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Heme oxygenase-1 (HO-1) catalyzes the oxidation of heme to generate carbon monoxide, biliverdin, and iron. Because these products have antiatherogenic properties, HO-1 may play a protective role against atherosclerosis. However, plasma HO-1 levels in patients with carotid atherosclerosis have not been reported.We investigated plasma HO-1 levels by ELISA in 136 subjects (age, 66±9 years) undergoing carotid ultrasonography.Of the 136 study subjects, carotid plaque was found in 61 subjects (45%). Compared with 75 subjects without plaque, 61 with plaque were older and predominantly male (P<0.05). Plasma HO-1 levels were higher in subjects with plaque than in those without plaque (median, 0.56 versus 0.44 ng/mL; P<0.05). The percentage of subjects with HO-1 level >0.50 ng/mL was higher in subjects with plaque than without plaque (66% versus 44%; P<0.025). In multivariate analysis, HO-1 level was a significant factor for carotid plaque independent of atherosclerotic risk factors. Odds ratio for plaque was 2.33 (95% CI, 1.15–4.75) for HO-1 level >0.50 ng/mL.Plasma HO-1 levels were high in subjects with carotid plaques, probably reflecting a protective response against carotid atherosclerosis.