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  Vol. 160 No. 7, April 10, 2000 TABLE OF CONTENTS
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Hyperhomocyst(e)inemia and the Increased Risk of Venous Thromboembolism

More Evidence From a Case-Control Study

Loralie J. Langman, PhD; Joel G. Ray, MD, FRCPC; Jovan Evrovski, PhD; Erik Yeo, MD, FRCPC; David E.C. Cole, MD, FRCPC

Arch Intern Med. 2000;160:961-964.

Background  Elevation of plasma homocyst(e)ine level is an independent risk factor for arterial and venous thrombosis. We studied the degree to which hyperhomocyst(e)inemia contributes to the development of venous thromboembolism, using a retrospective case-control study design.

Methods  Cases were individuals with objectively confirmed venous thromboembolism and no history of atherosclerosis seen at the Toronto Hospital Thrombosis Clinic, Toronto, Ontario, between January 1, 1996, and July 31, 1998. Three controls were matched for every case according to sex and age within 5 years and were derived from a large community cohort. All subjects underwent assessment for fasting plasma homocyst(e)ine levels. Hyperhomocyst(e)inemia was defined as a fasting total homocyst(e)ine concentration above the 95th percentile control value.

Results  Seventy cases and 210 matched controls were included. Men and women were equally represented, and most were younger than 60 years. Among cases with venous thromboembolism, the mean (± SD) plasma homocyst(e)ine level was significantly higher than in controls (13.0 ± 6.9 µmol/L vs 9.0 ± 4.8 µmol/L, respectively; P<.001). Sixteen (23%) of 70 cases had hyperhomocyst(e)inemia compared with 10 (5%) of 210 controls (odds ratio, 5.9; 95% confidence interval [CI], 2.5-13.8). Among subjects aged 60 years or younger, the odds ratio was 4.9 (95% CI, 1.4-16.4), while for those aged 60 years or older, it was 7.3 (95% CI, 2.2-24.0). Even with the exclusion of cases showing abnormal renal function or low serum vitamin B12 or folate levels, the odds ratio remained significantly elevated at 3.3 (95% CI, 1.1-10.0).

Conclusions  We found that fasting hyperhomocyst(e)inemia is a significant risk factor for venous thromboembolic disease in patients at a thrombosis clinic. Given the magnitude of effect and consistency across these studies, it is likely that homocyst(e)ine plays a causative role in the development of venous thrombosis, and it should be considered in the workup for venous thromboembolism.


From the Departments of Medicine (Drs Langman, Ray, Yeo, and Cole), Laboratory Medicine and Pathobiology (Drs Langman, Evrovski, Yeo, and Cole), and Paediatrics (Genetics) (Dr Cole), University of Toronto, Toronto, Ontario; the Departments of Hematology (Dr Yeo) and Clinical Chemistry (Dr Cole), The Toronto Hospital, Toronto; and the Department of Clinical Epidemiology and Biostatistics (Dr Ray), McMaster University, Hamilton, Ontario.


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