Serum neopterin, nitric oxide, inducible nitric oxide synthase and tumor necrosis factor-α levels in patients with ischemic heart disease

Background: Atherosclerosis, a chronic inflammatory disease, underlies the pathogenesis of coronary artery disease. The present study assessed the diagnostic possibilities of inflammatory biomarkers, serum neopterin, nitrite/nitrate (NO2-/NO3-), inducible nitric oxide synthase (iNOS) and tumor necrosis factor-alpha (TNF-alpha), and their correlation with risk factors in patients with acute coronary syndromes and stable angina pectoris. Methods: We studied 44 patients with chronic stable angina pectoris, 46 with unstable angina, 55 with acute ST-elevation myocardial infarction and 39 age-matched healthy volunteers (control group). Serum neopterin, iNOS and TNF-alpha were determined with commercially available enzyme linked immunosorbent assay methods and NO2-/NO3- by the modified cadmium-reduction method. Results: Mean serum neopterin levels were significantly higher in patients with unstable and stable angina pectoris in comparison to control subjects (p<0.01 and p<0.05, respectively). Serum NO2-/NO3- values were significantly elevated (p<0.01) only in patients with unstable angina. ST-elevation myocardial infarction patients with cardiac death during follow-up showed significantly lower baseline neopterin values (p<0.001), and higher NO2-/NO3- levels (p<0.05) in comparison to those without adverse events. Significantly higher NO2-/NO3- values (p<0.05) were also found in patients who had myocardial reinfarction. Serum iNOS and TNF- a in all patient groups were within control ranges. A strong correlation was found between neopterin and both smoking (p<0.01) and triglycerides (p<0.05) in un- stable angina patients. In stable angina patients, neopterin, iNOS and TNF- a significantly correlated with hypertension (p<0.01) and triglycerides (p<0.05). A significant difference in neopterin concentration was found between smokers and non-smokers (p<0.05). Conclusions: The results of this study suggest that in stable angina patients, if studied over time, serum neopterin or NO2-/NO3- levels may indicate future plaque instability. In ST-elevation myocardial infarction patients, neopterin and/or NO2-/NO3- levels may identify patients at long-term risk of death or recurrent acute coronary events after myocardial infarction.