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dc.contributor.authorHolmes, Michael Vaclav-
dc.contributor.authorSimon, Tabassome-
dc.contributor.authorExeter, Holly J.-
dc.contributor.authorFolkersen, Lasse-
dc.contributor.authorAsselbergs, Folkert W.-
dc.contributor.authorGuardiola, Montse-
dc.contributor.authorCooper, Jackie A.-
dc.contributor.authorPalmen, Jutta A.-
dc.contributor.authorHubacek, Jaroslav Alois-
dc.contributor.authorCarruthers, Kathryn F.-
dc.contributor.authorHorne, Benjamin D.-
dc.contributor.authorAdamkova, Vera-
dc.contributor.authorBaldassarre, Damiano-
dc.contributor.authorVeglia, Fabrizio-
dc.contributor.authorHoldt, Lesca Miriam-
dc.contributor.authorBeutner, Frank-
dc.contributor.authorSpiering, Wilko-
dc.contributor.authorGansevoort, Ron T.-
dc.contributor.authorNavis, Gerjan J.-
dc.contributor.authorBreitling, Lutz Philipp H-
dc.contributor.authorBrenner, Hermann Hermann-
dc.contributor.authorOlsson, Anders G.-
dc.contributor.authorThiery, Joachim J.-
dc.contributor.authorDallmeier, Dhayana-
dc.contributor.authorBoer, Jolanda Ma A-
dc.contributor.authorStephens, Jeffrey W.-
dc.contributor.authorHofker, Marten-
dc.contributor.authorTedgui, Alain S.-
dc.contributor.authorWatkins, Hugh C.-
dc.contributor.authorHofman, Albert-
dc.contributor.authorUitterlinden, Andre Gerardus-
dc.contributor.authorPiťha, Jan-
dc.contributor.authorOnland-Moret, N. Charlotte-
dc.contributor.authorFord, Ian-
dc.contributor.authorCramer, Maarten Jan M-
dc.contributor.authorNathoe, H.-
dc.contributor.authorKlungel, Olaf H H-
dc.contributor.authorKumari, Meena-
dc.contributor.authorWhincup, Peter H.-
dc.contributor.authorMorrow, David A.-
dc.contributor.authorMorris, Richard W.-
dc.contributor.authorBraund, Peter S.-
dc.contributor.authorHall, Alistair S.-
dc.contributor.authorDoevendans, Pieter A F M-
dc.contributor.authorTrip, Mieke D.-
dc.contributor.authorPrice, Jackie F.-
dc.contributor.authorTobin, Martin D.-
dc.contributor.authorHamsten, Anders-
dc.contributor.authorKoenig, Wolfgang-
dc.contributor.authorNicolaides, Andrew N.-
dc.contributor.authorTeupser, Daniel-
dc.contributor.authorDay, Ian N.M.-
dc.contributor.authorJukema, Johan Wouter Outer-
dc.contributor.authorCarlquist, John F.-
dc.contributor.authorGaunt, Tom R.-
dc.contributor.authorSattar, Naveed A.-
dc.contributor.authorTsimikas, Sotirios-
dc.contributor.authorFox, Keith A.A.-
dc.contributor.authorSchwartz, Gregory G.-
dc.contributor.authorLawlor, Debbie A.-
dc.contributor.authorSandhu, Manjinder S.-
dc.contributor.authorPoledne, Rudolf-
dc.contributor.authorMaitland-van Der Zee, Anke Hilse-
dc.contributor.authorKhaw, Kay Tee T-
dc.contributor.authorEriksson, Per Olof-
dc.contributor.authorKeating, Brendan J.-
dc.contributor.authorVan Der Harst, Pim-
dc.contributor.authorMehta, Shamir R.-
dc.contributor.authorYusuf, Salim M.-
dc.contributor.authorBrunisholz, Kimberly D.-
dc.contributor.authorWitteman, Jacqueline C M-
dc.contributor.authorFranco, Oscar H.-
dc.contributor.authorDe Knijff, Peter-
dc.contributor.authorTybjærg-Hansen, Anne-
dc.contributor.authorRader, Daniel J.-
dc.contributor.authorFarrall, Martin J.-
dc.contributor.authorVerschuren, Jeffrey J W-
dc.contributor.authorSamani, Nilesh-
dc.contributor.authorKivimaki, Mika-
dc.contributor.authorHumphries, Steve Eric-
dc.contributor.authorAnderson, Jeffrey L.-
dc.contributor.authorDanchin, N.-
dc.contributor.authorBoekholdt, S. Matthijs-
dc.contributor.authorPalmer, Tom M.-
dc.contributor.authorPare, Guillaume J.-
dc.contributor.authorHingorani, Aroon D.-
dc.contributor.authorSabatine, Marc S.-
dc.contributor.authorMallat, Ziad-
dc.contributor.authorGoel, Anuj K.-
dc.contributor.authorCasas, Juan Pablo-
dc.contributor.authorTalmud, Philippa J.-
dc.contributor.authorMega, Jessica-
dc.contributor.authorVan Iperen, Erik P A-
dc.contributor.authorTremoli, Elena-
dc.contributor.authorLeusink, Maarten-
dc.contributor.authorTrompet, Stella-
dc.contributor.authorHovingh, Gerald Kees-
dc.contributor.authorDehghan, Abbas Jan-
dc.contributor.authorNelson, Christopher P.-
dc.contributor.authorKotti, Salma-
dc.contributor.authorMateo Leach, Irene-
dc.contributor.authorScholz, Markus R.-
dc.contributor.authorHaase, Christiane L.-
dc.contributor.authorRothenbacher, Dietrich-
dc.contributor.authorSwerdlow, Daniel I.-
dc.contributor.authorFranco-Cereceda, Anders-
dc.contributor.authorKuchenbaecker, Karoline B.-
dc.contributor.authorStaines-Urias, Eleonora-
dc.contributor.authorVan 'T Hooft, Ferdinand M.-
dc.contributor.authorGertow, Karl-
dc.contributor.authorDe Faire, Ulf H.-
dc.contributor.authorPanayiotou, Andrie G.-
dc.date.accessioned2015-04-20T07:27:40Z-
dc.date.accessioned2015-12-08T11:10:04Z-
dc.date.available2015-04-20T07:27:40Z-
dc.date.available2015-12-08T11:10:04Z-
dc.date.issued2013-11-19-
dc.identifier.citationJournal of the American College of Cardiology, 2013, vol. 62, no. 21, pp. 1966-1976en_US
dc.identifier.issn15583597-
dc.identifier.urihttps://hdl.handle.net/20.500.14279/3677-
dc.description.abstractObjectives This study sought to investigate the role of secretory phospholipase A2 (sPLA2)-IIA in cardiovascular disease. Background Higher circulating levels of sPLA2-IIA mass or sPLA 2 enzyme activity have been associated with increased risk of cardiovascular events. However, it is not clear if this association is causal. A recent phase III clinical trial of an sPLA2 inhibitor (varespladib) was stopped prematurely for lack of efficacy. Methods We conducted a Mendelian randomization meta-analysis of 19 general population studies (8,021 incident, 7,513 prevalent major vascular events [MVE] in 74,683 individuals) and 10 acute coronary syndrome (ACS) cohorts (2,520 recurrent MVE in 18,355 individuals) using rs11573156, a variant in PLA2G2A encoding the sPLA2-IIA isoenzyme, as an instrumental variable. Results PLA2G2A rs11573156 C allele associated with lower circulating sPLA2-IIA mass (38% to 44%) and sPLA2 enzyme activity (3% to 23%) per C allele. The odds ratio (OR) for MVE per rs11573156 C allele was 1.02 (95% confidence interval [CI]: 0.98 to 1.06) in general populations and 0.96 (95% CI: 0.90 to 1.03) in ACS cohorts. In the general population studies, the OR derived from the genetic instrumental variable analysis for MVE for a 1-log unit lower sPLA2-IIA mass was 1.04 (95% CI: 0.96 to 1.13), and differed from the non-genetic observational estimate (OR: 0.69; 95% CI: 0.61 to 0.79). In the ACS cohorts, both the genetic instrumental variable and observational ORs showed a null association with MVE. Instrumental variable analysis failed to show associations between sPLA 2 enzyme activity and MVE. Conclusions Reducing sPLA2-IIA mass is unlikely to be a useful therapeutic goal for preventing cardiovascular events.en_US
dc.formatpdfen_US
dc.language.isoenen_US
dc.relation.ispartofJournal of the American College of Cardiologyen_US
dc.rights© American College of Cardiology Foundationen_US
dc.subjectCardiovascular diseasesen_US
dc.subjectDrug developmenten_US
dc.subjectEpidemiologyen_US
dc.subjectGeneticsen_US
dc.subjectMendelian randomizationen_US
dc.titleSecretory phospholipase A2-IIA and cardiovascular disease: a mendelian randomization studyen_US
dc.typeArticleen_US
dc.collaborationUniversity College Londonen_US
dc.collaborationHôpital Saint-Antoineen_US
dc.collaborationUniversité Pierre et Marie Curieen_US
dc.collaborationKarolinska Instituteten_US
dc.collaborationKarolinska University Hospitalen_US
dc.collaborationUniversity Medical Center Utrechten_US
dc.collaborationDurrer Center for Cardiogenetic Researchen_US
dc.collaborationUniversitat Rovira i Virgilien_US
dc.collaborationInstitute for Clinical and Experimental Medicineen_US
dc.collaborationThe University of Edinburghen_US
dc.collaborationIntermountain Medical Centeren_US
dc.collaborationUniversity of Utah School of Medicineen_US
dc.collaborationHarvard Universityen_US
dc.collaborationUniversity of Amsterdamen_US
dc.collaborationUniversity of Pennsylvaniaen_US
dc.collaborationUtrecht Universityen_US
dc.collaborationLeiden Universityen_US
dc.collaborationErasmus University Rotterdamen_US
dc.collaborationNetherlands Consortium for Healthy Agingen_US
dc.collaborationUniversity of Leicesteren_US
dc.collaborationGlenfield Hospitalen_US
dc.collaborationHôpital Européen Georges Pompidouen_US
dc.collaborationUniversite Parisen_US
dc.collaborationUniversity of Leipzigen_US
dc.collaborationCopenhagen University Hospitalen_US
dc.collaborationUlm Universityen_US
dc.collaborationGerman Cancer Research Centeren_US
dc.collaborationUniversity of Cambridgeen_US
dc.collaborationLondon School of Hygiene and Tropical Medicineen_US
dc.collaborationUniversity of Oxforden_US
dc.collaborationCyprus University of Technologyen_US
dc.collaborationUniversitá di Milanoen_US
dc.collaborationCentro Cardiologico Monzinoen_US
dc.collaborationUniversity Hospital Leipzigen_US
dc.collaborationUniversity of Leipzigen_US
dc.collaborationUniversity Medical Center Groningenen_US
dc.collaborationUniversity of Ulm Medical Centeren_US
dc.collaborationSwansea Universityen_US
dc.collaborationUniversity of Groningenen_US
dc.collaborationInserm Research Uniten_US
dc.collaborationSt George's University of Londonen_US
dc.collaborationUniversity of Leedsen_US
dc.collaborationLinköping Universityen_US
dc.collaborationImperial College Londonen_US
dc.collaborationLudwig Maximilians Universityen_US
dc.collaborationUniversity of Bristolen_US
dc.collaborationUniversity of Glasgowen_US
dc.collaborationUniversity of Californiaen_US
dc.collaborationUniversity of Coloradoen_US
dc.collaborationChildrens Hospital of Philadelphiaen_US
dc.collaborationMcMaster Universityen_US
dc.collaborationInteruniversity Cardiology Institute of the Netherlandsen_US
dc.collaborationLeiden Universityen_US
dc.collaborationPenn Heart and Vascular Centeren_US
dc.collaborationUniversity of Warwicken_US
dc.subject.categoryClinical Medicineen_US
dc.journalsSubscriptionen_US
dc.reviewPeer Revieweden
dc.countryUnited Kingdomen_US
dc.countryFranceen_US
dc.countrySwedenen_US
dc.countryNetherlandsen_US
dc.countrySpainen_US
dc.countryCzech Republicen_US
dc.countryUnited Statesen_US
dc.countryGermanyen_US
dc.countryCyprusen_US
dc.countryDenmarken_US
dc.countryItalyen_US
dc.countryCanadaen_US
dc.subject.fieldMedical and Health Sciencesen_US
dc.publicationPeer Revieweden_US
dc.identifier.doi10.1016/j.jacc.2013.06.044en_US
dc.identifier.pmid23916927-
dc.dept.handle123456789/108en
dc.relation.issue21en_US
dc.relation.volume62en_US
cut.common.academicyear2013-2014en_US
dc.identifier.spage1966en_US
dc.identifier.epage1976en_US
item.fulltextNo Fulltext-
item.languageiso639-1en-
item.grantfulltextnone-
item.openairecristypehttp://purl.org/coar/resource_type/c_6501-
item.cerifentitytypePublications-
item.openairetypearticle-
crisitem.journal.journalissn0735-1097-
crisitem.journal.publisherElsevier-
crisitem.author.deptDepartment of Rehabilitation Sciences-
crisitem.author.facultyFaculty of Health Sciences-
crisitem.author.orcid0000-0002-6085-568X-
crisitem.author.parentorgFaculty of Health Sciences-
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