High-normal serum homocysteine concentrations are associated with an increased risk of early atherosclerotic carotid artery wall lesions in healthy subjects

OBJECTIVEModerate hyperhomocysteinaemia is common in the general population and has been linked with systemic atherosclerotic vascular disease. We studied the relation of sonographically determined carotid intima–media wall thickness to serum homocysteine concentrations in asymptomatic, healthy subjects. METHODS AND RESULTSSeventy-five male and female untreated subjects (mean age 49 years, range 22–75) with normal serum folate concentrations were included. High-resolution duplex sonography was used to determine intima-media thickness of the common carotid artery. Serum homocysteine concentration was measured by high-performance liquid chromotography with fluorescence detection. Mean intima–media thickness (± SD) was 0.78 ± 0.19 mm (range 0.5–1.35) and mean serum homocysteine concentration was 10.5 ± 2.81 μmol/l (range 5.7–19.6). In stepwise regression models, statistically significant predictors of intima-media thickness included age, body mass index, LDL cholesterol and homocysteine (R = 0.51). Homocysteine concentration was independently associated with intimamedia thickness after adjustment for the other variables (P < 0.001) and explained an additional 18% of the variation of intima–media thickness. CONCLUSIONSIn healthy subjects, high-normal serum homocysteine concentrations are associated with an increased prevalence of carotid artery wall thickening. The significance of the contribution of homocysteine to the variation of carotid intima-media thickness, even at concentrations previously believed to be normal, suggests a role for homocysteine as an independent risk factor for early carotid artery atherosclerosis in the asymptomatic subjects.