摘要
目的测定心力衰竭(heart failure,HF)合并心房颤动患者的血浆可溶性致癌抑制因子2(soluble suppression of tumorigenicity-2,sST2)水平,探讨其在HF合并房颤患者中的临床诊断及预后价值。方法前瞻性队列研究,连续选取2018年1至6月期间泰达国际心血管病医院心内科和CCU住院的HF患者185例,按入院前是否合并房颤分为窦性心律HF(heart falilure with sinus rhythm,HF-SR)组90例和合并房颤的HF(heart falilure with atrial fibrillation,HF-AF)组95例。收集同期健康体检者40名为对照组。比较HF-SR与HF-AF的基线资料及不同射血分数分组中的血浆sST2水平。sST2采用酶联免疫法测定。采用非参数检验及Spearman相关性分析等统计方法进行分析。采用受试者工作曲线(ROC)分析sST2在HF-SR和HF-AF中的诊断价值,采用COX风险模型对患者预后进行分析。结果HF患者的血浆sST2水平[32.93(20.31~51.39)]ng/mL高于健康对照组[15.99(7.97~22.69)]ng/mL(Z=-4.373,P<0.001),HF-AF组[39.86(27.20~59.21)]ng/mL高于HF-SR组[24.74(14.83~44.11)]ng/mL患者(Z=-6.783,P<0.001),在射血分数中间值的HF和射血分数保留的HF亚组,HF-AF组患者的血浆sST2水平均高于HF-SR组(Z=-2.381,P=0.017;Z=-3.701,P<0.001),Spearman相关性分析显示,在HF-AF患者中,sST2与舒张压、高血压、纽约心脏病协会(New York Association,NYHA)心功能分级Ⅲ~Ⅳ级、丙氨酸氨基转移酶(alanine aminotransferase,ALT)、Υ-谷氨酰基转肽酶(Υ-glutamine transaminase,Υ-GT)、外周血白细胞数(white blood cell,WBC)、B-型利钠肽(BNP)呈正相关(r>0,P<0.05),sST2与左心室射血分数(left ventricular ejection fraction,LVEF)、估算肾小球滤过率(estimated glomerular filtration rate,eGFR)呈负相关(r<0,P<0.05)。sST2诊断HF-AF的ROC曲线下面积(AUC)为0.872,(95%CI:0.805~0.935,P<0.001),最佳临界值为25.33 ng/mL在此临界值下的敏感度为81.1%,特异度为87.5%。sST2诊断HF-SR时ROC的AUC为0.665(95%CI:0.570~0.761,P<0.001),最佳临界值为23.34 ng/mL,在此临界值下的敏感度为55.6%,特异度为77.5%。BNP和sST2在鉴别诊断HF-SR、HF-AF时ROC的AUC分别为0.604、0.699,sST2高于BNP。经多因素COX分析后,血浆sST2水平、BNP、NYHA心功能分级是HF患者心脏事件的危险因素,血浆sST2、左心房直径(left atrium diameter,LA-D)、伴发心肌病是HF-AF患者心脏事件的危险因素。血浆sST2≥20.31 ng/mL的HF患者随访6个月内心脏事件发生率明显高于sST2<20.31 ng/mL的患者(χ2=7.625,P=0.006)。血浆sST2≥39.86 ng/mL的HF-AF患者心脏事件发生率明显高于sST2<39.86 ng/mL的患者(χ2=4.287,P=0.038)。结论HF-AF组患者血浆sST2水平明显高于HF-SR组和健康对照组患者,血浆sST2在HF-AF组患者的诊断价值高于HF-SR组患者;在鉴别诊断HF-SR、HF-AF时,sST2价值高于BNP。血浆sST2≥39.86 ng/mL的HF-AF患者易发生心血管事件。
Objective To determine the level of Soluble Suppression of Tumorigenicity-2(sST2)in patients with heart failure(HF)and atrial fibrillation(AF),and to explore its diagnostic and prognostic value in patients with HF and AF.Methods A prospective cohort study was carried out to investigate the data of 185 HF patients who were hospitalized between January 2018 and June 2018 in department of cardiology or department of cardiac care unit in TEDA International Cardiovascular Hospital.And according to whether they had atrial fibrillation before admission,we categorized patients into:HF with sinus rhythm(HF-SR,n=90)and HF with AF(HF-AF,n=95).Meanwhile,40 healthy controls were collected.Baseline data of HF-SR and HF-AF groups and plasma sST2 levels in different ejection fraction groups were compared.Plasma sST2 level was determined by enzyme-linked immunosorbent assay(ELISA).Statistical methods such as nonparametric test and Spearman correlation analysis were used.The receiver operating characteristic curve was applied to evaluate the diagnostic value of sST2 in HF-SR and HF-AF groups.And by using the COX risk model,Multi-factor COX analysis was used to analyze the prognosis of patients.Results Compared with healthy controls,the median(P25,P75)of Plasma sST2 levels in HF patients increased remarkably[32.93(20.31-51.39)ng/mL vs 15.99(7.97-22.69)ng/mL,Z=-4.373,P<0.001].Patients with HF-AF group had significantly higher test results[39.86(27.20-59.21)]ng/mL than HF-SR group[24.74(14.83-44.11)]ng/mL,Z=-6.783,P<0.001].In the HFmrEF and HFpEF subgroups,the plasma sST2 level of patients in the HF-AF group was higher than that in the HF-SR group(Z=-2.381,P=0.017;Z=-3.701,P<0.001).Spearman correlation analysis showed that,in HF-AF patients,plasma sST2 level was positively correlated with diastolic blood pressure,Hypertension,New York Association(NYHA)cardiac function classificationⅢtoⅣ,white blood count(WBC),and the level of Alanine Aminotransferase(ALT),Υ-glutamine transaminase(Υ-GT),B-type natriuretic peptide(BNP)(r>0,P<0.05).Also,there is a negative correlation between sST2,left ventricular ejection fraction(LVEF)and estimated Glomerular Filtration Rate(eGFR)(r<0,P<0.05).At ROC analysis,sST2 showed predictive value in both HF-AF and HF-SR group,with an optimal cut-off value of 25.33 ng/mL(AUC 0.872,95%CI:0.805-0.935,P<0.001,sensitivity 81.1%,specificity 87.5%)and 23.34 ng/mL(AUC 0.665,95%CI:0.570-0.761,P<0.001,sensitivity 55.6%,specificity 77.5%).The AUC of BNP and sST2 in differential diagnosis of HF-SR and HF-AF was 0.604 and 0.699,respectively,and the AUC of sST2 was higher than that of BNP.Multi-factor COX analysis indicated that plasma sST2 level,BNP,NYHA cardiac function grading could be risk factors for cardiac events in HF patients.Plasma sST2,left atrial diameter(LA-D),and associated cardiomyopathy are risk factors for cardiac events in patients with HF-AF.The incidence of cardiac events in HF patients with sST2≥20.31 ng/mL was significantly higher than that of patients with sST2<20.31 ng/mL(χ2=7.625,P=0.006).The incidence of cardiac events in HF-AF patients with plasma sST2≥39.86 ng/mL was significantly higher than that in patients with sST2<39.86 ng/mL(χ2=4.287,P=0.038).Conclusions The plasma sST2 level in patients with HF-AF is significantly higher than that both in HF-SR and healthy controls.The diagnostic value of plasma sST2 in patients with HF-AF is higher than that in patients with HF-SR.It is suggested that sST2 are more valuable for the differential diagnosis of HF-SR,HF-AF than BNP.HF-AF Patients with plasma sST2≥39.86 ng/mL are prone to cardiovascular events.
作者
王云平
梁新妹
郑笑荣
贾克刚
陈珍妮
周田
韩雪晶
石萍
Wang Yunping;Liang Xinmei;Zheng Xiaorong;Jia Kegang;Chen Zhenni;Zhou Tian;Han Xuejing;Shi Ping(Department of Clinical Laboratory,Tianjin Medical University Cardiovascular College,Tianjin 300457,China;Department of Clinical Laboratory,Tianjin Binhai New Area Hospital of Traditional Chinese Medicine,Tianjin 300451,China;Department of Clinical Laboratory,Tianjin Medical University Cardiovascular College,TEDA International Cardiovascular Hospital,Tianjin 300457,China)
出处
《中华检验医学杂志》
CAS
CSCD
北大核心
2019年第11期933-941,共9页
Chinese Journal of Laboratory Medicine
基金
天津市卫生计生行业高层次人才选拔培养工程,津门医学英才基金。
关键词
血浆可溶性致癌抑制因子2
心力衰竭
心房颤动
诊断
预后
Soluble suppression of tumorigenicity-2
Heart failure
Atrial fibrillation
Diagnostic
Prognosis
