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Neopterin as a Predictor of Functional Outcome and Mortality in Chinese Patients with Acute Ischemic Stroke

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Abstract

Immune responses and inflammation play an important role in the pathogenesis of ischemic stroke. We therefore evaluated the 6-month prognostic value of early measurement of serum neopterin levels, a marker of inflammation and immune system activation, in Chinese patients with acute ischemic stroke (AIS). Consecutive AIS patients admitted to the emergency department were identified. Clinical information was collected. Serum concentration of neopterin and NIH stroke scale (NIHSS) were measured at the time of admission. Functional outcome was measured by modified Rankin scale (mRS) 6 months after admission. Multivariate analyses were performed using logistic regression models. During the inclusion period, 312 patients with first-ever AIS were included and 290 completed follow-up. The results indicated that the serum neopterin levels were significantly (P < 0.0001) higher in acutely ischemic stroke patients as compared to normal controls. Neopterin was an independent prognostic marker of 6-month functional outcome and death [odds ratio (OR) 4.33 (1.83–10.32) and 6.68 (2.44–12.13), respectively, P < 0.0001 for both, adjusted for NIHSS, other predictors and vascular risk factors] in patients with AIS. Neopterin improved the area under the receiver operating characteristic curve of the NHISS score for functional outcome from 0.75 (95 % CI 0.69–0.83) to 0.85 (95 % CI 0.79–0.91; P < 0.001) and for mortality from 0.76 (95 % CI 0.68–0.85) to 0.87 (95 % CI 0.81–0.94; P < 0.001). Serum neopterin is a useful, independent tool to predict functional outcome and mortality 6 months after stroke.

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References

  1. Macrez R, Ali C, Toutirais O et al (2011) Stroke and the immune system: from pathophysiology to new therapeutic strategies. Lancet Neurol 10:471–480

    Article  CAS  PubMed  Google Scholar 

  2. Song FY, Wu MH, Zhu L et al (2014) Elevated serum mannose-binding lectin levels are associated with poor outcome after acute ischemic stroke in patients with type 2 diabetes. Mol Neurobiol. doi:10.1007/s12035-014-8941-0

    Google Scholar 

  3. Slot KB, Berge E, Dorman P, Lewis S, Dennis M, Sandercock P (2008) Impact of functional status at six months on long term survival in patients with ischaemic stroke: prospective cohort studies. BMJ 336:376–379

    Article  PubMed  PubMed Central  Google Scholar 

  4. Tu WJ, Dong X, Zhao SJ, Yang DG, Chen H (2013) Prognostic value of plasma neuroendocrine biomarkers in patients with acute ischaemic stroke. J Neuroendocrinol 25:771–778

    Article  CAS  PubMed  Google Scholar 

  5. Jin R, Liu L, Zhang S et al (2013) Role of inflammation and its mediators in acute ischemic stroke. J Cardiovasc Transl Res 6:834–851

    Article  PubMed  Google Scholar 

  6. Jin R, Yang G, Li G (2010) Inflammatory mechanisms in ischemic stroke: role of inflammatory cells. J Leukoc Biol 87:779–789

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Parker DC, Mielke MM, Yu Q et al (2013) Plasma neopterin level as a marker of peripheral immune activation in amnestic mild cognitive impairment and Alzheimer’s disease. Int J Geriatr Psychiatry 28:149–154

    Article  PubMed  Google Scholar 

  8. Alanbay I, Mutlu Ercan C, Coksuer H et al (2012) Neopterin: a promising marker for the inflammation in polycystic ovary syndrome. Gynecol Endocrinol 28:879–883

    Article  CAS  PubMed  Google Scholar 

  9. Celik C, Erdem M, Caycı T et al (2010) The association between serum levels of neopterin and number of depressive episodes of major depression. Prog Neuro-Psychopharmacol Biol Psychiatry 34:372–375

    Article  CAS  Google Scholar 

  10. Fuchs D, Weiss G, Reibnegger G, Wachter H (1992) The role of neopterin as a monitor of cellular immune activation in transplantation, inflammatory, infectious, and malignant diseases. Crit Rev Clin Lab Sci 29(3–4):307–341

    Article  CAS  PubMed  Google Scholar 

  11. Widner B, Laich A, Sperner-Unterweger B et al (2002) Neopterin production, tryptophan degradation, and mental depression—what is the link? Brain Behav Immun 16:590–595

    Article  CAS  PubMed  Google Scholar 

  12. De Rosa S, Cirillo P, Pacileo M et al (2011) Neopterin: from forgotten biomarker to leading actor in cardiovascular pathophysiology. Curr Vasc Pharmacol 9:188–199

    Article  PubMed  Google Scholar 

  13. Pedersen ER, Midttun Ø, Ueland PM et al (2011) Systemic markers of interferon-γ–mediated immune activation and long-term prognosis in patients with stable coronary artery disease. Arterioscler Thromb Vasc Biol 31:698–704

    Article  CAS  PubMed  Google Scholar 

  14. Lin HS, Tsai TH, Liu CF et al (2012) Serum level and prognostic value of neopterin in patients after ischemic stroke. Clin Biochem 45:1596–1601

    Article  CAS  PubMed  Google Scholar 

  15. Ganz P, Amarenco P, Goldstein LB et al (2013) Association of MCP-1, hsCRP, Neopterin, MMP-9 and NT-proBNP with coronary heart disease risk in patients with prior stroke or transient ischemic attack. Results of the analysis of 13 biomarkers from the SPARCL trial. Circulation 128:A14940

    Google Scholar 

  16. Hatano S (1976) Experience from a multicentre stroke register: a preliminary report. Bull World Health Organ 54:541–553

    CAS  PubMed  PubMed Central  Google Scholar 

  17. Adams HP Jr, Bendixen BH, Kappelle LJ, Biller J, Love BB, Gordon DL et al (1993) Classification of subtype of acute ischemic stroke. Definitions for use in a multicenter clinical trial. TOAST. Trial of Org 10172 in Acute Stroke Treatment. Stroke 24:35–41

    Article  PubMed  Google Scholar 

  18. Bamford J, Sandercock P, Dennis M et al (1991) Classification and natural history of clinically identifiable subtypes of cerebral infarction. Lancet 337:1521–1526

    Article  CAS  PubMed  Google Scholar 

  19. Brott T, Marler JR, Olinger CP, Adams HP Jr, Tomsick T, Barsan WG et al (1989) Measurements of acute cerebral infarction: lesion size by computed tomography. Stroke 20:871–875

    Article  CAS  PubMed  Google Scholar 

  20. Sims JR (2009) Gharai, L R, Schaefer, P.W, et al. ABC/2 for rapid clinical estimate of infarct, perfusion, and mismatch volumes. Neurology 72:2104–2110

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Bonita RBR (1988) Modification of Rankin Scale: recovery of motor function after stroke. Stroke 19:1497–1500

    Article  CAS  PubMed  Google Scholar 

  22. Fuchs D, Avanzas P, Arroyo-Espliguero R et al (2009) The role of neopterin in atherogenesis and cardiovascular risk assessment. Curr Med Chem 16:4644–4653

    Article  CAS  PubMed  Google Scholar 

  23. Yan J, Tan C, Wu J et al (2013) Neopterin negatively regulates expression of ABCA1 and ABCG1 by the LXRα signaling pathway in THP-1 macrophage-derived foam cells. Mol Cell Biochem 379:123–131

    Article  CAS  PubMed  Google Scholar 

  24. Tu WJ, Zhao SJ, Liu TG, Yang DG, Chen H (2013) Combination of high-sensitivity C-reactive protein and homocysteine predicts the shortterm outcomes of Chinese patients with acute ischemic troke. Neurol Res 35:912–921

    Article  CAS  PubMed  Google Scholar 

  25. Markaki I, Franzén I, Talani C, Loizou L, Kostulas N (2013) Long-term survival of ischemic cerebrovascular disease in the acute inflammatory stroke study, a hospital-based cohort described by TOAST and ASCO. Cerebrovasc Dis 35:213–219

    Article  CAS  PubMed  Google Scholar 

  26. Whiteley W, Jackson C, Lewis S, Lowe G, Rumley A et al (2009) inflammatory markers and poor outcome after stroke: a prospective cohort study and systematic review of interleukin-6. PLoS Med 6(9):e1000145

    Article  PubMed  PubMed Central  Google Scholar 

  27. Lyu Y, Jiang X, Dai W (2015) The roles of a novel inflammatory neopterin in subjects with coronary atherosclerotic heart disease. Int Immunopharmacol 24:169–172

    Article  CAS  PubMed  Google Scholar 

  28. Kaski JC, Consuegra-Sanchez L, Fernandez-Berges DJ et al (2008) Elevated serum neopterin levels and adverse cardiac events at 6 months follow-up in Mediterranean patients with non-ST-segment elevation acute coronary syndrome. Atherosclerosis 201(1):176–183

    Article  CAS  PubMed  Google Scholar 

  29. Grammer TB, Fuchs D, Boehm BO, Winkelmann BR, Maerz W (2009) Neopterin as a predictor of total and cardiovascular mortality in individuals undergoing angiography in the Ludwigshafen Risk and Cardiovascular Health Study. Clin Chem 55:1135–1146

    Article  CAS  PubMed  Google Scholar 

  30. Zacho J, Tybjærg-Hansen A, Jensen JS et al (2008) Genetically elevated C-reactive protein and ischemic vascular disease. N Engl J Med 359:1897–1908

    Article  CAS  PubMed  Google Scholar 

  31. Avanzas P, Arroyo-Espliguero R, Cosín-Sales J, Aldama G, Pizzi C, Quiles J et al (2004) Markers of inflammation and multiple complex stenoses (pancoronary plaque vulnerability) in patients with non-ST segment elevation acute coronary syndromes. Heart 90:847–852

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Murr C, Widner B, Wirleitner B et al (2002) Neopterin as a marker for immune system activation. Curr Drug Metab 3:175–187

    Article  CAS  PubMed  Google Scholar 

  33. Avanzas P, Arroyo-Espliguero R, Kaski JC (2009) Neopterin and cardiovascular disease: growing evidence for a role in patient risk stratification. Clin Chem 55:1056–1057

    Article  CAS  PubMed  Google Scholar 

  34. Hoffmann G, Rieder J, Smolny M et al (1999) Neopterin-induced expression of intercellular adhesion molecule-1 (ICAM-1) in type II-like alveolar epithelial cells. Clin Exp Immunol 118:435–440

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgments

We also express our gratitude to all the patients who participated in this study and thereby made this work possible.

Conflict of Interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Department of Neurosurgery, The Affiliated Hospital of Weifang Medical College, 2428 Yuhe Road, Weifang, Shandong, 261031, China

    Xianwei Zeng, Guoqing Zhang, Bin Yang, Bo Zhang, Linpeng Zhang, Ying Ni, Chen Liu & Yumeng Luo

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  1. Xianwei Zeng
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  2. Guoqing Zhang
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Correspondence to Xianwei Zeng.

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Zeng, X., Zhang, G., Yang, B. et al. Neopterin as a Predictor of Functional Outcome and Mortality in Chinese Patients with Acute Ischemic Stroke. Mol Neurobiol 53, 3939–3947 (2016). https://doi.org/10.1007/s12035-015-9310-3

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