Mild-to-Moderate Kidney Dysfunction and Cardiovascular Disease: Observational and Mendelian Randomization Analyses. Issue 20 (31st October 2022)

• Record Type: Journal Article
• Authors: Gaziano, Liam; Sun, Luanluan; Arnold, Matthew; Bell, Steven; Cho, Kelly; Kaptoge, Stephen K.; Song, Rebecca J.; Burgess, Stephen; Posner, Daniel C.; Mosconi, Katja; Robinson-Cohen, Cassianne; Mason, Amy M.; Bolton, Thomas R.; Tao, Ran; Allara, Elias; Schubert, Petra; Chen, Lingyan; Staley, James R.; Staplin, Natalie; Altay, Servet; Amiano, Pilar; Arndt, Volker; Ärnlöv, Johan; Barr, Elizabeth L.M.; Björkelund, Cecilia; Boer, Jolanda M.A.; Brenner, Hermann; Casiglia, Edoardo; Chiodini, Paolo; Cooper, Jackie A.; Coresh, Josef; Cushman, Mary; Dankner, Rachel; Davidson, Karina W.; de Jongh, Renate T.; Donfrancesco, Chiara; Engström, Gunnar; Freisling, Heinz; de la Cámara, Agustín Gómez; Gudnason, Vilmundur; Hankey, Graeme J.; Hansson, Per-Olof; Heath, Alicia K.; Hoorn, Ewout J.; Imano, Hironori; Jassal, Simerjot K.; Kaaks, Rudolf; Katzke, Verena; Kauhanen, Jussi; Kiechl, Stefan; Koenig, Wolfgang; Kronmal, Richard A.; Kyrø, Cecilie; Lawlor, Deborah A.; Ljungberg, Börje; MacDonald, Conor; Masala, Giovanna; Meisinger, Christa; Melander, Olle; Moreno Iribas, Conchi; Ninomiya, Toshiharu; Nitsch, Dorothea; Nordestgaard, Børge G.; Onland-Moret, Charlotte; Palmieri, Luigi; Petrova, Dafina; Garcia, Jose Ramón Quirós; Rosengren, Annika; Sacerdote, Carlotta; Sakurai, Masaru; Santiuste, Carmen; Schulze, Matthias B.; Sieri, Sabina; Sundström, Johan; Tikhonoff, Valérie; Tjønneland, Anne; Tong, Tammy; Tumino, Rosario; Tzoulaki, Ioanna; van der Schouw, Yvonne T.; Monique Verschuren, W.M.; Völzke, Henry; Wallace, Robert B.; Wannamethee, S. Goya; Weiderpass, Elisabete; Willeit, Peter; Woodward, Mark; Yamagishi, Kazumasa; Zamora-Ros, Raul; Akwo, Elvis A.; Pyarajan, Saiju; Gagnon, David R.; Tsao, Philip S.; Muralidhar, Sumitra; Edwards, Todd L.; Damrauer, Scott M.; Joseph, Jacob; Pennells, Lisa; Wilson, Peter W.F.; Harrison, Seamus; Gaziano, Thomas A.; Inouye, Michael; Baigent, Colin; Casas, Juan P.; Langenberg, Claudia; Wareham, Nick; Riboli, Elio; Gaziano, J.Michael; Danesh, John; Hung, Adriana M.; Butterworth, Adam S.; Wood, Angela M.; Di Angelantonio, Emanuele;
• Other Names: Koettgen Anna author non-byline.; Shaw Jonathan author non-byline.; Atkins Robert author non-byline.; Zimmet Paul author non-byline.; Whincup Peter author non-byline.; Willeit Peter author non-byline.; Willeit Johann author non-byline.; Leitner Christoph author non-byline.; Casiglia Edoardo author non-byline.; Tikhonoff Valérie author non-byline.; Tybjaerg-Hansen Anne author non-byline.; Schnohr Peter author non-byline.; Afzal Shoaib author non-byline.; Pablos David Lora author non-byline.; Arriscado Cristina Martin author non-byline.; Ferreiro Carmen Romero author non-byline.; Wallace Robert B. author non-byline.; Stocker Hannah author non-byline.; Schöttker Ben author non-byline.; Holleczek Bernd author non-byline.; Chetrit Angela author non-byline.; Welin Lennart author non-byline.; Svärdsudd Kurt author non-byline.; Welin Lennart author non-byline.; Svärdsudd Kurt author non-byline.; Lissner Lauren author non-byline.; Hange Dominique author non-byline.; Mehlig Kirsten author non-byline.; Nagel Dorothea author non-byline.; Norman Paul E. author non-byline.; Almeida Osvaldo author non-byline.; Flicker Leon author non-byline.; Hata Jun author non-byline.; Honda Takanori author non-byline.; Furuta Yoshihiko author non-byline.; Iso Hiroyasu author non-byline.; Kitamura Akihiko author non-byline.; Muraki Isao author non-byline.; Salonen Jukka T. author non-byline.; Tuomainen Tomi-Pekka author non-byline.; van Zutphen E. M. author non-byline.; van Schoor N. M. author non-byline.; Donfrancesco Chiara author non-byline.; Lo Noce Cinzia author non-byline.; Palmieri Luigi author non-byline.; Cushman Mary author non-byline.; Kronmal Richard author non-byline.; Koenig Wolfgang author non-byline.; Meisinger Christa author non-byline.; Lappas Georg author non-byline.; Nilsson Peter M. author non-byline.; Melander Olle author non-byline.; Hedblad Bo author non-byline.; Nitsch Dorothea author non-byline.; Cooper Jackie A. author non-byline.; Shaffer Jonathan author non-byline.; Schwartz Joseph author non-byline.; Shimbo Daichi author non-byline.; Sato Shinichi author non-byline.; Iso Hiroyasu author non-byline.; Hayama-Terada Mina author non-byline.; Jassal Simerjot author non-byline.; Aspelund Thor author non-byline.; Thorsson Bolli author non-byline.; Sigurdsson Gunnar author non-byline.; Chaker Layal author non-byline.; Ikram Kamran M. author non-byline.; Kavousi Maryam author non-byline.; Tunstall-Pedoe Hugh author non-byline.; Woodward Mark author non-byline.; Völzke Henry author non-byline.; Can Günay author non-byline.; Yüksel Hüsniye author non-byline.; Özkan Uğur author non-byline.; Nakagawa Hideaki author non-byline.; Morikawa Yuko author non-byline.; Ishizaki Masao author non-byline.; Ärnlöv Johan author non-byline.; Arndt Volker author non-byline.; Feskens Edith author non-byline.; Geleijnse Johanna M author non-byline.; Kromhout Daan author non-byline.;
• Is Part Of: Circulation. Volume 146:Issue 20(2022)
• Page Start: 1507
• Page End: 1517
• Publication Date: 2022-10-31
• Subjects: cardiovascular diseases -- coronary disease -- kidney diseases -- stroke; Blood -- Circulation -- Periodicals; Cardiovascular system -- Periodicals; Cardiology -- Periodicals; Heart -- Diseases -- Periodicals; Blood Circulation; Cardiovascular System; Vascular Diseases; 616.1
• DOI: 10.1161/CIRCULATIONAHA.122.060700
• Languages: English
• ISSNs: 0009-7322

Abstract

Abstract : 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.