Hyperhomocysteinemia and thrombosis.
Homocysteine (Hcy) is a sulfhydryl amino acid derived from the metabolic conversion of methionine, which is dependent on vitamins (folic acid, B12, and B6) as cofactors or cosubstrates. In 1969, McCully first reported the presence of severe atherosclerotic lesions in patients with severe hyperhomocysteinemia and hypothesized the existence of a pathogenic link between hyperhomocysteinemia and atherogenesis. Several case-control and cross-sectional studies were consistent with the initial hypothesis of McCully, showing that moderate hyperhomocysteinemia is also associated with heightened risk of occlusive arterial disease. Less consistent results have been reported by prospective cohort studies of subjects who were healthy at the time of their enrollment, whereas prospective cohort studies of patients with overt coronary artery disease or other conditions at risk consistently confirmed the association between moderate hyperhomocysteinemia and cardiovascular morbidity and mortality. More recently, an association between moderate hyperhomocysteinemia and heightened risk of venous thromboembolism has been documented, suggesting that hyperhomocysteinemia might be involved not only in atherogenesis, but also in thrombogenesis. The mechanisms by which hyperhomocysteinemia might contribute to atherogenesis and thrombogenesis are incompletely understood. The mainstay of treatment of hyperhomocysteinemia is folic acid, alone or in combination with vitamin B12 and vitamin B6. Although it is quite clear that vitamins effectively reduce the plasma levels of total homocysteine (tHcy), we do not yet know whether they will decrease the risk of vascular disease. The results of ongoing randomized, placebo-controlled, double-blind trials of the effects of vitamins on the thrombotic risk will help in defining whether the relationship between hyperhomocysteinemia and thrombosis is causal, and will potentially have a dramatic effect in the prevention of thromboembolic events.
Cattaneo
M
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Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Department of Internal Medicine, IRCCS Ospedale Maggiore, University of Milano, Italy. marco.cattaneo@unimi.it
D000818:Animals; D001161:Arteriosclerosis / Q000150:complications; D016022:Case-Control Studies; D003430:Cross-Sectional Studies; D006710:Homocysteine / Q000097:blood; D006801:Humans; D020138:Hyperhomocysteinemia / Q000150:complications* / Q000175:diagnosis / Q000235:genetics / Q000628:therapy; D012307:Risk Factors; D013927:Thrombosis / Q000150:complications*; D020246:Venous Thrombosis / Q000150:complications
D006710:Homocysteine