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dc.contributor.authorPerrot, Nicolasen
dc.contributor.authorThériault, Sébastienen
dc.contributor.authorDina, Christianen
dc.contributor.authorChen, Hao Yuen
dc.contributor.authorBoekholdt, S Matthijsen
dc.contributor.authorRigade, Sidwellen
dc.contributor.authorDesprés, Audrey-Anneen
dc.contributor.authorPoulin, Anthonyen
dc.contributor.authorCapoulade, Romainen
dc.contributor.authorLe Tourneau, Thierryen
dc.contributor.authorMessika-Zeitoun, Daviden
dc.contributor.authorTrottier, Mikaëlen
dc.contributor.authorTessier, Michelen
dc.contributor.authorGuimond, Jeanen
dc.contributor.authorNadeau, Maximeen
dc.contributor.authorEngert, James Cen
dc.contributor.authorKhaw, Kay-Teeen
dc.contributor.authorWareham, Nicholasen
dc.contributor.authorDweck, Marc Ren
dc.contributor.authorMathieu, Patricken
dc.contributor.authorPibarot, Philippeen
dc.contributor.authorSchott, Jean-Jacquesen
dc.contributor.authorThanassoulis, Georgeen
dc.contributor.authorClavel, Marie-Annicken
dc.contributor.authorBossé, Yohanen
dc.contributor.authorArsenault, Benoit Jen
dc.date.accessioned2019-06-20T23:31:04Z
dc.date.available2019-06-20T23:31:04Z
dc.date.issued2019-07en
dc.identifier.issn2380-6583
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/293794
dc.description.abstractImportance: Genetic variants at the LPA locus are associated with both calcific aortic valve stenosis (CAVS) and coronary artery disease (CAD). Whether these variants are associated with CAVS in patients with CAD vs those without CAD is unknown. Objective: To study the associations of LPA variants with CAVS in a cohort of patients undergoing heart surgery and LPA with CAVS in patients with CAD vs those without CAD and to determine whether first-degree relatives of patients with CAVS and high lipoprotein(a) (Lp[a]) levels showed evidence of aortic valve microcalcification. Design, Setting, and Participants: This genetic association study included patients undergoing cardiac surgery from the Genome-Wide Association Study on Calcific Aortic Valve Stenosis in Quebec (QUEBEC-CAVS) study and patients with CAD, patients without CAD, and control participants from 6 genetic association studies: the UK Biobank, the European Prospective Investigation of Cancer (EPIC)-Norfolk, and Genetic Epidemiology Research on Aging (GERA) studies and 3 French cohorts. In addition, a family study included first-degree relatives of patients with CAVS. Data were collected from January 1993 to September 2018, and analysis was completed from September 2017 to September 2018. Exposures: Case-control studies. Main Outcomes and Measures: Presence of CAVS according to a weighted genetic risk score based on 3 common Lp(a)-raising variants and aortic valve microcalcification, defined as the mean tissue to background ratio of 1.25 or more, measured by fluorine 18-labeled sodium fluoride positron emission tomography/computed tomography. Results: This study included 1009 individuals undergoing cardiac surgery and 1017 control participants in the QUEBEC-CAVS cohort; 3258 individuals with CAVS and CAD, 41 100 controls with CAD, 2069 individuals with CAVS without CAD, and 380 075 control participants without CAD in the UK Biobank, EPIC-Norfolk, and GERA studies and 3 French cohorts combined; and 33 first-degree relatives of 17 patients with CAVS and high Lp(a) levels (≥60 mg/dL) and 23 control participants with normal Lp(a) levels (<60 mg/dL). In the QUEBEC-CAVS study, each SD increase of the genetic risk score was associated with a higher risk of CAVS (odds ratio [OR], 1.35 [95% CI, 1.10-1.66]; P = .003). Each SD increase of the genetic risk score was associated with a higher risk of CAVS in patients with CAD (OR, 1.30 [95% CI, 1.20-1.42]; P < .001) and without CAD (OR, 1.33 [95% CI, 1.14-1.55]; P < .001). The percentage of individuals with a tissue to background ratio of 1.25 or more or CAVS was higher in first-degree relatives of patients with CAVS and high Lp(a) (16 of 33 [49%]) than control participants (3 of 23 [13%]; P = .006). Conclusions and Relevance: In this study, a genetically elevated Lp(a) level was associated with CAVS independently of the presence of CAD. These findings support further research on the potential usefulness of Lp(a) cascade screening in CAVS.
dc.format.mediumPrinten
dc.languageengen
dc.publisherAmerican Medical Association
dc.rightsAll rights reserved
dc.rights.uri
dc.subjectAortic Valveen
dc.subjectHumansen
dc.subjectAortic Valve Stenosisen
dc.subjectCalcinosisen
dc.subjectGenetic Predisposition to Diseaseen
dc.subjectLipoprotein(a)en
dc.subjectRisk Factorsen
dc.subjectProspective Studiesen
dc.subjectPedigreeen
dc.subjectAgeden
dc.subjectFemaleen
dc.subjectMaleen
dc.subjectClinical Trials as Topicen
dc.subjectCoronary Artery Diseaseen
dc.subjectGenome-Wide Association Studyen
dc.titleGenetic Variation in LPA, Calcific Aortic Valve Stenosis in Patients Undergoing Cardiac Surgery, and Familial Risk of Aortic Valve Microcalcification.en
dc.typeArticle
prism.endingPage627
prism.issueIdentifier7en
prism.publicationDate2019en
prism.publicationNameJAMA cardiologyen
prism.startingPage620
prism.volume4en
dc.identifier.doi10.17863/CAM.40907
dcterms.dateAccepted2019-03-30en
rioxxterms.versionofrecord10.1001/jamacardio.2019.1581en
rioxxterms.versionAM
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserveden
rioxxterms.licenseref.startdate2019-07en
dc.contributor.orcidDina, Christian [0000-0002-7722-7348]
dc.contributor.orcidChen, Hao Yu [0000-0001-8885-7583]
dc.contributor.orcidBoekholdt, S Matthijs [0000-0002-0861-0765]
dc.contributor.orcidCapoulade, Romain [0000-0002-7233-7409]
dc.contributor.orcidEngert, James C [0000-0001-8411-4790]
dc.contributor.orcidWareham, Nicholas [0000-0003-1422-2993]
dc.contributor.orcidDweck, Marc R [0000-0001-9847-5917]
dc.contributor.orcidClavel, Marie-Annick [0000-0002-8924-740X]
dc.identifier.eissn2380-6591
rioxxterms.typeJournal Article/Reviewen
pubs.funder-project-idMRC (MC_UU_12015/1)
pubs.funder-project-idDepartment of Health (via National Institute for Health Research (NIHR)) (NF-SI-0617-10149)
pubs.funder-project-idMEDICAL RESEARCH COUNCIL (MR/N003284/1)
pubs.funder-project-idMRC (G0401527)
pubs.funder-project-idMRC (G1000143)
rioxxterms.freetoread.startdate2020-05-29


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