Mild-to-Moderate Kidney Dysfunction and Cardiovascular Disease: Observational and Mendelian Randomization Analyses
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Mild-to-Moderate Kidney Dysfunction and Cardiovascular Disease : Observational and Mendelian Randomization Analyses. / 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.; Kyrø, Cecilie; Nordestgaard, Børge G.; Tjønneland, Anne; Tybjaerg-Hansen, Anne; Afzal, Shoaib; Emerging Risk Factors Collaboration/EPIC-CVD/Million Veteran Program.
In: Circulation, Vol. 146, No. 20, 2022, p. 1507-1517.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Mild-to-Moderate Kidney Dysfunction and Cardiovascular Disease
T2 - Observational and Mendelian Randomization Analyses
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 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 Gómez
AU - Gudnason, Vilmundur
AU - Hankey, Graeme J.
AU - Hansson, Per Olof
AU - Heath, Alicia K.
AU - Hoorn, Ewout J.
AU - Kyrø, Cecilie
AU - Nordestgaard, Børge G.
AU - Tjønneland, Anne
AU - Tybjaerg-Hansen, Anne
AU - Afzal, Shoaib
AU - Emerging Risk Factors Collaboration/EPIC-CVD/Million Veteran Program
N1 - Publisher Copyright: © 2022 The Authors.
PY - 2022
Y1 - 2022
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
U2 - 10.1161/CIRCULATIONAHA.122.060700
DO - 10.1161/CIRCULATIONAHA.122.060700
M3 - Journal article
C2 - 36314129
AN - SCOPUS:85143192673
VL - 146
SP - 1507
EP - 1517
JO - Circulation
JF - Circulation
SN - 0009-7322
IS - 20
ER -
ID: 329614581