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

作者：Liam Gaziano, Luanluan Sun, Matthew G. Arnold, Steven Bell, Kelly Cho, Stephen K. Kaptoge, Rebecca J. Song, Stephen Burgess, Daniel Posner, Katja Mosconi, Cassianne Robinson‐Cohen, Amy M. Mason, Thomas R Bolton, Ran Tao, Elias Allara, Petra L. 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 S. Dankner, Karina W. Davidson, Renate T. de JONGH, Chiara Donfrancesco, Gunnar Engström, Heinz Freisling, Agustı́n Gómez de la Cámara, Vilmundur G. Gudnason, Graeme J. Hankey, Per‐Olof Hansson, Alicia K. Heath, Ewout Jasper Hoorn, Hironori Imano, Simerjot Kaur Jassal, Rudolf Kaaks, Verena Andrea Katzke, Jussi Kauhanen, Stefan Julia Kiechl, Wolfgang Köenig, Richard A. Kronmal, Cecilie Kyrø, Deborah A. Lawlor, Börje Ljungberg, Conor‐James MacDonald, Giovanna Masala, Christa Meisinger, Olle Melander, Conchi Moreno Iribas, Toshiharu Ninomiya, Dorothea Nitsch, Børge Grønne Nordestgaard, N. Charlotte Onland‐Moret, Luigi Palmieri, Dafina Petrova, Jose Ramón Quirós Garcia, Annika Rosengren, Carlotta Sacerdote, Masaru Sakurai, Carmen Santiuste, Matthias Bernd Schulze, Sabina Sieri, Johan Sundström, Valérie Tikhonoff, Anne Marie 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 A M Pennells, Peter W.F. Wilson, Seamus C. Harrison, Thomas Andrew Gaziano, Michael Inouye, Colin Baigent, Juan Pablo Casas, Claudia Langenberg, Nicholas J. Wareham, Elio Ríboli, J. Michael Gaziano, John Danesh, Adriana M. Hung, Adam S. Butterworth, ANGELA M. WOOD, Emanuele Di Angelantonio, Anna Koettgen, Jonathan Edward 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 Pablos, Cristina Martin Arriscado, Carmen Romero Ferreiro, Robert B. Wallace, Hannah R. Stocker, Ben Schöttker, Bernd Holleczek, Angela Chetrit, Lennart Welin, Kurt Svärdsudd, Lennart Welin, Kurt Svärdsudd, Lauren Lissner, Dominique Hange, Kirsten Mehlig, Dorothea Nagel, Paul Edward Norman, Osvaldo P. Almeida, Leon A Flicker, Jun Hata, Takanori Honda, Yoshihiko Furuta, Hiroyasu Iso, Akihiko Kitamura, Isao Muraki, Jukka T. Salonen, Tomi-Pekka Tuomainen, Elisabeth Maria 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 Kaur Jassal, Thor Aspelund, Bolli Þórsson, Gunnar Th Sigurdsson, Layal Chaker, Kamran M. 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 Marianne Geleijnse, Daan Kromhout · 发表于：Circulation · 年份：2022 · DOI：10.1161/circulationaha.122.060700 · 被引用次数：60 · 研究领域：Chronic Kidney Disease and Diabetes、Genetic Associations and Epidemiology、Renal Diseases and Glomerulopathies

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 ...