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Licensed Unlicensed Requires Authentication Published by De Gruyter June 11, 2014

Plasma homocysteine and markers for oxidative stress and inflammation in patients with coronary artery disease – a prospective randomized study of vitamin supplementation

Torfi Jonasson , Ann-Kristin Öhlin , Anders Gottsäter , Björn Hultberg and Hans Öhlin


Background: Elevated plasma levels of total homocysteine (tHcy) are associated with an increased risk of developing occlusive vascular diseases. To better illustrate the relationship between plasma tHcy concentration, oxidative stress, and inflammation in patients with coronary artery disease (CAD), we measured plasma 8-isoprostane-prostaglandin F 2 (Iso-P), plasma malondialdehyde (MDA), and several markers of inflammation. We also aimed to demonstrate the effects of vitamin supplementation on these markers.

Methods: A total of 93 patients with ischemic heart disease were investigated. Of these, 34 had plasma tHcy ≤8μmol/L, while 59 had plasma tHcy ≥15.0 μmol/L. The 59 patients were randomized to open therapy with folic acid, 5mg, pyridoxine, 40mg, and cyancobalamin, 1mg once daily for 3months (n=29) or to no vitamin treatment (n=30). Blood samples were obtained from both groups before randomization and 3months later. A sample was also obtained from the remaining 34 patients.

Results: Plasma Iso-P, serum amyloid A (S-AA), and plasma intercellular adhesion molecule-1 (ICAM-1) concentrations were higher in patients with high plasma tHcy levels than in patients with low to normal tHcy levels. Plasma levels of P-, L-, E-selectins, MDA, C-reactive protein (CRP), and orosomucoid did not differ between the groups. Vitamin therapy reduced plasma tHcy from 17.4 (15.3/20.1) to 9.2 (8.3/10.3)μmol/L (25th and 75th percentiles in parentheses) (p<0.0001). Plasma levels of Iso-P remained unchanged and, of all inflammatory markers, only the S-AA concentrations were slightly reduced by the vitamin treatment, from 5.3 (2.2/7.0)ng/L at baseline to 4.6 (2.1/6.9)ng/L (p<0.05) after 3months of vitamin supplementation.

Conclusion: Patients with CAD and high plasma tHcy levels had elevated plasma levels of Iso-P. The increase remained unaffected by plasma tHcy-lowering therapy, suggesting that homocysteine per se does not cause increased lipid peroxidation. Levels of plasma ICAM-1 and S-AA were increased in patients with high plasma tHcy, suggesting an association between homocysteinemia and low-grade inflammation.

Corresponding author: Torfi Jonasson, Department of Cardiology, University Hospital, 101 Reykjavik, Iceland Phone: +354-5431000, Fax: +354-5436467


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Received: 2004-9-27
Accepted: 2005-4-12
Published Online: 2014-6-11
Published in Print: 2005-6-1

© Walter de Gruyter Berlin New York

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