Increased risk of deep vein thrombosis, pulmonary embolism, and all-cause mortality in chronic venous disorder: a large-scale retrospective cohort study

Eva Lotta Moderegger¹Sören Dräger^1,2Sophie Lena Preuss¹Artem Vorobyev¹Patrick Terheyden¹Khalaf Kridin³Katja Bieber²Ralf J Ludwig²Birgit Kahle¹Philip Curman^4,5*

• ¹Universitatsklinikum Schleswig-Holstein Campus Lubeck, Lübeck, Germany
• ²Universitat zu Lubeck Institut fur Experimentelle Dermatologie, Lübeck, Germany
• ³Bar-Ilan University, Ramat Gan, Israel
• ⁴Karolinska Institutet (KI), Solna, Sweden
• ⁵Karolinska Universitetssjukhuset, Stockholm, Sweden

Background: Chronic venous disorder (CVD), often overlooked as a significant medical burden, has recently been linked to severe health risks, especially deep vein thrombosis (DVT), and pulmonary embolism (PE). However, large-scale data are lacking. Specifically, the impact of CVD severity on the risk of thromboembolic events and the impact of procedural interventions on these risks are unknown. Methods: A retrospective cohort study of mortality and serious adverse events was conducted using electronic health records derived from the TriNetX database. Propensity-score matching and sensitivity analyses were performed to mitigate bias. Results: We included 463,313 patients with CVD. An increased risk of superficial vein thrombosis (SVT) (hazard ratio [HR], 19.0, 95% confidence interval [CI] 17.1-21.0, p<0.0001), DVT (3.3, 3.2-3.6), PE (2.1, 2-2.1), and mortality (1.8, 1.8-1.8) were observed. These results persisted in two sensitivity analyses. When stratifying CVD for disease severity into chronic venous disease and -insufficiency, elevated risks of thromboembolic events and all-cause mortality were observed in both groups. Comparing CVD patients with interventions to those without, the risk of DVT (0.9, 0.8-0.9), PE (0.6, 0.5-0.6) and all-cause mortality (0.5, 0.5-0.5) decreased. Conversely, the risk of SVT increased (1.8, 1.6-2.0). Discussion: Independently of disease severity, CVD entails an increased risk for venous thromboembolic events and all-cause mortality. In CVD patients, procedural interventions are associated with reduced risks for DVT, PE and all-cause mortality. Confirmation of these potentially clinically relevant findings necessitates prospective randomized trials.