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dc.contributor.authorvan der Laan, Sander W
dc.contributor.authorFall, Tove
dc.contributor.authorSourmare, Aicha
dc.contributor.authorTeumer, Alexander
dc.contributor.authorSedaghat, Sanaz
dc.contributor.authorBaumert, Jens
dc.contributor.authorZahaneh, Delilah
dc.contributor.authorvan Setten, Jessica
dc.contributor.authorIsgum, Ivana
dc.contributor.authorGalesloot, Tessel E.
dc.contributor.authorArpegård, Johannes
dc.contributor.authorAmouyel, Philippe
dc.contributor.authorTrompet, Stella
dc.contributor.authorWaldenberger, Melanie
dc.contributor.authorDörr, Marcus
dc.contributor.authorMagnusson, Patrik K.
dc.contributor.authorGiedraitis, Vilmantas
dc.contributor.authorLarsson, Anders
dc.contributor.authorMorris, Andrew P.
dc.contributor.authorFelix, Janine F.
dc.contributor.authorMorrison, Alanna C.
dc.contributor.authorFranceschini, Nora
dc.contributor.authorBis, Joshua C.
dc.contributor.authorKavousi, Maryam
dc.contributor.authorO'Donnell, Christopher J.
dc.contributor.authorDrenos, Fotios
dc.contributor.authorTragante, Vinicius
dc.contributor.authorMunroe, Patricia B.
dc.contributor.authorMalik, Rainer
dc.contributor.authorDichgans, Martin
dc.contributor.authorWorrall, Bradford B.
dc.contributor.authorErdmann, Jeanette
dc.contributor.authorNelson, Christopher P.
dc.contributor.authorSamani, Nilesh J.
dc.contributor.authorSchunkert, Heribert
dc.contributor.authorMarchini, Jonathan
dc.contributor.authorPatel, Riyaz S.
dc.contributor.authorHingorani, Aroon D.
dc.contributor.authorLind, Lars
dc.contributor.authorPedersen, Nancy L.
dc.contributor.authorde Graaf, Jacqueline
dc.contributor.authorKiemeney, Lambertus A.L.M.
dc.contributor.authorBaumeister, Sebastian E.
dc.contributor.authorFranco, Oscar H.
dc.contributor.authorHofman, Albert
dc.contributor.authorUitterlinden, André G.
dc.contributor.authorKoenig, Wolfgang
dc.contributor.authorMeisinger, Christa
dc.contributor.authorPeters, Annette
dc.contributor.authorThorand, Barbara
dc.contributor.authorJukema, J.Wouter
dc.contributor.authorEriksen, Bjørn Odvar
dc.contributor.authorToft, Ingrid
dc.contributor.authorWilsgaard, Tom
dc.contributor.authorOnland-Moret, N. Charlotte
dc.contributor.authorvan der Schouw, Yvonne T.
dc.contributor.authorDebette, Stéphanie
dc.contributor.authorKumari, Meena
dc.contributor.authorSvensson, Per
dc.contributor.authorvan der Harst, Pim
dc.contributor.authorKivimäki, Mika
dc.contributor.authorKeating, Brendan J.
dc.contributor.authorSattar, Naveed
dc.contributor.authorDehghan, Abbas
dc.contributor.authorReiner, Alex P.
dc.contributor.authorIngelsson, Erik
dc.contributor.authorDen Ruijter, Hester M.
dc.contributor.authorde Bakker, Paul I.W.
dc.contributor.authorPasterkamp, Gerard
dc.contributor.authorÄrnlöv, Johan
dc.contributor.authorHolmes, Michael V.
dc.contributor.authorAsselbergs, Folkert W.
dc.date.accessioned2017-02-23T14:52:27Z
dc.date.available2017-02-23T14:52:27Z
dc.date.issued2016-08-30
dc.description.abstractBACKGROUND<br> Epidemiological studies show that high circulating cystatin C is associated with risk of cardiovascular disease (CVD), independent of creatinine-based renal function measurements. It is unclear whether this relationship is causal, arises from residual confounding, and/or is a consequence of reverse causation.<br> OBJECTIVES<br>The aim of this study was to use Mendelian randomization to investigate whether cystatin C is causally related to CVD in the general population.<br> METHODS<br> We incorporated participant data from 16 prospective cohorts (n ¼ 76,481) with 37,126 measures of cystatin C and added genetic data from 43 studies (n ¼ 252,216) with 63,292 CVD events. We used the common variant rs911119 in CST3 as an instrumental variable to investigate the causal role of cystatin C in CVD, including coronary heart disease, ischemic stroke, and heart failure.<br> RESULTS<br> Cystatin C concentrations were associated with CVD risk after adjusting for age, sex, and traditional risk factors (relative risk: 1.82 per doubling of cystatin C; 95% confidence interval [CI]: 1.56 to 2.13; p ¼ 2.12 10 14). The minor allele of rs911119 was associated with decreased serum cystatin C (6.13% per allele; 95% CI: 5.75 to 6.50; p ¼ 5.95 10 211), explaining 2.8% of the observed variation in cystatin C. Mendelian randomization analysis did not provide evidence for a causal role of cystatin C, with a causal relative risk for CVD of 1.00 per doubling cystatin C (95% CI: 0.82 to 1.22; p ¼ 0.994), which was statistically different from the observational estimate (p ¼ 1.6 10 5). A causal effect of cystatin C was not detected for any individual component of CVD.<br>CONCLUSIONS<br> Mendelian randomization analyses did not support a causal role of cystatin C in the etiology of CVD. As such, therapeutics targeted at lowering circulating cystatin C are unlikely to be effective in preventing CVD. (J Am Coll Cardiol 2016;68:934–45) © 2016 The Authors. Published by Elsevier Inc. on behalf of the American College of Cardiology Foundation. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/ licenses/by-nc-nd/4.0/).en_US
dc.descriptionSource: <a href=http:dx.doi.org/10.1016/j.jacc.2016.05.092>doi: 10.1016/j.jacc.2016.05.092</a>en_US
dc.identifier.citationvan der Laan SW, Fall T, Sourmare, Teumer A, Sedaghat S, Baumert, Zahaneh, van Setten J, Isgum, Galesloot TE, Arpegård, Amouyel P, Trompet S, Waldenberger M, Dörr M, Magnusson PK, Giedraitis V, Larsson A, Morris AP, Felix JF, Morrison AC, Franceschini N, Bis JC, Kavousi M, O'Donnell CJ, Drenos F, Tragante V, Munroe PB, Malik R, Dichgans M, Worrall BB, Erdmann J, Nelson CP, Samani NJ, Schunkert H, Marchini J, Patel, Hingorani AD, Lind L, Pedersen NL, de Graaf J, Kiemeney LA, Baumeister, Franco OH, Hofman A, Uitterlinden AG, Koenig W, Meisinger C, Peters A, Thorand B, Jukema J, Eriksen BO, Toft I, Wilsgaard T, Onland-Moret NC, van der Schouw YT, Debette, Kumari M, Svensson P, van der Harst P, Kivimäki M, Keating BJ, Sattar N, Dehghan A, Reiner AP, Ingelsson E, Den Ruijter HM, de Bakker PI, Pasterkamp G, Ärnlöv J, Holmes MV, Asselbergs FW. Cystatin C and cardiovascular disease: a Mendelian randomization study. Journal of the American College of Cardiology. 2016;68(9):934-945en_US
dc.identifier.issn0735-1097
dc.identifier.issn1558-3597
dc.identifier.otherFRIDAID 1415474
dc.identifier.other10.1016/j.jacc.2016.05.092
dc.identifier.urihttp://hdl.handle.net/10037/10354
dc.language.isoengen_US
dc.publisherElsevieren_US
dc.relation.journalJournal of the American College of Cardiology
dc.rights.accessRightsopenAccessen_US
dc.subjectVDP::Medisinske Fag: 700::Helsefag: 800::Samfunnsmedisin, sosialmedisin: 801en_US
dc.subjectVDP::Medical disciplines: 700::Health sciences: 800::Community medicine, Social medicine: 801en_US
dc.titleCystatin C and cardiovascular disease: a Mendelian randomization studyen_US
dc.typeJournal articleen_US
dc.typeTidsskriftartikkelen_US
dc.typePeer revieweden_US


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