Study On The Relationship Of Peripheral Neutrophil Count With Intracranial Atherosclerotic Stenosis

Background and Objective:Intracranial atherosclerotic lesions are characterized by progressive lipid deposition,fibrous tissue proliferation and inflammatory cell infiltration and involve the intracranial supply artery system,eventually resulting in intracranial atherosclerotic stenosis.Previous studies have shown that in the worldwide,especially in the Asian population,intracranial atherosclerotic lesions are not only the main risk factors of ischemic stroke,but also an important pathogenesis.Thus,many researchers are paying more and more attention to the etiology of intracranial atherosclerosis.There is evidence suggesting that inflammatory processes contribute to both the initiation and progression of atherosclerosis.Neutrophils are the largest number of natural immune effector cells.In the past,they were considered to be the main role of acute inflammation.In recent years,neutrophils are considered to be the main participants in chronic inflammation,especially in the evolution of atherosclerosis.Although intracranial atherosclerosis is viewed as a part of atherosclerotic disease,it is still unclear whether ICAS is also related to the inflammatory response because of the particularity of the anatomical structure of intracranial artery compared with extracranial artery.Accordingly,the purpose of this study was to assess the relationship between peripheral neutrophil count and the presence of ICAS,which was helpful for early identification of high-risk patients,early diagnosis and control of the occurrence and progress of ICAS,so as to provide some valuable clues for disease prevention and clinical treatment.Methods:Study subjects were prospectively recruited from January 2014 to June 2018 of Department of Neurology of Qingdao Municipal Hospital.All subjects met the inclusion criteria and had complete clinical data.A total of 2847 individuals were included in our study in strict accordance with the inclusion criteria,including 1363 with acute ischemic stroke and 1484 normal controls without stroke.We have strict age and gender matching between the case and control subjects.The presence of ICAS was determined by magnetic resonance angiography(MRA),and the effect of neutrophil count on different locations of ICAS and ICAS burdens were also evaluated to help us develop a deeper understanding of ICAS.Depending on the presence of ICAS,the patients were divided into subjects with ICAS and without ICAS,and the number and different locations of ICAS were recorded.The basic clinical data,including age,gender,hypertension,diabetes,coronary heart disease,history of smoking,history of alcohol use and previous history of stenosis,were collected.And all of them accepted related blood biochemical tests including lipoprotein,triglyceride,total cholesterol,high-density lipoprotein(HDL),low-density lipoprotein(LDL),neutrophils,lymphocytes,neutrophil to lymphocyte ratio(NLR)and glucose.Statistical analysis was performed using R statistical software(version 3.4.3).The survey population according to the neutrophil count value quartile levels into Q1,Q2,Q3 and Q4 four groups.Logistic regression analysis was performed across neutrophil quartiles to examine the association of neutrophil count with ICAS.Results:Among 2847 individuals included in this study,individuals with ICAS had higher neutrophil counts than those without ICAS in groups with and without stroke(4.320(3.493-5.880)VS 3.990(3.150-5.040),P<0.0001 for stroke group,3.670(2.850-4.625)VS 3.420(2.750-4.270),P=0.0097 for group without stroke).The multivariable logistic regression analysis showed that the third and fourth quartiles were independent predictors of ICAS in all the subjects(Q3:OR 1.81,95%CI 1.39-2.37,P<0.0001,Q4:OR 2.29,95%CI 1.70-3.10,P<0.0001)and patients in the fourth quartile had a higher risk for the occurrence of ICAS in stroke group(Q4:OR 2.82,95%CI 1.79-4.48,P<0.0001).However,there was no significant association between neutrophil count and ICAS in the group without stroke(P>0.05).Conclusions:The levels of circulating neutrophils were associated with the presence of ICAS.Our findings suggest that neutrophils may play a role in the pathogenesis of stroke related to ICAS and emphasize the need to develop proper strategies to control neutrophil response for the treatment of ICAS.Given the difference in neutrophil count between subjects with and without stroke,neutrophils may increase the occurrence of symptomatic intracranial atherosclerotic stenosis.