Patients with atherosclerotic vascular disease: how low should plasma homocyst(e)ine levels go?
Plasma homocyst(e)ine level is a strong independent risk factor for vascular disease. The spelling of homocyst(e)ine reflects that what is measured, and what constitutes the risk factor; it includes homocysteine, homocystine (the dimer of homocysteine) and mixed cysteine-homocysteine disulfide. Homocyst(e)ine levels above 10.2 micro mol/L are associated with a doubling of coronary risk, and levels above 20 micro mol/L are associated with a 9.9-fold increase in risk compared with levels below 9 micro mol/L. The mechanisms by which homocyst(e)ine promotes vascular disease include increased thrombosis, consumption of nitric oxide, endothelial injury, and reduced thrombolysis. Homocyst(e)ine is an independent predictor of carotid atherosclerosis. Vitamin therapy with folate, pyridoxine (vitamin B(6)), and cyanocobalamin (vitamin B(12)) reduces blood levels of homocyst(e)ine, improves endothelial function, reduces levels of fibrinogen and lipoprotein(a), improves thrombolysis, and in uncontrolled clinical observation, leads to regression of carotid plaque. These lines of evidence support a causal relationship between homocyst(e)ine and atherosclerosis, and suggest that in patients with vascular disease, an appropriate target level for therapy may be below 9 or 10 micro mol/L. Randomized controlled studies are under way to determine whether vitamin therapy is effective in secondary prevention of myocardial infarction and stroke.
Spence
J D
JD
Stroke Prevention and Atherosclerosis Research Centre, Siebens-Drake/Robarts Research Institute, London, Ontario, Canada. dspence@rri.on.ca
D001161:Arteriosclerosis / Q000097:blood* / Q000188:drug therapy / Q000517:prevention & control*; D002986:Clinical Trials as Topic; D004151:Dipeptides / Q000097:blood*; D005492:Folic Acid / Q000627:therapeutic use; D006710:Homocysteine / Q000097:blood*; D006711:Homocystine / Q000097:blood*; D006801:Humans; D011736:Pyridoxine / Q000627:therapeutic use; D012307:Risk Factors; D014805:Vitamin B 12 / Q000627:therapeutic use
D004151:Dipeptides; D006710:Homocysteine; D006711:Homocystine; C022802:cysteinylhomocysteine mixed disulfide; D005492:Folic Acid; D011736:Pyridoxine; D014805:Vitamin B 12