Association between vitamin D deficiency and incident varicose veins: a propensity score-matched cohort study

Evidence linking vitamin D deficiency (VDD) to varicose veins remains limited and largely derived from small or cross-sectional studies. We examined whether VDD is associated with incident varicose veins in a large real-world cohort.

Using the TriNetX Global Collaborative Network, we conducted a retrospective propensity score-matched cohort study of adults aged ≥40 years with at least two serum 25-hydroxyvitamin D [25(OH)D] measurements between 2010 and 2023. VDD was defined as two measurements ≤19.9 ng/mL, and controls had two measurements ≥30.0 ng/mL. A 1-year landmark design was applied. The primary outcome was 5-year incident varicose veins of the lower extremities. Secondary outcomes included varicose veins with ulceration, inflammation, and other complications. Cox proportional hazards models were used to estimate hazard ratios (HRs) with 95% confidence intervals (CIs).

After matching, 257,651 patients were included in each cohort. VDD was associated with a higher risk of incident varicose veins (HR 1.62, 95% CI 1.50-1.75; p < 0.001). Increased risks were also observed for varicose veins with ulceration (HR 2.22), inflammation (HR 2.71), and complications (HR 1.45) (all p < 0.001). Findings were consistent across sensitivity and subgroup analyses. Vitamin D insufficiency (20.0-29.9 ng/mL) was also associated with increased risk (HR 1.56, p < 0.001).

VDD was associated with an increased risk of incident varicose veins in this large cohort. This association was also observed among older adults and individuals with diabetes, suggesting potential effect modification by age and diabetic status. These findings suggest that reduced vitamin D status may be relevant to venous disease risk, although causality cannot be inferred. Further prospective studies are needed to determine whether correction of VDD can modify this risk.