Homocyst(e)ine, endothelial dysfunction and cardiovascular risk. Pathomechanisms and therapeutical options

Elevated homocyst(e)ine plasma concentrations are an independent risk facto r for cardiovascular disease. Hyperhomocyst(e)inaemia is common in patients with peripheral arterial occlusive disease, coronary heart disease, cerebr ovascular disease, carotid artery stenosis and venous thromboembolism. Endo thelial dysfunction may be one underlying cause leading to proatherogenic e ffects associated with hyperhomocyst(e) inaemia. However, the mechanisms wh ich lead to impaired endothelial function in hyperhomocyst(e)inaemia are no t fully understood. Recent evidence suggests that homocyst(e)ine may intera ct with physiological mediators of the endothelial matrix. Oxidative mechan isms and decreased biological activity of endothelium-derived nitric oxide (NO) may also contribute to homocyst(e)ine-associated endothelial dysfuncti on. B vitamins are essential cofactors in the metabolism of homocyst(e)ine to methionine via the remethylation-pathway (vitamin B12, folic acid) and t o cystathionine via the transsulphuration-pathway (vitamin B6). Dietary def iciencies of folic acid, vitamin B12, and vitamin B6 appear to be common am ong elderly people in the western world and represent one pathogenic factor related to the incidence of hyperhomocyst(e)inaemia. Several studies have demonstrated that dietary supplementation with folic acid and the vitamins B12 and B6 is an efficient means to decrease plasma homocyst(e)ine. No clin ical studies are available to date to prove whether reducing homocyst(e)ine levels to the normal range by supplementary B vitamins will also beneficia lly affect vascular function or cardiovascular risk. Furthermore it is unkn own whether moderately elevated homocyst(e)ine concentrations per se may pr edispose to development of vascular disease, or whether homocyst(e)ine is a n indirect marker of cardiovascular disease. Further investigations will be necessary to elucidate the causal relationship between elevated homocyst(e )ine plasma concentrations and the incidence of cardiovascular events, espe cially since the therapeutic strategies in hyperhomocyst(e)inaemia would di ffer depending on the underlying pathophysiological mechanisms.