Abstract / Summary
We aimed to gather and summarize evidence on the potential links between chronic venous disease (CVeD), cardiovascular events and mortality in adults. A systematic search of the PubMed database was conducted in accordance with PRISMA guidelines in October 2025. Observational studies or registries were eligible. Adults diagnosed with CVeD were compared with controls free of CVeD or varicose veins. Primary outcomes were cardiovascular events (angina, atrial fibrillation, chronic heart failure, coronary artery disease, deep vein thrombosis, stroke, myocardial infarction, peripheral artery disease, pulmonary embolism, transient ischaemic attack, composite of MACE) and all-cause mortality. Secondary outcomes focused on coronary artery and heart disease. Random-effects meta-analyses of time-to-event outcomes determined pooled hazard ratios (HRs) and 95% confidence intervals (CIs). The I 2 statistic assessed heterogeneity. Thirteen studies (6.4 million participants; 342,110 with CVeD) were included. Meta-analysis of nine studies (280,252 participants with CVeD) reported that CVeD was associated with a significantly increased risk of cardiovascular events (HR 1.5; 95% CI 1.1, 2.0; p = 0.006). Sensitivity analyses yielded consistent results. CVeD was also associated with an increased risk of all-cause mortality (five studies; 16,749 participants; HR 1.3; 95% CI 1.2, 1.6; p < 0.001) and of coronary artery and heart disease (six studies; 38,331 participants; HR 1.3; 95% CI 1.1, 1.6; p = 0.006). Heterogeneity was high ( I 2 71%–95%). Patients with CVeD appear to be at increased risk of cardiovascular events and all-cause mortality, particularly those with severe disease. Based on these data, the incremental value of including CVeD in cardiovascular risk assessments should be evaluated prospectively.