Cystatin C and Cardiovascular Disease: A Mendelian Randomization Study

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van der Laan, Sander W.Univ Med Ctr Utrecht, Div Heart & Lungs, Lab Expt Cardiol, Heidelberglaan 100, NL-3584 CX Utrecht, Netherlands. (author)

Cystatin C and Cardiovascular Disease : A Mendelian Randomization Study

Article/chapterEnglish2016

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Elsevier BV,2016
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LIBRIS-ID:oai:DiVA.org:uu-303737
https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-303737URI
https://doi.org/10.1016/j.jacc.2016.05.092DOI
http://kipublications.ki.se/Default.aspx?queryparsed=id:134089247URI
https://urn.kb.se/resolve?urn=urn:nbn:se:du-23629URI

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Language:English
Summary in:English

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Subject category:art swepub-publicationtype

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De två första författarna delar förstaförfattarskapet.
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.

Subject headings and genre

MEDICIN OCH HÄLSOVETENSKAP Klinisk medicin Kardiologi hsv//swe
MEDICAL AND HEALTH SCIENCES Clinical Medicine Cardiac and Cardiovascular Systems hsv//eng
MEDICIN OCH HÄLSOVETENSKAP Klinisk medicin hsv//swe
MEDICAL AND HEALTH SCIENCES Clinical Medicine hsv//eng
coronary heart disease
genetics
heart failure
ischemic stroke
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Fall, ToveUppsala universitet,Molekylär epidemiologi,Science for Life Laboratory, SciLifeLab(Swepub:uu)tovfa878 (author)
Soumare, AichaUniv Bordeaux, INSERM, U1219, Team Vintage, Bordeaux, France. (author)
Teumer, AlexanderUniv Med Greifswald, Inst Community Med, Dept SHIP KEF, Greifswald, Germany.;German Ctr Cardiovasc Res, DZHK, Partner Site, Greifswald, Germany. (author)
Sedaghat, SanazErasmus 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. (author)
Baumert, JensGerman Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Epidemiol 2, Neuherberg, Germany. (author)
Zabaneh, DelilahUCL, Dept Genet Environm & Evolut, London, England.;UCL, Genet Inst, London, England. (author)
van Setten, JessicaUniv Med Ctr Utrecht, Div Heart & Lungs, Lab Expt Cardiol, Heidelberglaan 100, NL-3584 CX Utrecht, Netherlands. (author)
Isgum, IvanaUniv 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. (author)
Galesloot, Tessel E.Radboud Univ Nijmegen, Med Ctr, Radboud Inst Hlth Sci, Nijmegen, Netherlands. (author)
Arpegard, JohannesKarolinska Univ Hosp Solna, Dept Emergency Med, Stockholm, Sweden.;Karolinska Inst, Dept Med Solna, Stockholm, Sweden. (author)
Amouyel, PhilippeUniv Lille, INSERM, Lille, France.;Inst Pasteur, Lille, France. (author)
Trompet, StellaLeiden Univ, Med Ctr, Dept Cardiol P C5, Leiden, Netherlands.;Leiden Univ, Med Ctr, Dept Gerontol & Geriatr, Leiden, Netherlands. (author)
Waldenberger, MelanieGerman 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. (author)
Doerr, MarcusGerman Ctr Cardiovasc Res, DZHK, Partner Site, Greifswald, Germany.;Univ Med Greifswald, Dept Internal Med B, Greifswald, Germany. (author)
Magnusson, Patrik K.Karolinska Institutet,Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden. (author)
Giedraitis, VilmantasUppsala universitet,Geriatrik(Swepub:uu)vigie517 (author)
Larsson, AndersUppsala universitet,Biokemisk struktur och funktion,Radboud Univ Nijmegen, Med Ctr, Radboud Inst Hlth Sci, Nijmegen, Netherlands.(Swepub:uu)andlarss (author)
Morris, Andrew P.Univ Liverpool, Dept Biostat, Liverpool, Merseyside, England.;Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England. (author)
Felix, Janine F.Erasmus Univ, Med Ctr, Dept Epidemiol, Rotterdam, Netherlands. (author)
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Franceschini, NoraUniv N Carolina, Dept Epidemiol, Chapel Hill, NC USA. (author)
Bis, Joshua C.Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA USA. (author)
Kavousi, MaryamErasmus Univ, Med Ctr, Dept Epidemiol, Rotterdam, Netherlands. (author)
O'Donnell, ChristopherBoston Vet Adm Healthcare, Dept Cardiol, West Roxbury, MA USA.;NHLBI, Framingham Heart Study, Framingham, MA USA. (author)
Drenos, FotiosUCL, Inst Cardiovasc Sci, Ctr Cardiovasc Genet, London, England.;Univ Bristol, Sch Social & Community Med, MRC Integrat Epidemiol Unit, Bristol, Avon, England. (author)
Tragante, ViniciusUniv Med Ctr Utrecht, Dept Cardiol, Div Heart & Lungs, Heidelberglaan 100, NL-3584 CX Utrecht, Netherlands. (author)
Munroe, Patricia B.Queen Mary Univ London, William Harvey Res Inst, Natl Inst Hlth Res, Cardiovasc Biomed Res Unit, London, England. (author)
Malik, RainerUniv Munich, Klinikum Univ Munchen, Inst Stroke & Dementia Res, Munich, Germany. (author)
Dichgans, MartinUniv Munich, Klinikum Univ Munchen, Inst Stroke & Dementia Res, Munich, Germany.;Munich Cluster Syst Neurol SyNergy, Munich, Germany. (author)
Worrall, Bradford B.Univ Virginia, Dept Neurol, Charlottesville, VA USA.;Univ Virginia, Dept Hlth Evaluat Sci, Charlottesville, VA USA. (author)
Erdmann, JeanetteUniv Lubeck, Inst Integrat & Expt Genom, Lubeck, Germany. (author)
Nelson, Christopher P.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. (author)
Samani, Nilesh J.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. (author)
Schunkert, HeribertTech Univ Munich, Deutsch Herzzentrum Munchen, Munich, Germany.;German Ctr Cardiovasc Res, DZHK, Munich Heart Alliance, Partner Site, Munich, Germany. (author)
Marchini, JonathanUniv Oxford, Dept Stat, Oxford, England. (author)
Patel, Riyaz S.Karolinska Institutet (author)
Hingorani, Aroon D.UCL, Inst Cardiovasc Sci, Genet Epidemiol Res Grp, London, England. (author)
Lind, LarsKarolinska Institutet,Uppsala universitet,Kardiovaskulär epidemiologi,Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden.(Swepub:uu)larslind (author)
Pedersen, Nancy L.Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden. (author)
de Graaf, JacquelineRadboud Univ Nijmegen, Med Ctr, Radboud Inst Hlth Sci, Nijmegen, Netherlands.;Radboud Univ Nijmegen, Med Ctr, Dept Internal Med, Nijmegen, Netherlands. (author)
Kiemeney, Lambertus A. L. M.Radboud Univ Nijmegen, Med Ctr, Radboud Inst Hlth Sci, Nijmegen, Netherlands. (author)
Baumeister, Sebastian E.Univ Med Greifswald, Inst Community Med, Dept SHIP KEF, Greifswald, Germany.;Univ Regensburg, Inst Epidemiol & Prevent Med, Regensburg, Germany. (author)
Franco, Oscar H.Erasmus Univ, Med Ctr, Dept Epidemiol, Rotterdam, Netherlands. (author)
Hofman, AlbertErasmus Univ, Med Ctr, Dept Epidemiol, Rotterdam, Netherlands. (author)
Uitterlinden, Andre G.Erasmus Univ, Med Ctr, Dept Internal Med, Rotterdam, Netherlands. (author)
Koenig, WolfgangGerman 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. (author)
Meisinger, ChristaGerman Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Epidemiol 2, Neuherberg, Germany. (author)
Peters, AnnetteGerman Ctr Cardiovasc Res, DZHK, Partner Site, Greifswald, Germany.;German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Epidemiol 2, Neuherberg, Germany. (author)
Thorand, BarbaraGerman Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Epidemiol 2, Neuherberg, Germany. (author)
Jukema, J. WouterLeiden Univ, Med Ctr, Dept Cardiol P C5, Leiden, Netherlands.;ICIN Netherlands Heart Inst, Durrer Ctr Cardiogenet Res, Utrecht, Netherlands. (author)
Eriksen, Bjorn OdvarUiT Arctic Univ Norway, Metab & Renal Res Grp, Tromso, Norway.;Univ Hosp North Norway, Nephrol Sect, Tromso, Norway. (author)
Toft, IngridUniv Hosp North Norway, Nephrol Sect, Tromso, Norway. (author)
Wilsgaard, TomUiT Arctic Univ Norway, Dept Community Med, Tromso, Norway. (author)
Onland-Moret, N. CharlotteUniv Med Ctr Utrecht, Julius Ctr Hlth Sci & Primary Care, Utrecht, Netherlands. (author)
van der Schouw, Yvonne T.Univ Med Ctr Utrecht, Julius Ctr Hlth Sci & Primary Care, Utrecht, Netherlands. (author)
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Kumari, MeenaUniv Essex, Biol & Social Epidemiol, Inst Social & Econ Res, Colchester CO4 3SQ, Essex, England. (author)
Svensson, PerKarolinska Univ Hosp Solna, Dept Emergency Med, Stockholm, Sweden.;Karolinska Inst, Dept Med Solna, Stockholm, Sweden. (author)
van der Harst, PimICIN 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. (author)
Kivimaki, MikaUCL, Dept Epidemiol & Publ Hlth, London, England. (author)
Keating, Brendan J.Univ Penn, Dept Surg, Div Transplantat, Perelman Sch Med, Philadelphia, PA 19104 USA. (author)
Sattar, NaveedUniv Glasgow, Glasgow, Lanark, Scotland. (author)
Dehghan, AbbasErasmus Univ, Med Ctr, Dept Epidemiol, Rotterdam, Netherlands. (author)
Reiner, Alex P.Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. (author)
Ingelsson, ErikUppsala universitet,Molekylär epidemiologi,Science for Life Laboratory, SciLifeLab,Stanford Univ, Dept Med, Sch Med, Div Cardiovasc Med, Stanford, CA 94305 USA.(Swepub:uu)ering425 (author)
den Ruijter, Hester M.Univ Med Ctr Utrecht, Div Heart & Lungs, Lab Expt Cardiol, Heidelberglaan 100, NL-3584 CX Utrecht, Netherlands. (author)
de Bakker, Paul I. W.Univ Med Ctr Utrecht, Julius Ctr Hlth Sci & Primary Care, Utrecht, Netherlands.;Univ Med Ctr Utrecht, Ctr Mol Med, Dept Med Genet, Utrecht, Netherlands. (author)
Pasterkamp, GerardUniv 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. (author)
Ärnlöv, JohanHögskolan Dalarna,Uppsala universitet,Kardiovaskulär epidemiologi,Medicinsk vetenskap,Uppsala university(Swepub:du)jan (author)
Holmes, Michael V.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. (author)
Asselbergs, Folkert W.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. (author)
Univ Med Ctr Utrecht, Div Heart & Lungs, Lab Expt Cardiol, Heidelberglaan 100, NL-3584 CX Utrecht, Netherlands.Molekylär epidemiologi (creator_code:org_t)

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