Enhanced In Vivo Lipid Peroxidation at Elevated Plasma Total Homocysteine Levels

Abstract

—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 μmol/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 2 -isoprostane were tHcy (standardized coefficient 0.33, P P =0.042), carbohydrate-deficient transferrin (0.15, P =0.132), and plasma lipid-standardized α-tocopherol (−0.11, P =0.252) ( R ² =0.24, P 2 -isoprostane levels increased linearly across quintiles of tHcy ( P 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.