0.001). This relationship was attenuated, but remained significant, after additional adjustment for the HDL cholesterol level (odds ratio per 1-SD increase, 0.75; 95% CI, 0.63 to 0.90; P = 0.002) or apolipoprotein A-I level (odds ratio per 1-SD increase, 0.74; 95% CI, 0.61 to 0.89; P = 0.002). Additional studies showed enhanced efflux capacity in patients with the metabolic syndrome and low HDL cholesterol levels who were treated with pioglitazone, but not in patients with hypercholesterolemia who were treated with statins. CONCLUSIONS Cholesterol efflux capacity from macrophages, a metric of HDL function, has a strong inverse association with both carotid intima–media thickness and the likelihood of angiographic coronary artery disease, independently of the HDL cholesterol level. (Funded by the National Heart, Lung, and Blood Institute and others.)

Subfields: Endocrinology, Diabetes and Metabolism, Surgery

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In Endocrinology, Diabetes and Metabolism

1. I. Graham
2. Børge G. Nordestgaard
3. Jan Boren
4. A. Tybjærg-Hansen
5. Marja-Riitta Taskinen
6. L. Tokgözoğlu

In Surgery

1. I. Graham
2. Jan Boren
3. A. Tybjærg-Hansen
4. Børge G. Nordestgaard
5. Marja-Riitta Taskinen
6. L. Tokgözoğlu

Citations in the corpus

• 2016 ESC/EAS Guidelines for the Management of Dyslipidaemias. (2016, methodology): “development of atherosclerosis than the HDL-C level.(93) – 95 Most available assays are of high quality, but the method used should be evaluated against the available reference methods and controlled in international quality programmes.”
• Triglyceride-rich lipoproteins and high-density lipoprotein cholesterol in patients at high risk of cardiovascular disease: evidence and guidance for management (2011, background): “was recently shown to be relevant both to carotid-intima thickness and coronary artery disease.(71)”
• Pathophysiology of Type 2 Diabetes Mellitus (2020, background): “The impaired RCT activity has been associated with increased risk of CAD [219] and with flow-mediated vasodilation in T2DM patients [220].”
• Atherosclerotic Cardiovascular Disease and Heart Failure in Type 2 Diabetes – Mechanisms, Management, and Clinical Considerations (2016, neutral): “Although pharmacologically increasing HDL cholesterol concentrations has not been demonstrated to reduce ASCVD, it is possible that HDL cholesterol function, or cholesterol efflux capacity, is a more important determinant of cardiovascular risk.(218) Given the data presented above, the opinions of t”