Homocysteine has been proposed as a risk factor for atherosclerosis. The association between plasma total homocysteine (tHcy) concentration and carotid atherosclerosis has not been thoroughly studied in high-risk populations with vascular disease. For this study, carotid atherosclerosis was assessed by measurements of carotid intima-media thickness (IMT) and plaque calcification in 923 patients with vascular disease or diabetes. Associations with tHcy and plasma folate concentrations were examined. The mean and single maximum carotid IMT were 1.27 +/- 0.34 mm and 2.41 +/- 0.83 mm, respectively. The mean segment plaque calcification score was 27.8%. tHcy correlated with mean (r = 0.13; p < 0.001) and single maximum (r = 0.12; p < 0.001) carotid IMT. There was a progressive increase in mean and single maximum carotid IMT across quartiles of tHcy (p < 0.0001 for trend). These associations were no longer significant after adjusting for other CV risk factors. A trend towards an inverse association between plasma folate and mean max carotid IMT was found in both univariate and multivariable analyses. However, the plaque calcification score increased across quartiles of tHcy (p < 0.01) and decreased across quartiles of plasma folate concentrations (p < 0.05) after multiple adjustments. In conclusion, in high-risk individuals, tHcy and low folate concentrations were only weakly associated with carotid IMT. In contrast, we found an independent association with the plaque calcification score, a measure of more advanced atherosclerosis. The effect of tHcy lowering on carotid atherosclerosis and stroke prevention warrants further investigation.
Trial registration: ClinicalTrials.gov NCT00106886 NCT00217178.