Clinical Studies
Increased Neopterin in Patients With Chronic and Acute Coronary Syndromes

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Abstract

Objectives. The aim of our study was to determine neopterin levels in patients with chronic and acute coronary syndromes.

Background. In chronic and acute coronary syndromes the release of different cytokines activates cellular defense. Infiltration of neutrophils and monocytes/macrophages is detected in the vessel wall as well as in the myocardium. Neopterin, which is a by-product of the guanosine triphosphate–biopterin pathway, is a marker for those activated macrophages.

Methods. We studied 123 subjects: 1) 21 consecutive patients (17 men, 4 women; mean age ± SD 66 ± 15 years, range 31 to 87) with acute myocardial infarction (AMI); 2) 62 consecutive patients (50 men, 12 women; mean age 61 ± 8 years, range 43 to 81) with signs and symptoms of clinically stable coronary artery disease (CAD); and 3) 40 healthy blood donors (28 men, 12 women; mean age 35 ± 13 years). Neopterin levels were determined with a commercially available enzyme-linked immunosorbent assay method.

Results. In patients with AMI before thrombolytic therapy, neopterin levels were significantly higher than levels in patients with CAD and control subjects (13.7 vs. 8.6 and vs. 6.8 nmol/liter, p < 0.0001). Values also differed significantly between patients with CAD and control subjects (p < 0.0001). Neopterin levels in patients with AMI were measured seven times during a 72-h period. Within-group comparison showed significant differences over this period (p < 0.00001). The lowest value (11.4 nmol/liter) was observed after 4 h and differed significantly from the initial value and values after 24 and 72 h (p < 0.05). After 72 h, neopterin increased to 14.9 nmol/liter, a value significantly different from all values other than the initial one. There was no correlation between neopterin and creatine kinase (CK); CK, MB isoenzyme; or lactate dehydrogenase as markers for the extent of the myocardial infarction during the observation period.

Conclusions. Our data support the hypothesis of an activation of monocytes and macrophages in patients with an acute or chronic coronary syndrome. Neopterin as a marker for macrophage activation is significantly increased in patients with chronic CAD and more pronounced in patients with AMI shortly after the onset of symptoms.

Abbreviations

AMI
acute myocardial infarction
ANOVA
analysis of variance
CAD
coronary artery disease
CK
creatine kinase
CK-MB
creatine kinase, MB isoenzyme
HDL
high density lipoprotein
LDH
lactate dehydrogenase
LDL
low density lipoprotein
mRNA
messenger ribonucleic acid
TNF
tumor necrosis factor

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This study was supported in part by Project SFB 709 from the Austrian Science Foundation.

1

Deceased.