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

Abstract

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.

Keywords: TriNetX; chronic venous disease; chronic venous disorder; chronic venous insufficiency; mortality; pulmonary embolism; thrombosis; varicose veins.

Figure 1

Study flow chart. CVD, chronic venous disorder; CVDis, chronic venous disease; CVI, chronic venous insufficiency; ICD-10CM, international classification of diseases, 10^th edition, clinical modification.

Figure 2

Outcomes for the chronic venous disorder (CVD) cohort, as well as chronic venous disease (CVDis) and chronic venous insufficiency (CVI) from 1 day to any time after index (a) and the same cohorts but excluding all interventions (b). Results for the first 3 months after index are shown in the subfigure (c).

Figure 3

Nelson-Aalen plots (a–c) of the study outcomes and Kaplan-Meier plot (d) of the endpoint all-cause mortality in interventional chronic venous disorder (blue line) and non-interventional chronic venous disorder (orange line). All results are significant (p-value < 0.0001). CVD, chronic venous disorder.