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Association of HDL cholesterol efflux capacity with incident coronary heart disease events: a prospective case-control study.

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cam.issuedOnline2015-05-27
dc.contributor.authorSaleheen, Danish
dc.contributor.authorScott, Robert
dc.contributor.authorJavad, Sundas
dc.contributor.authorZhao, Wei
dc.contributor.authorRodrigues, Amrith
dc.contributor.authorPicataggi, Antonino
dc.contributor.authorLukmanova, Daniya
dc.contributor.authorMucksavage, Megan L
dc.contributor.authorLuben, Robert
dc.contributor.authorBillheimer, Jeffery
dc.contributor.authorKastelein, John JP
dc.contributor.authorBoekholdt, S Matthijs
dc.contributor.authorKhaw, Kay-Tee
dc.contributor.authorWareham, Nick
dc.contributor.authorRader, Daniel J
dc.contributor.orcidLuben, Robert [0000-0002-5088-6343]
dc.contributor.orcidKhaw, Kay-Tee [0000-0002-8802-2903]
dc.contributor.orcidWareham, Nicholas [0000-0003-1422-2993]
dc.date.accessioned2018-11-09T00:30:08Z
dc.date.available2018-11-09T00:30:08Z
dc.date.issued2015-07
dc.description.abstractBACKGROUND: Although HDL cholesterol concentrations are strongly and inversely associated with risk of coronary heart disease, interventions that raise HDL cholesterol do not reduce risk of coronary heart disease. HDL cholesterol efflux capacity-a prototypical measure of HDL function-has been associated with coronary heart disease after adjusting for HDL cholesterol, but its effect on incident coronary heart disease risk is uncertain. METHODS: We measured cholesterol efflux capacity and assessed its relation with vascular risk factors and incident coronary heart disease events in a nested case-control sample from the prospective EPIC-Norfolk study of 25 639 individuals aged 40-79 years, assessed in 1993-97 and followed up to 2009. We quantified cholesterol efflux capacity in 1745 patients with incident coronary heart disease and 1749 control participants free of any cardiovascular disorders by use of a validated ex-vivo radiotracer assay that involved incubation of cholesterol-labelled J774 macrophages with apoB-depleted serum from study participants. FINDINGS: Cholesterol efflux capacity was positively correlated with HDL cholesterol concentration (r=0·40; p<0·0001) and apoA-I concentration (r=0·22; p<0·0001). It was also inversely correlated with type 2 diabetes (r=-0·18; p<0·0001) and positively correlated with alcohol consumption (r=0·12; p<0·0001). In analyses comparing the top and bottom tertiles, cholesterol efflux capacity was significantly and inversely associated with incident coronary heart disease events, independent of age, sex, diabetes, hypertension, smoking and alcohol use, waist:hip ratio, BMI, LDL cholesterol concentration, log-triglycerides, and HDL cholesterol or apoA-I concentrations (odds ratio 0·64, 95% CI 0·51-0·80). After a similar multivariable adjustment the risk of incident coronary heart disease was 0·80 (95% CI 0·70-0·90) for a per-SD change in cholesterol efflux capacity. INTERPRETATION: HDL cholesterol efflux capacity might provide an alternative mechanism for therapeutic modulation of the HDL pathway beyond HDL cholesterol concentration to help reduce risk of coronary heart disease. FUNDING: US National Institutes of Health, UK Medical Research Council, Cancer Research UK.
dc.format.mediumPrint-Electronic
dc.identifier.doi10.17863/CAM.32243
dc.identifier.eissn2213-8595
dc.identifier.issn2213-8587
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/284870
dc.languageeng
dc.language.isoeng
dc.publisherLancet Publishing Group
dc.publisher.urlhttp://dx.doi.org/10.1016/s2213-8587(15)00126-6
dc.rightsAttribution 4.0 International
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.subjectAdult
dc.subjectAged
dc.subjectCase-Control Studies
dc.subjectCholesterol, HDL
dc.subjectCoronary Disease
dc.subjectFemale
dc.subjectHumans
dc.subjectMale
dc.subjectMiddle Aged
dc.subjectProspective Studies
dc.subjectRisk Factors
dc.titleAssociation of HDL cholesterol efflux capacity with incident coronary heart disease events: a prospective case-control study.
dc.typeArticle
dcterms.dateAccepted2015-04-21
prism.endingPage513
prism.issueIdentifier7
prism.publicationDate2015
prism.publicationNameLancet Diabetes Endocrinol
prism.startingPage507
prism.volume3
pubs.funder-project-idMedical Research Council (G1000143)
pubs.funder-project-idMedical Research Council (MC_UU_12015/1)
pubs.funder-project-idMedical Research Council (G0401527)
pubs.funder-project-idMedical Research Council (MC_U106179471)
pubs.funder-project-idNational Heart Lung and Blood Institute (R01HL111398)
pubs.funder-project-idMedical Research Council (G0401527/1)
rioxxterms.licenseref.startdate2015-07
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserved
rioxxterms.typeJournal Article/Review
rioxxterms.versionVoR
rioxxterms.versionofrecord10.1016/S2213-8587(15)00126-6

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