期刊
CIRCULATION
卷 146, 期 20, 页码 1507-1517出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1161/CIRCULATIONAHA.122.060700
关键词
cardiovascular diseases; coronary disease; kidney diseases; stroke
资金
- British Heart Foundation (BHF) [SP/09/002, RG/13/13/30194, RG/18/13/33946]
- BHF Centre of Research Excellence [RE/18/1/34212]
- UK Medical Research Council [MR/L003120/1]
- National Institute for Health and Care Research (NIHR) Cambridge Biomedical Research Centre - UK NIHR [BRC-1215-20014]
- British United Provident Association UK Foundation
- GlaxoSmithKline
- Health Data Research UK - UK Medical Research Council
- Engineering and Physical Sciences Research Council
- Economic and Social Research Council
- Department of Health and Social Care (England)
- Chief Scientist Office of the Scottish Government Health and Social Care Directorates
- Health and Social Care Research and Development Division (Welsh Government)
- Public Health Agency (Northern Ireland)
- BHF
- Wellcome Trust
- European Research Council [268834]
- European Commission Framework Programme 7 [HEALTH-F2-2012-279233]
- International Agency for Research on Cancer (IARC)
- Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London
- Danish Cancer Society (Denmark)
- Ligue Contre le Cancer (France)
- Institut Gustave Roussy, Mutuelle Generale de l'Education Nationale (France)
- Institut National de la Sante et de la Recherche Medicale (INSERM) (France)
- German Cancer Aid, German Cancer Research Center (DKFZ) (Germany)
- German Institute of Human Nutrition PotsdamRehbruecke (DIfE) (Germany)
- Federal Ministry of Education and Research (BMBF) (Germany)
- Associazione Italiana per la Ricerca sul Cancro-AIRC-Italy
- Compagnia di SanPaolo and National Research Council (Italy)
- Dutch Ministry of Public Health (The Netherlands)
- Welfare and Sports (VWS) (The Netherlands)
- Netherlands Cancer Registry (NKR) (The Netherlands)
- LK Research Funds (The Netherlands)
- Dutch Prevention Funds (The Netherlands)
- Dutch ZON (Zorg Onderzoek Nederland) (The Netherlands)
- World Cancer Research Fund (WCRF) (The Netherlands)
- Statistics Netherlands (The Netherlands)
- Health Research Fund (FIS) - Instituto de Salud Carlos III (ISCIII) (Spain)
- Regional Governments of Andalucia, Asturias, Basque Country, Murcia and Navarra (Spain)
- Catalan Institute of Oncology - ICO (Spain)
- Swedish Cancer Society (Sweden)
- Swedish Research Council (Sweden)
- County Councils of Skane and Vasterbotten (Sweden)
- Cancer Research UK [14136, C8221/A29017]
- Medical Research Council, United Kingdom [1000143, MR/M012190/1]
- EU Sixth Framework Programme (FP6) [LSHM_ CT_2006_037197]
- Medical Research Council Epidemiology Unit [MC_UU_12015/1, MC_UU_12015/5]
- Million Veteran Program, Office of Research and Development, and Veterans Health Administration [I01-BX004821, I01-BX003360, IK2-CX001780]
- VA Office of Research and Development [CX001780, CX001897, BX003362-01, R01DK122075]
- BHF Programme [RG/18/13/33946]
- BHF Chair [CH/12/2/29428]
- EU/EFPIA Innovative Medicines Initiative Joint Undertaking BigData@Heart [116074]
- NIHR BTRU in Donor Health and Genomics [NIHR BTRU-2014-10024]
- Munz Chair of Cardiovascular Prediction and Prevention
- NIHR Cambridge Biomedical Research Centre [BRC-1215-20014]
- UK Economic and Social Research 878 Council [ES/T013192/1]
- NIHR Senior Investigator Award
- Innovative Medicines Initiative-2 Joint Undertaking [116074]
- BHF-Turing Cardiovascular Data Science Award [BCDSA\100005]
The study results suggest that mild-to-moderate kidney dysfunction is causally related to the risk of coronary heart disease in people without manifest cardiovascular disease or diabetes.
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 personyears 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 (25917 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 eG FR values <60 or >105 mL.min(-1).1.73 m(-2), compared with those with eG FR 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 eG FR, but not for those with eG FR >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 Alc, 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.
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