N Engl J Med 1998; 338(15): 1042-1050
Welch,George; Loscalzo,Joseph
Since this review article does not contain an abstract, we provide you with the first paragraph
In 1969, McCully made the clinical observation linking elevated plasma homocyst(e)ine concentrations with vascular disease. He reported autopsy evidence of extensive arterial thrombosis andatherosclerosis in two children with elevated plasma homocyst(e)ine concentrations and homocystinuria.On the basis of this observation, he proposed that elevated plasma homocyst(e)ine (hyperhomocyst(e)inemia)can cause atherosclerotic vascular disease. The term “homocyst(e)ine” is used to define the combinedpool of homocysteine, homocystine, mixed disulfides involving homocysteine, and homocysteine thiolactone found in the plasma of patients with hyperhomocyst(e)inemia.
Subsequent investigations have confirmed Mc-Cully’s hypothesis, and it has recently become clear that hyperhomocyst(e)inemia is an independent risk factor for atherosclerosis and atherothrombosis. Althoughsevere hyperhomocyst(e)inemia is rare, mild hyperhomocyst(e)inemia occurs in approximately 5 to 7 percent of the general population.
Patients with mild hyperhomocyst(e)inemia have none of the clinical signs of severe hyperhomocyst(e)inemia or homocystinuria and are typically asymptomatic until the third or fourth decade of life when prematurecoronary artery disease develops, as well as recurrent arterial and venous thrombosis. Abundant epidemiologicevidence has demonstrated that the presence of mild hyperhomocyst(e)inemia is an independent riskfactor for atherosclerosis in the coronary, cerebral, and peripheral vasculature (see below).
Although the molecular mechanism by which homocyst(e)ine or a related metabolite promotes atherothrombosisis unknown, the epidemiologic evidence of the association of hyperhomocyst(e)inemia with atherothromboticvascular disease is convincing. In this review, we will evaluate the evidence of a relation betweenelevated plasma homocyst(e)ine concentrations and vascular disease. Potential mechanisms for this effectare also discussed.