The Relationship Between Plasma Soluble Receptor Of Advanced Glycation End-products (sRAGE) And Cardioembolic Stroke

Objective: It has been found the receptor for advanced glycation end-products(RAGE)and its soluble forms-collectively known as sRAGE-were increasingly implicated in host defence from infections,inflammation,atrial fibrillation,cardiometabolic disorders,and cardiac structural remodeling in recent years,The high level of sRAGE in circulation reflected the over-stimulation of RAGE on the cell surface.If it continued,it would lead to the amplification of the pro-inflammatory process and the deterioration of the pathological state.sRAGE could be used as a potential biomarker of disease risk and adverse outcomes.However,its role in cerebral embolism was still controversial.We aimed to explore the relationship between plasma sRAGE and cardioembolic stroke.Methods: A total of 210 patients with acute ischemic stroke,including 98 patients with cardioembolic stroke and 112 patients with non-cardioembolic stroke,and 107 healthy patients in the same period,were selected from the patients admitted to the Affiliated Hospital of Qingdao University from June 2020 to August 2021.The baseline data of all patients were collected,and their blood samples were collected.The plasma sRAGE levels of all patients were measured by enzyme-linked immunosorbent assay(ELISA)and the differences among groups were compared.The independent risk factors of cardioembolic stroke were screened by binary logistic regression analysis.The predictive value of plasma sRAGE level for cardioembolic stroke was evaluated by calculating the receiver operating characteristic curve(ROC).NIHSS(National Institutes of Health Stroke Scale)score reflected the severity of the stroke,and m RS(modified Rankin Scale)score reflected the prognosis of three months after the onset of the stroke,The relationship between plasma sRAGE level and stroke severity and prognosis was evaluated by Spearman correlation analysis.The relationship among plasma sRAGE,brain natriuretic peptide(BNP),and left atrial diameter(LAD)was evaluated by Pearman correlation analysis.Results: Plasma sRAGE levels were significantly increased in patients with acute ischemic stroke(186.21±173.1pg/m L),especially in patients with cardioembolic stroke(251.18±175.62 pg/m L).Binary logistic regression analysis showed that plasma sRAGE(OR = 1.004,95% CI: 1.002-1.006),LAD(OR = 8.945,95% CI: 1.833-43.652),and BNP(OR = 9.534,95% CI:2.158～ 49.634)were independent risk factors for cardioembolic stroke.The areas under the receiver operating characteristic(ROC)curve of patients with cardioembolic stroke predicted by sRAGE,LAD,BNP,and the combined model of three indexes were 0.703,0.81,0.801,and 0.863 respectively(P < 0.001).The plasma sRAGE level of 123.83pg/ml was the best cut-off value for predicting cardioembolic stroke,with a sensitivity of 90.6% and a specificity of 60.7%.There was a positive correlation between plasma sRAGE level and admission NIHSS score in the cardioembolic stroke group(r = 0.367,P < 0.001).There was a positive correlation between plasma sRAGE and 3-month m RS in the cardioembolic stroke group(r = 0.413,P < 0.001).The patients with high plasma sRAGE levels in the cardioembolic stroke group had poor prognoses at 3 months(P < 0.001).There was a positive correlation between plasma sRAGE and BNP,LAD in the cardioembolic stroke group(r = 0.401,P <0.001;r=0.207,P =0.041),and between BNP and LAD(r = 0.262,P = 0.009).Conclusion: The level of plasma sRAGE in cardioembolic stroke was higher than that in non-cardioembolic stroke.SRAGE could be used as a plasma biomarker for cardiogenic stroke.The combined predictive model of sRAGE,LAD,and BNP could be used as a screening tool for early identification of cardioembolic stroke,which maybe help clinicians to make an accurate diagnosis and timely anticoagulation therapy.