| BackgroundIschemic stroke is the most common cerebrovascular disease in neurology,which is the first cause of death in China.Because of its high incidence and disability,it has a profound impact on human health.Therefore,early diagnosis and predicting prognosis are required for reducing the risk of ischaemic stroke.As a hotspot of recent research,more and more evidence indicates that Apelin-13/APJ signaling pathway is composed of Apelin-13 and its receptor APJ is associated with ischemic stroke and involves various physiological and pathological processes in regulating ischemic stroke,at the same time it can promote the angiogenesis after ischemic stroke,inhibit neurons and nerve cells damage,increase the stability of atherosclerotic plaque and regulate the inflammatory response after stroke.Therefore,Apelin-13/APJ plays a protective role in acute ischemic stroke.PurposeThe purpose of this study is to research the diagnostic and prognostic value of serum Apelin-13 concentration in acute ischemic stroke,and to explore the correlation between Apelin-13 concentration and the severity of clinical symptoms in patients with acute ischemic stroke and its change with time.MethodsThe study consisted of two parts: case-control study and cohort study.The subjects in the case-control study were continuously included patients with acute ischemic stroke admitted to the Department of Neurology,the First Affiliated Hospital of Zhengzhou University from October 2015 to May 2018,whose venous blood sample was collected within 24 hours from the onset of the disease;and healthy individuals without previous stroke or myocardial infarction.The medical history and related examination results of the subjects were recorded,SPSS 24.0(Statistical Product and Service Solutions version 24.0)and GraphPad Prism 7.0 were used for data analysis.Quantitative data that conform to the normal distribution expressed as mean ± standard deviation(Mean ± SD),while those that do not conforms to the normal distribution expressed by the median and interquartile range(Median,IQR).Qualitative data were expressed as frequency and percentage(N,%).For the qualitative data of two independent samples,the Pearson χ2 test was used.For the quantitative data of two independent samples,the t/corrected t-test shall be applied if they comply with the normal distribution,while the Mann-Whitney U test shall be used if they do not comply with the normal distribution.For the determination of serum Apelin-13 concentration,an enzyme-linked immunosorbent assay(ELISA)method was used.In order to balance the difference in baseline data between the case group and the control group,propensity score matching was used to match the two groups,in which the match tolerance is 0.1,then compared the difference in Apelin-13 concentration between the two groups.Mann-Whitney U test was used to analyze the difference in serum Apelin-13 concentration between different NIHSS score groups.The main purpose of the cohort study was to investigate the dynamic changes of Apelin-13 with time and the prognosis of patients.The prognosis of patients was obtained by a neurologist who did not participate in the work by telephone follow-up or outpatient review.The indicators included: clinical outcomes(poor functional outcome,recurrent stroke),mRS,etc.For the study of functional prognosis,univariate logistic regression was used to screen for prognostic-related risk factors such as age,gender,traditional risk factors,serum Apelin-13 concentration,and then multivariate logistic regression analysis was used to correct the effects of other factors,expressed by odds ratio(OR)and 95% confidence interval(CI).Multivariate Cox regression model was used to analyze the correlation between different levels of Apelin-13 and all-cause death or cardiovascular and cerebrovascular events and survival time after acute ischemic stroke.Statistical significance was set at P< 0.05(bilateral).Results1.A total of 244 patients with acute ischemic stroke who received venous blood samples less than 24 hours from the onset and 167 healthy people were selected for case-control study.The concentration of Apelin-13 in the patients [38.63(29.86-50.99)]ng/mL was lower than that in the healthy controls [42.50(31.25-59.17)] ng/mL(P=0.017).There was still a statistical difference in Apelin-13 concentration between the patients and the healthy controls after the propensity score matched the age,gender,hypertension,diabetes mellitus,atrial fibrillation,coronary heart disease,hyperlipidemia,smoking,and stroke history.2.NIHSS was divided into two groups: NIHSS≤3(n=139)and NIHSS > 3(n=105).It was found that patients with NIHSS≤3 had higher Apelin-13 concentration than patients with NIHSS > 3[40.02(30.41-54.98)ng/mL VS 35.97(28.19-49.04)ng/mL](P=0.048).3.The serum Apelin-13 concentration in patients with acute ischemic stroke changed with time.The concentration of Apelin-13 measured at the first time of admission(according to the onset of 16.46±6.70h)was significantly lower than that at the time of discharge(according to the onset of 187.82±33.55h)[34.51(27.45-41.20)ng/mL VS 40.07(31.59-56.80)ng/mL](P<0.001).4.Poor functional outcome(mRS=3-6)was defined as the primary outcome during the follow-up.During the 3-month follow-up,univariate logistic regression analysis showed that Apelin-13 level(per standard deviation unit)was associated with poor outcome at the 3-month follow-up(OR: 0.349;95% CI:0.155-0.785;P=0.011);multivariate logistic regression analysis adjusted for age,gender,NIHSS on first admission,hypertension,diabetes and other traditional risk factors,Apelin-13 level was still associated with poor outcome(OR:0.313;95%CI:0.114-0.856;P=0.024).At the 6-month follow-up,Apelin-13 level was still associated with functional outcome.At the 1-year follow-up,lower serum Apelin-13 level was associated with poor functional outcome and all-cause death or cardiovascular and cerebrovascular events(HR: 0.236,95% CI: 0.091-0.609,P=0.003).Conclusions1.The serum Apelin-13 concentration of patients with acute ischemic stroke was lower than that in healthy controls,which was helpful in determining whether the patient had a stroke.2.The serum Apelin-13 concentration of patients with acute ischemic stroke at admission was correlated with the severity of the patients: the lower concentration may have more severe neurological impairment.3.The serum Apelin-13 concentration of patients with acute ischemic stroke changed with time.4.In patients within 24 hours of onset,lower serum Apelin-13 level was associated with poor functional outcome and all-cause death or cardiovascular and cerebrovascular events. |
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