Hyperhomocysteinemia, atherosclerosis and thrombosis.

High plasma levels of homocysteine are the results of the interplay between congenital and environmental factors. In the last two decades, a growing amount of interest has focused on mild-to-moderate hyperhomocysteinemia as a risk factor of thromboembolic diseases. Case-control and cross-sectional studies clearly indicated that mild-to-moderate hyperhomocysteinemia is associated with heightened risk of both arterial and venous thrombosis. On the other hand, prospective studies did not unequivocally show that hyperhomocysteinemia is associated with a high thrombotic risk. Therefore, additional studies are needed to define whether hyperhomocysteinemia is a risk factor for thrombosis, especially of the venous circulation. Among these, prospective cohort studies will clarify better the temporal relationship between high homocysteine levels and the thrombotic event. Most importantly, however, randomized, placebo-controlled, double-blind trials of the effects of homocysteine-lowering vitamins on the thrombotic risk are urgently needed. Not only will they help in defining whether the relationship between hyperhomocysteinemia and thrombosis is causal, they will also have a potential dramatic impact in the prevention of thromboembolic events.