| BackgroundWith the development of economy and the change of lifestyle,the incidence of stroke is getting higher.Because of the characteristics of high fatality rate and high disability rate of stroke,it has become a major public health challenge in the whole country and the whole world.Previous studies have shown that traditional risk factors can’t fully explain the occurrence of death,disability and cardiovascular events after ischemic stroke.Recent studies have found that infection and angiogenesis may have an impact on the prognosis of stroke.Our study include two parts.The first part uses the data of "Effects of infection factors and acute inflammatory markers on prognosis of acute ischemic stroke(IIPAIS)"project.We conduct this research to study the effect of cytomegalovirus(HCMV)infection on short-term adverse prognosis of ischemic stroke.The second part was based on the China Antihypertensive Trial in Acute Ischemic Stroke(CATIS)to study the effect of endostatin(ES),an angiogenesis inhibitor,on the long-term adverse prognosis of ischemic stroke.Part ⅠObjectiveOn the basis of IIPAIS projects that have completed the inclusion of subjects,baseline data collection,and 14 days(or discharge)follow-up after onset,we conduct this research to investigate the relationship between HCMV infection and short-term poor prognosis of ischemic stroke(death,cardiovascular events,compound outcome of death and severe disability and compound outcome of death and cardiovascular events).Subjects and methodsIn this study,1150 patients with ischemic stroke who participated in the IIPAIS trial were enrolled in the study.The baseline data such as demographic information,lifestyle factors,clinical features,disease history and disease medication history were collected by questionnaire.The blood routine detection indexes were collected,and HCMV-IgM was detected by automatic enzyme-linked immunosorbent assay.The patients were followed up 14 days after onset(or at discharge).The adverse prognosis included death,cardiovascular events,combined outcome of death and disability,and combined outcome of death and cardiovascular events.Logistic regression model was used to analyze the correlation between serum HCMV-IgM and adverse outcomes 14 days after onset(or at discharge).The ratio(OR)and the 95%confidence interval(CI)were calculated.Restricted cubic splines combined with Logistic regression model was used to evaluate the dose-response relationship between serum HCMV-IgM level and poor prognosis.At the same time,the subjects were stratified according to sex,age(<65 vs>65 years),admission systolic blood pressure(<140 mm Hg vs>140 mm Hg)and admission NIHSS score(<4 vs>4).The relationship between serum HCMV-IgM and poor prognosis at 14 days(or discharge)was analyzed in each layer.At the same time,we also calculated the net reclassification index(NRI)and integrated discrimination improvement(IDI)to evaluate the ability of serum HCMV-IgM to predict the short-term poor prognosis of patients with acute ischemic stroke.ResultsA total of 1150 patients with acute ischemic stroke were enrolled in this study.There were 787 males(68.43%)and 363 females(31.57%)with an average age of 62.39±11.19 years.On the 14th day of onset(or discharge),19 died,23 had cardiovascular events,351 cases had a combined outcome of death and disability,and 40 cases had a combined outcome of death or cardiovascular events.Compared with the lowest quartile group of serum HCMV-IgM,the combined outcome of death and severe disability at 14 days of onset(or at discharge)in the highest quartile group(OR 1.65;95%CI 1.03-2.64)and the combined outcome of death and cardiovascular events(OR 5.72;95%CI 1.24-26.36)was significantly increased.Restrictive cubic splines showed a dose-response relationship between serum HCMV-IgM and the risk of combined outcomes of death and severe disability(linear trend test P=0.003).The addition of serum HCMV-IgM level to the traditional predictive model significantly improve the predictive ability of the model for death of 14 days after onset(or discharge)in patients with ischemic stroke(NRI%22.41,P=0.022;IDI%2.08,P=0.024).ConclusionThe results showed that HCMV infection could increase the risk of short-term adverse outcomes in patients with ischemic stroke,and the addition of serum HCMV-IgM level to the traditional model could increase the predictive ability of the model for short-term death of ischemic stroke.Part ⅡObjectiveThis part of the study is on the basis of completed CATIS clinical trials.We do this study to investigate the relationship between plasma ES level and long-term adverse prognosis of ischemic stroke(death,cardiovascular event,combined outcome of death and severe disability and combined outcome of death and cardiovascular event).Subjects and methods3463 subjects from CATIS were enrolled in this study.Baseline data was collected within 24 hours of admission including demographic characteristics,lifestyle risk factors,clinical features,disease history,ischemic stroke subtypes and drug use history.The data of the first routine hematological examination were collected,and the plasma ES was detected by double antibody sandwich enzyme-linked immunosorbent assay(Elisa).The patients were followed up for 3 months.The adverse prognosis included death,cardiovascular events,combined outcome of death and disability,and combined outcome of death and cardiovascular events.Logistic regression model was used to analyze the correlation between plasma ES level and adverse outcomes 3 months after onset.The OR and the 95%CI were calculated.Restricted cubic splines combined with Logistic regression model was used to evaluate the dose-response relationship between plasma ES and the outcome of the study.At the same time,the subjects were divided into multiple subgroups according to sex,age(<65 vs≥ 65 years),admission systolic blood pressure(<140 mm Hg vs>140 mm Hg)and admission NIHSS score(<4 vs>4).The relationship between plasma ES level and poor prognosis 3 months after ischemic stroke was analyzed in each subgroup.At the same time,we also calculated the NRI and IDI to evaluate the ability of plasma ES levels to predict the long-term poor prognosis of patients with acute ischemic stroke.ResultAfter 3-months follow up,81 patients died,101 patients had cardiovascular events,401 patients had the combined outcome of death and disability,139 patients had the combined outcome of death and cardiovascular events.Compared with those in the lowest quartile group,the highest quartile group had a significantly higher risk of 3-month death from ischemic stroke(OR 2.57;95%CI 1.25-5.27).There was a dose-response relationship between plasma ES level and death(P=0.008)and the combined outcome of death and disability(P=0.044).The addition of plasma ES to the traditional prediction model could significantly improve the predictive ability of the model for the risk of 3-month death in patients with ischemic stroke(NRI 13.97%,P=0.028;IDI 1.41%,P=0.011).ConclusionOur results suggest that higher plasma ES levels are associated with long-term poor prognosis of ischemic stroke.The level of plasma ES may predict the prognosis of stroke patients. |
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