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Mild-to-Moderate Kidney Dysfunction and Cardiovascular Disease: Observational and Mendelian Randomization Analyses
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 popul...
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Lippincott Williams & Wilkins
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9662821/ https://www.ncbi.nlm.nih.gov/pubmed/36314129 http://dx.doi.org/10.1161/CIRCULATIONAHA.122.060700 |
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author | 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 |
author_facet | 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 |
author_sort | Gaziano, Liam |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-9662821 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Lippincott Williams & Wilkins |
record_format | MEDLINE/PubMed |
spelling | pubmed-96628212022-11-21 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. 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 Circulation Original Research Articles 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. Lippincott Williams & Wilkins 2022-10-31 2022-11-15 /pmc/articles/PMC9662821/ /pubmed/36314129 http://dx.doi.org/10.1161/CIRCULATIONAHA.122.060700 Text en © 2022 The Authors. https://creativecommons.org/licenses/by/4.0/Circulation is published on behalf of the American Heart Association, Inc., by Wolters Kluwer Health, Inc. This is an open access article under the terms of the Creative Commons Attribution (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution, and reproduction in any medium, provided that the original work is properly cited. |
spellingShingle | Original Research Articles 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 Mild-to-Moderate Kidney Dysfunction and Cardiovascular Disease: Observational and Mendelian Randomization Analyses |
title | Mild-to-Moderate Kidney Dysfunction and Cardiovascular Disease: Observational and Mendelian Randomization Analyses |
title_full | Mild-to-Moderate Kidney Dysfunction and Cardiovascular Disease: Observational and Mendelian Randomization Analyses |
title_fullStr | Mild-to-Moderate Kidney Dysfunction and Cardiovascular Disease: Observational and Mendelian Randomization Analyses |
title_full_unstemmed | Mild-to-Moderate Kidney Dysfunction and Cardiovascular Disease: Observational and Mendelian Randomization Analyses |
title_short | Mild-to-Moderate Kidney Dysfunction and Cardiovascular Disease: Observational and Mendelian Randomization Analyses |
title_sort | mild-to-moderate kidney dysfunction and cardiovascular disease: observational and mendelian randomization analyses |
topic | Original Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9662821/ https://www.ncbi.nlm.nih.gov/pubmed/36314129 http://dx.doi.org/10.1161/CIRCULATIONAHA.122.060700 |
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mildtomoderatekidneydysfunctionandcardiovasculardiseaseobservationalandmendelianrandomizationanalyses AT warehamnick mildtomoderatekidneydysfunctionandcardiovasculardiseaseobservationalandmendelianrandomizationanalyses AT ribolielio mildtomoderatekidneydysfunctionandcardiovasculardiseaseobservationalandmendelianrandomizationanalyses AT gazianojmichael mildtomoderatekidneydysfunctionandcardiovasculardiseaseobservationalandmendelianrandomizationanalyses AT daneshjohn mildtomoderatekidneydysfunctionandcardiovasculardiseaseobservationalandmendelianrandomizationanalyses AT hungadrianam mildtomoderatekidneydysfunctionandcardiovasculardiseaseobservationalandmendelianrandomizationanalyses AT butterworthadams mildtomoderatekidneydysfunctionandcardiovasculardiseaseobservationalandmendelianrandomizationanalyses AT woodangelam mildtomoderatekidneydysfunctionandcardiovasculardiseaseobservationalandmendelianrandomizationanalyses AT diangelantonioemanuele mildtomoderatekidneydysfunctionandcardiovasculardiseaseobservationalandmendelianrandomizationanalyses |