Homocysteine and markers of coagulation and endothelial cell activation

Abstract

Objective: In vitro studies suggest an influence of hyperhomocysteinemia on the coagulation system, but the influence of mild hyperhomocysteinemia in vivo is unclear. Methods and results: We studied the relation between homocysteine and markers of coagulation activation and endothelial cell activation in 279 patients with established atherosclerotic disease. In addition, we perfortned an investigator-blinded placebo-controlled cross-over study to investigate the influence of acute hyperhomocysteinemia by oral methionine load on these markers in 20 healthy volunteers. In the atherosclerotic patients prothrombin fragment F1 + 2 and soluble thrombomodulin (sTM) were associated with homocysteine in univariate analyses (P = 0.003 and P = 0.001, respectively), but not in multivariate analyses. Age, creatinine and MTHFR C677T polymorphism were major determinants of homocysteine concentration. MTHFR C677T polymorphism status was not associated with F1 + 2 and sTM. Median homocysteine concentrations increased in the healthy volunteers after methione load. However, after methionine load or after placebo, we did not observe different plasma concentrations of F1 + 2 (0.9 nmol L-1 vs. 0.9 nmol L-1, P = 0.39), d-dimer (153 μg L-1 vs. 151 μg L-1, P = 0.63) and von Willebrand factor (103% vs. 107%, P = 1.00). Conclusion: These results provide evidence against a major effect of mild hyperhomocysteinemia on activation of the coagulation system and endothelial cell activation in vivo. © 2004 International Society on Thrombosis and Haemostasis.