Genetic susceptibility to uric acid and selected cardiovascular outcomes: a systematic review and meta-analysis of Mendelian randomization studies
In brief
Higher genetically predicted urate raises heart attack risk by 13%
A meta-analysis of Mendelian randomization studies found that each 1.5 mg/dL increase in genetically predicted serum urate was linked to a 13% higher odds of myocardial infarction and a 17% higher odds of coronary artery disease. The associations persisted after multiple sensitivity checks, but evidence for other cardiovascular outcomes was weaker, leaving the benefit of urate-lowering drugs uncertain.
- Journal
- Frontiers in endocrinology (Q1)
- Published
- 24 July 2026
- Study design
- Systematic review of cohort studies
- Evidence level
- Level 2, Moderate (CEBM 2a)
- Authors
- Chunping Li, Ping Chen, Fangda Zheng
- PMID
- 42568465
- DOI
- 10.3389/fendo.2026.1880061
Why clinicians should know about it
- Picked for Rheumatology (top studies of the week, 9 August 2026).
Abstract
BACKGROUND: Serum urate has been associated with cardiovascular disease in observational studies, but whether genetically predicted higher serum urate levels contribute to specific cardiovascular outcomes remains uncertain. We conducted a systematic review and meta-analysis of Mendelian randomization (MR) studies evaluating serum urate-, hyperuricemia-, or gout-related genetic susceptibility in relation to selected cardiovascular outcomes. METHODS: PubMed, Embase, and Web of Science were searched from inception to April 6, 2026. Eligible studies were one-sample or two-sample MR studies assessing relevant urate-related exposures and cardiovascular outcomes. Reporting completeness, overlapping or duplicate estimates, exposure-outcome GWAS sample overlap, and MR-specific risk of bias were assessed before quantitative synthesis. Effect estimates were harmonized and standardized to a 1.5 mg/dL increase in serum urate where applicable. Random-effects inverse-variance meta-analyses, Egger regression tests, leave-one-out analyses, Hartung-Knapp adjusted analyses, and stepwise GWAS-source-restricted sensitivity analyses were performed where applicable. RESULTS: Thirty-two MR studies reporting 105 MR analyses were included. After estimate-level screening and MR-specific risk-of-bias assessment, 26 MR estimates were retained for quantitative synthesis. In primary analyses, genetically predicted higher serum urate was associated with increased risks of coronary heart disease (OR = 1.13, 95% CI: 1.10-1.15), myocardial infarction (OR = 1.13, 95% CI: 1.08-1.17), coronary artery disease (OR = 1.17, 95% CI: 1.08-1.26), atrial fibrillation (OR = 1.07, 95% CI: 1.02-1.12), and heart failure based on IVW estimates (OR = 1.08, 95% CI: 1.05-1.11). However, the atrial fibrillation association did not remain statistically significant after Hartung-Knapp adjustment and was reduced to a single estimate after GWAS-source restriction. In GWAS-source-restricted sensitivity analyses, only myocardial infarction and coronary artery disease retained at least three estimates and remained positively associated with serum urate. CONCLUSION: Evidence was most consistent for myocardial infarction and coronary artery disease. Findings for coronary heart disease, atrial fibrillation, and heart failure were more limited after stricter source restriction. These results do not establish a broad causal effect on cardiovascular disease as a whole or direct cardiovascular benefit from urate-lowering therapy. SYSTEMATIC REVIEW REGISTRATION: https://www.crd.york.ac.uk/PROSPERO/, identifier CRD420261380161.
Abstract as published, via PubMed.
For healthcare professionals. The summary is generated by AI from the published abstract, and the evidence level is assigned automatically from the study design on the Oxford CEBM hierarchy. Neither is medical advice. Read the full paper before changing practice.