Arteriosclerosis, Thrombosis, and Vascular Biology. 1999;19:1263-1266
© 1999 American Heart Association, Inc.
Atherosclerosis and Lipoproteins |
Enhanced In Vivo Lipid Peroxidation at Elevated Plasma Total Homocysteine Levels
From the Research Institute of Public Health, University of Kuopio, Kuopio, Finland (S.V., K.N., J.T.S.), the Division of Clinical Pharmacology, Vanderbilt University Medical Center, Nashville, TN (J.D.M., L.J.R.), the Departments of Nutrition (G.A.), and Mental Health and Alcohol Research (H.A.), National Public Health Institute, Helsinki, Finland.
Correspondence to Dr J.T. Salonen, Research Institute of Public Health, University of Kuopio, PO Box 1627, 70211 Kuopio, Finland. E-mail Salonen{at}reivi.uku.fi
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 F2-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
F2-isoprostane assays. The mean tHcy was 11.0
µmol/L, and the mean F2-isoprostanes was 29.6 ng/L. The
simple correlation coefficient for association between tHcy and
F2-isoprostane was 0.40 (P<0.001). In a
linear regression model, the variables with the strongest
associations with F2-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 
-tocopherol (-0.11,
P=0.252) (R2=0.24,
P<0.001 for model). Plasma F2-isoprostane
levels increased linearly across quintiles of tHcy
(P<0.001). The unadjusted mean (95% confidence
interval) F2-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 F2-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.
Key Words: homocysteine • F2-isoprostanes • lipid peroxidation • cardiovascular diseases
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