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

Abstract

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. 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. 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-alpha 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 unstable angina patients. In stable angina patients, neopterin, iNOS and TNF-alpha 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). 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.