Hyperhomocysteinaemia and atherothrombosis.
Homocysteine (Hcy) is a sulfhydryl amino acid derived from the metabolic conversion of methionine that 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 hyperhomocysteinaemia and hypothesized the existence of a pathogenic link between hyperhomocysteinaemia and atherogenesis. Several case-control and cross-sectional studies confirmed the initial hypothesis of McCully, showing that also moderate hyperhomocysteinaemia is associated with a 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 risk conditions consistently confirmed the association between moderate hyperhomocysteinaemia and the risk of cardiovascular morbidity and mortality. More recently, an association between moderate hyperhomocysteinaemia and heightened risk of venous thromboembolism has been documented, suggesting that hyperhomocysteinaemia might be involved not only in atherogenesis, but also in thrombogenesis. The mechanisms by which hyperhomocysteinaemia might contribute to atherogenesis and thrombogenesis are incompletely understood. The mainstay of treatment of hyperhomocysteinaemia is folic acid, alone or in combination with vitamins B12 and B6. Although it is quite clear that vitamins effectively reduce the plasma levels of total Hcy, we do not yet know whether they will decrease the risk of vascular disease. The results of ongoing randomized, placebo-controlled, double-blinded trials on the effects of vitamins on thrombotic risk will help in defining whether the relationship between hyperhomocysteinaemia and thrombosis is causal, and will potentially have a dramatic impact on the prevention of thromboembolic events.
Cattaneo
M
M
Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Department of Internal Medicine, IRCCS Ospedale Maggiore, University of Milan, Italy. marco.cattaneo@unimi.it
D015984:Causality; D015897:Comorbidity; D003327:Coronary Disease / Q000503:physiopathology; D006710:Homocysteine / Q000097:blood; D006801:Humans; D020138:Hyperhomocysteinemia / Q000175:diagnosis / Q000453:epidemiology* / Q000503:physiopathology; D007676:Kidney Failure, Chronic / Q000503:physiopathology; D013927:Thrombosis / Q000453:epidemiology* / Q000503:physiopathology
D006710:Homocysteine