高血浆组蛋白是脓毒症心肌病发生的独立危险因素

Elevated plasma histone is an independent risk factor for the development of septic cardiomyopathy

目的探讨脓毒症心肌病的流行病学及其独立危险因素.方法采用前瞻性研究,选择2016年5月到2019年8月扬州大学附属江苏省苏北人民医院、首都医科大学附属北京复兴医院和国家电网公司北京电力医院重症医学科(ICU)收治的诊断为脓毒症的患者.入选患者均按照"拯救脓毒症运动"(SSC)指南给予规范化治疗.入院24 h内收集患者血液标本,用酶联免疫吸附试验(ELISA)检测血浆组蛋白H4、心肌肌钙蛋白I(cTnI)、N末端脑钠肽前体(NT-proBNP)水平;并行经胸超声心动图检查,记录超声相关参数;记录序贯器官衰竭评分(SOFA)、血管活性药物使用、ICU预后等指标.根据是否发生心肌病将患者分为两组,比较组间各指标的差异;分析血浆组蛋白H4与SOFA评分、cTnI和NT-proBNP的相关性;采用多因素二元Logistic回归分析脓毒症心肌病的独立危险因素;用受试者工作特征曲线(ROC)分析组蛋白H4对脓毒症心肌病的预测价值.结果共纳入脓毒症患者121例,其中60例(49.6%)发生脓毒症心肌病;ICU死亡36例,ICU病死率为29.8%.①相关性分析显示,脓毒症心肌病患者血浆组蛋白H4与cTnI、SOFA评分、NT-proBNP均呈正相关(r值分别为0.512、0.403、0.274,均P<0.01).②与非心肌病组比较,心肌病组患者血浆组蛋白H4、cTnI、血管活性药物使用率、SOFA评分、ICU病死率均明显升高〔组蛋白H4(mg/L):0.26(0.23,0.30)比0.22(0.17,0.27),cTnI(μg/L):0.21(0.17,0.30)比0.18(0.14,0.22),血管活性药物使用率:83.3%(50/60)比65.6%(40/61),SOFA(分):11(9,12)比9(8,10),ICU病死率:40.0%(24/60)比19.7%(12/61),均P<0.05〕.多因素二元Logistic回归分析显示,高组蛋白H4水平〔优势比(OR)=6.502,95%可信区间(95%CI)为1.203~78.231,P=0.044〕和血管活性药物使用(OR=2.622,95%CI为1.034~6.849,P=0.042)是脓毒症心肌病发生的独立危险因素.④组蛋白H4预测脓毒症心肌病的最佳阈值为0.24 mg/L,ROC曲线下面积为0.684(P<0.01),敏感度为65.2%,特异度为68.9%.结论脓毒症心肌病发生率高,高血浆水平组蛋白H4和血管活性药物使用是脓毒症心肌病发生的独立危险因素.

Objective To investigate the epidemiology and independent risk factors of septic cardiomyopathy.Methods A prospective study was conducted.Patients with sepsis in intensive care unit(ICU)of Subei People's Hospital of Jiangsu Province,Yangzhou University,Fuxing Hospital,Capital Medical University and Beijing Electric Power Hospital from May 2016 to August 2019 were enrolled.All patients received standardized treatments according to the Surviving Sepsis Campaign(SSC)guidelines.Blood were collected within 24 hours of admission to ICU,and plasma histone H4,cardiac troponin I(cTnI)and N-terminal pro-brain natriuretic peptide(NT-proBNP)were detected by enzyme linked immunosorbent assay(ELISA).Transthoracic echocardiography was performed to record the ultrasonic parameters within 24 hours after admission.Sequential organ failure assessment(SOFA)score,usage of vasopressor drugs,and the prognosis of ICU were recorded.Patients were divided into two groups according to whether cardiomyopathy occurred or not,and the differences of each index between the two groups were compared.The correlation between plasma histone H4 and SOFA score,cTnI,NT-proBNP were investigated.Multivariate binaryLogistic regression was used to determine the risk factors for septic cardiomyopathy.The predictive value of histone H4 in septic cardiomyopathy was shown by the receiver operating characteristic(ROC)curve.Results 121 patients were included in this study,and there were 60 patients(49.6%)with septic cardiomyopathy.Thirty-six patients died,with an ICU mortality of 29.8%.①Correlation analysis showed that plasma histone H4 in patients with septic cardiomyopathy was positively correlated with cTnI,SOFA score and NT-proBNP(r value was 0.512,0.403 and 0.274,respectively,all P<0.01).②Compared with the non-cardiomyopathy group,the plasma histone H4,cTnI,usage of vasopressor drugs,SOFA score and ICU mortality in the cardiomyopathy group were significantly increased[histone H4(mg/L):0.26(0.23,0.30)vs.0.22(0.17,0.27),cTnI(μg/L):0.21(0.17,0.30)vs.0.18(0.14,0.22),usage of vasopressor drugs:83.3%(50/60)vs.65.6%(40/61),SOFA score:11(9,12)vs.9(8,10),ICU mortality:40.0%(24/60)vs.19.7%(12/61),all P<0.05].Multivariate binary Logistic regression analysis showed that high histone H4 level[odds ratio(OR)=6.502,95%confidence interval(95%CI)was 1.203-78.231,P=0.044]and usage of vasopressor drugs(OR=2.622,95%CI was 1.034-6.849,P=0.042)were independent risk factors for septic cardiomyopathy.④ROC curve analysis showed the cut-off of histones H4 for predicting septic cardiomyopathy was 0.24 mg/L,the area under the curve was 0.684(P<0.01),with the sensitivity of 65.2%,and specificity of 68.9%.Conclusions Septic cardiomyopathy had a high incidence.Higher plasma histone H4 and the usage of vasopressor drugs were independent risk factors for septic cardiomyopathy.