Elevated Serum Neopterin is Associated with Increased Risk of Cardiovascular Events in Acute Coronary Syndromes

Anwar Santoso, Sri Wardani, Ketut Surayana

Abstract


BACKGROUND: Neopterin is a soluble biomarker of monocyte activation and its increased concentration might be expressed in atherosclerosis. Until recently, there has been lacking of information on the prognostic role of neopterin in acute coronary syndromes (ACS). The study was aimed at measuring the associations between elevated serum neopterin and increased risk of cardiovascular (CV) events in ACS.

METHODS: This was a prospective cohort study, recruited 71 ACS patients from January 31 through August 31, 2007 in Sanglah Hospital of Udayana School of Medicine, Denpasar – Bali. Cardiovascular events, such as: CV death, recurrent myocardial infarction, stroke and recurrent myocardial ischemia were previously defined. Relative risk and survival rate were measured successively by Cox proportional model and Kaplan-Meier curve.

RESULTS: Of 71 ACS patients aged 56.8 ± 9.5 years, 21 (29.5%) subjects underwent CV events. Overall mean followup was 151.6 (95% CI: 129.7 – 173.5) days. Baseline characteristic were similarly distributed between groups with the highest quartile neopterin level (≥ 14.7 nmol/L) than those with lowest quartile (≤ 6.2 nmol/L). Patients with the highest quartile had the worst survival curve than those with the lowest quartile (log-rank test; P = 0.047). On Cox proportional model, relative risk of highest quartile group was 5.84 (95% CI: 1.19 – 28.47; P = 0.029) compared to lowest quartile, after being adjusted with other predictors.

CONCLUSIONS: Elevated serum neopterin is associated with increased risk of CV events in acute coronary syndromes.

KEYWORDS: neopterin, cardiovascular events, acute coronary syndromes


Full Text:

PDF

References


Ross R. The pathogenesis of atherosclerosis: a perspective for the 1990s. Nature. 1993; 362: 801-9, CrossRef.

Galis ZS, Sukhova GK, Lark MW, Libby P. Increased expression of matrix metalloproteinases and matrix degrading activity in vulnerable regions of human atherosclerotic plaques. J Clin Invest. 1994; 94: 2493-503, CrossRef.

Hannson GK. Inflammation, Atherosclerosis, and Coronary Artery Disease. N Eng J Med. 2005; 352: 1685-95, CrossRef.

Huber C, Batchelor JR, Fuchs D, Hausen A, Lang A, Niederwieser D, et al. Immune response-associated production of neopterin. Release from macrophages primarily under control of interferon-gamma. J Exp Med. 1984; 160: 310-6, CrossRef.

Werner-Felmayer G, Werner ER, Fuchs D, Hausen A, Reibnegger G, Schmidt K, et al. Pteridine biosynthesis in human endothelial cells. Impact on nitric oxide-mediated formation of cyclic GMP. J Biol Chem. 1993; 268: 1842-6, PMID.

Berdowska A, Zwirska-Korczala K. Neopterin measurement in clinical diagnosis. J Clin Pharm Ther. 2001; 26: 319-29, CrossRef.

Avanzas P, Arroyo-Espliguero R, Cosin-Sales J, Aldama G, Pizzi C, Quiles J, et al. Markers of inflammation and multiple complex stenoses (pancoronary plaque vulnerability) in patients with non-ST segment elevation acute coronary syndromes. Heart. 2004; 90: 847-52, CrossRef.

Avanzas P, Arroyo-Espliguero R, Quiles J, Roy D, Kaski JC. Elevated serum neopterin predicts future adverse cardiac events in patients with chronic stable angina pectoris. Eur Heart J. 2005; 26: 457-63, CrossRef.

Gupta S, Frederick S, Schwartzman RA, Holt DW, Kaski JC. Serum neopterin in acute coronary syndromes. Lancet. 1997; 349: 1252-3, CrossRef.

Garcia-Moll X, Cole D, Zouridakis E, Kaski JC. Increased serum neopterin: a marker of coronary artery disease activity in women. Heart. 2000; 83: 346-50, CrossRef.

Avanzas P, Arroyo-Espliguero R, Cosin-Sales J, Quiles J, Zouridakis E, Kaski JC. Prognostic value of neopterin levels in treated patients with hypertension and chest pain but without obstructive coronary artery disease. Am J Cardiol. 2004; 93: 627-9, CrossRef.

Ray KK, Morrow DA, Sabatine MC, Shui A, Rifai N, Cannon CP, et al. Long-term prognostic value of neopterin. A novel marker of monocyte activation in patients with acute coronary syndrome. Circulation. 2007; 115: 3071-8, CrossRef.

Chobanian AV, Bakris GL, Black HR, Chusman WC, Green LA, Izzo Jr. JL, et al. The seventh report of the Joint Committee on Prevention, Detection, Evaluation and Treatment of High Blood Pressure. JAMA. 2003; 289: 2560-72, CrossRef.

American Diabetes Association. Standard of medical care in diabetes. Diabetes Care. 2006; 29: S4-S42, article.

Al-Delaemy WK, Willet DC, Manson JE, Speizer FE, Hu FB. Smoking and mortality among women with type-2 diabetes. Diabetes Care. 2001; 24: 2043-8, CrossRef.

Westermann J, Thiemann F, Gerstner L, Tatzber F, Kozák I, Bertsch T, et al. Evaluation of a new simple and rapid enzym-linked immunosorbent assay kit for neopterin determination. Clin Chem Lab Med. 2000; 38: 345-53, PMID.

Liuzzo G, Goronzy SL, Yang H, Kopecky SL, Holmes DR, Frye RL, et al. Monoconal T-cell proliferation and plaque instability in acute coronary syndromes. Circulation. 2000; 101: 2883-8, CrossRef.

Serneri GGN, Prisco D, Martini F, Gori AM, Brunelli T, Poggesi L, et al. Acute T-cell activation is detectable in unstable angina. Circulation. 1997; 95: 1806-12, CrossRef.

Hansson GK. Inflammation, atherosclerosis, and coronary artery disease. N Eng J Med. 2005; 352: 1685-95, CrossRef.

Auer J, Berent R, Labetanig E, Eber B. Serum neopterin and activity of coronary artery disease. Heart Dis. 2001; 3: 297-301, CrossRef.

Werner ER, Bichler A, Dexenbichler G, Fuche D, Fulth LC, Hausen A, et al. Determination of neopterin in serum and urine. Clin Chem. 1987; 33: 62-6, PMID.

Santoso A, Wita W, Suastika K. Risk of acute myocardial infarction was associated with hypoadiponectinemia. Folia Medica Indonesiana. 2006; 42 (Suppl 5): 241-6.

Van Haelst PL, Liem A, van Boven AJ, Veeger NJ, van Veldheuisen DJ, Gans RO, et al. Usefulness of elevated neopterin and C-reactive protein levels in predicting cardiovascular events in patients with non-Q wave myocardial infarction. Am J Cardiol. 2003; 92: 1201-3, CrossRef.




DOI: https://doi.org/10.18585/inabj.v1i1.84

Copyright (c) 2009 The Prodia Education and Research Institute

Creative Commons License
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

 

Indexed by:

                  

               

                   

 

 

The Prodia Education and Research Institute