Vol. 43 | No. 2 | July-December 2015 Back

Open Access

The Neutrophil-Lymphocyte Ratio Predicts Mortality in Acute Coronary Syndrome (NLR-ACS): A Meta-analysis

Edgar Wilson G. Timbol, John Daniel A. Ramos, Jaime Alfonso M. Aherrera, Lowe L. Chiong, Felix Eduardo R. Punzalan Jr
Dec 2015 DOI 10.69944/pjc.b163abe16b

Abstract

BACKGROUND: The neutrophil to lymphocyte ratio (NLR) is a recently described biomarker of inflammation that is an independent predictor of death and myocardial infarction. It integrates two leukocyte subtype counts with opposing actions in terms of vascular inflammation. This can be readily derived from a simple routine complete blood count taken during admission. We conducted a meta-analysis on the usefulness of a high NLR value in predicting mortality among patients with acute coronary syndrome (ACS). 

OBJECTIVE: To determine the association of neutrophil to lymphocyte ratio and mortality among patients with acute coronary syndrome. 

METHODS: We conducted a systematic search of studies using MEDLINE, EMBASE, ScienceDirect, and Cochrane Central Register of Controlled Trials databases and examined reference lists of studies that used the NLR in ACS patients in reporting mortality. We identified 12 studies that met inclusion criteria including 2 local studies. The study title, follow-up period, neutrophil-lymphocyte ratio, and mortality outcomes were extracted from these studies. Each study was assessed using the Newcastle-Ottawa Quality Assessment Scale. These were done independently by the authors resolving disagreements, if any, by discussion. The outcome of interest was assessed using Mantel Haenzel analysis to compute for odds ratio, and evaluation of heterogeneity were carried out using Review Manager (RevMan) 5.0.18 (The Nordic Cochrane Centre, The Cochrane Collaboration). 

RESULTS: Data were combined from 12 studies enrolling 9,835 patients. Pooled analysis showed that a high NLR was predictive of increased total mortality among patients presenting with ACS compared to those patients whose NLR were not high (8.65% vs 2.26%, OR 4.10, 95% CI 3.36, 5.00; p<0.00001). Data were homogenous (I2=0%) and there was no evidence of publication bias by funnel-plot method. Thirty-day mortality, including in-hospital death, was likewise increased among those with high NLR (7.78% vs 2.22%, OR 3.67, 95% CI 2.93, 4.58; p<0.00001; I2=0%). 

CONCLUSION: A high NLR value is associated with high mortality among patients with ACS. This parameter can be easily derived from a routine complete blood count taken during hospital admission and is a useful parameter to determine prognosis and may indicate a more intensive approach to therapy. 

Keywords: neutrophil-lymphocyte ratio, NLR, acute coronary syndrome, mortality, ACS, NSTEMI, STEMI, unstable angina, ST-segment myocardial infarction, non-ST-segment myocardial infarction

References
  1. Braunwald E, Antman EM. ST-Elevation Myocardial Infarction: Pathology, Pathophysiology, and Clinical Features. In: Libby P, Bonow RO, Mann DL, Zipes DP (eds). Braunwald’s Heart Disease: A Textbook of Cardiovascular Medicine, 8th ed. Philadelphia: Saunders Elsevier; 2007. 
  2. Cho KH, Jeong MH, Ahmed K, et al. Value of early risk stratification using hemoglobin level and neutrophil-to-lymphocyte ratio in patients with ST-elevation myocardial infarction undergoing primary percutaneous coronary intervention. Am J Cardiol. 2011 Mar 15;107(6):849-56. 
  3. Park JJ, Jang HJ, Oh IY, et al. Prognostic value of neutrophil to lymphocyte ratio in patients presenting with ST-elevation myocardial infarction undergoing primary percutaneous coronary intervention. Am J Cardiol. 2013 Mar 1;111(5):636-42. 
  4. Nunez J, Nunez E, Bodi V, Sanchis J, et al. Usefulness of the Neutrophil to Lymphocyte Ratio in Predicting Long-Term Mortality in ST Segment Elevation Myocardial Infarction. Am J Cardiol. 2008 Mar 15;101(6):747-52. 
  5. Wang X. Neutrophil to lymphocyte ratio in relation to risk of all-cause mortality and cardiovascular events among patients undergoing angiography or cardiac revascularization: A meta analysis of observational studies. Atherosclerosis. 2014;234(1):206– 13. 
  6. Aherrera J, Chiong L, Reganit P, Punzalan F. Association of Neutrophil-Lymphocyte Ration (NLR) with Outcomes in Patients Admitted for and Acute Coronary Syndrome. Philipp J Cardiol 2014;42(1):1-9. 
  7. Ross R. Atherosclerosis—An inflammatory disease. N Engl J Med 1999;340:115-126. 
  8. Haim M, Bokyo V, Goldbourt U, Battler A, Behar S. Predictive value of elevated white blood cell count in patients with preexisting coronary heart disease: the Bezafibrate Infarction Prevention Study. Arch Int Med 2004;164; 433-9. 
  9. Balgua J, Tenerife A, Caole I. Association of elevated white blood cell count in myocardial infarction: Prospective cross sectional study. Unpublished. 
  10. Raguero M, Gumatay W, Nierras P, Te C Sison E, Punzalan F. Association of white blood cell (WBC) count in predicting risk for adverse cardiovascular events and in-hospital outcome among patients with acute myocardial infarction: A prospective cohort study. Unpublished. 
  11. Tousoulis D, Antoniades C, Koumallos N, Stefanadis C. Pro inflammatory cytokines in acute coronary syndromes: from bench to bedside. Cytokine Growth Factor Rev 2006;17:225-33. 
  12. Kirtane AJ, Bui A, Murphy SA, Barron HV, Gibson CM. Association of peripheral neutrophilia with adverse angiographic outcomes in ST-elevation myocardial infarction. Am J Cardiol 2004;93:532-6. 
  13. Ommen SR, Gibbons RJ, Hodge DO, Thomson SP. Usefulness of the lymphocyte concentration as a prognostic marker in coronary artery disease. Am J Cardiol 1997;79:812-4. 
  14. Chatterjee S, Wetterslev J, Sharma A, Mukherjee D. Association of Blood Transfusion with Increased Mortality in Myocardial Infarction. JAMA Int Med 2013;173(2):132-139. 
  15. Tamhane UU, Aneja S, Montgomery D, Rogers EK, Eagle KA, Gurm HS. Association between admission neutrophil to lymphocyte ratio and outcomes in patients with acute coronary syndrome. Am J Cardiol. 2008 Sep 15;102(6):653-7. 
  16. Azab B, Zaher M, Weiserbs KF, Torbey E, Lacossiere K, Gaddam S, Gobunsuy R, Jadonath S, Baldari D, McCord D, Lafferty J. Usefulness of neutrophil to lymphocyte ratio in predicting short- and long-term mortality after non-ST-elevation myocardial infarction. Am J Cardiol 2010;106:470e476. 
  17. Gul M, Uyarel H, Ergelen M, et al. Predictive Value of Neutrophil to Lymphocyte Ratio in Clinical Outcomes of Non-ST Elevation Myocardial Infarction and Unstable Angina Pectoris: A 3-Year Follow-Up. Clin Appl Thromb Hemost 2014;20(4):378-384. 
  18. Han YC, Yang TH, Kim DI, et al. Neutrophil to Lymphocyte Ratio Predicts Long-Term Clinical Outcomes in Patients with ST-Segment Elevation Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention. Korean Circ J 2013;43:93-9. 
  19. Akpek M, Kaya MG, Lam YY, Sahin O, Elcik D, Celik T, Ergin A, Gibson CM. Relation of neutrophil-lymphocyte ratio to coronary flow to in-hospital major adverse cardiac events in patients with ST-elevated myocardial infarction undergoing primary coronary intervention. Am J Cardiol. 2012 Sep 1;110(5):621-7. 
  20. Punzalan KA, Encabo RR. Neutrophil to Lymphocyte Ratio on Admission as a Predictor of In-Hospital Mortality Among Acute Coronary Syndrome Patients in Cardinal Santos Medical Center. Presented at: 32nd World Congress of Internal Medicine (October 24-28, 2014). 
  21. Duffy BK, Gurm HS, Rajagopal V, Gupta R, Ellis SG, Bhatt DL. Usefulness of an elevated neutrophil to lymphocyte ratio in predicting long-term mortality after percutaneous coronary intervention. Am J Cardiol. 2006;97:993–996. 
  22. Ergelen M, Urarel H, et al. Predictive Value of Elevated Neutrophil to Lymphocyte Ratio in Patients Undergoing Primary Angioplasty for ST Segment Elevation Myocardial Infarction. Clin Appl Thromb Hemost 2014;20(4):427-432. 
  23. Blum A, Sclarovsky S, Rehavia E, Shohat B. Levels of T-lymphocyte sub- populations, interleukin-1 beta, and soluble interleukin-2 receptor in acute myocardial infarction. Am Heart J 1994;127:1226- 30. 
  24. Baldus S, Heeschen C, Meinertz T, et al. Myeloperoxidase serum levels predict risk in patients with acute coronary syndromes. Circulation 2003;108:1440-5. 
  25. Chia S, Nagurney JT, Brown DF, et al. Association of leukocyte and neutrophil counts with infarct size, left ventricular function and outcomes after percutaneous coronary intervention for ST-elevation myocardial infarction. Am J Cardiol. 2009;103(3):333-337. 
  26. Mallat Z, et al. Immunomodulation to combat atherosclerosis: The potential role of immune regulatory cells. Expert Opin Biol Ther 2004;4:1387-1393. 
  27. Nunez J, et al. Relationship between low lymphocyte count and major cardiac events in patients with acute chest pain, a nondiagnostic electrocardiogram and normal troponin levels. Atherosclerosis 2009;206:251-257. 
  28. Furman MI, Gore JM, Anderson FA, et al. Elevated leukocyte count and adverse hospital events in patients with acute coronary syndromes: findings from the Global Registry of Acute Coronary Events (GRACE). Am Heart J 2004;147:42-8. 
  29. Horne BD, Anderson JL, John JM, Weaver A, Bair TL, Jensen KR, Renlund DG, Muhlestein JB. Which white blood cell subtypes predict increased cardiovascular risk? J Am Coll Cardiol 2005;45:1638e1643. 
  30. Azab B, Chainani V, et al. Neutrophil–Lymphocyte Ratio as a Predictor of Major Adverse Cardiac Events Among Diabetic Population: A 4Year Follow-Up Study. Angiology 2013;64(6):456-465.
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