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Endothelial dysfunction in patients with spontaneous venous thromboembolism

From the Division of Internal and Cardiovascular Medicine, Department of Internal Medicine, University of Perugia (RM, CB, MCV, GG, EF, GA, PG); Department of Medical and Surgical Sciences, 2nd Chair of Internal Medicine, University of Padua (RP, FDV, PP); Department of Medicine and Aging, Drug Sciences, University of Chieti, Italy (GD, GC)

Correspondence: Paolo Gresele, M.D., Ph. D., Department of Internal Medicine, Division of Internal and Cardiovascular Medicine, University of Perugia, Via E. Dal Pozzo, 06126 Perugia, Italy. E-mail: grespa{at}unipg.it

Background and Objectives: A high incidence of atherosclerotic lesions and cardiovascular events has been reported in patients with spontaneous venous thromboembolism. Endothelial dysfunction is an early marker of atherosclerosis and has predictive value for ischemic events. We have evaluated endothelial function in patients with a history of spontaneous venous thromboembolism.

Design and Methods: Patients with a history of symptomatic, objectively confirmed, spontaneous venous thromboembolism were included in a case-control study. Exclusion criteria were any known risk factors for cardiovascular diseases, other conditions associated with endothelial dysfunction, estro-progestinic therapy or pregnancy. Controls were age-(±5 years) and sex-matched subjects with the same exclusion criteria but without previous venous thromboembolism. Endothelial function was evaluated by the non-invasive measurement of flow-mediated vasodilation of the brachial artery and of plasma markers of endothelium activation; platelet activation parameters were also measured.

Results: Twenty-eight cases (8 females; mean age 59±15 years) and 28 controls (8 females; mean age 58±15) were studied. Flow-mediated vasodilation was 3.5±0.6% in cases (95% CIs: 2.2 to 4.8) and 5.7±0.6% (4.2 to 6.8) in controls (p=0.015). Brachial artery blood flow and hyperemic blood flow did not differ between the two groups. Plasma von Willebrand factor and soluble P-selectin levels were significantly higher in patients with venous thromboembolism, while plasma soluble CD40 ligand and urinary 11-dehydro-TxB₂ levels were similar in cases and controls.

Interpretation and Conclusions: Patients with spontaneous venous thromboembolism have endothelial dysfunction, unlike age- and sex- matched controls. This finding suggests that spontaneous venous thromboembolism may be a condition associated with an enhanced risk of atherosclerosis.

Key words: atherosclerosis, endothelium, thrombosis.