HDL cholesterol efflux capacity and incident cardiovascular events

Anand K Rohatgi, Amit Khera, Jarett D Berry, Edward G. Givens, Colby R. Ayers, Kyle E. Wedin, Ian J Neeland, Ivan S. Yuhanna, Daniel R. Rader, James A de Lemos, Philip W Shaul

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)2383-2393
Number of pages11
JournalNew England Journal of Medicine
Volume371
Issue number25
DOIs
StatePublished - Dec 18 2014

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HDL Cholesterol
Cholesterol
HDL Lipoproteins
Cardiovascular Diseases
Confidence Intervals
Population
Cause of Death
Atherosclerosis
Epidemiology
Biomarkers
Stroke
Macrophages
Myocardial Infarction
Incidence

ASJC Scopus subject areas

  • Medicine(all)

Cite this

HDL cholesterol efflux capacity and incident cardiovascular events. / Rohatgi, Anand K; Khera, Amit; Berry, Jarett D; Givens, Edward G.; Ayers, Colby R.; Wedin, Kyle E.; Neeland, Ian J; Yuhanna, Ivan S.; Rader, Daniel R.; de Lemos, James A; Shaul, Philip W.

In: New England Journal of Medicine, Vol. 371, No. 25, 18.12.2014, p. 2383-2393.

Research output: Contribution to journalArticle

Rohatgi, Anand K ; Khera, Amit ; Berry, Jarett D ; Givens, Edward G. ; Ayers, Colby R. ; Wedin, Kyle E. ; Neeland, Ian J ; Yuhanna, Ivan S. ; Rader, Daniel R. ; de Lemos, James A ; Shaul, Philip W. / HDL cholesterol efflux capacity and incident cardiovascular events. In: New England Journal of Medicine. 2014 ; Vol. 371, No. 25. pp. 2383-2393.
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abstract = "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.",
author = "Rohatgi, {Anand K} and Amit Khera and Berry, {Jarett D} and Givens, {Edward G.} and Ayers, {Colby R.} and Wedin, {Kyle E.} and Neeland, {Ian J} and Yuhanna, {Ivan S.} and Rader, {Daniel R.} and {de Lemos}, {James A} and Shaul, {Philip W}",
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T1 - HDL cholesterol efflux capacity and incident cardiovascular events

AU - Rohatgi, Anand K

AU - Khera, Amit

AU - Berry, Jarett D

AU - Givens, Edward G.

AU - Ayers, Colby R.

AU - Wedin, Kyle E.

AU - Neeland, Ian J

AU - Yuhanna, Ivan S.

AU - Rader, Daniel R.

AU - de Lemos, James A

AU - Shaul, Philip W

PY - 2014/12/18

Y1 - 2014/12/18

N2 - 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.

AB - 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.

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DO - 10.1056/NEJMoa1409065

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JF - New England Journal of Medicine

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