Risk of Venous Thromboembolism in Patients with Presumed Primary Raynaud's Syndrome: A Propensity-Matched Study Using the TriNetX Database.

Background: Raynaud's syndrome (RS) is traditionally considered a benign vasospastic disorder; however, emerging evidence suggests that it may reflect systemic vascular dysfunction and a prothrombotic state. Emerging epidemiological evidence suggests an association between RP and VTE, but further validation across different populations and analytical approaches is needed. Methods: We conducted a retrospective cohort study with the TriNetX global electronic health record database. Adult patients diagnosed with RS between 2015 and 2024 were identified and matched 1:1 with individuals without RS by using propensity score matching, adjusting for demographics, comorbidities, medical utilization, and laboratory parameters. Patients with autoimmune diseases, malignancy, thrombophilia, vascular disease, pregnancy, or anticoagulant and hormonal contraceptive use were excluded to minimize confounding. The primary outcome was incident VTE, including deep vein thrombosis (DVT) and pulmonary embolism (PE), assessed with Cox proportional hazards models. Results: After matching, 93,263 patients were included in each group. During follow-up, VTE occurred in 1,407 patients in the RS group and 1,179 patients in the non-RS group. RS was associated with a significantly increased risk of VTE (hazard ratio [HR] 1.33; 95% confidence interval [CI] 1.24-1.44). Increased risks were observed for both DVT (HR: 1.30; 95% CI: 1.18-1.43) and PE (HR: 1.38; 95% CI: 1.24-1.54). Subgroup analyses showed a more pronounced association in younger individuals and consistent effects across sexes. Conclusions: RS is associated with an increased risk of venous thromboembolism independent of major confounding conditions.