Clinical Relevance Of CRAGE Plasma Levels With Disease Severity And Functional Outcome In Aneurysmal Subarachnoid Hemorrhage

PurposeAneurysmal subarachnoid hemorrhage(aSAH)is a life-threatening subtype of cerebralvascular diseases,induced by the rupture of intracranial aneurysms.It may trigger amounts of physiopathological processes such as inflammation.Cleaved receptor for advanced glycation end-products(cRAGE)has been introduced as a new inflammatory marker.The role of cRAGE in ischemic stroke has been evaluated,which is still unclear in aSAH.Our present study aims to clarify the associations between cRAGE levels,disease severity and functional outcome in aSAH.MethodsIn this prospective,observational study,plasma levels of total soluble RAGE(sRAGE)and endogenous secretory RAGE(esRAGE)were quantified in 108 aSAH patients and 108 healthy controls.The level of cRAGE was calculated by subtracting the level of esRAGE from that of sRAGE.World Federation of Neurological Surgeons(WFNS)score,modified Fisher score,and Hunt Hess(HH)score were recorded to assess aSAH severity.Receiver operating characteristic curve(ROC)was applied and the area under curve(AUC)with 95%confidence interval(CI)was calculated.The cutoff value of plasma cRAGE level was confirmed according to the sensitivity and specificity of ROC.Relationship between plasma cRAGE levels and 6-month poor outcome(Glasgow Outcome Scale score of 1-3)was assessed using multivariate analysis.ResultsThe median value of plasma cRAGE level in aSAH patients was 1.6mg/dl with 1.3-2.1mg/dl interquartile range;while the median value in healthy controls was 0.7mg/d1 with 0.5-0.9mg/dl interquartile range.Plasma cRAGE levels were significantly higher in patients than in controls.Its levels were significantly correlated with WNFS score,modified Fisher score and HH score of patients.Plasma cRAGE emerged as an in-dependent predictor for 6-month poor outcome.82.5%sensitivity and 75.0%specificity were indicated for predicting 6 months poor outcome when plasma cRAGE level was greater than 1.7mg/dl using ROC.Area under receiver operating characteristic curve(AUC)of this biomarker was similar to those of WNFS score,modified Fisher score and HH score.Moreover,it significantly improved the predictive value of WNFS score,modified Fisher score and HH score.ConclusionBy comparing between aSAH patients and healthy controls,the present prospective study indicated that the plasma cRAGE levels are highly associated with the severity and poor prognosis in aSAH,showing remarkable prognosis prediction value.