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慢性心力衰竭(chronic heart failure,CHF)是血液动力负荷过重、冠状动脉粥样硬化、心肌梗死等原因造成心肌损伤,心肌结构和功能改变,导致心室充盈及泵血功能降低,是老年人中常见的晚期心脏疾病[1]。研究[2]显示,在发达国家,心力衰竭的患病率为1%~2%,其中70岁以上的病人超过10%。目前CHF的早期诊断主要依赖病人临床表现、心脏彩超相关指标如左心室射血分数(left ventricular ejection fraction,LVEF)等,但由于CHF病人早期症状不典型,当已出现典型临床症状时心功能衰竭多已不可逆转[3]。因此,深入研究冠心病发生发展的机制,筛选新的CHF早期诊断、治疗及预后判断的血清生物标志物,具有重要的临床意义。可溶性ST2(soluable ST2,sST2)基因位于染色体2q12上,当心肌细胞受到压力负荷、容量负荷及缺血再灌注损伤等刺激时,其表达水平显著升高,发挥抑制心肌纤维化、抑制心肌细胞凋亡等心脏保护功能[4]。激活素A(actin-A,ACT-A)是转化生长因子β家族成员,其作为一种促炎细胞因子,参与炎症反应、免疫及组织纤维化等病理生理过程。近年来研究[5]发现,CHF病人血清中ACT-A表达异常升高,并与心力衰竭程度密切相关,参与心力衰竭发生发展的过程。N-末端脑钠肽前体(NT-proBNP)是B型钠尿肽(BNP)的无活性的裂解产物,与BNP相比,具有较长的半衰期、良好的体外稳定性及较高的外周血浓度,有助于反映CHF病人的心功能状况[6]。本研究通过检测CHF病人血清sST2、ACT-A、NT-proBNP的表达,初步探讨三者在CHF病人病情发生发展中的临床意义。
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与对照组相比,CHF组病人血清LDL-C、hsCRP、sST2、ACT-A、NT-proBNP较高(P < 0.01),LVEF较低(P < 0.01),而2组在高血压史、吸烟史、TC、TG、HDL-C、FPG、HbA1c及血肌酐间差异均无统计学意义(P>0.05)(见表 1)。
临床资料 对照组
(n=50)CHF组
(n=149)t P 性别 男
女31
1989
600.08△ >0.05 年龄/岁 60.1±7.2 62.6±8.7 1.83 >0.05 高血压史 有
无27
2382
670.02△ >0.05 吸烟史 有
无19
3140
1092.23△ >0.05 TC/(mmol/L) 4.42±0.93 4.38±1.01 0.25 >0.05 TG/(mmol/L) 1.43±0.64 1.56±0.66 1.21 >0.05 LDL-C/(mmol/L) 1.12±0.32 1.41±0.70 2.828 < 0.01 HDL-C/(mmol/L) 2.11±0.74 1.93±0.65 1.64 >0.05 FPG/(mol/L) 5.81±1.65 6.37±1.78 1.96 >0.05 HbA1c/% 5.57±1.15 6.69±1.34 1.28 >0.05 hsCRP/(mg/L) 1.05±0.20 6.32±1.34 27.66 < 0.01 血肌酐/(μmol/L) 95.58±21.42 101.18±23.52 1.49 >0.05 LVEF/% 63.61±9.05 44.86±8.34 13.46 < 0.01 sST2/(μg/L) 0.32±0.07 1.20±0.12 49.08 < 0.01 ACT-A/(pg/mL) 262.56±53.72 709.38±73.62 39.50 < 0.01 NT-proBNP/(pg/mL) 107.87±70.79 2 316.33±110.19 132.71 < 0.01 △示χ2值 表 1 2组一般临床资料比较(x±s)
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不同NYHA分级CHF病人血清sST2、ACT-A、NT-proBNP间差异均有统计学意义(P < 0.05)。NYHA Ⅳ级CHF病人的血清sST2、ACT-A、NT-proBNP均高于Ⅲ级CHF的病人(P < 0.05);NYHA Ⅲ级CHF病人的血清sST2、ACT-A、NT-proBNP均高于Ⅱ级病人(P < 0.05)(见表 2)。
分组 n sST2/(μg/L) ACT-A/(pg/mL) NT-proBNP/(pg/mL) NYHA Ⅱ级组 49 1.05±0.11 673.12±67.94 2027.19±115.67 NYHA Ⅲ级组 55 1.21±0.12* 711.27±71.82* 2308.70±110.22* NYHA Ⅳ级组 45 1.35±0.13*# 746.55±75.69*# 2639.40±104.19*# F — 73.64 12.31 361.59 P — 0.01 0.01 0.01 MS组内 — 0.014 5 151.873 12 163.555 q检验:与NYHA Ⅱ级组比较*P < 0.05;与NYHA Ⅲ级组比较#P < 0.05 表 2 不同NYHA分级CHF病人血清sST2、ACT-A、NT-proBNP比较(x±s)
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CHF组病人血清sST2、ACT-A、NT-proBNP水平与NYHA分级均呈明显正相关关系(P < 0.01),与LVEF均呈负相关关系(P < 0.05~P < 0.01),而与病人年龄、TC、TG、hsCRP、HDL-C、LDL-C、hs-CRP、HbA1c均无明显相关关系(P>0.05)(见表 3)。
临床参数 sST2 ACT-A NT-proBNP TC 0.056 0.081* 0.072 TG 0.170 0.087 0.118 HDL-C -0.201 -0.154 -0.187 LDL-C 0.146 0.068 0.139 hsCRP 0.123 0.078 0.160 FPG 0.064 -0.077 0.112 HbA1c/% -0.081 -0.341 0.129 NYHA分级 0.469** 0.483** 0.512** LVEF -0.422* -0.540** -0.452** *P < 0.05,**P < 0.01 表 3 血清sST2、ACT-A、NT-proBNP水平与CHF病人临床参数相关关系(r)
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对所有149例CHF病人进行随访,随访12个月,记录心血管不良事件发生情况。结果未发生心血管不良事件CHF病人107例,发生心血管不良事件CHF病人中,死亡17例,死因为恶性心律失常、心源性猝死等,而因心脏衰竭再次住院的CHF病人25例。
应用ROC曲线分析血清sST2、ACT-A、NT-proBNP对CHF病人心血管事件的预测价值,结果显示, sST2、ACT-A、NT-proBNP的曲线下面积(AUC)分别为0.803、0.715、0.692,三者联合检测的AUC为0.891,预测价值高于任一单一指标,敏感性为0.714,特异性为0.920,特异性高于任意单一指标(见表 4)。
检测指标 AUC 95%CI 截断值 敏感度 特异度 ACT-A 0.715 0.655~0.832 936.80 pg/mL 0.78 0.75 sST2 0.803 0.715~0.904 1.14 μg/L 0.77 0.73 NT-proBNP 0.692 0.621~0.824 2 309.10 pg/mL 0.74 0.63 联合检测 0.891 0.732~0.912 — 0.71 0.92 表 4 血清sST2、ACT-A、NT-proBNP对CHF病人心血管事件的诊断价值
血清sST2、ACT-A及NT-proBNP在慢性心力衰竭病人病情发生及发展中的临床意义
Clinical significance of the serum sST2, ACT-A and NT-proBNP in the occurrence and development of chronic heart failure
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摘要:
目的研究血清可溶性ST2(sST2)、激活素A(ACT-A)及N-末端脑钠肽前体(NT-proBNP)的表达及在慢性心力衰竭(CHF)病人病情发生发展中的临床意义。 方法选取149例CHF病人为CHF组,以50名健康查体人群作为对照组。分析sST2、ACT-A、NT-proBNP的组间表达差异及三指标与临床参数的相关性。应用ROC曲线分析血清sST2、ACT-A、NT-proBNP对CHF病人心血管事件的预测价值。 结果与对照组相比,CHF组病人血清sST2、ACT-A、NT-proBNP水平较高,而左心室射血分数(LVEF)水平较低(P < 0.01)。NYHA心功能分级Ⅳ级的CHF病人血清sST2、ACT-A、NT-proBNP高于Ⅲ级,且Ⅲ级高于Ⅱ级(P < 0.05)。CHF组病人血清sST2、ACT-A、NT-proBNP水平与NYHA分级呈明显正相关关系(P < 0.05),与LVEF呈明显负相关关系(P < 0.05),与年龄、TC、TG、hsCRP、HDL-C、LDL-C、hs-CRP、HbA1c无明显相关关系(P>0.05)。ROC曲线分析结果显示,sST2、ACT-A、NT-proBNP的曲线下面积(AUC)分别为0.803、0.715、0.692,三者联合检测的AUC为0.891,预测价值高于任一单一指标。 结论CHF病人血清sST2、ACT-A、NT-proBNP的表达升高,并且三者的表达水平与NYHA分级呈明显正相关关系,与LVEF呈明显负相关关系,三者联合检测检测对CHF病人心血管事件具有较高的预测价值。 Abstract:ObjectiveTo investigate the serum levels of soluble ST2(sST2), activin A(ACT-A), and N-terminal brain natriuretic peptide precursor(NT-proBNP), and its clinical significance in the occurrence and development of chronic heart failure(CHF). MethodsA total of 149 patients with CHF and 50 healthy people were divided into the CHF group and control group, respectively.The differences of the serum levels of sST2, ACT-A, NT-proBNP between two groups, and correlation between three indicators and clinical parameters were analyzed.The ROC curves were used to analyze the predictive value of serum sST2, ACT-A and NT-proBNP in cardiovascular events of patients with CHF. ResultsCompared with the control group, the serum levels of sST2, ACT-A, NT-proBNP in patients with CHF were significantly higher(P < 0.01), while the Left Ventricular Ejection Fractions(LVEF) was significantly lower(P < 0.01).The serum levels of sST2, ACT-A, NT-proBNP in patients with NYHA grade Ⅳ were significantly higher than those in grade Ⅲ, and which in patients with grade Ⅲ was significantly higher than grade Ⅱ(P < 0.05).The serum levels of sST2, ACT-A, NT-proBNP in patients with CHF were significantly positively correlated with NYHA classification, and negatively correlated with LVEF(P < 0.05), but which were not related to the age, TC, TG, hsCRP, HDL-C, and LDL-C, hs-CRP and HbA1c(P>0.05).The ROC curve analysis results showed that the area under the curve(AUC) of sST2, ACT-A, and NT-proBNP was 0.803, 0.715, and 0.692, respectively.The combined detection AUC of all three was 0.891, and the predicted value of which was higher than that of any single indicator. ConclusionsThe serum levels of sST2, ACT-A, NT-proBNP in patients with CHF increase, and the expression levels of the three are significantly positively correlated with NYHA classification, and negatively correlated with LVEF.The combined detection in CHF patients has a high predictive value in cardiovascular events. -
Key words:
- heart failure /
- soluble ST2 /
- activin A /
- N-terminal brain natriuretic peptide precursor
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表 1 2组一般临床资料比较(x±s)
临床资料 对照组
(n=50)CHF组
(n=149)t P 性别 男
女31
1989
600.08△ >0.05 年龄/岁 60.1±7.2 62.6±8.7 1.83 >0.05 高血压史 有
无27
2382
670.02△ >0.05 吸烟史 有
无19
3140
1092.23△ >0.05 TC/(mmol/L) 4.42±0.93 4.38±1.01 0.25 >0.05 TG/(mmol/L) 1.43±0.64 1.56±0.66 1.21 >0.05 LDL-C/(mmol/L) 1.12±0.32 1.41±0.70 2.828 < 0.01 HDL-C/(mmol/L) 2.11±0.74 1.93±0.65 1.64 >0.05 FPG/(mol/L) 5.81±1.65 6.37±1.78 1.96 >0.05 HbA1c/% 5.57±1.15 6.69±1.34 1.28 >0.05 hsCRP/(mg/L) 1.05±0.20 6.32±1.34 27.66 < 0.01 血肌酐/(μmol/L) 95.58±21.42 101.18±23.52 1.49 >0.05 LVEF/% 63.61±9.05 44.86±8.34 13.46 < 0.01 sST2/(μg/L) 0.32±0.07 1.20±0.12 49.08 < 0.01 ACT-A/(pg/mL) 262.56±53.72 709.38±73.62 39.50 < 0.01 NT-proBNP/(pg/mL) 107.87±70.79 2 316.33±110.19 132.71 < 0.01 △示χ2值 表 2 不同NYHA分级CHF病人血清sST2、ACT-A、NT-proBNP比较(x±s)
分组 n sST2/(μg/L) ACT-A/(pg/mL) NT-proBNP/(pg/mL) NYHA Ⅱ级组 49 1.05±0.11 673.12±67.94 2027.19±115.67 NYHA Ⅲ级组 55 1.21±0.12* 711.27±71.82* 2308.70±110.22* NYHA Ⅳ级组 45 1.35±0.13*# 746.55±75.69*# 2639.40±104.19*# F — 73.64 12.31 361.59 P — 0.01 0.01 0.01 MS组内 — 0.014 5 151.873 12 163.555 q检验:与NYHA Ⅱ级组比较*P < 0.05;与NYHA Ⅲ级组比较#P < 0.05 表 3 血清sST2、ACT-A、NT-proBNP水平与CHF病人临床参数相关关系(r)
临床参数 sST2 ACT-A NT-proBNP TC 0.056 0.081* 0.072 TG 0.170 0.087 0.118 HDL-C -0.201 -0.154 -0.187 LDL-C 0.146 0.068 0.139 hsCRP 0.123 0.078 0.160 FPG 0.064 -0.077 0.112 HbA1c/% -0.081 -0.341 0.129 NYHA分级 0.469** 0.483** 0.512** LVEF -0.422* -0.540** -0.452** *P < 0.05,**P < 0.01 表 4 血清sST2、ACT-A、NT-proBNP对CHF病人心血管事件的诊断价值
检测指标 AUC 95%CI 截断值 敏感度 特异度 ACT-A 0.715 0.655~0.832 936.80 pg/mL 0.78 0.75 sST2 0.803 0.715~0.904 1.14 μg/L 0.77 0.73 NT-proBNP 0.692 0.621~0.824 2 309.10 pg/mL 0.74 0.63 联合检测 0.891 0.732~0.912 — 0.71 0.92 -
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