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

L. Gaziano; L. Sun; M. Arnold; S. Bell; K. Cho; S. K. Kaptoge; R. J. Song; S. Burgess; D. C. Posner; K. Mosconi; C. Robinson-Cohen; A. M. Mason; T. R. Bolton; R. Tao; E. Allara; P. Schubert; L. Chen; J. R. Staley; N. Staplin; S. Altay; P. Amiano; V. Arndt; J. Arnlov; E. L. M. Barr; C. Bjorkelund; J. M. A. Boer; H. Brenner; E. Casiglia; P. Chiodini; J. A. Cooper; J. Coresh; M. Cushman; R. Dankner; K. W. Davidson; Jongh R. T. De; C. Donfrancesco; G. Engstrom; H. Freisling; La Camara A. G. De; V. Gudnason; G. J. Hankey; Hansson P. -O.; A. K. Heath; E. J. Hoorn; H. Imano; S. K. Jassal; R. Kaaks; V. Katzke; J. Kauhanen; S. Kiechl; W. Koenig; R. A. Kronmal; C. Kyro; D. A. Lawlor; B. Ljungberg; C. MacDonald; G. Masala; C. Meisinger; O. Melander; Iribas C. Moreno; T. Ninomiya; D. Nitsch; B. G. Nordestgaard; C. Onland-Moret; L. Palmieri; D. Petrova; J. R. Q. Garcia; A. Rosengren; Carlotta SACERDOTE; M. Sakurai; C. Santiuste; M. B. Schulze; S. Sieri; J. Sundstrom; V. Tikhonoff; A. Tjonneland; T. Tong; R. Tumino; I. Tzoulaki; Der Schouw Y. T. Van; Verschuren W. M. Monique; H. Volzke; R. B. Wallace; S. G. Wannamethee; E. Weiderpass; P. Willeit; M. Woodward; K. Yamagishi; R. Zamora-Ros; E. A. Akwo; S. Pyarajan; D. R. Gagnon; P. S. Tsao; S. Muralidhar; T. L. Edwards; S. M. Damrauer; J. Joseph; L. Pennells; P. W. F. Wilson; S. Harrison; T. A. Gaziano; M. Inouye; C. Baigent; J. P. Casas; C. Langenberg; N. Wareham; E. Riboli; J. M. Gaziano; J. Danesh; A. M. Hung; A. S. Butterworth; A. M. Wood; Angelantonio E. Di; A. Koettgen; J. Shaw; R. Atkins; P. Zimmet; P. Whincup; J. Willeit; C. Leitner; A. Tybjaerg-Hansen; P. Schnohr; S. Afzal; D. L. Pablos; C. M. Arriscado; C. R. Ferreiro; H. Stocker; B. Schottker; B. Holleczek; A. Chetrit; L. Welin; K. Svardsudd; L. Lissner; D. Hange; K. Mehlig; D. Nagel; P. E. Norman; O. Almeida; L. Flicker; J. Hata; T. Honda; Y. Furuta; H. Iso; A. Kitamura; I. Muraki; J. T. Salonen; Tuomainen T. -P.; Zutphen E. M. Van; Schoor N. M. Van; Noce C. Lo; G. Lappas; P. M. Nilsson; B. Hedblad; J. Shaffer; J. Schwartz; D. Shimbo; S. Sato; M. Hayama-Terada; T. Aspelund; B. Thorsson; G. Sigurdsson; L. Chaker; K. M. Ikram; M. Kavousi; H. Tunstall-Pedoe; G. Can; H. Yuksel; U. Ozkan; H. Nakagawa; Y. Morikawa; M. Ishizaki; E. Feskens; J. M. Geleijnse; D. Kromhout

doi:10.1161/CIRCULATIONAHA.122.060700

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

L. Gaziano, L. Sun, M. Arnold, S. Bell, K. Cho, S. K. Kaptoge, R. J. Song, S. Burgess, D. C. Posner, K. Mosconi, C. Robinson-Cohen, A. M. Mason, T. R. Bolton, R. Tao, E. Allara, P. Schubert, L. Chen, J. R. Staley, N. Staplin, S. AltayP. Amiano, V. Arndt, J. Arnlov, E. L. M. Barr, C. Bjorkelund, J. M. A. Boer, H. Brenner, E. Casiglia, P. Chiodini, J. A. Cooper, J. Coresh, M. Cushman, R. Dankner, K. W. Davidson, Jongh R. T. De, C. Donfrancesco, G. Engstrom, H. Freisling, La Camara A. G. De, V. Gudnason, G. J. Hankey, Hansson P. -O., A. K. Heath, E. J. Hoorn, H. Imano, S. K. Jassal, R. Kaaks, V. Katzke, J. Kauhanen, S. Kiechl, W. Koenig, R. A. Kronmal, C. Kyro, D. A. Lawlor, B. Ljungberg, C. MacDonald, G. Masala, C. Meisinger, O. Melander, Iribas C. Moreno, T. Ninomiya, D. Nitsch, B. G. Nordestgaard, C. Onland-Moret, L. Palmieri, D. Petrova, J. R. Q. Garcia, A. Rosengren, Carlotta SACERDOTE, M. Sakurai, C. Santiuste, M. B. Schulze, S. Sieri, J. Sundstrom, V. Tikhonoff, A. Tjonneland, T. Tong, R. Tumino, I. Tzoulaki, Der Schouw Y. T. Van, Verschuren W. M. Monique, H. Volzke, R. B. Wallace, S. G. Wannamethee, E. Weiderpass, P. Willeit, M. Woodward, K. Yamagishi, R. Zamora-Ros, E. A. Akwo, S. Pyarajan, D. R. Gagnon, P. S. Tsao, S. Muralidhar, T. L. Edwards, S. M. Damrauer, J. Joseph, L. Pennells, P. W. F. Wilson, S. Harrison, T. A. Gaziano, M. Inouye, C. Baigent, J. P. Casas, C. Langenberg, N. Wareham, E. Riboli, J. M. Gaziano, J. Danesh, A. M. Hung, A. S. Butterworth, A. M. Wood, Angelantonio E. Di, A. Koettgen, J. Shaw, R. Atkins, P. Zimmet, P. Whincup, J. Willeit, C. Leitner, A. Tybjaerg-Hansen, P. Schnohr, S. Afzal, D. L. Pablos, C. M. Arriscado, C. R. Ferreiro, H. Stocker, B. Schottker, B. Holleczek, A. Chetrit, L. Welin, K. Svardsudd, L. Lissner, D. Hange, K. Mehlig, D. Nagel, P. E. Norman, O. Almeida, L. Flicker, J. Hata, T. Honda, Y. Furuta, H. Iso, A. Kitamura, I. Muraki, J. T. Salonen, Tuomainen T. -P., Zutphen E. M. Van, Schoor N. M. Van, Noce C. Lo, G. Lappas, P. M. Nilsson, B. Hedblad, J. Shaffer, J. Schwartz, D. Shimbo, S. Sato, M. Hayama-Terada, T. Aspelund, B. Thorsson, G. Sigurdsson, L. Chaker, K. M. Ikram, M. Kavousi, H. Tunstall-Pedoe, G. Can, H. Yuksel, U. Ozkan, H. Nakagawa, Y. Morikawa, M. Ishizaki, E. Feskens, J. M. Geleijnse, D. Kromhout

Dipartimento di Scienze della Salute

Risultato della ricerca: Contributo su rivista › Articolo in rivista › peer review

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.

Lingua originale	Inglese
pagine (da-a)	1507-1517
Numero di pagine	11
Rivista	Circulation
Volume	146
Numero di pubblicazione	20
DOI	https://doi.org/10.1161/CIRCULATIONAHA.122.060700
Stato di pubblicazione	Pubblicato - 2022

Keywords

cardiovascular diseases
coronary disease
kidney diseases
stroke

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Accesso al documento

10.1161/CIRCULATIONAHA.122.060700

https://hdl.handle.net/11579/198121

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Gaziano, L., Sun, L., Arnold, M., Bell, S., Cho, K., Kaptoge, S. K., Song, R. J., Burgess, S., Posner, D. C., Mosconi, K., Robinson-Cohen, C., Mason, A. M., Bolton, T. R., Tao, R., Allara, E., Schubert, P., Chen, L., Staley, J. R., Staplin, N., ... Kromhout, D. (2022). Mild-to-Moderate Kidney Dysfunction and Cardiovascular Disease: Observational and Mendelian Randomization Analyses. Circulation, 146(20), 1507-1517. https://doi.org/10.1161/CIRCULATIONAHA.122.060700

@article{529e786a82d240cba3f2aaecd226737d,

title = "Mild-to-Moderate Kidney Dysfunction and Cardiovascular Disease: Observational and Mendelian Randomization Analyses",

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.",

keywords = "cardiovascular diseases, coronary disease, kidney diseases, stroke, cardiovascular diseases, coronary disease, kidney diseases, stroke",

author = "L. Gaziano and L. Sun and M. Arnold and S. Bell and K. Cho and Kaptoge, {S. K.} and Song, {R. J.} and S. Burgess and Posner, {D. C.} and K. Mosconi and C. Robinson-Cohen and Mason, {A. M.} and Bolton, {T. R.} and R. Tao and E. Allara and P. Schubert and L. Chen and Staley, {J. R.} and N. Staplin and S. Altay and P. Amiano and V. Arndt and J. Arnlov and Barr, {E. L. M.} and C. Bjorkelund and Boer, {J. M. A.} and H. Brenner and E. Casiglia and P. Chiodini and Cooper, {J. A.} and J. Coresh and M. Cushman and R. Dankner and Davidson, {K. W.} and De, {Jongh R. T.} and C. Donfrancesco and G. Engstrom and H. Freisling and De, {La Camara A. G.} and V. Gudnason and Hankey, {G. J.} and -O., {Hansson P.} and Heath, {A. K.} and Hoorn, {E. J.} and H. Imano and Jassal, {S. K.} and R. Kaaks and V. Katzke and J. Kauhanen and S. Kiechl and W. Koenig and Kronmal, {R. A.} and C. Kyro and Lawlor, {D. A.} and B. Ljungberg and C. MacDonald and G. Masala and C. Meisinger and O. Melander and Moreno, {Iribas C.} and T. Ninomiya and D. Nitsch and Nordestgaard, {B. G.} and C. Onland-Moret and L. Palmieri and D. Petrova and Garcia, {J. R. Q.} and A. Rosengren and Carlotta SACERDOTE and M. Sakurai and C. Santiuste and Schulze, {M. B.} and S. Sieri and J. Sundstrom and V. Tikhonoff and A. Tjonneland and T. Tong and R. Tumino and I. Tzoulaki and Van, {Der Schouw Y. T.} and Monique, {Verschuren W. M.} and H. Volzke and Wallace, {R. B.} and Wannamethee, {S. G.} and E. Weiderpass and P. Willeit and M. Woodward and K. Yamagishi and R. Zamora-Ros and Akwo, {E. A.} and S. Pyarajan and Gagnon, {D. R.} and Tsao, {P. S.} and S. Muralidhar and Edwards, {T. L.} and Damrauer, {S. M.} and J. Joseph and L. Pennells and Wilson, {P. W. F.} and S. Harrison and Gaziano, {T. A.} and M. Inouye and C. Baigent and Casas, {J. P.} and C. Langenberg and N. Wareham and E. Riboli and Gaziano, {J. M.} and J. Danesh and Hung, {A. M.} and Butterworth, {A. S.} and Wood, {A. M.} and Di, {Angelantonio E.} and A. Koettgen and J. Shaw and R. Atkins and P. Zimmet and P. Whincup and J. Willeit and C. Leitner and A. Tybjaerg-Hansen and P. Schnohr and S. Afzal and Pablos, {D. L.} and Arriscado, {C. M.} and Ferreiro, {C. R.} and H. Stocker and B. Schottker and B. Holleczek and A. Chetrit and L. Welin and K. Svardsudd and L. Lissner and D. Hange and K. Mehlig and D. Nagel and Norman, {P. E.} and O. Almeida and L. Flicker and J. Hata and T. Honda and Y. Furuta and H. Iso and A. Kitamura and I. Muraki and Salonen, {J. T.} and -P., {Tuomainen T.} and Van, {Zutphen E. M.} and Van, {Schoor N. M.} and Lo, {Noce C.} and G. Lappas and Nilsson, {P. M.} and B. Hedblad and J. Shaffer and J. Schwartz and D. Shimbo and S. Sato and M. Hayama-Terada and T. Aspelund and B. Thorsson and G. Sigurdsson and L. Chaker and Ikram, {K. M.} and M. Kavousi and H. Tunstall-Pedoe and G. Can and H. Yuksel and U. Ozkan and H. Nakagawa and Y. Morikawa and M. Ishizaki and E. Feskens and Geleijnse, {J. M.} and D. Kromhout",

year = "2022",

doi = "10.1161/CIRCULATIONAHA.122.060700",

language = "English",

volume = "146",

pages = "1507--1517",

journal = "Circulation",

issn = "0009-7322",

publisher = "Lippincott Williams and Wilkins",

number = "20",

}

Gaziano, L, Sun, L, Arnold, M, Bell, S, Cho, K, Kaptoge, SK, Song, RJ, Burgess, S, Posner, DC, Mosconi, K, Robinson-Cohen, C, Mason, AM, Bolton, TR, Tao, R, Allara, E, Schubert, P, Chen, L, Staley, JR, Staplin, N, Altay, S, Amiano, P, Arndt, V, Arnlov, J, Barr, ELM, Bjorkelund, C, Boer, JMA, Brenner, H, Casiglia, E, Chiodini, P, Cooper, JA, Coresh, J, Cushman, M, Dankner, R, Davidson, KW, De, JRT, Donfrancesco, C, Engstrom, G, Freisling, H, De, LCAG, Gudnason, V, Hankey, GJ, -O., HP, Heath, AK, Hoorn, EJ, Imano, H, Jassal, SK, Kaaks, R, Katzke, V, Kauhanen, J, Kiechl, S, Koenig, W, Kronmal, RA, Kyro, C, Lawlor, DA, Ljungberg, B, MacDonald, C, Masala, G, Meisinger, C, Melander, O, Moreno, IC, Ninomiya, T, Nitsch, D, Nordestgaard, BG, Onland-Moret, C, Palmieri, L, Petrova, D, Garcia, JRQ, Rosengren, A, SACERDOTE, C, Sakurai, M, Santiuste, C, Schulze, MB, Sieri, S, Sundstrom, J, Tikhonoff, V, Tjonneland, A, Tong, T, Tumino, R, Tzoulaki, I, Van, DSYT, Monique, VWM, Volzke, H, Wallace, RB, Wannamethee, SG, Weiderpass, E, Willeit, P, Woodward, M, Yamagishi, K, Zamora-Ros, R, Akwo, EA, Pyarajan, S, Gagnon, DR, Tsao, PS, Muralidhar, S, Edwards, TL, Damrauer, SM, Joseph, J, Pennells, L, Wilson, PWF, Harrison, S, Gaziano, TA, Inouye, M, Baigent, C, Casas, JP, Langenberg, C, Wareham, N, Riboli, E, Gaziano, JM, Danesh, J, Hung, AM, Butterworth, AS, Wood, AM, Di, AE, Koettgen, A, Shaw, J, Atkins, R, Zimmet, P, Whincup, P, Willeit, J, Leitner, C, Tybjaerg-Hansen, A, Schnohr, P, Afzal, S, Pablos, DL, Arriscado, CM, Ferreiro, CR, Stocker, H, Schottker, B, Holleczek, B, Chetrit, A, Welin, L, Svardsudd, K, Lissner, L, Hange, D, Mehlig, K, Nagel, D, Norman, PE, Almeida, O, Flicker, L, Hata, J, Honda, T, Furuta, Y, Iso, H, Kitamura, A, Muraki, I, Salonen, JT, -P., TT, Van, ZEM, Van, SNM, Lo, NC, Lappas, G, Nilsson, PM, Hedblad, B, Shaffer, J, Schwartz, J, Shimbo, D, Sato, S, Hayama-Terada, M, Aspelund, T, Thorsson, B, Sigurdsson, G, Chaker, L, Ikram, KM, Kavousi, M, Tunstall-Pedoe, H, Can, G, Yuksel, H, Ozkan, U, Nakagawa, H, Morikawa, Y, Ishizaki, M, Feskens, E, Geleijnse, JM & Kromhout, D 2022, 'Mild-to-Moderate Kidney Dysfunction and Cardiovascular Disease: Observational and Mendelian Randomization Analyses', Circulation, vol. 146, n. 20, pagg. 1507-1517. https://doi.org/10.1161/CIRCULATIONAHA.122.060700

TY - JOUR

T1 - Mild-to-Moderate Kidney Dysfunction and Cardiovascular Disease: Observational and Mendelian Randomization Analyses

AU - Gaziano, L.

AU - Sun, L.

AU - Arnold, M.

AU - Bell, S.

AU - Cho, K.

AU - Kaptoge, S. K.

AU - Song, R. J.

AU - Burgess, S.

AU - Posner, D. C.

AU - Mosconi, K.

AU - Robinson-Cohen, C.

AU - Mason, A. M.

AU - Bolton, T. R.

AU - Tao, R.

AU - Allara, E.

AU - Schubert, P.

AU - Chen, L.

AU - Staley, J. R.

AU - Staplin, N.

AU - Altay, S.

AU - Amiano, P.

AU - Arndt, V.

AU - Arnlov, J.

AU - Barr, E. L. M.

AU - Bjorkelund, C.

AU - Boer, J. M. A.

AU - Brenner, H.

AU - Casiglia, E.

AU - Chiodini, P.

AU - Cooper, J. A.

AU - Coresh, J.

AU - Cushman, M.

AU - Dankner, R.

AU - Davidson, K. W.

AU - De, Jongh R. T.

AU - Donfrancesco, C.

AU - Engstrom, G.

AU - Freisling, H.

AU - De, La Camara A. G.

AU - Gudnason, V.

AU - Hankey, G. J.

AU - -O., Hansson P.

AU - Heath, A. K.

AU - Hoorn, E. J.

AU - Imano, H.

AU - Jassal, S. K.

AU - Kaaks, R.

AU - Katzke, V.

AU - Kauhanen, J.

AU - Kiechl, S.

AU - Koenig, W.

AU - Kronmal, R. A.

AU - Kyro, C.

AU - Lawlor, D. A.

AU - Ljungberg, B.

AU - MacDonald, C.

AU - Masala, G.

AU - Meisinger, C.

AU - Melander, O.

AU - Moreno, Iribas C.

AU - Ninomiya, T.

AU - Nitsch, D.

AU - Nordestgaard, B. G.

AU - Onland-Moret, C.

AU - Palmieri, L.

AU - Petrova, D.

AU - Garcia, J. R. Q.

AU - Rosengren, A.

AU - SACERDOTE, Carlotta

AU - Sakurai, M.

AU - Santiuste, C.

AU - Schulze, M. B.

AU - Sieri, S.

AU - Sundstrom, J.

AU - Tikhonoff, V.

AU - Tjonneland, A.

AU - Tong, T.

AU - Tumino, R.

AU - Tzoulaki, I.

AU - Van, Der Schouw Y. T.

AU - Monique, Verschuren W. M.

AU - Volzke, H.

AU - Wallace, R. B.

AU - Wannamethee, S. G.

AU - Weiderpass, E.

AU - Willeit, P.

AU - Woodward, M.

AU - Yamagishi, K.

AU - Zamora-Ros, R.

AU - Akwo, E. A.

AU - Pyarajan, S.

AU - Gagnon, D. R.

AU - Tsao, P. S.

AU - Muralidhar, S.

AU - Edwards, T. L.

AU - Damrauer, S. M.

AU - Joseph, J.

AU - Pennells, L.

AU - Wilson, P. W. F.

AU - Harrison, S.

AU - Gaziano, T. A.

AU - Inouye, M.

AU - Baigent, C.

AU - Casas, J. P.

AU - Langenberg, C.

AU - Wareham, N.

AU - Riboli, E.

AU - Gaziano, J. M.

AU - Danesh, J.

AU - Hung, A. M.

AU - Butterworth, A. S.

AU - Wood, A. M.

AU - Di, Angelantonio E.

AU - Koettgen, A.

AU - Shaw, J.

AU - Atkins, R.

AU - Zimmet, P.

AU - Whincup, P.

AU - Willeit, J.

AU - Leitner, C.

AU - Tybjaerg-Hansen, A.

AU - Schnohr, P.

AU - Afzal, S.

AU - Pablos, D. L.

AU - Arriscado, C. M.

AU - Ferreiro, C. R.

AU - Stocker, H.

AU - Schottker, B.

AU - Holleczek, B.

AU - Chetrit, A.

AU - Welin, L.

AU - Svardsudd, K.

AU - Lissner, L.

AU - Hange, D.

AU - Mehlig, K.

AU - Nagel, D.

AU - Norman, P. E.

AU - Almeida, O.

AU - Flicker, L.

AU - Hata, J.

AU - Honda, T.

AU - Furuta, Y.

AU - Iso, H.

AU - Kitamura, A.

AU - Muraki, I.

AU - Salonen, J. T.

AU - -P., Tuomainen T.

AU - Van, Zutphen E. M.

AU - Van, Schoor N. M.

AU - Lo, Noce C.

AU - Lappas, G.

AU - Nilsson, P. M.

AU - Hedblad, B.

AU - Shaffer, J.

AU - Schwartz, J.

AU - Shimbo, D.

AU - Sato, S.

AU - Hayama-Terada, M.

AU - Aspelund, T.

AU - Thorsson, B.

AU - Sigurdsson, G.

AU - Chaker, L.

AU - Ikram, K. M.

AU - Kavousi, M.

AU - Tunstall-Pedoe, H.

AU - Can, G.

AU - Yuksel, H.

AU - Ozkan, U.

AU - Nakagawa, H.

AU - Morikawa, Y.

AU - Ishizaki, M.

AU - Feskens, E.

AU - Geleijnse, J. M.

AU - Kromhout, D.

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

KW - cardiovascular diseases

KW - coronary disease

KW - kidney diseases

KW - stroke

UR - https://iris.uniupo.it/handle/11579/198121

U2 - 10.1161/CIRCULATIONAHA.122.060700

DO - 10.1161/CIRCULATIONAHA.122.060700

M3 - Article

SN - 0009-7322

VL - 146

SP - 1507

EP - 1517

JO - Circulation

JF - Circulation

IS - 20

ER -

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

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