Clinical usefulness of plasma homocysteine in vascular disease.

Raised plasma homocysteine (tHcy) concentrations are caused by genetic mutations, vitamin deficiencies, renal and other diseases, numerous drugs, and increasing age. Raised tHcy concentrations are associated with laboratory evidence of atherogenesis (eg, endothelial dysfunction) and thrombosis, and epidemiological evidence of an increased risk of atherothrombotic vascular disease. An association between raised tHcy concentration and an increased risk of atherothrombosis is independent of other vascular risk factors, strong, dose-related and biologically plausible, but has not been proven to be causal in randomised controlled trials. A recent trial identified no significant benefit from lowering tHcy concentration by folic-acid-based multivitamin therapy among 3680 patients with recent ischaemic stroke, but did not reliably exclude a modest but important reduction in the relative risk of stroke of up to 20%; a difference of only 2 mmol/L in tHcy concentration between the two treatment groups was probably due to widespread vitamin use and fortification of grains and staple foods with folate in North America. There is currently insufficient evidence to recommend routine screening and treatment of high tHcy concentrations with folic acid and other vitamins to prevent atherothrombotic vascular disease.