Moderately high levels of plasma homocyst(e)ine are associated with subsequent risk of MI independent of other coronary risk factors. Because high levels can often be easily treated with vitamin supplements, homocyst(e)ine may be an independent, modifiable risk factor.

A micromethod adapted for automated determinations was used to measure basal plasma levels of homocyst(e)ine [H(e)J. These levels included the sum of free and bound forms of homocysteine, its disulfide oxidation product, homocystine, and the homocysteine-cysteinemixed disulfide. Two groups of subjects were studied: apparently healthy individuals (n = 103) and patients with peripheral arterial occlusive disease (PAOD) (n= 47). Because age in PAOD patients was higher than in control subjects, the control subjects were subdivided into younger and older groups (aged 60 years or less and more than 60 years, respectively). The H(e) levels in the younger groups were 11.18±3.58 (mean+SD, expressed as homocysteine) and 8.58 +2.82 nmol/ml in men and women, respectively; in the older groups, the levels were 10.74±2.16 and 9.04+2.16 nmol/ml in men and women, respectively. There was a positive correlation of H(e) levels with age in the younger control women (r=0.373; p <0.02); no significant correlations were present in the other three control groups. Levels of H(e) in PAOD patients (15.44±5.76 and 17.04±8.26 nmol/ml in men and women, respectively) were significantly higher than those indicated above in the older controls. Next, the PAOD patients were assigned to two subgroups: 1) those with normal levels of H(e) (within two standard deviations of the mean of the control values) and 2) those with elevated levels of H(e). Age, cholesterolemia, and the prevalence of smoking and diabetes were similar in both subgroups. These results suggest that elevated plasma H(e) is an independent risk factor for arterial occlusive disease. (Circulation 1989;79:1180-1188

Cereal fortified with folic acid has the potential to increase plasma folic acid levels and reduce plasma homocyst(e)ine levels. Further clinical trials are required to determine whether folic acid fortification may prevent vascular disease. Until then, our results suggest that folic acid fortification at levels higher than that recommended by the FDA may be warranted.

Background-Endothelial function is impaired by hyperhomocyst(e)inemia. We have previously shown that homocyst(e)ine (Hcy) inhibits NO production by cultured endothelial cells by causing the accumulation of asymmetric dimethylarginine (ADMA). The present study was designed to determine if the same mechanism is operative in humans. Methods and Results-We studied 9 patients with documented peripheral arterial disease (6 men; 3 women; age, 64Ϯ3 years), 9 age-matched individuals at risk for atherosclerosis (older adults; 9 men; age, 65Ϯ1 years), and 5 young control subjects (younger adults; 5 men; age, 31Ϯ1 years) without evidence of or risk factors for atherosclerosis. Endothelial function was measured by flow-mediated vasodilatation of the brachial artery before and 4 hours after a methionineloading test (100 mg/kg body weight, administered orally). In addition, blood was drawn at both time points for measurements of Hcy and ADMA concentrations. Plasma Hcy increased after the methionine-loading test in each group (all, PϽ0.001). Plasma ADMA levels rose in all subjects, from 0.9Ϯ0.2 to 1.6Ϯ0.2 mol/L in younger adults, from 1.5Ϯ0.2 to 3.0Ϯ0.4 mol/L in older adults, and from 1.8Ϯ0.1 to 3.9Ϯ0.3 mol/L in peripheral arterial disease patients (all, PϽ0.001). Flow-mediated vasodilatation was reduced from 13Ϯ2% to 10Ϯ1% in younger adults, from 6Ϯ1% to 5Ϯ1% in older adults, and from 7Ϯ1% to 3Ϯ1% in peripheral arterial disease patients (all, PϽ0.001