Hyperhomocysteinemia as a Risk Factor for Deep-Vein Thrombosis
Martin den Heijer, M.D., Ted Koster, M.D., Henk J. Blom, Ph.D., Gerard M.J. Bos, M.D., Ernest Briët, M.D., Pieter H. Reitsma, Ph.D., Jan P. Vandenbroucke, M.D., and Frits R. Rosendaal, M.D.
Background Previous studies have suggested that hyperhomocysteinemiamay be a risk factor for venous thrombosis. To assess the riskof venous thrombosis associated with hyperhomocysteinemia, westudied plasma homocysteine levels in patients with a firstepisode of deep-vein thrombosis and in normal control subjects.
Methods We measured plasma homocysteine levels in 269 patientswith a first, objectively diagnosed episode of deep-vein thrombosisand in 269 healthy controls matched to the patients accordingto age and sex. Hyperhomocysteinemia was defined as a plasmahomocysteine level above the 95th percentile in the controlgroup (18.5 µmol per liter).
Results Of the 269 patients, 28 (10 percent) had plasma homocysteinelevels above the 95th percentile for the controls, as comparedwith 13 of the controls (matched odds ratio, 2.5; 95 percentconfidence interval, 1.2 to 5.2). The association between elevatedhomocysteine levels and venous thrombosis was stronger amongwomen than among men and increased with age. The exclusion ofsubjects with other established risk factors for thrombosis(e.g., a deficiency of protein C, protein S, or antithrombin;resistance to activated protein C; pregnancy or recent childbirth;or oral-contraceptive use) did not materially affect the riskestimates.
Conclusions High plasma homocysteine levels are a risk factorfor deep-vein thrombosis in the general population.
Source Information
From the Department of Hematology, Municipal Hospital Leyenburg, The Hague (M.H., G.M.J.B.); the Departments of Clinical Epidemiology (T.K., J.P.V., F.R.R.) and Hematology (E.B., P.H.R., F.R.R.), University Hospital, Leiden; and the Laboratory of Pediatrics and Neurology, Department of Pediatrics, University Hospital, Nijmegen (H.J.B.) all in the Netherlands.
Address reprint requests to Dr. den Heijer at the Department of Hematology, Municipal Hospital Leyenburg, P.O. Box 40551, 2504 LN The Hague, the Netherlands.
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