TY - JOUR
T1 - Mild-to-Moderate Kidney Dysfunction and Cardiovascular Disease
T2 - Observational and Mendelian Randomization Analyses
AU - Gaziano, Liam
AU - Sun, Luanluan
AU - Emerging Risk Factors Collaboration/EPIC-CVD/Million Veteran Program
AU - Arnold, Matthew
AU - Bell, Steven
AU - Cho, Kelly
AU - Kaptoge, Stephen K.
AU - Song, Rebecca J.
AU - Burgess, Stephen
AU - Posner, Daniel C.
AU - Mosconi, Katja
AU - Robinson-Cohen, Cassianne
AU - Mason, Amy M.
AU - Bolton, Thomas R.
AU - Tao, Ran
AU - Allara, Elias
AU - Schubert, Petra
AU - Chen, Lingyan
AU - Staley, James R.
AU - Staplin, Natalie
AU - Altay, Servet
AU - Amiano, Pilar
AU - Arndt, Volker
AU - Ärnlöv, Johan
AU - Barr, Elizabeth L. M.
AU - Björkelund, Cecilia
AU - Boer, Jolanda M. A.
AU - Brenner, Hermann
AU - Casiglia, Edoardo
AU - Chiodini, Paolo
AU - Cooper, Jackie A.
AU - Coresh, Josef
AU - Cushman, Mary
AU - Dankner, Rachel
AU - Davidson, Karina W.
AU - de Jongh, Renate T.
AU - Donfrancesco, Chiara
AU - Engström, Gunnar
AU - Freisling, Heinz
AU - de la Cámara, Agustín G. mez
AU - Gudnason, Vilmundur
AU - Hankey, Graeme J.
AU - Hansson, Per-Olof
AU - Heath, Alicia K.
AU - Hoorn, Ewout J.
AU - Imano, Hironori
AU - Jassal, Simerjot K.
AU - Kaaks, Rudolf
AU - Katzke, Verena
AU - Kauhanen, Jussi
AU - Kiechl, Stefan
AU - Koenig, Wolfgang
AU - Kronmal, Richard A.
AU - Kyrø, Cecilie
AU - Lawlor, Deborah A.
AU - Ljungberg, B. rje
AU - MacDonald, Conor
AU - Masala, Giovanna
AU - Meisinger, Christa
AU - Melander, Olle
AU - Moreno Iribas, Conchi
AU - Ninomiya, Toshiharu
AU - Nitsch, Dorothea
AU - Nordestgaard, B. rge G.
AU - Onland-Moret, Charlotte
AU - Palmieri, Luigi
AU - Petrova, Dafina
AU - Garcia, Jose Ramón Quirós
AU - Rosengren, Annika
AU - Sacerdote, Carlotta
AU - Sakurai, Masaru
AU - Santiuste, Carmen
AU - Schulze, Matthias B.
AU - Sieri, Sabina
AU - Sundström, Johan
AU - Tikhonoff, Valérie
AU - Tjønneland, Anne
AU - Tong, Tammy
AU - Tumino, Rosario
AU - Tzoulaki, Ioanna
AU - van der Schouw, Yvonne T.
AU - Monique Verschuren, W. M.
AU - Völzke, Henry
AU - Wallace, Robert B.
AU - Wannamethee, S. Goya
AU - Weiderpass, Elisabete
AU - Willeit, Peter
AU - Woodward, Mark
AU - Yamagishi, Kazumasa
AU - Zamora-Ros, Raul
AU - Akwo, Elvis A.
AU - Pyarajan, Saiju
AU - Gagnon, David R.
AU - Tsao, Philip S.
AU - Muralidhar, Sumitra
AU - Edwards, Todd L.
AU - Damrauer, Scott M.
AU - Joseph, Jacob
AU - Pennells, Lisa
AU - Wilson, Peter W. F.
AU - Harrison, Seamus
AU - Gaziano, Thomas A.
AU - Inouye, Michael
AU - Baigent, Colin
AU - Casas, Juan P.
AU - Langenberg, Claudia
AU - Wareham, Nick
AU - Riboli, Elio
AU - Gaziano, J. Michael
AU - Danesh, John
AU - Hung, Adriana M.
AU - Butterworth, Adam S.
AU - Wood, Angela M.
AU - di Angelantonio, Emanuele
AU - Koettgen, Anna
AU - Shaw, Jonathan
AU - Atkins, Robert
AU - Zimmet, Paul
AU - Whincup, Peter
AU - Willeit, Johann
AU - Leitner, Christoph
AU - Tybjaerg-Hansen, Anne
AU - Schnohr, Peter
AU - Afzal, Shoaib
AU - Pablos, David Lora
AU - Arriscado, Cristina Martin
AU - Ferreiro, Carmen Romero
AU - Stocker, Hannah
AU - Schöttker, Ben
AU - Holleczek, Bernd
AU - Chetrit, Angela
AU - Welin, Lennart
AU - Svärdsudd, Kurt
AU - Lissner, Lauren
AU - Hange, Dominique
AU - Mehlig, Kirsten
AU - Nagel, Dorothea
AU - Norman, Paul E.
AU - Almeida, Osvaldo
AU - Flicker, Leon
AU - Hata, Jun
AU - Honda, Takanori
AU - Furuta, Yoshihiko
AU - Iso, Hiroyasu
AU - Kitamura, Akihiko
AU - Muraki, Isao
AU - Salonen, Jukka T.
AU - Tuomainen, Tomi-Pekka
AU - van Zutphen, E. M.
AU - van Schoor, N. M.
AU - Lo Noce, Cinzia
AU - Lappas, Georg
AU - Nilsson, Peter M.
AU - Hedblad, Bo
AU - Shaffer, Jonathan
AU - Schwartz, Joseph
AU - Shimbo, Daichi
AU - Sato, Shinichi
AU - Hayama-Terada, Mina
AU - Aspelund, Thor
AU - Thorsson, Bolli
AU - Sigurdsson, Gunnar
AU - Chaker, Layal
AU - Ikram, Kamran M.
AU - Kavousi, Maryam
AU - Tunstall-Pedoe, Hugh
AU - Can, G. nay
AU - Yüksel, H. sniye
AU - Özkan, U. ur
AU - Nakagawa, Hideaki
AU - Morikawa, Yuko
AU - Ishizaki, Masao
AU - Feskens, Edith
AU - Geleijnse, Johanna M.
AU - Kromhout, Daan
N1 - Funding Information:
The Emerging Risk Factors Collaboration (ERFC) coordinating center was underpinned by program grants from the British Heart Foundation (BHF; SP/09/002; RG/13/13/30194; RG/18/13/33946), BHF Centre of Research Excellence (RE/18/1/34212), the UK Medical Research Council (MR/L003120/1), and the National Institute for Health and Care Research (NIHR) Cambridge Biomedical Research Centre (BRC-1215-20014), with project-specific support received from the UK NIHR, British United Provident Association UK Foundation, and an unrestricted educational grant from GlaxoSmithKline. This work was supported by Health Data Research UK, which is funded by the UK Medical Research Council, the Engineering and Physical Sciences Research Council, the Economic and Social Research Council, the Department of Health and Social Care (England), the Chief Scientist Office of the Scottish Government Health and Social Care Directorates, the Health and Social Care Research and Development Division (Welsh Government), the Public Health Agency (Northern Ireland), the BHF, and the Wellcome Trust. A variety of funding sources have supported recruitment, follow-up, and laboratory measurements in the studies contributing data to the ERFC, which are listed on the ERFC website ( www.phpc.cam.ac.uk/ceu/erfc/list-of-studies ). EPIC-CVD (European Prospective Investigation into Cancer and Nutrition–Cardiovascular Disease Study) was funded by the European Research Council (268834) and the European Commission Framework Programme 7 (HEALTH-F2-2012-279233). The coordination of EPIC is financially supported by International Agency for Research on Cancer (IARC) and also by the Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London which has additional infrastructure support provided by the NIHR Imperial Biomedical Research Centre (BRC). The national cohorts are supported by: Danish Cancer Society (Denmark); Ligue Contre le Cancer, Institut Gustave Roussy, Mutuelle Générale de l’Education Nationale, Institut National de la Santé et de la Recherche Médicale (INSERM) (France); German Cancer Aid, German Cancer Research Center (DKFZ), German Institute of Human Nutrition PotsdamRehbruecke (DIfE), 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, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), Statistics Netherlands (The Netherlands); Health Research Fund (FIS) - Instituto de Salud Carlos III (ISCIII), Regional Governments of Andalucía, Asturias, Basque Country, Murcia and Navarra, and the Catalan Institute of Oncology - ICO (Spain); Swedish Cancer Society, Swedish Research Council and County Councils of Skåne and Västerbotten (Sweden); Cancer Research UK (14136 to EPIC-Norfolk; C8221/A29017 to EPIC-Oxford), Medical Research Council, United Kingdom (1000143 to EPIC-Norfolk; MR/M012190/1 to EPIC-Oxford). The establishment of the EPIC-InterAct subcohort (used in the EPIC-CVD study) and conduct of biochemical assays was supported by the EU Sixth Framework Programme (FP6) (grant LSHM_CT_2006_037197 to the InterAct project) and the Medical Research Council Epidemiology Unit (grants MC_UU_12015/1 and MC_UU_12015/5). This research is based on data from the Million Veteran Program, Office of Research and Development, and Veterans Health Administration and was supported by award I01-BX004821 (principal investigators, Drs Peter W.F. Wilson and Kelly Cho) and I01-BX003360 (principal investigators, Dr Adriana M. Hung). Dr Damrauer is supported by IK2-CX001780. Dr Hung is supported by CX001897. Dr Tsao is supported by BX003362-01 from VA Office of Research and Development. Dr Robinson-Cohen is supported by R01DK122075. Dr Sun was funded by a BHF Programme Grant (RG/18/13/33946). Dr Arnold was funded by a BHF Programme Grant (RG/18/13/33946). Dr Kaptoge is funded by a BHF Chair award (CH/12/2/29428). Dr Mason is funded by the EU/EFPIA Innovative Medicines Initiative Joint Undertaking BigData@Heart grant 116074. Dr Bolton was funded by the NIHR BTRU in Donor Health and Genomics (NIHR BTRU-2014-10024). Dr Allara is funded by a BHF Programme Grant (RG/18/13/33946). Prof Inouye is supported by the Munz Chair of Cardiovascular Prediction and Prevention and the NIHR Cambridge Biomedical Research Centre (BRC-1215-20014). Prof Inouye was also supported by the UK Economic and Social Research 878 Council (ES/T013192/1). Prof Danesh holds a British Heart Foundation Professorship and a NIHR Senior Investigator Award. Prof Wood is part of the BigData@Heart Consortium, funded by the Innovative Medicines Initiative-2 Joint Undertaking under grant agreement No 116074. Prof Wood was supported by the BHF-Turing Cardiovascular Data Science Award (BCDSA\100005). Prof Di Angelantonio holds a NIHR Senior Investigator Award.
Publisher Copyright:
© 2022 The Authors.
PY - 2022/11/15
Y1 - 2022/11/15
N2 - 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.
AB - 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.
KW - cardiovascular diseases
KW - coronary disease
KW - kidney diseases
KW - stroke
UR - https://www.scopus.com/pages/publications/85143192673
U2 - 10.1161/CIRCULATIONAHA.122.060700
DO - 10.1161/CIRCULATIONAHA.122.060700
M3 - Article
C2 - 36314129
SN - 0009-7322
VL - 146
SP - 1507
EP - 1517
JO - Circulation
JF - Circulation
IS - 20
ER -
SDG 3 Good Health and Well-being