title: HDL cholesterol efflux capacity and incident cardiovascular events.
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. (Funded by the Donald W. Reynolds Foundation and others.).
authors.affiliation: From the Division of Cardiology, Department of Internal Medicine (A.R., A.K., J.D.B., E.G.G., C.R.A., I.J.N., J.A.L.), and the Center for Pulmonary and Vascular Biology, Department of Pediatrics (I.S.Y., P.W.S.), University of Texas Southwestern Medical Center, Dallas; the Department of Internal Medicine, Emory University, Atlanta (K.E.W.); and the Departments of Genetics and Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia (D.R.R.).
authors.forename: Anand
authors.initials: A
authors.lastname: Rohatgi
authors.forename: Amit
authors.initials: A
authors.lastname: Khera
authors.forename: Jarett D
authors.initials: JD
authors.lastname: Berry
authors.forename: Edward G
authors.initials: EG
authors.lastname: Givens
authors.forename: Colby R
authors.initials: CR
authors.lastname: Ayers
authors.forename: Kyle E
authors.initials: KE
authors.lastname: Wedin
authors.forename: Ian J
authors.initials: IJ
authors.lastname: Neeland
authors.forename: Ivan S
authors.initials: IS
authors.lastname: Yuhanna
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Rader
authors.forename: James A
authors.initials: JA
authors.lastname: de Lemos
authors.forename: Philip W
authors.initials: PW
authors.lastname: Shaul
mesh_terms: D000328:Adult; D050197:Atherosclerosis / Q000453:epidemiology / Q000378:metabolism; D001692:Biological Transport; D015415:Biomarkers / Q000378:metabolism; D002318:Cardiovascular Diseases / Q000453:epidemiology / Q000378:metabolism* / Q000401:mortality; D008078:Cholesterol, LDL / Q000097:blood; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D015994:Incidence; D008075:Lipoproteins, HDL / Q000097:blood / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D012307:Risk Factors
chemical_list: D015415:Biomarkers; D008078:Cholesterol, LDL; D008075:Lipoproteins, HDL