The Association Between The Level Of C-reactive Protein In The Acute Phase Of Stroke And Post-stroke Depression: A Systematic Review And Meta-analysis

Background:According to the survey in 2019,a lifetime risk of stroke was up to 39.9%in China,and it is also the leading disease cause of loss of life expectancy.Post-stroke depression is a common emotional disorder syndrome after stroke,which seriously affects the neurological recovery and the abilities to return to society of stroke patients.Early prediction and identification of post-stroke depression with timely implementation of treatment measures can effectively reduce its negative impact on survival rates of post-stroke survivors.Objective:The levels of C-reactive protein in the acute phase of stroke in patients with post-stroke depression would be compared with those without depression,to determine whether C-reactive protein could be a biomarker for predicting post-stroke depression.Methods:China National Knowledge Infrastructure,Wanfang Database,China Biomedical Abstraction Database,VIP Chinese Journal Full-text Database,Pub Med,Web of Science,Embase and The Cochrane Library were systematically searched.According to the specified criteria,qualified studies reflecting the relationship between the concentration of C-reactive protein in the acute stage of stroke and post-stroke depression were screened out.Quality assessment,information and data extraction were carried out for the included investigations.A meta-analysis of the included data was performed using STATA 14.0.The standardized mean difference and 95%confidence interval were used to describe the continuous variable,and I~2 was used to evaluate the heterogeneity.I~2>50%indicated a high heterogeneity.Sensitivity analysis,meta-regression analysis and subgroup analyses were conducted to find out the causes of heterogeneity.Additionally,the publication bias of the article was evaluated by funnel plot and the Egger test.Results:A total of 26 studies concentrated on the correlation between the level of C-reactive protein in the acute stage of stroke and post-stroke depression were selected and included.There were 5507 patients with acute stroke,of whom1719 were suffered from post-stroke depression.The incidence of post-stroke depression was 31.2%.During the acute phase of stroke,patients with post-stroke depression had significantly higher blood levels of CRP than those without post-stroke depression(SMD=0.64,95%CI=0.34—0.93,I~2=95.7%).Sensitivity analysis showed this conclusion had strong stability.Meta-regression analysis suggested that the main sources of high heterogeneity were the differences in the depression evaluation criteria(p=0.046),the type of stroke(p=0.028)and the express methods of original data(p=0.011).To exclude heterogeneity,a new meta-analysis was conducted after screening the studies again,and the results showed that in the acute phase of stroke,the levels of C-reactive protein in patients with post-stroke depression were still significantly higher than that in patients without depression(SMD=0.21,95%CI=0.11—0.31,I~2=44.3%).Subgroup analyses indicated that these findings were not statistically significant when depression was assessed by using depression scales(SMD=1.091,95%CI=-0.442—2.642)or when depression was assessed 3 months after stroke(SMD=0.72,95%CI=-0.029—1.469).The funnel plot and Egger test(p=0.153,95%CI=-1.92987—11.63716)confirmed that there was no obvious publication bias in this meta-analysis,and the conclusion was relatively reliable.Conclusions:Patients with post-stroke depression had higher levels of C-reactive protein during the acute phase of stroke compared to those without depressive symptoms.Therefore,the level of C-reactive protein in the acute phase of stroke is a potential biomarker for predicting the occurrence of post-stroke depression,especially for patients who develop depressive symptoms within 3 months after stroke.In addition,post-stroke depression increases all-cause mortality,high levels of C-reactive protein in the blood during the acute phase may predict poor prognosis.At the same time,the follow-up time for post-stroke depression should be extended,and the correlation between PSD and C-reactive protein remains to be further studied in regions besides China.