Associations Of The Neutrophil To Lymphocyte Ratio With Intracranial Artery Stenosis And Ischemic Stroke

Objective: Acute ischemic stroke(AIS),which can cause neurological deficits worldwide,imposes a heavy burden on the global economy.AIS caused by ICAS can still face a heavy difficulty in treatment.With advances in medication and mechanical throttling recanalization,more and more patients get recovery from AIS.However,there is still a great need to develop neuroprotective therapeutic agents targeting the pathogenesis of AIS to extend the time window of intervention and further improve functional prognosis.Although a large number of studies have explored the risk factors of AIS,and the management of risk factors has achieved effective prevention effect.But due to the failure of identifying potential molecular mechanisms of AIS,there is a lack of personalized treatment and post-stroke management for different patients.Inflammation has been found to play a vital role in the formation and development of atherosclerosis,with various inflammatory parameters being associated with artery stenosis as well as ischemic events.Neutrophil to lymphocyte ratio(NLR)is an indicator of overall systemic inflammatory status in the Asian population.However,the pathogenicity of ICAS and the association of NLR with ICAS remains unclear.Moreover,research focusing on the risk of AIS with the presence of high NLR and ICAS is limited.Accordingly,this study aimed to examine the differential associations of NLR with ICAS and ischemic stroke among a large and high-risk population,in order to explore whether ICAS mediates the association between NLR level and AIS risk.Methods: A total of 2989 participants aged at least 40 years old were included in this study.All participants were from the cerebrovascular database established by the Department of Neurology of Qingdao Municipal Hospital.To assess ICAS and AIS status,all participants underwent cranial magnetic resonance imaging.Acute infection,tumor and other diseases can cause changes in serum NLR level,and atrial fibrillation and other diseases can cause pathological changes in AIS and ICAS.All participants excluded related factors.All fasting blood samples were collected within 24 hours after admission.The clinical history and other relevant information are provided by the relevant records and questionnaires in the case system.Based on AIS diagnosis and ICAS status,the cerebrovascular database was grouped in two ways: AIS vs.non-AIS;ICAS vs.non-ICAS.Continuous variables were expressed as median(50th)values and interquartile ranges(25th and 75th),compared by the Mann–Whitney U-test while categorical variables were presented as frequency and percentage,analyzed by χ2 test.The main analyses were conducted in 2 steps.Firstly,multivariable logistic regression was used to estimate the odds ratio(OR)of NLR for ischemic stroke.Unadjusted ORs were calculated from a univariable model(model 1).In model 2,risk factors-adjusted OR was estimated.In model 3,the presence of ICAS was added to model 2.Secondly,to estimate the mediated proportion of the effect of NLR on ischemic stroke,a parametric mediation analysis was conducted.In this mediation analysis,the effect was defined in terms of the difference in regression coefficient by logistic regression models.The total effect(TE)of NLR on AIS was estimated and was divided into direct effect and the mediated effect(ME)through ICAS.Additionally,the mediated proportion(ie,ME/TE)was estimated.For the comparison among groups and regression analysis,SPSS software version 23.0for Windows(SPSS Inc.,Chicago,IL)was used.For mediate analysis,R software was used.The results were all considered as statistically significant if the two-tailed P value was less than 0.05.Results: A total of 2989 individuals were included in this analysis,among whom 1867 patients with acute ischemic stroke(612 with ICAS and 1255 without ICAS)and 1122non-stroke controls(239 with ICAS and 883 without ICAS).NLR levels(median 2.01,interquartile range 1.49–3.00)were higher in patients with stroke than those(median 1.76,interquartile range 1.33–2.44,p < 0.001)in controls without stroke.Patients with ICAS had higher NLR levels than those without ICAS(p < 0.001).In the multivariate logistic analysis adjusted for potential risk factors,NLR(OR = 1.125,95%CI 1.070–1.183)and ICAS(OR = 1.638,95%CI 1.364–1.967)were significantly associated with AIS;NLR levels were also related to ICAS risk.Furthermore,four groups were divided according to the quartile of NLR concentration.Compared with the first quartile,the second(OR =1.276,95%CI 1.030–1.580),third(OR = 1.528,95%CI 1.228–1.903)and fourth(OR =1.870,95%CI 1.487–2.353)quartiles were independent risk predictors for ischemic stroke(P for trend < 0.001);the third(OR = 1.394,95%CI 1.092–1.779)and forth(OR = 2.196,95%CI 1.729–2.790)quartiles were independent predictors for ICAS risk(P for trend <0.001).Mediation analysis showed that the 14.4% risk of AIS associated with NLR was mediated by ICAS.Conclusions and Significance: The current study demonstrated that NLR was significantly associated with ICAS and ischemic stroke;ICAS partially mediated the association between NLR and AIS.The results suggest that the dynamics of inflammatory cells are involved in atherosclerotic plaque rupture,and serum NLR level may be a novel marker for predicting the risk of ICAS and AIS.