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

Abstract

Background

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. To overcome these challenges, we employed a two-sample Mendelian randomization (MR) approach to investigate the causal link between serum uric acid and CVD.

Methods

We utilized Genome-wide association study (GWAS) data for serum uric acid and six CVD: coronary artery disease (CAD), hypertension, myocardial infarction (MI), heart failure (HF), angina, and coronary heart disease (CHD). MR analyses employed inverse variance weighting (IVW), MR-Egger, weighted median, and weighted model. Sensitivity analyses were conducted to assess result reliability, including Cochrane’s Q test, MR-Egger intercept, MR-PRESSO, and the leave-one-out approach.

Results

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), 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 analysis research results have robustness.

Conclusion

This MR 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.