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

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