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

Abstract

Summary. 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.

Higher soluble P-selectin is associated with chronic venous insufficiency: The San Diego Population Study

“…This would be consistent with knowledge that P-selectin is involved in vein fibrosis after thrombosis [16]. In addition, prior studies have reported associations of other circulating proteins involved in thrombosis and inflammation with CVI or post-thrombotic syndrome [8, 21]. Our study expands the association of P-selectin with VTE to the complications following thrombotic events and to CVI in general.…”

“…PTS can also occur after asymptomatic DVT, thus explaining some fraction of CVI in the general population [7]. Prior research in our lab revealed an association between hemostatic factors and CVI including higher factor VIII, von Willebrand factor, and D-dimer, supporting this concept [8]. …”

Heart Disease and Stroke Statistics—2017 Update: A Report From the American Heart Association

“…31 Blood coagulation disorders and inflammatory biomarkers, which are risk factors for DVT, are also associated with an increased risk of CVI, consistent with the hypothesis that venous thrombosis predisposes to CVI. 7,32 …”

Body size measures, hemostatic and inflammatory markers and risk of venous thrombosis: The Longitudinal Investigation of Thromboembolism Etiology

“…Our prior report from the LITE study that persons with longer legs have higher risk of VT corroborates this hypothesis[29], as do the similar associations of fat-free mass and fat mass with VT seen here; this finding is also not surprising given the lack of mediation of obesity and VT risk by biomarkers related to adipose tissue that we observed. Obesity is also associated with venous insufficiency[30, 31], thus obesity may cause impaired venous return, which can lead to chronic venous insufficiency and/or DVT. One cross-sectional study reported higher levels of the adipokines resistin, leptin and tumor necrosis factor-alpha (TNF-alpha) with venous insufficiency, independent of BMI[32].…”