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Mild-to-Moderate Kidney Dysfunction and Cardiovascular Disease: Observational and Mendelian Randomization Analyses

2022; Lippincott Williams & Wilkins; Volume: 146; Issue: 20 Linguagem: Inglês

10.1161/circulationaha.122.060700

1524-4539

Liam Gaziano, Luanluan Sun, Matthew Arnold, Steven Bell, Kelly Cho, Stephen Kaptoge, Rebecca J. Song, Stephen Burgess, Daniel Posner, Katja Mosconi, Cassianne Robinson‐Cohen, Amy M. Mason, Thomas R Bolton, Ran Tao, Elias Allara, Petra Schubert, Lingyan Chen, James R Staley, Natalie Staplin, Servet Altay, Pilar Amiano, Volker Arndt, Johan Ärnlöv, Elizabeth Barr, Cecilia Björkelund, Jolanda M.A. Boer, Hermann Brenner, Edoardo Casiglia, Paolo Chiodini, Jackie A. Cooper, Josef Coresh, Mary Cushman, Rachel Dankner, Karina W. Davidson, Renate T. de Jongh, Chiara Donfrancesco, Gunnar Engström, Heinz Freisling, Agustı́n Gómez de la Cámara, Vilmundur Guðnason, Graeme J. Hankey, Per‐Olof Hansson, Alicia K. Heath, Ewout J. Hoorn, Hironori Imano, Simerjot K Jassal, Rudolf Kaaks, Verena Katzke, Jussi Kauhanen, Stefan Kiechl, Wolfgang Köenig, Richard A. Kronmal, Cecilie Kyrø, Debbie A. Lawlor, Börje Ljungberg, Conor‐James MacDonald, Giovanna Masala, Christa Meisinger, Olle Melander, Conchi Moreno Iribas, Toshiharu Ninomiya, Dorothea Nitsch, Børge G. Nordestgaard, N. Charlotte Onland‐Moret, Luigi Palmieri, Dafina Petrova, J.R. García, Annika Rosengren, Carlotta Sacerdote, Masaru Sakurai, Carmen Santiuste, Matthias B. Schulze, Sabina Sieri, Johan Sundström, Valérie Tikhonoff, Anne Tjønneland, Tammy Y. N. Tong, ­Rosario ­Tumino, Ioanna Tzoulaki, Yvonne T. van der Schouw, W. M. Monique Verschuren, Henry Völzke, Robert B. Wallace, S. Goya Wannamethee, Elisabete Weiderpass, Peter Willeit, Mark Woodward, Kazumasa Yamagishi, Raúl Zamora‐Ros, Elvis A. Akwo, Saiju Pyarajan, David R. Gagnon, Philip S. Tsao, Sumitra Muralidhar, Todd L. Edwards, Scott M. Damrauer, Jacob Joseph, Lisa Pennells, Peter W.F. Wilson, Seamus C. Harrison, Thomas A. Gaziano, Michael Inouye, Colin Baigent, Juan P. Casas, Claudia Langenberg, Nicholas J. Wareham, Elio Ríboli, J. Michael Gaziano, John Danesh, Adriana M. Hung, Adam S. Butterworth, Angela Wood, Emanuele Di Angelantonio, Anna Koettgen, Jonathan E. Shaw, Robert C. Atkins, Paul Zimmet, Peter H. Whincup, Peter Willeit, Johann Willeit, Christoph Leitner, Edoardo Casiglia, Valérie Tikhonoff, Anne Tybjærg‐Hansen, Peter Schnohr, Shoaib Afzal, David Lora, Cristina Martín‐Arriscado Arroba, Carmen Romero, Robert B. Wallace, Hannah Stocker, Ben Schöttker, Bernd Holleczek, Angela Chetrit, Lennart Welin, Kurt Svärdsudd, Lennart Welin, Kurt Svärdsudd, Lauren Lissner, Dominique Hange, Kirsten Mehlig, Dorothea Nagel, Paul E. Norman, Osvaldo P. Almeida, Leon Flicker, Jun Hata, Takanori Honda, Yoshihiko Furuta, Hiroyasu Iso, Akihiko Kitamura, Isao Muraki, Jukka T. Salonen, Tomi-Pekka Tuomainen, Elisabeth M. van Zutphen, Natasja M. van Schoor, Chiara Donfrancesco, Cinzia Lo Noce, Luigi Palmieri, Mary Cushman, Richard A. Kronmal, Wolfgang Köenig, Christa Meisinger, Georg Lappas, Peter M Nilsson, Olle Melander, Bo Hedblad, Dorothea Nitsch, Jackie A. Cooper, Jonathan A. Shaffer, Joseph E. Schwartz, Daichi Shimbo, S Sato, Hiroyasu Iso, Mina Hayama‐Terada, Simerjot K Jassal, Thor Aspelund, Bolli Þórsson, Gunnar Sigurðsson, Layal Chaker, Kamran Ikram, Maryam Kavousi, Hugh Tunstall‐Pedoe, Mark Woodward, Henry Völzke, Günay Can, Hüsniye Yüksel, Uğur Özkan, Hideaki Nakagawa, Yuko Morikawa, Masao Ishizaki, Johan Ärnlöv, Volker Arndt, Edith J. M. Feskens, Johanna M. Geleijnse, Daan Kromhout,

Birth, Development, and Health

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. 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. There were U-shaped observational associations of creatinine-based eGFR with CHD and stroke, with higher risk in participants with eGFR values 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 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. 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.