Impact of urinary sodium on cardiovascular disease and risk factors: A 2 sample Mendelian randomization study

Background: Although sodium increases the risk of coronary artery disease and hypertension, whether sodium also impacts other cardiovascular disease (CVD) and its risk factors is less clear. We examined the causal role of urinary sodium in these CVDs and risk factors using Mendelian randomization. Methods: We identified strong, independent single nucleotide polymorphisms (SNPs) of urinary sodium from the most up to date genome wide association studies (GWAS) (n = 446,237) and applied them to GWAS of stroke and its subtypes (40,585 cases and 406,111 non-cases), atrial fibrillation (60,620 cases and 970,216 non-cases) and heart failure (47,309 cases and 930,014 non-case). We assessed the impact of sodium on these diseases and associated risk factors using inverse variance weighting. Sensitivity analyses included weighted median, contamination mixture method, MR-PRESSO, and multivariable Mendelian randomization. Results: Higher log transformed urinary sodium was associated with higher risk of stroke (odds ratio (OR) 1.45, 95% confidence interval (CI) 1.01 to 2.08), ischemic stroke (OR 1.60 95% CI 1.12 to 2.30), heart failure (OR 1.77 95% CI 1.19 to 2.62), and type 2 diabetes (OR 4.17 95% CI 1.53 to 11.35). Sensitivity analyses produced directionally similar estimates. Conclusion: Higher sodium likely increases stroke, heart failure and type 2 diabetes risk. Our study further supports public health policies to minimize population sodium intake, so as to reduce the associated disease burden.