The prognostic value of hematological indices in patients with acute ischemic stroke and their correlation with major adipokines

Stella Bouziana, Konstantinos Tziomalos, Antonis Goulas, Timoleon-Achilleas Vyzantiadis, Maria Papadopoulou, Apostolos Ηatzitolios


Introduction-Aim: The association between peripheral blood haematological indices and acute ischemic stroke severity, in-hospital and long-term outcome is controversial. We aimed to evaluate this relationship and the potential association of haematological indices with serum adipokines levels and systemic inflammation.

Patients and Methods: We prospectively studied 93 patients consecutively hospitalized for acute ischemic stroke (39.8% males, age 79.7±6.3 years). Peripheral blood haematological indices and serum adiponectin, leptin and resistin levels were determined at admission. The haematological indices that were evaluated were total white blood cells count (WBC), absolute neutrophil count (NC), absolute lymphocyte count (LC), absolute monocyte count (MC), red blood cells count (RBC), hemoglobin (Hb), hematocrit (Ht), platelet count (PC), mean platelet volume (MPV) and the ratios MPV/PC (MPR), NC/LC (NLR) and PC/LC (PLR). Stroke severity at admission was evaluated with the National Institutes of Health Stroke Scale (NIHSS). In-hospital outcome was evaluated by dependency rates at discharge and in-hospital mortality. One year after discharge, functional status, incidence of cardiovascular events and all-cause mortality were recorded. Functional status was evaluated with the modified Rankin scale (mRS).

Results: None of the haematological indices predicted stroke severity or in-hospital mortality. However, patients with dependency at discharge had higher WBC (p<0.05) and NC (p<0.05). Independent predictors of dependency at discharge were prior history of acute ischemic stroke [Risk Ratio (RR) 7.55, 95% Confidence Interval (CI) 1.69-33.58, p<0.01], NIHSS score at admission (RR 1.47, 95% CI 1.17-1.84, p<0,001) and serum triglyceride levels (RR 0.98, 95% CI 0.96-0.99, p<0.05). None of the haematological indices predicted cardiovascular events or all-cause mortality during 1-year-follow-up after discharge. However, patients with adverse outcome had higher NC (p<0.05), lower LC (p<0.05) and higher NLR (p<0.05) and PLR (p<0.05). In multivariate analysis, the mRS score at discharge was the only independent predictor of adverse outcome 1 year after discharge (RR 2.78, 95% CI 1.54-5.00, p<0.001). Regarding the correlation of haematological indices with major adipokines, there was a positive correlation of adiponectin levels with NLR (r=0.295, p=0.012) and PLR (r=0.378, p=0.001), while there was a negative correlation with Hb (r=-0.252, p=0.033). The NLR (r=0.277, p=0.019) and PLR (r=0.240, p=0.043) were also positively correlated with high-sensitivity C-reactive protein (hsCRP) levels. Serum resistin levels were positively correlated with NC (r=0.278, p=0.018). The WBC (r=0.295, p=0.012) and NC (r=0.401, p<0.001) showed a positive correlation with hsCRP levels. Regarding leptin, none of the haematological indices appeared to correlate with leptin levels.   

Conclusions: Higher WBC and NC at admission predict a worse functional outcome of patients with acute ischemic stroke at hospital discharge and one year after hospitalization, due to more severe stroke with greater systemic inflammation. In addition, lower LC and higher NLR and PLR at admission seem to be associated with adverse outcome at 1 year after discharge due to a higher degree of systemic inflammation and greater disability at discharge. Adipokines appear to affect peripheral blood cell counts and are associated with haematological indices. In particular, adiponectin was positively correlated with NLR and PLR, while negatively with Hb. In addition, resistin was positively correlated with NC. These associations reflect the role of haematological indices as biomarkers of inflammation and possibly their determinant effect, through adipokines and inflammation, on the pathophysiology and prognosis of acute ischemic stroke.


acute ischemic stroke; haematological indices; adipokines; severity; in-hospital outcome; long-term outcome

Full Text:



Benjamin EJ, Blaha MJ, Chiuve SE, et al. Heart Disease and Stroke Statistics-2017 Update: A Report From the American Heart Association. Circulation 2017; 135:e146.

Bouziana S, Tziomalos K, Goulas A, et al. The role of adipokines in ischemic stroke risk stratification. Int J Stroke 2016; 11: 389-398.

Shah AD, Denaxas S, Nicholas O, et al. Neutrophil Counts and Initial Presentation of 12 Cardiovascular Diseases: A CALIBER Cohort Study. J Am Coll Cardiol 2017; 69(9): 1160-69.

Zia E, Melander O, Björkbacka H, et al. Total and differential leucocyte counts in relation to incidence of stroke subtypes and mortality: a prospective cohort study. J Intern Med 2012; 272(3): 298-304.

Pfister R, Sharp SJ, Luben R, et al. Differential white blood cell count and incident heart failure in men and women in the EPIC-Norfolk study. Eur Heart J 2012; 33(4): 523-30.

Wang Q, Tang XN, Yerani MA. The inflammatory response in stroke. J Neuroimmunol 2007; 184: 53–68.

Chu SG, Becker RC, Berger PB, et al. Mean platelet volume as a predictor of cardiovascular risk: a systematic review and meta-analysis. J Thromb Haemost 2010;8:148–56.

Quan W, Chen Z, Yang X, et al. Mean platelet volume/platelet count ratio as a predictor of 90-day outcome in large artery atherosclerosis stroke patients. Int J Neurosci 2017; 127(11): 1019-27.

Fang YN, Tong MS, Sung PH, et al. Higher neutrophil counts and neutrophil-to-lymphocyte ratio predict prognostic outcomes in patients after non-atrial fibrillation-caused ischemic stroke. Biomed J 2017; 40(3): 154-62.

Idil Soylu A, Arıkan Cortcu S, Uzunkaya F, et al. The correlation of the platelet-to-lymphocyte ratio with the severity of stenosis and stroke in patients with carotid arterial disease. Vascular 2017; 25(3): 299-306.

Li FY, Cheng KK, Lam KS, et al. Cross-talk between adipose tissue and vasculature: role of adiponectin. Acta Physiol (Oxf) 2011;203:167-80.

Maury E, Brichard SM. Adipokine dysregulation, adipose tissue inflammation and metabolic syndrome. Mol Cell Endocrinol 2010;314:1-16.

Blüher M, Mantzoros CS. From leptin to other adipokines in health and disease: facts and expectations at the beginning of the 21st century. Metabolism 2015;64:131-145.

Ding Q, White SP, Ling C, et al. Resistin and cardiovascular disease. Trends Cardiovasc Med 2011;21:20-27.

Athyros VG, Tziomalos K, Karagiannis A, et al. Should adipokines be considered in the choice of the treatment of obesity-related health problems? Curr Drug Targets 2010;11:122-135.

Hui X, Lam KS, Vanhoutte PM, et al. Adiponectin and cardiovascular health: an update. Br J Pharmacol 2012;165:574-590.

Dias CC, Nogueira-Pedro A, Barbosa CM, et al. Hematopoietic stem cell expansion caused by a synthetic fragment of leptin. Peptides 2013; 50: 24-7.

Claycombe K, King LE, Fraker PJ. A role for leptin in sustaining lymphopoiesis and myelopoiesis. Proc Natl Acad Sci U S A 2008; 105(6): 2017-21.

Masamoto Y, Arai S, Sato T, et al. Adiponectin Enhances Quiescence Exit of Murine Hematopoietic Stem Cells and Hematopoietic Recovery Through mTORC1 Potentiation. Stem Cells 2017; 35(7): 1835-48.

Procaccini C, La Rocca C, Carbone F, et al. Leptin as immune mediator: Interaction between neuroendocrine and immune system. Dev Comp Immunol 2017; 66: 120-29.

Moraes-Vieira PM, Larocca RA, Bassi EJ, et al. Leptin deficiency impairs maturation of dendritic cells and enhances induction of regulatory T and Th17 cells. Eur J Immunol 2014; 44: 794-806.

Luo Y, Liu M. Adiponectin: a versatile player of innate immunity. Journal of Molecular Cell Biology 2016; 8(2): 120-28.

Tan PH, Tyrrell HEJ, Gao L, et al. Adiponectin Receptor Signaling on Dendritic Cells Blunts Antitumor Immunity. Cancer research 2014; 74(20): 5711-22.

Han TJ, Wang X. Leptin and its receptor in hematologic malignancies. Int J Clin Exper Med 2015;8(11):19840-19849.

Aref S, Ibrahim L, Azmy E, et al. Impact of serum adiponectin and leptin levels in acute leukemia. Hematology 2013;18(4):198-203.

Hofmann JN, Liao LM, Pollak MN, et al. A prospective study of circulating adipokine levels and risk of multiple myeloma. Blood 2012;120:4418–20.

Chaliasos N, Challa A, Hatzimichael E, et al. Serum adipocytokine and vascular inflammation marker levels in Beta-thalassaemia major patients. Acta Haematol 2010;124(4):191-6.

Lewerin C, Johansson H, Lerner UH, et al. High serum adiponectin is associated with low blood haemoglobin in elderly men: the Swedish MrOS study. J Intern Med 2015;278:68-76.

Kohno K, Narimatsu H, Shiono Y, et al. High Serum Adiponectin Level Is a Risk Factor for Anemia in Japanese Men: A Prospective Observational Study of 1,029 Japanese Subjects. PLoS One 2016;11(12):e0165511.

Friedewald WT, Levy RI, Fredrickson DS. Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clin Chem 1972; 18: 499-502.

Levey AS, Bosch JP, Lewis JB, et al. A more accurate method to estimate glomerular filtration rate from serum creatinine: a new prediction equation. Modification of Diet in Renal Disease Study Group. Ann Intern Med 1999; 130: 461-470.

Matthews DR, Hosker JP, Rudenski AS, et al. Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 1985; 28: 412-419.

Katz A, Nambi SS, Mather K, et al. Quantitative insulin sensitivity check index: a simple, accurate method for assessing insulin sensitivity in humans. J Clin Endocrinol Metab 2000; 85: 2402-2410.

Madjid M, Fatemi O. Components of the complete blood count as risk predictors for coronary heart disease: in-depth review and update. Tex Heart Inst J 2013; 40(1): 17-29.

Cheng ML, Chen CM, Gu PW, et al. Elevated levels of myeloperoxidase, white blood cell count and 3-chlorotyrosine in Taiwanese patients with acute myocardial infarction. Clin Biochem 2008; 41(7-8): 554-60.

Libby P. Inflammation in atherosclerosis. Nature 2002; 420(6917): 868-74.

Povroznik JM, Engler-Chiurazzi EB, Nanavati T, et al. Absolute lymphocyte and neutrophil counts in neonatal ischemic brain injury. SAGE Open Med 2018; 6: 2050312117752613.

Mirabelli-Badenier M, Braunersreuther V, Lenglet S, et al. Pathophysiological role of inflammatory molecules in paediatric ischaemic brain injury. Eur J Clin Invest 2012; 42: 784–794.

Winderal M, Winderal ME, Kinn J, et al. Long lasting local and systemic inflammation after cerebral hypoxic ischemic in newborn mice. PLoS ONE 2012; 7: e36422.

Strecker JK, Schmidt A, Schäbitz WR, et al. Neutrophil granulocytes in cerebral ischemia - Evolution from killers to key players. Neurochem Int 2017; 107: 117-26.

Yilmaz E, Bayram Kacar A, et al. The relationship between hematological parameters and prognosis of children with acute ischemic stroke. Childs Nerv Syst 2018; 34(4): 655-61.

Fan L, Gui L, Chai EQ, et al. Routine hematological parameters are associated with short- and long-term prognosis of patients with ischemic stroke. J Clin Lab Anal 2018; 32(2).

Lee JH, Kwon KY, Yoon SY, et al. Characteristics of platelet indices, neutrophil-to-lymphocyte ratio and erythrocyte sedimentation rate compared with C reactive protein in patients with cerebral infarction: a retrospective analysis of comparing haematological parameters and C reactive protein. BMJ Open 2014; 4(11): e006275.

Farah R, Samra N. Mean platelets volume and neutrophil to lymphocyte ratio as predictors of stroke. J Clin Lab Anal 2018; 32(1).

Tokgoz S, Kayrak M, Akpinar Z, et al. Neutrophil lymphocyte ratio as a predictor of stroke. J Stroke Cerebrovasc Dis 201; 22(7): 1169-74.

Celikbilek A, Ismailogullari S, Zararsiz G. Neutrophil to lymphocyte ratio predicts poor prognosis in ischemic cerebrovascular disease. J Clin Lab Anal 2014; 28: 27–31.

Gokhan S, Ozhasenekler A, Mansur Durgun H, et al. Neutrophil lymphocyte ratios in stroke subtypes and transient ischemic attack. Eur Rev Med Pharmacol Sci 2013; 17: 653–57.

Yu S, Arima H, Bertmar C, et al. Neutrophil to lymphocyte ratio and early clinical outcomes in patients with acute ischemic stroke. J Neurol Sci 2018; 387: 115-18.

Maestrini I, Strbian D, Gautier S, et al. Higher neutrophil counts before thrombolysis for cerebral ischemia predict worse outcomes. Neurology 2015; 85: 1408–16.

Brooks SD, Spears C, Cummings C, et al. Admission neutrophil-lymphocyte ratio predicts 90 day outcome after endovascular stroke therapy. J Neurointerv Surg 2014; 6: 578–83.

Qun S, Tang Y, Sun J, et al. Neutrophil-To-Lymphocyte Ratio Predicts 3-Month Outcome of Acute Ischemic Stroke. Neurotox Res 2017; 31(3): 444-52.

Zhai M, Wang J, Yu L, et al. Neutrophil and lymphocyte ratios for the predictive analysis of the prognosis in patients with acute cerebral infarction. Chin J Cerebrovasc Dis 2017; 14: 82–6.

Zhao L, Chen X, Xu X, et al. Predictive value of leukocyte differential count in patients with acute cerebral infarction. J Med Postgra 2015; 28: 1148–51.

Gao W, Han Z, Du Y, et al. Association between neutrophil lymphocyte ratio and prognosis of acute ischemic stroke. J Clin Pathol Res 2014; 34: 509–13.

Guo Z, Yu S, Xiao L, et al. Dynamic change of neutrophil to lymphocyte ratio and hemorrhagic transformation after thrombolysis in stroke. J Neuroinflammation 2016; 13: 199.

Xue J, Huang W, Chen X, et al. Neutrophil-to-Lymphocyte Ratio Is a Prognostic Marker in Acute Ischemic Stroke. J Stroke Cerebrovasc Dis 2017; 26(3): 650-57.

Zhang J, Ren Q, Song Y, et al. Prognostic role of neutrophil-lymphocyte ratio in patients with acute ischemic stroke. Medicine (Baltimore) 2017; 96(45): e8624.

Balta S, Demirkol S, Kucuk U. The platelet lymphocyte ratio may be useful inflammatory indicator in clinical practice. Hemodial Int 2013; 17: 668–69.

Altintas O, Altintas MO, Tasal A, et al. The relationship of platelet-to-lymphocyte ratio with clinical outcome and final infarct core in acute ischemic stroke patients who have undergone endovascular therapy. Neurol Res 2016; 38(9): 759-65.

Mabuchi T, Yatsuya H, Tamakoshi K, et al. Association between serum leptin concentration and white blood cell count in middle-aged Japanese men and women. Diabetes Metab Res Rev 2005; 21(5): 441-7.

Laharrague P, Corberand J, Penicaud L, et al. Relationship of human plasma leptin concentration with blood cell parameters. Haematologica 2000; 85(9): 993-4.





  • There are currently no refbacks.