Cystatin C and Cardiovascular Disease: A Mendelian Randomization Study

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Fältnamn	Indikatorer	Metadata
000		15442naa a2201345 4500
001		oai:DiVA.org:uu-303737
003		SwePub
008		160923s2016 \| \|\|\|\|\|\|\|\|\|\|\|000 \|\|eng\|
009		oai:prod.swepub.kib.ki.se:134089247
009		oai:DiVA.org:du-23629
024	7	a https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-3037372 URI
024	7	a https://doi.org/10.1016/j.jacc.2016.05.0922 DOI
024	7	a http://kipublications.ki.se/Default.aspx?queryparsed=id:1340892472 URI
024	7	a https://urn.kb.se/resolve?urn=urn:nbn:se:du-236292 URI
040		a (SwePub)uud (SwePub)kid (SwePub)du
041		a engb eng
042		9 SwePub
072	7	a ref2 swepub-contenttype
072	7	a art2 swepub-publicationtype
100	1	a van der Laan, Sander W.u Univ Med Ctr Utrecht, Div Heart & Lungs, Lab Expt Cardiol, Heidelberglaan 100, NL-3584 CX Utrecht, Netherlands.4 aut
245	1 0	a Cystatin C and Cardiovascular Disease :b A Mendelian Randomization Study
264	1	b Elsevier BV,c 2016
338		a electronic2 rdacarrier
500		a De två första författarna delar förstaförfattarskapet.
520		a BACKGROUND 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. OBJECTIVES The aim of this study was to use Mendelian randomization to investigate whether cystatin C is causally related to CVD in the general population. METHODS We incorporated participant data from 16 prospective cohorts (n = 76,481) with 37,126 measures of cystatin C and added genetic data from 43 studies (n = 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. RESULTS 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 = 2.12 x 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 = 5.95 x 10(-211)), explaining 2.8% of the observed variation in cystatin C. Mendelian randomization analysis did not provide evidence fora 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 = 0,994), which was statistically different from the observational estimate (p = 1.6 x 10(-5)). A causal effect of cystatin C was not detected for any individual component of CVD. CONCLUSIONS 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.
650	7	a MEDICIN OCH HÄLSOVETENSKAPx Klinisk medicinx Kardiologi0 (SwePub)302062 hsv//swe
650	7	a MEDICAL AND HEALTH SCIENCESx Clinical Medicinex Cardiac and Cardiovascular Systems0 (SwePub)302062 hsv//eng
650	7	a MEDICIN OCH HÄLSOVETENSKAPx Klinisk medicin0 (SwePub)3022 hsv//swe
650	7	a MEDICAL AND HEALTH SCIENCESx Clinical Medicine0 (SwePub)3022 hsv//eng
653		a coronary heart disease
653		a genetics
653		a heart failure
653		a ischemic stroke
653		a Hälsa och välfärd
700	1	a Fall, Toveu Uppsala universitet,Molekylär epidemiologi,Science for Life Laboratory, SciLifeLab4 aut0 (Swepub:uu)tovfa878
700	1	a Soumare, Aichau Univ Bordeaux, INSERM, U1219, Team Vintage, Bordeaux, France.4 aut
700	1	a Teumer, Alexanderu Univ Med Greifswald, Inst Community Med, Dept SHIP KEF, Greifswald, Germany.;German Ctr Cardiovasc Res, DZHK, Partner Site, Greifswald, Germany.4 aut
700	1	a Sedaghat, Sanazu Erasmus Univ, Med Ctr, Dept Epidemiol, Rotterdam, Netherlands.,UCL, Inst Cardiovasc Sci, Genet Epidemiol Res Grp, London, England.;Barts Heart Ctr, London, England.;UCL, Farr Inst Hlth Informat, London, England.4 aut
700	1	a Baumert, Jensu German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Epidemiol 2, Neuherberg, Germany.4 aut
700	1	a Zabaneh, Delilahu UCL, Dept Genet Environm & Evolut, London, England.;UCL, Genet Inst, London, England.4 aut
700	1	a van Setten, Jessicau Univ Med Ctr Utrecht, Div Heart & Lungs, Lab Expt Cardiol, Heidelberglaan 100, NL-3584 CX Utrecht, Netherlands.4 aut
700	1	a Isgum, Ivanau Univ Med Ctr Utrecht, Image Sci Inst, Utrecht, Netherlands.,Univ Med Ctr Utrecht, Julius Ctr Hlth Sci & Primary Care, Utrecht, Netherlands.;Univ Med Ctr Utrecht, Ctr Mol Med, Dept Med Genet, Utrecht, Netherlands.4 aut
700	1	a Galesloot, Tessel E.u Radboud Univ Nijmegen, Med Ctr, Radboud Inst Hlth Sci, Nijmegen, Netherlands.4 aut
700	1	a Arpegard, Johannesu Karolinska Univ Hosp Solna, Dept Emergency Med, Stockholm, Sweden.;Karolinska Inst, Dept Med Solna, Stockholm, Sweden.4 aut
700	1	a Amouyel, Philippeu Univ Lille, INSERM, Lille, France.;Inst Pasteur, Lille, France.4 aut
700	1	a Trompet, Stellau Leiden Univ, Med Ctr, Dept Cardiol P C5, Leiden, Netherlands.;Leiden Univ, Med Ctr, Dept Gerontol & Geriatr, Leiden, Netherlands.4 aut
700	1	a Waldenberger, Melanieu German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Epidemiol 2, Neuherberg, Germany.;German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Res Unit Mol Epidemiol, Neuherberg, Germany.4 aut
700	1	a Doerr, Marcusu German Ctr Cardiovasc Res, DZHK, Partner Site, Greifswald, Germany.;Univ Med Greifswald, Dept Internal Med B, Greifswald, Germany.4 aut
700	1	a Magnusson, Patrik K.u Karolinska Institutet,Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden.4 aut
700	1	a Giedraitis, Vilmantasu Uppsala universitet,Geriatrik4 aut0 (Swepub:uu)vigie517
700	1	a Larsson, Andersu Uppsala universitet,Biokemisk struktur och funktion,Radboud Univ Nijmegen, Med Ctr, Radboud Inst Hlth Sci, Nijmegen, Netherlands.4 aut0 (Swepub:uu)andlarss
700	1	a Morris, Andrew P.u Univ Liverpool, Dept Biostat, Liverpool, Merseyside, England.;Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England.4 aut
700	1	a Felix, Janine F.u Erasmus Univ, Med Ctr, Dept Epidemiol, Rotterdam, Netherlands.4 aut
700	1	a Morrison, Alanna C.u Univ Texas Hlth Sci Ctr Houston, Dept Epidemiol Human Genet & Environm Sci, Houston, TX 77030 USA.4 aut
700	1	a Franceschini, Norau Univ N Carolina, Dept Epidemiol, Chapel Hill, NC USA.4 aut
700	1	a Bis, Joshua C.u Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA USA.4 aut
700	1	a Kavousi, Maryamu Erasmus Univ, Med Ctr, Dept Epidemiol, Rotterdam, Netherlands.4 aut
700	1	a O'Donnell, Christopheru Boston Vet Adm Healthcare, Dept Cardiol, West Roxbury, MA USA.;NHLBI, Framingham Heart Study, Framingham, MA USA.4 aut
700	1	a Drenos, Fotiosu UCL, Inst Cardiovasc Sci, Ctr Cardiovasc Genet, London, England.;Univ Bristol, Sch Social & Community Med, MRC Integrat Epidemiol Unit, Bristol, Avon, England.4 aut
700	1	a Tragante, Viniciusu Univ Med Ctr Utrecht, Dept Cardiol, Div Heart & Lungs, Heidelberglaan 100, NL-3584 CX Utrecht, Netherlands.4 aut
700	1	a Munroe, Patricia B.u Queen Mary Univ London, William Harvey Res Inst, Natl Inst Hlth Res, Cardiovasc Biomed Res Unit, London, England.4 aut
700	1	a Malik, Raineru Univ Munich, Klinikum Univ Munchen, Inst Stroke & Dementia Res, Munich, Germany.4 aut
700	1	a Dichgans, Martinu Univ Munich, Klinikum Univ Munchen, Inst Stroke & Dementia Res, Munich, Germany.;Munich Cluster Syst Neurol SyNergy, Munich, Germany.4 aut
700	1	a Worrall, Bradford B.u Univ Virginia, Dept Neurol, Charlottesville, VA USA.;Univ Virginia, Dept Hlth Evaluat Sci, Charlottesville, VA USA.4 aut
700	1	a Erdmann, Jeanetteu Univ Lubeck, Inst Integrat & Expt Genom, Lubeck, Germany.4 aut
700	1	a Nelson, Christopher P.u Univ Leicester, Glenfield Hosp, British Heart Fdn Cardiovasc, Res Ctr,Dept Cardiovasc Sci, Leicester, Leics, England.;Glenfield Hosp, Natl Inst Hlth Res Leicester, Cardiovasc Biomed Res Unit, Leicester, Leics, England.4 aut
700	1	a Samani, Nilesh J.u Univ Leicester, Glenfield Hosp, British Heart Fdn Cardiovasc, Res Ctr,Dept Cardiovasc Sci, Leicester, Leics, England.;Glenfield Hosp, Natl Inst Hlth Res Leicester, Cardiovasc Biomed Res Unit, Leicester, Leics, England.4 aut
700	1	a Schunkert, Heribertu Tech Univ Munich, Deutsch Herzzentrum Munchen, Munich, Germany.;German Ctr Cardiovasc Res, DZHK, Munich Heart Alliance, Partner Site, Munich, Germany.4 aut
700	1	a Marchini, Jonathanu Univ Oxford, Dept Stat, Oxford, England.4 aut
700	1	a Patel, Riyaz S.u Karolinska Institutet4 aut
700	1	a Hingorani, Aroon D.u UCL, Inst Cardiovasc Sci, Genet Epidemiol Res Grp, London, England.4 aut
700	1	a Lind, Larsu Karolinska Institutet,Uppsala universitet,Kardiovaskulär epidemiologi,Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden.4 aut0 (Swepub:uu)larslind
700	1	a Pedersen, Nancy L.u Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden.4 aut
700	1	a de Graaf, Jacquelineu Radboud Univ Nijmegen, Med Ctr, Radboud Inst Hlth Sci, Nijmegen, Netherlands.;Radboud Univ Nijmegen, Med Ctr, Dept Internal Med, Nijmegen, Netherlands.4 aut
700	1	a Kiemeney, Lambertus A. L. M.u Radboud Univ Nijmegen, Med Ctr, Radboud Inst Hlth Sci, Nijmegen, Netherlands.4 aut
700	1	a Baumeister, Sebastian E.u Univ Med Greifswald, Inst Community Med, Dept SHIP KEF, Greifswald, Germany.;Univ Regensburg, Inst Epidemiol & Prevent Med, Regensburg, Germany.4 aut
700	1	a Franco, Oscar H.u Erasmus Univ, Med Ctr, Dept Epidemiol, Rotterdam, Netherlands.4 aut
700	1	a Hofman, Albertu Erasmus Univ, Med Ctr, Dept Epidemiol, Rotterdam, Netherlands.4 aut
700	1	a Uitterlinden, Andre G.u Erasmus Univ, Med Ctr, Dept Internal Med, Rotterdam, Netherlands.4 aut
700	1	a Koenig, Wolfgangu German Ctr Cardiovasc Res, DZHK, Partner Site, Greifswald, Germany.;Tech Univ Munich, Deutsch Herzzentrum Munchen, Munich, Germany.;Univ Ulm, Med Ctr, Dept Internal Med Cardiol 2, Ulm, Germany.4 aut
700	1	a Meisinger, Christau German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Epidemiol 2, Neuherberg, Germany.4 aut
700	1	a Peters, Annetteu German Ctr Cardiovasc Res, DZHK, Partner Site, Greifswald, Germany.;German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Epidemiol 2, Neuherberg, Germany.4 aut
700	1	a Thorand, Barbarau German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Epidemiol 2, Neuherberg, Germany.4 aut
700	1	a Jukema, J. Wouteru Leiden Univ, Med Ctr, Dept Cardiol P C5, Leiden, Netherlands.;ICIN Netherlands Heart Inst, Durrer Ctr Cardiogenet Res, Utrecht, Netherlands.4 aut
700	1	a Eriksen, Bjorn Odvaru UiT Arctic Univ Norway, Metab & Renal Res Grp, Tromso, Norway.;Univ Hosp North Norway, Nephrol Sect, Tromso, Norway.4 aut
700	1	a Toft, Ingridu Univ Hosp North Norway, Nephrol Sect, Tromso, Norway.4 aut
700	1	a Wilsgaard, Tomu UiT Arctic Univ Norway, Dept Community Med, Tromso, Norway.4 aut
700	1	a Onland-Moret, N. Charlotteu Univ Med Ctr Utrecht, Julius Ctr Hlth Sci & Primary Care, Utrecht, Netherlands.4 aut
700	1	a van der Schouw, Yvonne T.u Univ Med Ctr Utrecht, Julius Ctr Hlth Sci & Primary Care, Utrecht, Netherlands.4 aut
700	1	a Debette, Stephanieu Univ Bordeaux, INSERM, U1219, Team Vintage, Bordeaux, France.4 aut
700	1	a Kumari, Meenau Univ Essex, Biol & Social Epidemiol, Inst Social & Econ Res, Colchester CO4 3SQ, Essex, England.4 aut
700	1	a Svensson, Peru Karolinska Univ Hosp Solna, Dept Emergency Med, Stockholm, Sweden.;Karolinska Inst, Dept Med Solna, Stockholm, Sweden.4 aut
700	1	a van der Harst, Pimu ICIN Netherlands Heart Inst, Durrer Ctr Cardiogenet Res, Utrecht, Netherlands.;Univ Groningen, Univ Med Ctr Groningen, Dept Cardiol, Groningen, Netherlands.;Univ Groningen, Univ Med Ctr Groningen, Dept Genet, Groningen, Netherlands.4 aut
700	1	a Kivimaki, Mikau UCL, Dept Epidemiol & Publ Hlth, London, England.4 aut
700	1	a Keating, Brendan J.u Univ Penn, Dept Surg, Div Transplantat, Perelman Sch Med, Philadelphia, PA 19104 USA.4 aut
700	1	a Sattar, Naveedu Univ Glasgow, Glasgow, Lanark, Scotland.4 aut
700	1	a Dehghan, Abbasu Erasmus Univ, Med Ctr, Dept Epidemiol, Rotterdam, Netherlands.4 aut
700	1	a Reiner, Alex P.u Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA.4 aut
700	1	a Ingelsson, Eriku Uppsala universitet,Molekylär epidemiologi,Science for Life Laboratory, SciLifeLab,Stanford Univ, Dept Med, Sch Med, Div Cardiovasc Med, Stanford, CA 94305 USA.4 aut0 (Swepub:uu)ering425
700	1	a den Ruijter, Hester M.u Univ Med Ctr Utrecht, Div Heart & Lungs, Lab Expt Cardiol, Heidelberglaan 100, NL-3584 CX Utrecht, Netherlands.4 aut
700	1	a de Bakker, Paul I. W.u Univ Med Ctr Utrecht, Julius Ctr Hlth Sci & Primary Care, Utrecht, Netherlands.;Univ Med Ctr Utrecht, Ctr Mol Med, Dept Med Genet, Utrecht, Netherlands.4 aut
700	1	a Pasterkamp, Gerardu Univ Med Ctr Utrecht, Div Heart & Lungs, Lab Expt Cardiol, Heidelberglaan 100, NL-3584 CX Utrecht, Netherlands.;Univ Med Ctr Utrecht, Div Labs & Pharm, Lab Clin Chem & Hematol, Utrecht, Netherlands.4 aut
700	1	a Ärnlöv, Johanu Högskolan Dalarna,Uppsala universitet,Kardiovaskulär epidemiologi,Medicinsk vetenskap,Uppsala university4 aut0 (Swepub:du)jan
700	1	a Holmes, Michael V.u Univ Oxford, Nuffield Dept Populat Hlth, Clin Trial Serv Unit, Richard Doll Bldg,Old Rd Campus,Roosevelt Dr, Oxford OX3 7LF, England.;Univ Oxford, Nuffield Dept Populat Hlth, Epidemiol Studies Unit CTSU, Richard Doll Bldg,Old Rd Campus,Roosevelt Dr, Oxford OX3 7LF, England.4 aut
700	1	a Asselbergs, Folkert W.u Univ Med Ctr Utrecht, Dept Cardiol, Div Heart & Lungs, Heidelberglaan 100, NL-3584 CX Utrecht, Netherlands.;ICIN Netherlands Heart Inst, Durrer Ctr Cardiogenet Res, Utrecht, Netherlands.;UCL, Fac Populat Hlth Sci, Inst Cardiovasc Sci, London, England.4 aut
710	2	a Univ Med Ctr Utrecht, Div Heart & Lungs, Lab Expt Cardiol, Heidelberglaan 100, NL-3584 CX Utrecht, Netherlands.b Molekylär epidemiologi4 org
773	0	t Journal of the American College of Cardiologyd : Elsevier BVg 68:9, s. 934-945q 68:9<934-945x 0735-1097x 1558-3597
856	4	u https://uu.diva-portal.org/smash/get/diva2:973929/FULLTEXT01.pdfx primaryx Raw objecty fulltext:print
856	4	u https://doi.org/10.1016/j.jacc.2016.05.092
856	4	u https://doi.org/10.1016/j.jacc.2016.05.092y Fulltext
856	4	u https://du.diva-portal.org/smash/get/diva2:1058062/FULLTEXT01.pdfx primaryx Raw objecty fulltext:print
856	4 8	u https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-303737
856	4 8	u https://doi.org/10.1016/j.jacc.2016.05.092
856	4 8	u http://kipublications.ki.se/Default.aspx?queryparsed=id:134089247
856	4 8	u https://urn.kb.se/resolve?urn=urn:nbn:se:du-23629

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