Hyperhomocysteinaemia: a newly recognized risk factor for vascular disease

In the past decade significant progress has been made in understanding of hyperhomocysteinaemia and its association with the proneness to premature development of vascular disease. Pooled data from a large number of studies demonstrate that mild hyperhomocysteinaemia after standardized methionine loading is present in 21% of patients with coronary artery disease, in 24% of patients with cerebrovascular disease, and in 32% of patients with peripheral vascular disease. A relative risk of 13.0 (95% confidence interval 5.9-28.1) of vascular disease at relatively young age can be calculated in subjects with such abnormal response to methionine loading. Pathological homocysteine levels are affected by genetic defects in homocysteine metabolism which have still not been completely clarified and which are more complex than originally supposed. Furthermore, a variety of non-genetic determinants such as deficiency of folate or vitamin B12 has to be taken into account. Mild hyperhomocysteinaemia can be reduced to normal in virtually all cases by simple and safe treatment with vitamin B6, folic acid, and betaine, each of which is involved in methionine metabolism. A clinically beneficial effect of such an intervention, which is currently under investigation, could make large-scale screening mandatory for this risk factor.