TY - JOUR
T1 - Mild-to-Moderate Kidney Dysfunction and Cardiovascular Disease
T2 - Observational and Mendelian Randomization Analyses
AU - Million Veteran Program
AU - Gaziano, Liam
AU - Sun, Luanluan
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
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, Agustin Gómez
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, Börje
AU - MacDonald, Conor
AU - Masala, Giovanna
AU - Meisinger, Christa
AU - Melander, Olle
AU - Moreno Iribas, Conchi
AU - Ninomiya, Toshiharu
AU - Nitsch, Dorothea
AU - Nordestgaard, Børge 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 - Goya Wannamethee, S
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 - Michael Gaziano, J
AU - Danesh, John
AU - Hung, Adriana M
AU - Butterworth, Adam S
AU - Wood, Angela M
AU - Di Angelantonio, Emanuele
PY - 2022/11
Y1 - 2022/11
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.
UR - http://www.scopus.com/inward/record.url?scp=85143192673&partnerID=8YFLogxK
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 -
