Causal Association of Chronic Venous Insufficiency and Cardiovascular Diseases: A Univariable and Multivariable Mendelian Randomization Study

Background: The causal relationship between chronic venous insufficiency (CVI) and cardiovascular diseases (CVDs) has yet to be elucidated. Herein, we implement Mendelian randomization (MR) analysis to investigate the causal association. Methods: A two-sample MR approach using genetic data from FinnGen and genome-wide association studies (GWAS) Catalog was applied to investigate the causal relationship between CVI and CVDs. This study assessed 77 single nucleotide polymorphisms (SNPs) as instrumental variables, employing random-effect inverse-variance-weighted MR, weighted median, Egger regression, Mendelian Randomization Pleiotropy RESidual Sum and Outlier (MR-PRESSO), and Robust Adjusted Profile Score (RAPS) methods. Multivariable MR (MVMR) considered confounding factors. Results: Genetically predicted CVI was associated with reduced heart failure risk (odds ratio (OR) = 0.96, 95% confidence interval (95% CI): 0.93–0.99, p = 0.025) and increased atrial fibrillation risk (OR = 1.06, 95% CI: 1.03–1.09, p = 0.0002). MVMR, adjusting for venous thromboembolism (VTE), lower limb ulceration, obesity, smoking, and alcohol, attenuated these associations. No significant links were found with hypertension, aortic aneurysm, coronary artery disease, myocardial infarction, valvular heart disease, or stroke. Conclusions: This MR study supports an association between CVI and CVDs, which may imply CVI should be monitored during the treatment of heart failure and atrial fibrillation.