The Correlation Of Growth Differentiation Factor-15 With Vascular Cognitive Impairment

Background:Vascular cognitive impairment(VCI)is a kind of syndrome with clinical stroke evidence or subclinical vascular brain injury,and cognitive function damage at least one cognitive domain.The symptoms are progressively worsening and about 30%patients will suffer from varying degrees of cognitive impairment after stroke.At present,VCI is considered to be the second largest influencing factor of senile dementia,second only to Alzheimer's disease(AD),which affects the hrqol of patients seriously,and also places a heavy burden on families and society.At present,the pathogenesis of VCI is generally considered as vascular diseases,including vascular hemorrhage,ischemia and occlusion.Growth differentiation factor-15(GDF-15)is a member of transforming growth factor beta(TGF-?)superfamily.In recent years,it has been found to be significantly elevated in the serum of patients with acute is-chemic stroke.In addition,the serum GDF-15 level of AD patients was significantly higher than that of normal people,and the increase was more significant in AD patients with cerebrovascular disease.However,it is still unknown whether the expression of GDF-15 in VCI has changed.The purpose of this paper is to discuss the changes of serum GDF-15 level in patients with VCI,and whether it can play a role as a new biomarker in VCI diagnosis and disease assessment which could improve the early detection and diagnosis rate of VCI.So as to take intervention early,delay the disease development and reduce the burden of patients.Mrethods:We've selected 30 hospitalized patients diagnosed with VCI in the second affiliated hospital of Dalian Medical University from August 2018 to December 2019,with 15 males and 15 females which average age is(64.9±9.1).At the same time,we selected 30 hospitalized patients who diagnosed with acute cerebral infarction(ACI)in the second affiliated hospital of Dalian Medical University,including 15 males and 15females,with an average age of(67.2±10.0).Besides,we've also randomly selected 30hospitalized patients in the same period without ACI and cognitive impairment in the second affiliated hospital of Dalian Medical University,including 13 males and 17females with an average age of(70±10.0).We've collected morning fasting venous blood and detect cholesterol(TC),triglyceride(TG),fasting blood glucose(FBG),hemo-globin A1c(Hb A1c),aspartate aminotransferase(AST),alanine aminotransferase(ALT),creatinine(Cr),uric acid(UA),and GDF-15 in 6am.We also counted the patients'smoking history,hypertension history and diabetes history.The differences of the above test results in the ACI group,the VCI group and the normal group were compared,and analyzed the correlation between GDF-15 serum level from the above general data and MMSE score in VCI group.Furthermore,we analyzed the receiver operating characteristic curve(ROC)of GDF-15 in diagnosing VCI and ACI which then calculated whether the area under ROC curve(AUC)was statistically significant.Results spss21.0 software was used for statistical processing.Results were statistically processed with SPSS21.0 software.Results:There were no significant differences in age,gender,BMI,hypertension,diabetes,smoking,TC,TG,FBG,Hb A1c,AST,ALT,Cr and UA between normal group,ACI group and VCI group(P>0.05).In terms of serum GDF-15 levels,there were statistical differences between the three groups(P<0.05),with the highest in the VCI group(33.95±20.19ng/ml),followed by the ACI group(19.25±15.63ng/ml),and the lowest in normal group(7.63±7.78ng/ml).There were also statistical differences between the three groups.Pairwise comparisons between the three groups also showed statistical differences which the distribution of GDF-15 was statistically different between the normal group and the ACI group(P=0.003),the normal group and the VCI group(P<0.0001),the ACI group and the VCI group(P=0.026).In addition,GDF-15serum level in the VCI group showed a weak positive correlation with age,hypertension,diabetes,and FBG(R=0.366,0.459,0.416,0.369,all P<0.05),a negative correlation with MMSE score(R=-0.684,P<0.05),and no correlation with gender,BMI,smoking history,TC,TG,Hb A1c,Cr,UA,ALT and AST.Furthermore,the scatter plot and 95%confidence region(R~2=0.468)of GDF-15 serum level and MMSE score in the VCI group were plotted.The receiver operating characteristic curve(ROC)indicated that the area under curve(AUC)of GDF-15 in patients with ACI was 0.765 which with VCI was 0.923.The AUC for distinguishing patients with ACI from VCI was 0.716.Further analysis showed that when the level of GDF-15 is 5.73ng/ml,the sensitivity for diagnosis of ACI was 83.3%and the specificity was 56.7%.When the serum GDF-15level was 9.10ng/ml,the sensitivity of diagnosing VCI was 96.7%,and the specificity was 73.3%.Conclusion:1.The serum GDF-15 level of VCI patients was higher than that of acute cerebral infarction patients and normal population.2.Serum GDF-15 level in VCI patients was positively correlated with age,hypertension and diabetes blood glucose level,but negatively correlated with cognitive function.3.GDF-15 can serve as a new diagnostic indicator for VCI and predict the severity of VCI.