[Homocysteine and cardiovascular risk]

Abstract

Homocysteine is an amino acid that plays a key role in methionine- and homocysteine metabolism. Homocystinuria has been described about four decades ago to be an inherited (autosomal recessive) disorder with rapid progressive atherosclerosis. Thus, homocysteine has been investigated intensively with respect to vascular wall injury and atherogenesis. Folic acid and vitamin B12 are cofactors of methioninsynthase, a key enzyme in homocysteine metabolism. Plasma levels of homocysteine are higher in patients with coronary artery disease documented by coronary angiography than in individuals with normal coronary arteries. Supplementation of folic acid is the treatment of choice to lower plasma homocysteine concentrations. Improvement in endothelial function could be documented in patients with folic acid supplementation. Large scaled clinical trials investigating folic acid supplementation in secondary prevention are now in progress. Today, homocysteine and its association with atherosclerosis raise a lot of questions to be answered. A distinct pathophysiological model linking hyperhomocysteinaemia and atherosclerosis is still not available. The presence of hyperhomocysteinemia in atherosclerotic vascular disease as a surrogate with no pathophysiological relevance itself cannot be ruled out. Routine testing of homocysteine levels is not yet recommended. Treatment of patients with folic acid or vitamin B for primary and secondary prevention of atherosclerotic vascular disease cannot be recommended today, because large scaled intervention trials on homocysteine lowering by vitamin B or folic acid are not available yet. Possible effects of these interventions on acute vascular events are not known.