Risk Factors Of White Matter Lesions And Its Correlation With Lipoprotein-associated Phospholipase A2

Background and ObjectiveWhite matter lesion was a common type of cerebral small vascular disease.On magnetic resonance imaging(MRI),it shows high signal on T2-weighted imaging and fluid attenuated inversion recovery(FLAIR),so it was also called white matter hyperintensities(WMH).Previous research suggested that WML is closely related to stroke,cognitive dysfunction,movement and gait abnormalities,which could seriously affect the health of the elderly people.The main risk factors of WML include age,hypertension and other vascular risk factors,but the specific etiology and pathogenesis of WML were not clear.WML could be divided into periventricular white matter lesions(PWML)and deep white matter lesions(DWML).Studies have shown that the incidence,clinical effect and pathogenesis of PWML and DWML are different.Previous studies have found that vascular inflammatory markers(such as C-reactive protein,homocysteine,etc.)are related to the severity of WML.Lipoprotein-associated phospholipase A2(Lp-PLA2),as a new vascular inflammatory marker,is mainly produced by inflammatory cells in atherosclerotic plaques and exists mainly in the form of low density lipoprotein(LDL)and high density lipoprotein(HDL)complex in blood circulation.Lp-PLA2 promotes atherosclerosis through a series of mechanisms,including vascular inflammation,endothelial dysfunction and plaque stability.Previous studies have found that Lp-PLA2 levels are closely related to coronary atherosclerotic heart disease and stroke.However,the relationship between Lp-PLA2 levels and white matter lesions is still controversial.The purpose of this study was to explore the risk factors of WML and its relationship with Lp-PLA2 levels.Materials and methods1.According to the inclusion and exclusion criteria,a total of 181 patients admitted to the Second Affiliated Hospital of Zhengzhou University from September 2017 to June 2019 were included in this study including 99 males and 82 females.Clinical data of patients,including age,gender,smoking,drinking,hypertension,diabetes,coronary heart disease,hyperlipidemia and atrial fibrillation were collected.2.Fasting blood samples were collected the next morning after admission,and Lp-PLA2 levels were measured by enzyme-linked immunosorbent assay(ELISA).At the same time,the results of relevant laboratory tests,including uric acid,total cholesterol,triglyceride,low density lipoprotein and high density lipoprotein,were recorded.3.All patients underwent 1.5T or 3.0T cranial MRI,including T1 and T2 weighted imaging,and fluid attenuated inversion recovery(FLAIR)images.The severity of WML was evaluated by Fazekas scale.WML was divided into two parts:periventricular white matter lesion(PWML)and deep white matter lesion(DWML).Among them,0-1 was divided into mild group and 2-3 was divided into moderate to severe group,the total score of 0-2 was divided into mild group,3-6 was divided into moderate to severe group.4.All the data were analyzed and processed by SPSS24.0.The normal distribution data were compared by independent sample t-test,the non-normal distribution were analyzed by mann-Whitney test,and the classification data were tested by analysis of variance.The Lp-PLA2 levels were divided into four grades according to the quartile method,and the lowest concentration level was regarded as the referrence.Firstly,the relationship between WML and risk factors were analyzed,and then the factors with P<0.1 were included in multivariate binary logistic regression analysis to analyze whether each risk factor was independently related to WML,and the relationship between PWML,DWML and risk factors were analyzed in the same way.Results1.A total of 184 patients were enrolled in this study.The average age of the subjects was 73.74 ± 13.94 years,of which 45.13%were female.There were 97(53.59%)patients with mild WML and 84(46.41%)patients with moderate to severe WML.2.Univariate analysis showed that age(P<0.001),hypertension(P<0.001),diabetes(P=0.053),coronary heart disease(P<0.001),low-density lipoprotein(P=0.072),Lp-PLA2 levels(P=0.014)were correlated with the severity of WML.After including the above variables in multivariate binary logistic regression analysis,age(OR=1.11 95%CI:1.07-1.15 P=0.000)and Lp-PLA2 levels(OR=3.33 95%CI:1.10-10.02 P=0.033)were independent risk factors for WML.Compared with the lowest concentration level of Lp-PLA2,the risk of moderate to severe WML in the highest concentration class increased about 3.33 times.3.Our research showed that age(P<0001),hypertension(P=0.001),smoking(P=0.032),diabetes(P=0.060),hyperlipidemia(P=0.082),coronary heart disease(P<0.001)and Lp-PLA2 levels(P=0.001)were possible risk factors for PWML.These variables were included in multivariate binary logistic regression analysis.As a result,age(OR=1.09 95%CI:1.05-1.13 P=0.000)and Lp-PLA2 levels(OR=6.11 95%CI:2.00-18.69 P=0.002)were independent risk factor for WML.Compared with the lowest concentration level of Lp-PLA2,the risk of moderate to severe PWML at the highest concentration level was 6.11 times higher.4.Univariate analysis showed that the possible risk factors for DWML were age(P<0.001),gender(P=0.091),hypertension(P<0.001),diabetes(P=0.076),coronary heart disease(P=0.002),total cholesterol(P=0.013),low-density lipoprotein(P=0.003).After the appeal variables were included in multivariate binary logistic regression analysis,only age(OR=1.05 95%CI:1.02-1.09 P=0.001)and hypertension(OR=2.52 95%CI:1.02-6.22 P=0.045)were independently related to DWML.Conclusions1.In patients with white matter lesions,the level of serum Lp-PLA2 can reflect the severity of white matter lesions,and the increase of Lp-PLA2 levels is significantly related to the severity of white matter lesions.2.In patients with periventricular white matter lesions,age and Lp-PLA2 levels are independent risk factors for moderate to severe periventricular white matter lesions.High levels of Lp-PLA2 have certain predictive value for moderate to severe periventricular white matter lesions.3.In patients with deep white matter lesions,age and hypertension are independent risk factors for deep white matter lesions,and Lp-PLA2 levels have no correlation with deep white matter lesions.