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Gaziano, L.* ; Sun, L.* ; Arnold, M.* ; Bell, S.* ; Cho, K.* ; Kaptoge, S.K.* ; Song, R.J.* ; Burgess, S.* ; Posner, D.C.* ; Mosconi, K.* ; Robinson-Cohen, C.* ; Mason, A.* ; Bolton, T.R.* ; Tao, R.* ; Allara, E.* ; Schubert, P.* ; Chen, L.* ; Staley, J.R.* ; Staplin, N.* ; Altay, S.* ; Amiano, P.* ; Arndt, V.* ; Ärnlöv, J.* ; Barr, E.L.M.* ; Björkelund, C.* ; Boer, J.M.A.* ; Brenner, H.* ; Casiglia, E.* ; Chiodini, P.* ; Cooper, J.A.* ; Coresh, J.* ; Cushman, M.* ; Dankner, R.* ; Davidson, K.W.* ; de Jongh, R.T.* ; Donfrancesco, C.* ; Engström, G.* ; Freisling, H.* ; de la Cámara, A.G.* ; Gudnason, V.* ; Hankey, G.J.* ; Hansson, P.O.* ; Heath, A.K.* ; Hoorn, E.J.* ; Imano, H.* ; Jassal, S.K.* ; Kaaks, R.* ; Katzke, V.* ; Kauhanen, J.* ; Kiechl, S.* ; Koenig, W.* ; Kronmal, R.A.* ; Kyrø, C.* ; Lawlor, D.A.* ; Ljungberg, B.* ; MacDonald, C.J.* ; Masala, G.* ; Meisinger, C. ; Melander, O.* ; Moreno Iribas, C.* ; Ninomiya, T.* ; Nitsch, D.* ; Nordestgaard, B.G.* ; Onland-Moret, C.N.* ; Palmieri, L.* ; Petrova, D.* ; Garcia, J.R.Q.* ; Rosengren, A.* ; Sacerdote, C.* ; Sakurai, M.* ; Santiuste, C.* ; Schulze, M.B.* ; Sieri, S.* ; Sundström, J.* ; Tikhonoff, V.* ; Tjønneland, A.* ; Tong, T.* ; Tumino, R.* ; Tzoulaki, I.* ; van der Schouw, Y.T.* ; Monique Verschuren, W.M.* ; Völzke, H.* ; Wallace, R.B.* ; Goya Wannamethee, S.* ; Weiderpass, E.* ; Willeit, P.* ; Woodward, M.* ; Yamagishi, K.* ; Zamora-Ros, R.* ; Akwo, E.A.* ; Pyarajan, S.* ; Gagnon, D.R.* ; Tsao, P.S.* ; Muralidhar, S.* ; Edwards, T.L.* ; Damrauer, S.M.* ; Joseph, J.* ; Pennells, L.* ; Wilson, P.W.F.* ; Harrison, S.C.* ; Gaziano, T.A.* ; Baigent, C.* ; Casas, J.P.* ; Langenberg, C.* ; Wareham, N.* ; Riboli, E.* ; Michael Gaziano, J.* ; Hung, A.M.* ; Butterworth, A.S.*

Mild-to-moderate kidney dysfunction and cardiovascular disease: Observational and mendelian randomization analyses.

Circulation 146, 1507-1517 (2022)
Postprint Research data DOI PMC
Open Access Gold (Paid Option)
Creative Commons Lizenzvertrag
BACKGROUND: End-stage renal disease is associated with a high risk of cardiovascular events. It is unknown, however, whether mild-to-moderate kidney dysfunction is causally related to coronary heart disease (CHD) and stroke. METHODS: Observational analyses were conducted using individual-level data from 4 population data sources (Emerging Risk Factors Collaboration, EPIC-CVD [European Prospective Investigation into Cancer and Nutrition-Cardiovascular Disease Study], Million Veteran Program, and UK Biobank), comprising 648 135 participants with no history of cardiovascular disease or diabetes at baseline, yielding 42 858 and 15 693 incident CHD and stroke events, respectively, during 6.8 million person-years of follow-up. Using a genetic risk score of 218 variants for estimated glomerular filtration rate (eGFR), we conducted Mendelian randomization analyses involving 413 718 participants (25 917 CHD and 8622 strokes) in EPIC-CVD, Million Veteran Program, and UK Biobank. RESULTS: There were U-shaped observational associations of creatinine-based eGFR with CHD and stroke, with higher risk in participants with eGFR values <60 or >105 mL·min-1·1.73 m-2, compared with those with eGFR between 60 and 105 mL·min-1·1.73 m-2. Mendelian randomization analyses for CHD showed an association among participants with eGFR <60 mL·min-1·1.73 m-2, with a 14% (95% CI, 3%-27%) higher CHD risk per 5 mL·min-1·1.73 m-2 lower genetically predicted eGFR, but not for those with eGFR >105 mL·min-1·1.73 m-2. Results were not materially different after adjustment for factors associated with the eGFR genetic risk score, such as lipoprotein(a), triglycerides, hemoglobin A1c, and blood pressure. Mendelian randomization results for stroke were nonsignificant but broadly similar to those for CHD. CONCLUSIONS: In people without manifest cardiovascular disease or diabetes, mild-to-moderate kidney dysfunction is causally related to risk of CHD, highlighting the potential value of preventive approaches that preserve and modulate kidney function.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Cardiovascular Diseases ; Coronary Disease ; Kidney Diseases ; Stroke; Glomerular-filtration-rate; Serum Creatinine; Instrumental Variables; Renal-disease; Cystatin C; Association; Mortality; Equation; Biobank; Design
ISSN (print) / ISBN 0009-7322
e-ISSN 1524-4539
Journal Circulation
Quellenangaben Volume: 146, Issue: 20, Pages: 1507-1517 Article Number: , Supplement: ,
Publisher Lippincott Williams & Wilkins
Publishing Place Two Commerce Sq, 2001 Market St, Philadelphia, Pa 19103 Usa
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Independent Research Group Clinical Epidemiology (KEPI)
Grants European Commission Framework Programme 7
International Agency for Research on Cancer (IARC)
Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London
Danish Cancer Society (Denmark)
Ligue Contre le Cancer (France)
Institut Gustave Roussy, Mutuelle Generale de l'Education Nationale (France)
Institut National de la Sante et de la Recherche Medicale (INSERM) (France)
German Institute of Human Nutrition PotsdamRehbruecke (DIfE) (Germany)
Federal Ministry of Education and Research (BMBF) (Germany)
Associazione Italiana per la Ricerca sul Cancro-AIRC-Italy
Compagnia di SanPaolo and National Research Council (Italy)
Dutch Ministry of Public Health (The Netherlands)
Welfare and Sports (VWS) (The Netherlands)
Netherlands Cancer Registry (NKR) (The Netherlands)
LK Research Funds (The Netherlands)
German Cancer Aid, German Cancer Research Center (DKFZ) (Germany)
British Heart Foundation (BHF)
BHF Centre of Research Excellence
UK Medical Research Council
National Institute for Health and Care Research (NIHR) Cambridge Biomedical Research Centre - UK NIHR
British United Provident Association UK Foundation
GlaxoSmithKline
European Research Council
Engineering and Physical Sciences Research Council
Economic and Social Research Council
Department of Health and Social Care (England)
Chief Scientist Office of the Scottish Government Health and Social Care Directorates
Health and Social Care Research and Development Division (Welsh Government)
Public Health Agency (Northern Ireland)
BHF
Wellcome Trust
Health Data Research UK - UK Medical Research Council
Million Veteran Program, Office of Research and Development, and Veterans Health Administration
VA Office of Research and Development
BHF Programme
Dutch Prevention Funds (The Netherlands)
EU/EFPIA Innovative Medicines Initiative Joint Undertaking BigData@Heart
NIHR BTRU in Donor Health and Genomics
Munz Chair of Cardiovascular Prediction and Prevention
NIHR Cambridge Biomedical Research Centre
UK Economic and Social Research 878 Council
NIHR Senior Investigator Award
Innovative Medicines Initiative-2 Joint Undertaking
BHF-Turing Cardiovascular Data Science Award
BHF Chair
Dutch ZON (Zorg Onderzoek Nederland) (The Netherlands)
World Cancer Research Fund (WCRF) (The Netherlands)
Statistics Netherlands (The Netherlands)
Health Research Fund (FIS) - Instituto de Salud Carlos III (ISCIII) (Spain)
Regional Governments of Andalucia, Asturias, Basque Country, Murcia and Navarra (Spain)
Catalan Institute of Oncology - ICO (Spain)
Swedish Cancer Society (Sweden)
County Councils of Skane and Vasterbotten (Sweden)
Cancer Research UK
Medical Research Council, United Kingdom
EU Sixth Framework Programme (FP6)
Medical Research Council Epidemiology Unit
Swedish Research Council (Sweden)