Enhanced in vivo lipid peroxidation at elevated plasma total homocysteine levels

An elevated plasma total homocysteine level (tHcy) is considered an independent risk factor for atherosclerosis, The mechanisms by which hyperhomocysteinemia induces atherosclerosis are only partially understood, but promotion of LDL oxidation and endothelial injury have been suggested. The purpose of this study was to test the hypothesis that a high plasma tHcy is associated in men with increased in vivo lipid peroxidation, as measured by plasma F-2-isoprostane concentrations. We investigated this association in a subset of the participants in the Antioxidant Supplementation in Atherosclerosis Prevention (ASAP) study. Of 256 male participants, a subsample of 100 consecutive men was selected for F-2-isoprostane assays. The mean tHcy was 11.0 mu mol/L, and the mean F-2-isoprostanes was 29.6 ng/L. The simple correlation coefficient for association between tHcy and F-2-isoprostane was 0.40 (P < 0.001). In a linear regression model, the variables with the strongest associations with F-2-isoprostane were tHcy (standardized coefficient 0.33, P < 0.001), serum triglycerides (0.21, P = 0.042), carbohydrate-deficient transferrin (0.15, P = 0.132), and plasma lipid-standardized alpha-tocopherol (-0.11, P = 0.252) (R-2 = 0.24, P < 0.001 for model). Plasma F-2-isoprostane levels increased linearly across quintiles of tHcy (P < 0.001), The unadjusted mean (95% confidence interval) F-2-isoprostanes was 47.5% greater in the highest tHcy quintile (37.4, 31.1 to 43.6 ng/L) than in the lowest quintile (25.3, 21.3 to 29.3 ng/L). Adjustment for the strongest other determinants of F-2-isoprostane reduced this difference to 28.2% (P = 0.010). Our present data suggest that elevated fasting plasma tHcy is associated with enhanced in vivo lipid peroxidation in men.