Study On The Correlation Between Leukoaraiosis And Novel Inflammatory Markers In Peripheral Blood

Background and purpose: leukoaraiosis(LA)is an imaging manifestation of white matter lesions caused by a variety of different causes,which is very common in the elderly.In magnetic resonance imaging,LA is usually divided into periventricular white matter hyperintensity(PVH)and deep white matter hyperintensity(DWMH)according to different anatomical regions.Lesions in different regions of the brain are associated with different clinical outcomes.At present,the pathogenesis of LA has not been fully elucidated.Inflammatory pathogenesis may be involved in white matter lesions.Novel inflammatory markers in peripheral blood: neutrophil-to-lymphocyte ratio(NLR),monocyte-to-lymphocyte ratio(MLR),platelet-to-lymphocyte ratio(PLR)and systemic immune-inflammation index(SII)are the research hotspots in recent years,they can reflect the inflammatory state of the body.A number of studies have confirmed its important reference value for the prognosis of a variety of diseases,but the correlation between them and LA is rarely reported.This study aims to analyze whether chronic low-level inflammation is involved in the occurrence and development of leukoaraiosis based on the levels of NLR,MLR,PLR and SII,and to explore whether there are differences in the correlation between different parts of white matter lesions,so as to provide a theoretical basis for better intervention measures.Methods: Inpatients who had completed cranial magnetic resonance imaging,blood cell and blood biochemical examinations in the 967 Hospital of the Joint Logistic Support Force of the Chinese People’s Liberation Army from February 2019 to June2020 were consecutively enrolled.Patients with severe organic intracranial lesions,hematological diseases,rheumatic immune diseases,malignant tumors,long-term use of immunosuppressants or glucocorticoids and other drugs that had an impact on the observed indicators,patients with acute or chronic infections or anti-infective drugs,and patients with recent stress such as surgery and trauma history were excluded.The patients were grouped according to the regions of white matter lesions and Fazekas visual score.The differences between the LA group and the non-LA group were compared,and binary Logistic regression model was used to analyze whether the occurrence of LA was independently associated with higher NLR,MLR,PLR,and SII.Based on the presence of LA,the patients were further grouped according to the regions of white matter lesions.The patients with PVH and DWMH only were compared to observe the differences in the levels of novel inflammatory markers in peripheral blood between different locations of white matter lesions.The degree of white matter lesions was further graded according to the Fazekas visual scale,and the ordinal logistic regression model was used to analyze the effect of NLR,MLR,PLR and SII on the aggravation of PVH and DWMH lesions.Results: 1.Univariate analysis showed that the proportion of high NLR in individuals with LA was higher than that in individuals without LA(P = 0.042).There was no significant difference in MLR,PLR,and SII between the two groups.After adjusting for a series of major confounding factors,multivariate Logistic regression analysis showed that NLR was not independently associated with the occurrence of LA(OR = 1.35,95%CI: 0.87～2.07,P = 0.178).2.There were significant differences in NLR and MLR levels between patients with only PVH and those with only DWMH.NLR and MLR levels were higher in patients with only PVH(NLR,P=0.026;MLR,P=0.001).3.There was a significant difference in NLR between the patients without PVH and those with PVH(P = 0.015),but there was no significant difference in MLR(P = 0.051).There was no significant difference in NLR and MLR levels between the group without DWMH and the group with DWMH(NLR,P=0.273;MLR,P=0.256).4.With the aggravation of PVH,the levels of NLR and MLR showed an increasing trend(NLR,P<0.001;MLR,P=0.012),and there was no significant difference in PLR and SII among groups.Further ordinal Logistic regression showed that after adjusting for a series of confounding factors,NLR level was still significantly positively correlated with the severity of PVH lesions(OR = 1.45,95%CI: 1.08～1.94,P = 0.013)were independent risk factors for the severity of PVH,while MLR was not associated with the severity of PVH(OR = 1.19,95%CI: 0.88～1.60;P = 0.252).There were no significant differences in NLR,MLR,PLR,SII among DWMH groups with different degrees of lesion.5.Age,hypertension and(or)stroke history were independently associated with the aggravation of PVH and DWMH(OR > 1,P < 0.05).The degree of PVH lesions was independently positively correlated with the level of homocysteine(OR = 1.034,95%CI:1.004～1.063;P = 0.025),and negatively correlated with uric acid level(OR = 0.998,95%CI: 0.996～0.999;P = 0.007).There was no correlation between the severity of DWMH and the levels of homocysteine and uric acid.Conclusions: A higher NLR level is associated with a higher risk of periventricular white matter lesions,but not with a higher risk of deep white matter lesions,suggesting that NLR-mediated inflammatory response reflecting the body’s chronic inflammatory state may be involved in the pathogenesis of periventricular white matter lesions.