| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Letters to the Editor |
Department of Cardiac, and Vascular Sciences, St. George’s, University of London, London, United Kingdom
aAddress correspondence to this author at: Department of Cardiac and Vascular Sciences., St. George’s, University of London, London SW17 0RE, UK. Fax 44-020-8725-3328; e-mail jkaski{at}sghms.ac.uk.
To the Editor:
We read with interest the recent authoritative review article by Apple et al. (1) regarding biomarkers and acute coronary syndromes (ACS). Although the article is both exhaustive and clinically relevant, we felt that the authors failed to recognize the potential value of neopterin as a marker of cardiovascular risk.
Neopterin, a pteridine derivative produced by activated macrophages in response to stimulation by interferon-
, is a marker of both immune activation and coronary artery disease (CAD) activity (2). Several studies have shown that circulating neopterin concentrations are higher in patients with ACS than in patients with chronic stable angina pectoris (CSA) and in apparently healthy persons. Increased neopterin is associated with the presence of vulnerable or disrupted atheromatous plaques (3) and represents a marker of increased risk of further events in patients with ACS (4). Moreover, recent studies from our group have shown that increased serum neopterin predicts rapid CAD progression (5) and the development of major adverse coronary events in patients with CSA (6)(7) and in hypertensive persons without obstructive CAD (8).
Neopterin has been also suggested to play a pathogenic role in CAD, and studies in recent years support the notion that neopterin may provide information complementary to that of C-reactive protein (CRP) regarding cardiovascular risk. Despite the wealth of evidence that CRP is a potentially useful marker of risk in the clinical setting, no head-to-head comparisons between CRP and other inflammatory markers such as neopterin have been carried out in large clinical trials. A recent study from our group (6), however, showed that CRP was not a significant predictor of risk in patients with CSA. In contrast, patients in the highest neopterin tertile (>7 nmol/L) had a 3-fold higher risk of developing adverse cardiovascular events (odds ratio = 3; 95% confidence interval, 1.25–7.2; P = 0.015) compared with those in the lowest tertile (<4.5 nmol/L), even after adjustment for potential confounders in multivariate analysis. In one relatively small study in patients with non-Q-wave myocardial infarction (4), combined measurements of CRP and neopterin were found to have a stronger predictive value than neopterin measurements alone.
Recent studies from our group suggest that neopterin may provide more comprehensive information regarding risk of cardiovascular events than do CRP measurements, particularly when macrophage activation is implicated, as seen in rapid CAD progression (5) and atheromatous plaque disruption (3). The numbers of patients in these studies, however, were small compared with the numbers in large clinical trials that have assessed the role of CRP. Further studies are therefore needed to substantiate these findings.
Regarding larger trials specifically aimed to carry out head-to-head comparisons of the prognostic role of inflammatory markers, the prospective Systemic Inflammation Evaluation in Patients with Non ST Segment Elevation Acute Coronary Syndromes (SIESTA) study (9) is likely to provide clinically useful answers. The SIESTA study was designed to compare the prognostic value of CRP, pro- and antiinflammatory cytokines, adhesion molecules, fibrinogen, leukocytes, and amyloid A serum protein, among other markers of inflammation, in patients with ACS.
Robust ELISAs are available for the assessment of neopterin with excellent agreement reported, particularly between the two most widely used assays (10)(11)(12). Intraassay CVs range from 1.5% to 9.1%, and interassay CVs from 3.0% to 10.8%. Assay detection limits range from 2 nmol/L to 50 nmol/L. In a study of 76 587 blood donors, the mean neopterin concentration was 5.4 nmol/L and the 95th percentile was 8.7 nmol/L. Of importance, 98.4% of the blood donors in the study had neopterin concentrations <10 nmol/L, and there was no sex or age (age range, 17–64 years) dependency regarding neopterin concentrations (13).
We would have thought that the available information regarding the role of neopterin as a marker of cardiovascular risk should have earned this molecule a place on the list of available biomarkers. Its omission in scholarly reviews such as that of Apple et al. (1) could deprive the medical community of potentially useful information.
Footnotes
1 Current affiliation: Department of Invasive Cardiology, Hospital Universitario Central de Asturias, Oviedo, Spain. 
2 Current affiliation: Department of Cardiology, Hospital General Universitario, Guadalajara, Spain.
References
The following articles in journals at HighWire Press have cited this article:
|
|
 |
|
  P. Avanzas, R. Arroyo-Espliguero, and J. C. Kaski Neopterin and Cardiovascular Disease: Growing Evidence for a Role in Patient Risk Stratification Clin. Chem., June 1, 2009; 55(6): 1056 - 1057. [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
