[Hyperhomocysteinemia, a cardiovascular risk factor.]

The rare syndrome of homocystinuria is characterized by very high plasma concentration of the amino acid homocysteine. Homocystinuric patients are at greatly increased risk of atherosclerotic complications independent of the underlying cause of the syndrome. Based on these observations, the homocysteine theory of atherosclerosis was formulated 20 years ago proposing that homocysteine as such was responsible for the vascular damage. It was also proposed that the mild hyperhomocysteinemia, commonly found in the general population, constituted a cardiovascular risk factor. The homocysteine theory of atherosclerosis is supported by the results of a few large prospective investigations and many small retrospective studies which showed significantly higher plasma homocysteine concentrations in patients suffering from atherosclerotic complications than in controls. Moreover, according to multiple regression analyses of these study results, the risk associated with hyperhomocysteinemia is independent of other cardiovascular risk factors. The mechanism is unclear but clinical studies and animal experiments indicate that homocysteine induces endothelial damage and influences blood coagulation. Treatment with folic acid effectively lowers plasma homocysteine concentration. To date, it is not known whether such treatment lowers the incidence of atherosclerotic complications.