摘要
目的分析血浆胰岛素样因子6(insulin-like factor 6,INSL6)水平对急性主动脉综合征(acute aortic syndromes,AAS)发生风险及不良预后预测的临床价值。方法纳入2021年4月至2023年6月在陆军军医大学第二附属医院心血管内科收治的194例AAS患者,以及按性别、年龄及体质指数匹配的2021年12月至2024年1月从健康体检中心招募的194例非主动脉疾病对照受试者,收集人口统计学特征以及部分检验结果等临床资料进行病例对照研究。采用酶联免疫吸附测定法检测血浆INSL6水平;通过比较2组间的临床基线资料,采用Spearman相关分析评估血浆INSL6与其他变量间的相关关系、受试者工作特征曲线(receiver operating characteristic curve,ROC)评估血浆INSL6水平对AAS发生的诊断效能、多因素条件Logistic回归模型评估血浆INSL6与AAS发病之间的关联;采用KaplanMeier生存曲线和多因素Cox比例风险回归模型分析急性期血浆INSL6水平与AAS不良预后的关联。结果纳入的AAS患者急性期血浆INSL6水平显著高于对照受试者[704.40(481.32~1152.62)vs141.24(107.60~163.72)pg/mL,P<0.001],但血浆INSL6水平在AAS各疾病亚型(主动脉夹层、主动脉壁间血肿、穿透性主动脉溃疡)之间差异无统计学意义。对AAS组患者进行Spearman相关性分析,发现其血浆INSL6水平与血小板数量(r=0.325,P<0.001)、血红蛋白浓度(r=0.186,P=0.009)呈正相关,与IL-6(r=-0.182,P=0.011)、INF-γ(r=-0.283,P<0.001)、D-二聚体(r=-0.195,P=0.006)的水平呈负相关。多因素条件Logistic回归分析结果显示,血浆INSL6水平与AAS发生独立相关(OR=28.634,95%CI:7.267~112.820,P<0.001);ROC曲线进一步证实,血浆INSL6水平预测AAS的最佳截断值为259.425 pg/mL,在此阈值下其预测的灵敏度为95.9%,特异度为98.5%。Kaplan-Meier曲线显示,低血浆INSL6水平的AAS患者其累计生存率(P=0.020)和无事件生存率(P=0.004)均显著低于高血浆INSL6水平的AAS患者。在多因素Cox回归分析中,校正性别、年龄、收缩压、ST分型和手术治疗后,急性期血浆INSL6水平与AAS患者在随访期间的全因死亡(HR:0.999,95%CI:0.999~1.000,P=0.023)、AAS相关死亡(HR:0.999,95%CI:0.998~1.000,P=0.012)和复合终点事件(HR:0.999,95%CI:0.999~1.000,P=0.026)的发生风险均独立相关。结论血浆INSL6水平与AAS的发生及不良预后密切相关,有望成为诊断AAS并判断其预后的有效生物标志物。
Objective To analyze the clinical value of plasma insulin-like factor 6(INSL6)in predicting the risk of acute aortic syndromes(AAS)and adverse outcomes.Methods A retrospective case-control trial was conducted on 194 AAS patients admitted to Department of Cardiovascular Diseases of Second Affiliated Hospital of Army Medical University between April 2021 and June 2023.Another 194 sex-,age-and BMI-matched individuals without aortic diseases were recruited from the health examination center between December 2021 and January 2024.Their plasma INSL6 level was measured with ELISA,and the general clinical data and results of some laboratory tests were collected and compared between the 2 groups.Spearman correlation analysis was used to assess the relationship between plasma INSL6 and other variables,receiver operating characteristic(ROC)curve was plotted to evaluate the diagnostic efficacy of INSL6 for AAS occurrence,multivariate conditional logistic regression model was utilized to analyze the association between plasma INSL6 and AAS onset,and Kaplan-Meier survival curve and multivariate Cox proportional hazards regression model was applied to analyze the relationship between acute-phase plasma INSL6 level and adverse prognosis in AAS patients.Results The plasma INSL6 level was significantly higher in AAS patients at acute phase than the control individuals[704.40(481.32~1152.62)vs 141.24(107.60~163.72)pg/mL,P<0.001],but no statistical difference was observed in the level among the patients with different AAS subtypes(aortic dissection,intramural hematoma,and penetrating aortic ulcer).Spearman correlation analysis showed that the plasma INSL6 level was positively correlated with platelet count(r=0.325,P<0.001)and hemoglobin concentration(r=0.186,P=0.009),and negatively with IL-6(r=-0.182,P=0.011),INF-γ(r=-0.283,P<0.001),and D-dimer levels(r=-0.195,P=0.006).Multivariate conditional logistic regression analysis revealed that plasma INSL6 level was independently associated with the occurrence of AAS(OR=28.634,95%CI:7.267~112.820,P<0.001).ROC curve analysis further confirmed that the optimal cutoff value of plasma INSL6 in predicting AAS was 259.425 pg/mL,with a sensitivity of 95.9%and a specificity of 98.5%at this threshold.Kaplan-Meier curve analysis demonstrated that AAS patients with low INSL6 level had significantly lower cumulative survival rates(P=0.020)and event-free survival rates(P=0.004)than those with high INSL6 level(P<0.05).Multivariate COX regression analysis revealed that,after adjusting for sex,age,systolic blood pressure,ST classification,and surgical treatment,acute-phase INSL6 level was independently associated with all-cause mortality(HR:0.999,95%CI:0.999~1.000,P=0.023),AAS-related mortality(HR:0.999,95%CI:0.998~1.000,P=0.012),and composite endpoint events(HR:0.999,95%CI:0.999~1.000,P=0.026)in AAS patients during follow-up.Conclusion Plasma INSL6 level is closely associated with the occurrence and adverse prognosis of AAS,and the indicator is expected to be an effective biomarker for diagnosing AAS and predicting its prognosis.
作者
董旺
王颖
张铭乐
高智春
尹纯
晋军
DONG Wang;WANG Ying;ZHANG Mingle;GAO Zhichun;YIN Chun;JIN Jun(Department of Cardiovascular Diseases,Second Affiliated Hospital,Army Medical University(Third Military Medical University),Chongqing;Department of Nephrology,No.920 Hospital of Joint Logistics Support Force of PLA,Kunming,Yunnan,China)
出处
《陆军军医大学学报》
北大核心
2025年第5期462-471,共10页
Journal of Army Medical University
基金
重庆市医学青年拔尖人才项目
重庆市临床重点专科建设精品项目。
