Hyperhomocysteinemia is not a risk factor for venous and arterial thrombosis, and is associated with elevated factor VIII levels

摘要

As prospective trials failed to establish a reduced risk of venous and arterial thrombosis in hyperhomocysteinemic subjects after supplementation with B-vitamins, we hypothesized that an associated condition, rather than hyperhomocysteinemia itself, is the thrombotic culprit. We assessed the contribution of elevated factor VIII levels to the risk of thrombosis in hyperhomocysteinemia in a retrospective family-cohort study. Relatives of consecutive probands, who had venous thrombosis or premature atherosclerosis, and hyperhomocysteinemia, elevated factor VIII levels, or both, were enrolled. 1052 relatives were analyzed. Hyperhomocysteinemic relatives had more often elevated factor VIII levels than normohomocysteinemic relatives (38% versus 28%, P =0.024). Other thrombophilic defects were equally divided. Hypertension and smoking were more often found in hyperhomocysteinemic relatives than in normohomocysteinemic relatives (28% versus 48%; P = 0.027, and 19% versus 38%; P = 0.029). After adjusting for these confounders, the relative risk of venous thrombosis in hyperhomocysteinemic relatives was 0.8 (95% confidence interval [CI] 0.3-1.7) and 0.9 (95% CI, 0.5-1.6) for arterial thrombosis. The absolute risk of venous thrombosis in hyperhomocysteinemia was 0.14% (95% CI, 0.06-0.30) and 0.31% (95% CI, 0.18-0.52) for arterial thrombosis. Hyperhomocysteinemia had no effect on the risk of venous thrombosis or arterial thrombosis in relatives with elevated factor VIII levels; relative risks 1.0 (95% CI, 0.4-2.3) and 1.1 (95% CI, 0.5-2.5), respectively. We conclude that hyperhomocysteinemia is not a risk factor for venous and arterial thrombosis, and is associated with elevated factor VIII levels. ? 2008 Elsevier Ltd. All rights reserved.