Publication: Mild-to-Moderate Kidney Dysfunction and Cardiovascular Disease: Observational and Mendelian Randomization Analyses.
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Identifiers
Date
2022-08-18
Authors
Gaziano, Liam
Sun, Luanluan
Arnold, Matthew
Bell, Steven
Cho, Kelly
Kaptoge, Stephen K
Song, Rebecca J
Burgess, Stephen
Posner, Daniel C
Mosconi, Katja
Advisors
Journal Title
Journal ISSN
Volume Title
Publisher
Lippincott Williams & Wilkins
Abstract
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 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 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.
Description
MeSH Terms
Humans
Mendelian Randomization Analysis
Prospective Studies
Cardiovascular Diseases
Coronary Disease
Risk Factors
Diabetes Mellitus
Stroke
Kidney
Mendelian Randomization Analysis
Prospective Studies
Cardiovascular Diseases
Coronary Disease
Risk Factors
Diabetes Mellitus
Stroke
Kidney
DeCS Terms
Accidente cerebrovascular
Análisis de la aleatorización mendeliana
Diabetes Mellitus
Enfermedad coronaria
Enfermedades cardiovasculares
Estudios prospectivos
Factores de riesgo
Humanos
Riñón
Análisis de la aleatorización mendeliana
Diabetes Mellitus
Enfermedad coronaria
Enfermedades cardiovasculares
Estudios prospectivos
Factores de riesgo
Humanos
Riñón
CIE Terms
Keywords
cardiovascular diseases, coronary disease, kidney diseases, stroke
Citation
Gaziano L, Sun L, Arnold M, Bell S, Cho K, Kaptoge SK, et al. Mild-to-Moderate Kidney Dysfunction and Cardiovascular Disease: Observational and Mendelian Randomization Analyses. Circulation. 2022 Nov 15;146(20):1507-1517.