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

Clin Chem Lab Med. 2008;46(8):1149-55. doi: 10.1515/CCLM.2008.213.


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-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).

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Biomarkers / blood
  • Female
  • Humans
  • Male
  • Middle Aged
  • Myocardial Ischemia / blood*
  • Neopterin / blood*
  • Nitric Oxide / blood*
  • Nitric Oxide Synthase Type II / blood*
  • Risk Factors
  • Tumor Necrosis Factor-alpha / blood*


  • Biomarkers
  • Tumor Necrosis Factor-alpha
  • Nitric Oxide
  • Neopterin
  • Nitric Oxide Synthase Type II