LETTER TO THE EDITOR
Neopterin—a forgotten biomarker
Juan Carlos Kaski, MD, DSc, FRCP, FESC, FACC,
Pablo Avanzas, MD and
Ramón Arroyo-Espliguero, MD
Department of Cardiological Sciences, Director of Coronary Artery Disease Research Unit, St. George's Hospital Medical School, London SW17 0RE, United Kingdom
jkaski{at}sghms.ac.uk
In a recent issue of the Journal, Blake and Ridker (1) summarized findings regarding the prognostic role of C-reactive protein (CRP) and other inflammatory markers in patients with acute coronary syndromes (ACS). We would like to point out that the investigators did not include the role of neopterin in this context. Neopterin (2), a pteridine derivative and a by-product of the guanosine triphosphate–biopterin pathway (3), is produced by activated macrophages and represents a marker of immune activation. Studies from our group (4) and others (5,6) have shown that circulating neopterin levels are higher in patients with ACS compared to patients with a history of myocardial infarction, patients with stable angina pectoris, or control subjects. High neopterin levels may be a marker of coronary disease activity, as suggested by its association with angiographically complex lesions in patients with unstable angina (7) and its role as a marker of future cardiovascular events in women with coronary artery disease (CAD) (8). The prognostic significance of neopterin in ACS patients has been reported by Auer et al. (9), albeit in a small group of patients. Preliminary prospective work from our unit has recently shown that, in patients with CAD, serum neopterin is an independent predictor of major adverse coronary events at one-year follow-up (data not published).
Finally, although convincing evidence exists regarding the prognostic value of inflammatory markers in patients with ACS, the independent and/or complementary role of different biomarkers has not been systematically investigated in large prospective studies. The ongoing SIESTA (Systemic Inflammation Evaluation in patients with non–ST-segment elevation Acute coronary syndromes) study (10)—a prospective multicenter trial designed to assess the relative prognostic role of diverse markers of inflammation, including, among many others, CRP, neopterin, cell adhesion molecules, and pregnancy-associated plasma protein A—will help to elucidate the issue.
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1. Blake GJ, Ridker PM. C-reactive protein and other inflammatory risk markers in acute coronary syndromes. J Am Coll Cardiol. 2003;41:S37–42[CrossRef]
2. Huber C, Batchelor JR, Fuchs D, et al. Immune response-associated production of neopterin. Release from macrophages primarily under control of interferongamma. J Exp Med. 1984;160:310–316[Abstract/Free Full Text]
3. Werner-Felmayer G, Werner ER, Fuchs D, et al. Pteridine biosynthesis in human endothelial cells. Impact on nitric oxide–mediated formation of cyclic GMP. J Biol Chem. 1993;268:1842–1846[Abstract/Free Full Text]
4. Gupta S, Fredericks S, Schwartzman RA, Holt DW, Kaski JC. Serum neopterin in acute coronary syndromes. Lancet. 1997;349:1252–1253[Medline]
5. Schumacher M, Eber B, Tatzber F, Kaufmann P, Esterbauer H, Klein W. Neopterin levels in patients with coronary artery disease. Atherosclerosis. 1992;94:87–88[CrossRef][Medline]
6. Schumacher M, Halwachs G, Tatzber F, et al. Increased neopterin in patients with chronic and acute coronary syndromes. J Am Coll Cardiol. 1997;30:703–707[Abstract]
7. Garcia-Moll X, Coccolo F, Cole D, Kaski JC. Serum neopterin and complex stenosis morphology in patients with unstable angina. J Am Coll Cardiol. 2000;35:956–962[Abstract/Free Full Text]
8. Garcia-Moll X, Cole D, Zouridakis E, Kaski JC. Increased serum neopterin: a marker of coronary artery disease activity in women. Heart. 2000;83:346–350[Abstract/Free Full Text]
9. Auer J, Berent R, Lassnig E, Weber T, Eber B. Prognostic significance of immune activation after acute coronary syndromes. J Am Coll Cardiol. 2002;39:1878[Free Full Text]
10. Kaski JC, Cruz-Fernandez JM, Fernandez-Berges D, et al. Inflammation markers and risk stratification in patients with acute coronary syndromes: design of the SIESTA study (Systemic Inflammation Evaluation in patients with non–ST-segment elevation Acute coronary syndromes). Rev Esp Cardiol. 2003;56:389–395[CrossRef][Medline]
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