Risk factors for peripheral venous disease resemble those for venous thrombosis: the San Diego Population Study

Background: Clinically silent deep vein thrombosis (DVT) is common and may cause chronic venous disease that resembles post-thrombotic syndrome. Objective: We evaluated whether peripheral venous disease in a general population shares risk factors with DVT. Methods: In an established cohort of 2404 men and women, the San Diego Population Study, peripheral venous disease was evaluated using physical examination, symptom assessment and venous ultrasound. We performed a case-control study including 308 cases in four hierarchical groups by severity and 346 controls without venous abnormalities, frequency matched to cases by 10-year age group, race and gender. Cases and controls had no prior history of venous thrombosis. Hemostatic risk factors were measured in cases and controls. Results: Accounting for age, obesity and family history of leg ulcer, odds ratios (ORs) of venous disease for elevated factor VIII, von Willebrand factor (VWF), D-dimer and for factor V Leiden were 1.4 (95% CI 0.9-2.1), 1.5 (CI 1.0-2.3), 1.7 (CI 1.1-2.8) and 1.1 (CI 0.5-2.4), respectively. These associations were larger for the two most severe case groups; ORs 2.0 (CI 1.0-3.8), 1.7 (CI 0.9-3.3), 2.7 (CI 1.2-6.1) and 2.3 (CI 0.8-7.1). Each hemostatic factor was also associated with severity of venous disease, for example elevated D-dimer was associated with a 2.2-fold increased odds of being in one higher severity case group. Prothrombin 20210A was not associated with venous disease. Conclusions: DVT risk factors are associated with presence and severity of peripheral venous disease. Results support a hypothesis that peripheral venous disease may sometimes be post-thrombotic syndrome as a result of a previous unrecognized DVT.