Causal relationship between serum uric acid and cardiovascular disease: a Mendelian randomization study

Abstract

Observational studies have established an association between serum uric acid and cardiovascular disease (CVD). However, these studies are susceptible to uncontrolled confounders and reverse causality bias, leading to ambiguity in the causal relationship. To overcome these challenges, our study employed a two-sample Mendelian randomization approach to investigate the causal link between serum uric acid and CVD. The data on serum uric acid and seven cardiovascular diseases are sourced from the IEU Open GWAS database. Mendelian randomization (MR) analyses employed inverse variance weighting (IVW), MR-Egger, weighted median, and weighted model methods. Sensitivity analyses, including Cochrane's Q test, MR-Egger intercept, MR-PRESSO, and the leave-one-out approach, were conducted to assess result reliability. IVW analysis revealed that a genetic predisposition to elevated serum uric acid levels significantly increases the risk of CVD, with higher odds ratios (ORs) observed for CAD (OR: 1.227; 95% CI: 1.107-1.360, P=0.0002), hypertension (OR: 1.318, 95%CI: 1.184-1.466, P=2.13E-06), MI (OR: 1.184, 95%CI: 1.108-1.266, P=2.13E-06), HF (OR: 1.158, 95%CI: 1.066–1.258, P=2.13E-06), AF (OR: 1.298, 95%CI: 1.125-1.497, P=0.0005), angina (OR: 1.150, 95%CI: 1.074-1.231, P=0.0002) and CHD (OR: 1.170, 95%CI: 1.072-1.276, P=0.0005). Sensitivity analyses detected no pleiotropy and heterogeneity (P>0.05). This Mendelian randomization study robustly demonstrates a significant causal relationship between genetically elevated serum uric acid and various cardiovascular diseases, suggesting that higher levels may enhance the risk of cardiovascular events. Consequently, patients with elevated uric acid levels warrant early and aggressive interventions to mitigate cardiovascular risks.