| Background and objective:About 20 to 40 percent of patients with acute ischemic stroke have early neurological deterioration(END)after hospitalization,which further aggravates the mortality and disability rate after stroke.And the incidence of spontaneous hemorrhagic transformation(HT)after acute cerebral infarction is 13%-43%.HT is a common and serious complication of ischemic stroke,which limits the application of thrombolytic therapy with Alteplase in acute ischemic stroke.The most important factor leading to END is symptomatic intracranial hemorrhage and malignant cerebral edema,which causes HT to occur mainly because of the damage of Blood-Brain Barrier(BBB)and ischemic vascular wall.Because END and HT following acute ischemic stroke strongly associated with poor outcome,so finding a effective biomarker early to predicting the occurrence of END and HT is the key to prevent adverse cerebral events.Caveolin-1(Cav-1)is an essential structural component of caveolae-a 50-100 nm micro-invaginations of the cell plasma membrane that are particularly abundant in endothelial cells and adipocytes and are involved in signal transduction,endocytosis and macromolecular permeability.Cav-1 involved in regulating the blood brain barrier permeability,oxidative stress,neuroinflammation,and also has participated in remyelination and synapses regeneration process,thus Cav-1 plays an important role in brain protection.However,the secretion of serum Cav-1 in patients with acute cerebral infarction is not clear,and the relationship between Cav-1 with END or HT is unknown.In this study,we analyzed the relationship between Cav-1 level and END or HT in patients with acute cerebral infarction,and explored the early predictors of END or HT.In addition,we assessed neurological deficits or prognosis by using the neurological score scale and explored the relationship between Cav-1 level and severity or prognosis.Methods:Part I:1.157 patients with acute cerebral infarction were enrolled in this study.The serum Cav-1 levels of all patients were detected by enzyme-linked immunosorbent assay(ELISA)test.The neurological deficits were assessed by the National Institutes of Health Stroke Scale(NIHSS)and the Glasgow Coma Scale(GCS)at the same time.Compared with the admission baseline NIHSS score,if second motor NIHSS score increased>1 point or the total NIHSS score increased>2 points within 3 days after hospitalization,while they were classified as END group,otherwise they were classified as non-END group.Multivariable logistic regression analysis was used to examine the independent predictors of END in patients.Receiver operating characteristic(ROC)curves were obtained to explore Caveolin-1 levels in predicting END.2.HT was diagnosed in patients using the head CT or MRI during 2 weeks after admission,and all patients were divided into HT group and non-HT group.According to the recommendations of the European Cooperative Acute Stroke Study(ECASS)standard,HT was divided into hemorrhagic infarction type 1,2 and parenchymal hematoma type 1,2.In addition,HT was divided into symptomatic HT(sHT)and asymptomatic HT(sHT)based on the severity of clinical symptoms.Unvariate factor analysis was used to examine the differences of clinical data between two groups,multivariate Logistic regression analysis was obtained to explore the independent predictor of HT in stroke patients,ROC curves were obtained to explore the accuracy of Cav-1 in predicting HT.Part II:1.Serum samples were taken from 157 patients and 40 healthy controls.The onset time of all patients was less than 72 hours.Neurological deficits were assessed using the National Institutes of Health Stroke Scale(NIHSS)and the Glasgow Coma Scale(GCS).Clinical data were collected and serum Caveolin-1 levels were measured.Final prognosis was evaluated by the modified Rankin Scale(mRS)or NIHSS score after 90 days of follow-up.Patients with disabled were defined as mRS scores≥3,while Patients with poor prognosis were defined as NIHSS scores ≥8.Unvariate factor analysis was used to examine the differences of clinical data between two groups,Pearson correlation coefficients were used to analyze the relationship between Caveolin-1 levels and NIHSS scores or GCS scores.Logistic regression analyses were used to assess the relationship between baseline characteristics and serum Caveolin-1 levels.Receiver operating characteristic(ROC)curves were used to determine Caveolin-1 levels in predicting functional prognosis.Results:Part I:1.157 patients with acute cerebral infarction were enrolled in this study.The END group had 52(33.1%),male had 27(51.9%).Serum Cav-1 levels in END group were significantly higher than those in non-END group[(29.94±18.63)ng/ml vs.(17.73±12.74)ng/ml,P=0.000].On univariate analysis,compared with non-END group,END group has more opportunity with atrial fibrillation,NIHSS score,hs-CRP,apolipoprotein B(apoB)(P<0.05,respectively),but lower opportunity with GCS score.Based on the receiver operating characteristic(ROC)curves,the best cut off serum Caveolin-1 value for predicting death was 28.77ng/ml,with a sensitivity of 85.7%and a specificity of 74.8%.Multivariable logistic regression analysis showed that Cav-1≥17.30ng/ml remained an independent predictor of END[OR:4.936,95%CI:1.608-15.155,P=0.005].2.About 157 patients with acute cerebral infarction,42(26.8%)were in the HT group,with 22 males(52.4%).Compared with the non-HT group,the HT group had a higher level of serum Cav-1[(31.71±15.07)ng/ml vs.(18.14± 14.74)ng/ml,P=0.000].The serum Cav-1 levels were higher in the HT patients who developed HI、PH、sHT(P<0.05,respectively).On unvariate analysis,HT group was higher than non-HT group in atrial fibrillation,BMI,fasting blood glucose level,hs-CRP,NIHSS score,and infarct volume(P<0.05,respectively),but HT group was lower than non-HT group in hypertension GCS score(P<0.05).Based on the ROC curves,the best cut off serum Caveolin-1 value for predicting HT was 15.20 ng/ml,with a sensitivity of 92.86%and a specificity of 61.74%;the best cut off serum Caveolin-1 value for predicting PH was 30.50ng/ml,with a sensitivity of 82.35%and a specificity of 72.00%;the best cut off serum Caveolin-1 value for predicting sHTwas 28.85 ng/ml,with a sensitivity of 69.23%and a specificity of 75.00%;Multivariable logistic regression analysis showed that Cav-1>15.20ng/ml remained an independent predictor of HT[OR:1.017,95%CI:0.977-1.059,P=0.001]。Part II:1.On unvariate analysis,smoking,drinking,history of hypertension,occurrence of atrial fibrillation,dyslipidemia,BMI,blood glucose level,and high-sensitivity c reactive protein level(hs-CRP)were higher in the patients group than in the control group(P<0.05,respectively).Serum Cav-1 levels in patients were significantly higher than those in healthy controls(21.77±15.97 ng/ml vs.8.76±3.99 ng/ml,p=0.00)and were positively correlated with NIHSS score(r=0.662,p=0.000),but negatively correlated with GCS score(r=-0.698,p=0.000).In addition,high serum Cav-1 levels were independently associated with NIHSS score and infarction volume(P=0.546,p=0.000 andβ=0.222,p=0.002,respectively).Based on the receiver operating characteristic curves,the best cut off serum Cav-1 value for predicting death was 25.50 ng/ml,with a sensitivity of 88.89%and a specificity of 70.95%;the best cut off serum Cav-1 value for predicting poor prognosis was 17.53 ng/ml,with a sensitivity of 93.75%and a specificity of 62.12%;the best cut off serum Cav-1 value for predicting disabled prognosis was 14.80 ng/ml,with a sensitivity of 74.36%and a specificity of 56.88%.Conclusions:1.Serum Caveolin-1(Cav-1)was elevated in patients with acute cerebral infarction,and serum Cav-1≥ 17.30 ng/ml as an independent predictor of END in patients with acute cerebral infarction.2.Serum Cav-1>15.20ng/ml as an independent predictor of HT in patients with acute cerebral infarction.3.The elevated level of Cav-1 in patients with acute cerebral infarction was associated with increased NIHSS score and enlarged infarct volume.4.Serum Cav-1 ≥17.53ng/ml as an independent predictor of poor prognosis in patients with acute cerebral infarction. |
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