Serum neopterin and activity of coronary artery disease

Inflammation plays a key role in the pathogenesis of atherosclerosis. In coronary artery disease (CAD), the release of different cytokines activates cellular defense. Infiltration of neutrophils and monocytes/macrophages is detected in the vessel wall in patients with CAD. Macrophages activated by interferon gamma synthesize metalloproteinases and neopterin, a pteridin derivative that has been used as an immune marker. To determine neopterin levels in patients with chronic CAD and acute coronary syndromes, the authors studied 116 subjects: 1) 25 consecutive patients (18 men, 7 women; mean age 68.5 +/- 14.3, range 40 to 86 years) with unstable angina or acute myocardial infarction (AMI); 2) 31 consecutive patients (25 men, 6 women; mean age 64 +/- 12.7, range 47 to 83 years) with signs and symptoms of clinically stable CAD; and 3) 60 consecutive healthy blood donors (38 men, 22 women; mean age 54.4 +/- 6.23, range 44 to 66 years). Neopterin levels were determined with a commercially available enzyme-linked immunosorbent assay method. In patients with unstable angina and AMI before thrombolytic therapy, neopterin levels were not significantly different from levels in patients with stable CAD (5.97 +/- 1.4 versus 7.84 +/- 3.56 nmol/L; P = 0.15). Neopterin levels in both patient groups did not significantly differ from levels in control subjects (P > 0.1). Neopterin levels in patients with unstable angina and AMI were measured four times during a 72-hour period. The lowest value was observed at baseline and differed significantly from values after 72 hours (P < 0.001; 5.97 +/- 1.4 versus 9.25 +/- 2.36). Neopterin levels after 72 hours were also significantly different from initial values in patients with stable CAD (P < 0.001). There was no correlation between neopterin and creatine kinase (CK) levels, CK-MB isoenzyme, or troponin I as markers for the extent of the myocardial injury during the observation period. These data do not support previous reports of higher baseline levels of serum neopterin in patients with unstable angina or AMI compared with patients with chronic, stable CAD and healthy controls. Neopterin as a marker of macrophage activation is significantly increased in patients with AMI and unstable angina shortly after the onset of symptoms (after a period of 72 hours), supporting the hypothesis of monocyte and macrophage activation in patients with an acute coronary syndrome or AMI.