Hyperhomocyst(e)inemia and the increased risk of venous thromboembolism - More evidence from a case-control study

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 thromboembo lism, using a retrospective case-control study design. Methods: Cases were individuals with objectively confirmed venous thromboem bolism and no history of atherosclerosis seen at the Toronto Hospital Throm bosis 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 under went assessment for fasting plasma homocyst(e)ine levels. Hyperhomocyst(e)i nemia 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 wome n were equally represented, and most were younger than 60 years. Among case s with venous thromboembolism, the mean (+/- SD) plasma homocyst(e)ine leve l was significantly higher than in controls (13.0 +/- 6.9 mu mol/L vs 9.0 /- 4.8 mu mol/L, respectively; P<.001). Sixteen (23%) of 70 cases had hyper homocyst(e)inemia compared with 10 (5%) of 210 controls (odds ratio, 5.9; 9 5% confidence interval [CI],2.5-13.8). Among subjects aged 60 years or youn ger, the odds ratio was 4.9 (95% CI, 1.4-16.4),while for those aged 60 year s 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 B-12 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 c linic. 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.