Mild-to-Moderate Kidney Dysfunction and Cardiovascular Disease: Observational and Mendelian Randomization Analyses.
Mild-to-Moderate Kidney Dysfunction and Cardiovascular Disease: Observational and Mendelian Randomization Analyses.
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DOI：
10.1161/circulationaha.122.060700
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发表时间：
2022-11-15
期刊：
影响因子：
37.8
通讯作者：
Di Angelantonio, Emanuele
中科院分区：
文献类型：
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作者：
Gaziano, Liam;Sun, Luanluan;Arnold, Matthew;Bell, Steven;Cho, Kelly;Kaptoge, Stephen K.;Song, Rebecca J.;Burgess, Stephen;Posner, Daniel C.;Mosconi, Katja;Cohen, Cassianne Robinson;Mason, Amy M.;Bolton, Thomas R.;Tao, Ran;Allara, Elias;Schubert, Petra;Chen, Lingyan;Staley, James R.;Staplin, Natalie;Altay, Servet;Amiano, Pilar;Arndt, Phar Volker;Arnlov, Johan;Barr, Elizabeth L. M.;Bjorkelund, 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;Engstrom, Gunnar;Freisling, Heinz;de la Camara, Agustin Gomez;Gudnason, Vilmundur;Hankey, Graeme J.;Hansson, PerOlof;Heath, Alicia K.;Hoorn, Ewout J.;Imano, Hironori;Jassal, Simerjot K.;Kaaks, Rudolf;Katzke, Verena;Kauhanen, Jussi;Kiechl, Stefan;Koenig, Wolfgang;Kronmal, Richard A.;Kyro, Cecilie;Lawlor, Deborah A.;Ljungberg, Borje;MacDonald, Conor;Masala, Giovanna;Meisinger, Christa;Melander, Olle;Iribas, Conchi Moreno;Ninomiya, Toshiharu;Nitsch, Dorothea;Nordestgaard, Borge G.;OnlandMoret, Charlotte;Palmieri, Luigi;Petrova, Dafina;Garcia, Jose Ramon Quiros;Rosengren, Annika;Sacerdote, Carlotta;Sakurai, Masaru;Santiuste, Carmen;Schulze, Matthias B.;Sieri, Sabina;Sundstrom, Johan;Tikhonoff, Valerie;Tjonneland, Anne;Tong, Tammy;Tumino, Rosario;Tzoulaki, Ioanna;van der Schouw, Yvonne T.;Verschuren, W. M. Monique;Volzke, Henry;Wallace, Robert B.;Wannamethee, S. Goya;Weiderpass, Elisabete;Willeit, Peter;Woodward, Mark;Yamagishi, Kazumasa;ZamoraRos, 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
终末期肾病与心血管事件的高风险相关。然而，尚不清楚轻中度肾功能不全是否与冠心病（CHD）和中风有因果关系。使用来自4个人群数据源的个体水平数据进行观察性分析（新兴风险因素协作，EPIC-CVD [欧洲癌症和营养-心血管疾病前瞻性研究]，百万退伍军人计划和英国生物银行），包括648 135名基线时无心血管疾病或糖尿病史的参与者，在680万人-年的随访中，分别产生了42858和15693例CHD和卒中事件。使用218种变异的遗传风险评分估计肾小球滤过率（eGFR），我们进行了孟德尔随机化分析，涉及EPIC-CVD，百万退伍军人计划和英国生物银行的413718名参与者（25917例CHD和8622例卒中）。基于肌酐的eGFR与CHD和卒中之间存在U形观察相关性，eGFR值<60 or >105 mL·min-1·1.73 m-2的参与者的风险高于eGFR值在60和105 mL·min-1·1.73 m-2之间的参与者。CHD的孟德尔随机化分析显示，eGFR <60 mL·min-1·1.73 m-2的参与者之间存在相关性，基因预测的eGFR每降低5 mL·min-1·1.73 m-2，CHD风险就增加14%（95% CI，3%-27%），但eGFR >105 mL·min-1·1.73 m-2的参与者则不存在相关性。在校正与eGFR遗传风险评分相关的因素（如脂蛋白（a）、甘油三酯、血红蛋白A1 c和血压）后，结果无实质性差异。中风的孟德尔随机化结果不显著，但与CHD的结果大致相似。在没有明显心血管疾病或糖尿病的人群中，轻度至中度肾功能不全与CHD风险存在因果关系，突出了保护和调节肾功能的预防方法的潜在价值。
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. 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. 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. 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.