Enhanced in vivo lipid peroxidation at elevated plasma total homocysteine levels

An elevated plasma total homocysteine level (tHcy) is considered an indepen dent risk factor for atherosclerosis, The mechanisms by which hyperhomocyst einemia induces atherosclerosis are only partially understood, but promotio n 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 associa ted in men with increased in vivo lipid peroxidation, as measured by plasma F-2-isoprostane concentrations. We investigated this association in a subs et of the participants in the Antioxidant Supplementation in Atherosclerosi s Prevention (ASAP) study. Of 256 male participants, a subsample of 100 con secutive 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 correla tion 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-tocophe rol (-0.11, P = 0.252) (R-2 = 0.24, P < 0.001 for model). Plasma F-2-isopro stane levels increased linearly across quintiles of tHcy (P < 0.001), The u nadjusted 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 dete rminants of F-2-isoprostane reduced this difference to 28.2% (P = 0.010). O ur present data suggest that elevated fasting plasma tHcy is associated wit h enhanced in vivo lipid peroxidation in men.