Predictive value of neutrophil to lymphocyte ratio for mortality in acute cerebral infarction patients Chun Li1, Gaofeng Zhao2, Qianyi He1, Hongcan Zhu1, Yanjie Jia1 and Junfang Teng1* 1

Department of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, PR China Department of Neurology, The Third People’s Hospital of Zhengzhou City, Zhengzhou, Henan Province, PR China

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Abstract: This study was to explore the correlation between the ratio of neutrophils and lymphocyte and the disease severity and prognosis of acute brain infarction. 506 cases of hospitalized patients with acute cerebral infarction (Group of acute cerebral infarction) were selected in neurology department of The First Affiliated Hospital of Zhengzhou University from January 2012 to December 2013. The routine blood test were detected and calculated along with the Neutrophil Count and Lymphocyte Count Ratio (NLR). National Institutes of Health Stroke Scale (NIHSS) was adopt to assess the illness severity. Modified Rankin Scale (MRS) were conducted to evaluate the prognosis of onset of 90 days. Patients general condition were inquired in detail. What had been detected were blood lipid, fasting blood glucose (FBG), uric acid (UA), homocysteine (Hcy), C-reactive protein (CRP), total bilirubin (TBIL) and carotid artery ultrasonography. 506 cases with healthy physical examination in the same period were selected as control group. the NLR of acute cerebral infarction group with 4.78±1.567 was significantly higher than control group with 3.64±1.090; the NLR of group with NIHSS less than 5 points was 3.36±0.610, the NLR of group with NIHSS not less than 5 points and not more than 20 points was 4.63±0.993, the NLR of group with NIHSS more than 20 points was 7.06±0.898, there were statistical differences between these three groups. The NLR of group with good prognosis was 3.99±1.910, the NLR of group with poor prognosis was 6.05±3.097, the NLR between these two groups were with statistically significance; the follow-up of 90th day onset, there were 56 patients death. And the NLR of death people group was 9.61±3.871, which was apparently higher than survival group with NLR of 4.21±2.346, there were statistically significant between these two groups. Unconditional Logistic regression analysis results showed that NLR, FBG, WBC, age, basic NIHSS score were the independent risk factors of cerebral infarction. The best cut-off value of NLR predicting death was 4.850. NLR was the independent risk factor to predict the short-term prognosis and death for patients with acute cerebral infarction. Keywords: Ratio of neutrophils and lymphocyte; acute cerebral infarction; neurologic deficits; prognosis.

INTRODUCTION Cerebral infarction was one of the disease with high incidence, morbidity and mortality. The improved prognosis could relieve the mental stress, and reduce the economic burden of the patients’ family and society. So the prevention of cerebral infarction was particularly significant. The report from home and abroad had reported the significance of age, hospitalized time, baseline NIHSS score and infarction volume on acute cerebral infarction (Baggs et al, 2002; Li FK et al, 2006; Wang J et al, 2014), but the conclusion was inconsistent. The existing research reported that NLR was correlated with variety of cardiovascular disease, severity of tumor and prognosis (Walsh SR et al, 2005; Tamhane UU et al, 2008; Azab B et al, 2010). There was few studies for the assessed significance of severity and prognosis for NLR and acute cerebral infarction. The ratio of neutrophils and lymphocyte was related with mortality of myocardial infarction and acute ischemic stroke, while, it was unclear that if it was related with severity of acute cerebral infarction and whether it could be the independent predictor factor of the mortality in cerebral infarction. *Corresponding author: e-mail: [email protected] Pak. J. Pharm. Sci., Vol.29, No.2(Suppl), March 2016, pp.737-743

Prospective research had been employed to analyze the relation of NLR and severity and short-term prognosis of acute cerebral infarction.

MATERIAL AND METHOD Study objective The 506 cases of hospitalized patients with acute cerebral infarction were selected in neurology department of The First Affiliated Hospital of Zhengzhou University from January 2012 to December 2013, Patient's age is greater than 18 years old, The trial has been approved by the local ethics committee; All the patients met the diagnosis standard requirement of China’s Guidelines of Diagnosis and Treatment of Acute Ischemic Stroke in 2010, the duration from onset to hospitalization was not more than 24 hours. Most patients were with focal neurologic deficits, and few happened nerve function defect symptoms and signs. The skull CT or MRI confirmed it lasted few hours. All cases of patients excluded the following situation: Onset time is more than 24 hours, brain cerebral hemorrhage were confirmed by CT or MRI; TIA; patients with sequela of stroke; patients with history of mental disease or confused neural function evaluation of other diseases; patients with tuberculosis, rheumatism,

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Predictive value of neutrophil to lymphocyte ratio for mortality in acute cerebral infarction patients tumors, acute infection, trauma or within 2 weeks after the surgery; patients applied steroid medicines; with brainstem (infratentorial) infarct, which is known to have a direct effect on mortality, patients with serious disease such as heart, liver, kidney and etc. There were 292 cases of male, 214 cases of female, aged 26~87. At the same time, 506 cases of age and gender matched healthy checkup people in the same period were randomly selected as normal controls. Method Firstly, while on admission, the elbow venous blood were collected for blood routine detection and random blood sugar. NLR and BP were detected by the same specially trained physician. NIHSS were adopt to evaluate the degree of nerve function defect score. According to the grading results, all the patients were divided into three groups: mild nerve function defect group with NIHSS less than 5 points, moderate nerve function defect group with NIHSS not less than 5 points and not more than 20 points and severe neurologic deficits group with NIHSS more than 20 points. Based on CISS classification, cerebral infarction could be classified into 5 types as atherothrombosis (AT), cardio embolism (CE), acute perforating small artery occlusion (APSAO), other etiologies (OE) and undetermined etiologies (UE). And collect the patient’s gender, age, smoking history, drinking, hypertension, diabetes, coronary heart disease and atrial fibrillation. Secondly, in the next morning of patient being hospitalized, the fasting median cubital vein blood had been collected to detect the blood lipid, FBG, UA, Hcy, CRP and TBIL. Then carotid arteries ultrasonography were performed. Thirdly, on the 90th day of cerebral infarction incidence, face to face follow-up or telephone follow-up were performed to query details of patient’s recovery. The modified Rankin Scale (MRS) were adopted to score, MRS score 0~2 points were the patients with good prognosis, 3 points or above, including death, were the patients with poor prognosis.

STATISTICAL ANALYSIS All data were adopt SPSS16.0 software. The measurement data were measured as mean ± standard deviation. Mean comparison between measurement data set were adopt independent sample t test. Multiply sets of measurement data comparison with analysis of variance. Comparison between each two groups were employed Bonferroni method. Comparison between count data set was used chi-square analysis. The factors associated with prognosis were first adopted for single factor Logistic regression analysis, then the influence factors with significant difference through single factor analysis were conducted for unconditioned Logistic regression analysis. Receiver operating characteristic (ROC) curves were drawn for the 738

NLR, WBC counting, FBG, age and basic NIHSS scoring. Area under curve (AUC) was calculated with 95% CI for these variables and compared with each other. Cut-off values were determined for each variable. Statistical diagnostic measures were calculated with 95% CI. P20 score were the group with severe neurologic deficits (n=106 NLR was 7.06±0.898, which were significantly higher than NIHSS