Inverse association between serum concentrations of neopterin and antioxidants in patients with and without angiographic coronary artery disease

Murr, Christian; Winklhofer-Roob, Brigitte M.; Schroecksnadel, Katharina; Maritschnegg, Michaela; Mangge, Harald; Böhm, Bernhard O.; Winkelmann, Bernhard R.; März, Winfried; Fuchs, Dietmar

doi:10.1016/j.atherosclerosis.2008.04.047

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Volume 202, Issue 2 , Pages 543-549, February 2009

Inverse association between serum concentrations of neopterin and antioxidants in patients with and without angiographic coronary artery disease

Christian Murr
- Division of Biological Chemistry, Biocenter, Innsbruck Medical University, Innsbruck, Austria
Brigitte M. Winklhofer-Roob
- Human Nutrition & Metabolism Research and Training Center, Institute of Molecular Biosciences, Karl-Franzens University, Graz, Austria
Katharina Schroecksnadel
- Division of Biological Chemistry, Biocenter, Innsbruck Medical University, Innsbruck, Austria
- Department of Internal Medicine, Innsbruck Medical University, Innsbruck, Austria
Michaela Maritschnegg
- Human Nutrition & Metabolism Research and Training Center, Institute of Molecular Biosciences, Karl-Franzens University, Graz, Austria
Harald Mangge
- Clinical Department of Medical and Chemical Laboratory Diagnostics, Graz Medical University, Graz, Austria
Bernhard O. Böhm
- Division of Endocrinology, Department of Medicine, University Hospital, Ulm, Germany
Bernhard R. Winkelmann
- Cardiology Group Sachsenhausen, Frankfurt am Main, Germany
Winfried März
- Synlab Center of Laboratory Diagnostics, Heidelberg, Germany
Dietmar Fuchs
- Division of Biological Chemistry, Biocenter, Innsbruck Medical University, Innsbruck, Austria
- Corresponding author. Tel.: +43 512 9003 70350; fax: +43 512 9003 73330.

Received 23 November 2007; received in revised form 25 April 2008; accepted 30 April 2008. published online 16 June 2008.

Abstract

Neopterin is released from human monocyte-derived macrophages upon stimulation with interferon-γ and is a sensitive indicator for cellular immune activation. Furthermore, reactive oxygen species (ROS) are produced in case of immune activation and inflammation.

In a cross-sectional approach, plasma concentrations of neopterin and of antioxidant compounds and vitamins were compared in 1463 patients investigated by coronary angiography, which were recruited within the LUdwigshafen RIsk and Cardiovascular Health (LURIC) study.

Serum neopterin concentrations were higher in patients with coronary artery disease (CAD; mean±S.D.: 8.7±7.3nmol/L) compared to controls (7.4±5.0nmol/L; Welch's t-test: p<0.001). Mean concentrations of ascorbic acid (p<0.0001), γ-tocopherol (p<0.05), lycopene (p<0.001), lutein+zeaxanthin (p<0.05), α-carotene (p<0.05) and β-carotene (p<0.05) were lower in CAD than in controls. Neopterin concentrations correlated with CAD-score (r_s=0.156; p<0.0001) and inversely with antioxidants lycopene (r_s=−0.277; p<0.0001) and lutein+zeaxanthin (r_s=−0.175; p<0.0001) levels and with vitamins ascorbic acid (r_s=−0.207; p<0.0001) and α-tocopherol (r_s=−0.105; p<0.0001).

The study demonstrates that higher neopterin production is associated with lower concentrations of antioxidant compounds in patients at risk for atherosclerosis. Results suggest that lower concentrations of antioxidant compounds may relate to higher grade of chronic immune activation in patients.

Keywords: Neopterin, Antioxidants, Vitamins, Immune activation, Coronary artery disease (CAD), Oxidative stress