血清生长分化因子-15、心脏型脂肪酸结合蛋白及脑利钠肽水平与肺炎合并心力衰竭患儿预后的关系

doi:10.3877/cma.j.issn.1673-5250.2019.06.013

中华妇幼临床医学杂志(电子版) ›› 2019, Vol. 15 ›› Issue (06) : 688 -694. doi: 10.3877/cma.j.issn.1673-5250.2019.06.013

所属专题：文献；

论著

血清生长分化因子-15、心脏型脂肪酸结合蛋白及脑利钠肽水平与肺炎合并心力衰竭患儿预后的关系

李清涛¹, 陈红云², 田利远¹^,^†(

)

^1. 河北省儿童医院呼吸一科，石家庄　050031
^2. 南皮县人民医院儿科，河北沧州　061500

收稿日期:2019-06-24 修回日期:2019-11-08 出版日期:2019-12-01
通信作者: 田利远

Relationship between serum levels of growth differentiation factor-15, heart-fatty acid-binding protein, brain natriuretic peptide and prognosis in children with pneumonia associated with heart failure

Qingtao Li¹, Hongyun Chen², Liyuan Tian¹^,^†()

^1. Department of Respiratory, Children′s Hospital of Hebei Province, Shijiazhuang 050031, Hebei Province, China
^2. Department of Pediatrics, Nanpi County People′s Hospital, Cangzhou 061500, Hebei Province, China

Received:2019-06-24 Revised:2019-11-08 Published:2019-12-01
Corresponding author: Liyuan Tian
About author:
Corresponding author: Tian Liyuan, Email: Tianly2007@ sina.com
Supported by:
Key Project Plan of Medical Science Research of Hebei Province in 2018(20180628)

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引用本文：

李清涛, 陈红云, 田利远. 血清生长分化因子-15、心脏型脂肪酸结合蛋白及脑利钠肽水平与肺炎合并心力衰竭患儿预后的关系[J/OL]. 中华妇幼临床医学杂志(电子版), 2019, 15(06): 688-694.

Qingtao Li, Hongyun Chen, Liyuan Tian. Relationship between serum levels of growth differentiation factor-15, heart-fatty acid-binding protein, brain natriuretic peptide and prognosis in children with pneumonia associated with heart failure[J/OL]. Chinese Journal of Obstetrics & Gynecology and Pediatrics(Electronic Edition), 2019, 15(06): 688-694.

目的

探讨血清生长分化因子(GDF)-15、心脏型脂肪酸结合蛋白(H-FABP)及脑利钠肽(BNP)水平与肺炎合并心力衰竭(HF)患儿预后的关系。

方法

选择2016年5月至2018年5月，于河北省儿童医院诊断的80例肺炎合并HF患儿为研究对象，纳入研究组。选择同期于本院进行儿童保健的80例健康儿童为对照，纳入对照组。采用酶联免疫吸附试验(ELISA)，检测2组受试儿血清GDF-15、H-FABP、BNP水平和HF标志蛋白心肌肌钙蛋白(cTnI)、肌酸激酶(CK)-MB水平。2组受试儿血清GDF-15、H-FABP、BNP、cTnI、CK-MB水平比较，采用成组t检验。研究组患儿血清GDF-15、H-FABP及BNP水平与HF标志蛋白cTnI、CK-MB的相关性分析，采用Pearson相关性分析。采用Cox比例风险回归模型，分析血清GDF-15、H-FABP、BNP水平与肺炎合并HF患儿预后的关系。本研究遵循的程序符合2013年修订的《世界医学协会赫尔辛基宣言》要求，2组受试儿监护人均签署临床研究知情同意书。2组受试儿性别构成比、出生胎龄、出生体重、年龄等一般临床资料比较，差异均无统计学意义(P>0.05)。

结果

①研究组患儿血清GDF-15、H-FABP、BNP、cTnI、CK-MB水平，分别为(5.01±0.73) ng/mL、(36.2±6.2) ng/mL、(899.8±300.3) pg/mL、(0.31±0.10) μg/L、(36.2±5.3) U/L，均显著高于对照组的(0.59±0.10) ng/mL、(1.2±0.3) ng/mL、(21.4±4.3) pg/mL、(0.06±0.02) μg/L、(18.4±2.6) U/L，并且2组比较，差异均有统计学意义(t＝53.652、50.432、26.164、21.931、26.973，P均<0.001)。②肺炎合并HF患儿血清GDF-15、BNP水平与血清cTnI水平，均呈正相关关系(r＝0.340、P＝0.002，r＝0.285、P＝0.010)；血清GDF-15、H-FABP水平与血清CK-MB水平，均呈正相关关系(r＝0.765、P<0.001，r＝0.302、P＝0.006)。③Cox比例风险回归模型分析结果显示，血清GDF-15、H-FABP、BNP高表达患儿的不良预后风险，分别是血清GDF-15、H-FABP、BNP低表达患儿的2.319倍(HR＝2.319，95%CI：1.306～4.118，P＝0.004)，1.737倍(HR＝1.737，95%CI：1.027～2.937，P＝0.039)及1.904倍(HR＝1.904，95%CI：1.135～3.195，P＝0.015)。

结论

血清GDF-15、H-FABP、BNP在肺炎合并HF患儿中表达增高，并且与患儿不良预后密切相关。由于本研究纳入样本量相对较小，这3个指标与肺炎合并HF患儿预后的关系，以及对于该病患儿预后的判断价值，仍然有待大样本、多中心、随机对照试验进一步研究、证实。

关键词: 生长分化因子, 脂肪酸结合蛋白质类, 利钠肽，脑, 生物学标记, 肺炎合并心力衰竭, 心肌肌钙蛋白, 肌酸激酶, 儿童

Objective

To investigate the relationship between serum levels of growth differentiation factor (GDF)-15, heart-fatty acid-binding protein (H-FABP) and brain natriuretic peptide (BNP) and the prognosis of children with pneumonia associated with heart failure (HF).

Methods

Eighty children with pneumonia associated with HF diagnosed in Children′s Hospital of Hebei Province from May 2016 to May 2018 were selected as research subjects and were enrolled into study group. And 80 healthy children who received child care in the same hospital during the same period were selected as control and were enrolled into control group. The serum levels of GDF-15, H-FABP, BNP and HF marker proteins cardiac troponin (cTnI) and creatine kinase (CK)-MB of two groups were detected by enzyme-linked immunosorbent assay (ELISA) and compared by independent-samples t test. Pearson correlation analysis was used to analyze the correlation between serum levels of GDF-15, H-FABP, BNP and HF marker protein cTnI and CK-MB. Cox proportional hazard model was used to analyze the relationship between serum levels of GDF-15, H-FABP, BNP and prognosis of children with pneumonia associated with HF. The procedures followed in this study met the requirements of World Association Declaration of Helsinki revised in 2013. The guardians of all research subjects signed clinical research informed consent. There were no statistical differences between two groups in the general clinical data, such as gender composition ratio, birth gestational age, birth age, age and so on.

Results

①The serum levels of GDF-15, H-FABP, BNP, cTnI and CK-MB in study group were (5.01±0.73) ng/mL, (36.2±6.2) ng/mL, (899.8±300.3) pg/mL, (0.31±0.10) μg/L, and (36.2±5.3) U/L, respectively, which all were statistically higher than those in control group (0.59±0.10) ng/mL, (1.2±0.3) ng/mL, (21.4±4.3) pg/mL, (0.06±0.02) μg/L, (18.4±2.6) U/L, and all the differences were statistically significant (t=53.652, 50.432, 26.164, 21.931, 26.973, all P<0.001). ②Among children with pneumonia associated with HF, the serum levels of GDF-15 and BNP of both were positively correlated with serum level of cTnI (r=0.340, P=0.002; r=0.285, P=0.010). And the serum levels of GDF-15 and H-FABP both were positively correlated with serum level of CK-MB (r=0.765, P<0.001; r=0.302, P=0.006). ③Cox proportional hazard model analysis results showed that the risk of poor prognosis in children with high expression of serum GDF-15 was 2.319 times higher than that in children with low expression of serum GDF-15 (HR=2.319, 95%CI: 1.306-4.118, P=0.004). The risk of poor prognosis in children with high expression of serum H-FABP was 1.737 times higher than that in children with low expression of serum H-FABP (HR=1.737, 95%CI: 1.027-2.937, P=0.039). The risk of poor prognosis in children with high expression of serum BNP was 1.904 times higher than that in children with low expression (HR=1.904, 95%CI: 1.135-3.195, P=0.015).

Conclusions

Serum levels of GDF-15, H-FABP and BNP of children with pneumonia associated with HF are increased, and they are associated with poor prognosis of children with this disease. As the sample size in this study is relatively small, the relationships between these three indexes and the prognosis of children with pneumonia associated with HF, and its value in evaluating the prognosis of this disease, remain to be further confirmed by large-sample, multi-center, and randomized controlled trials.

Key words: Growth differentiation factors, Fatty acid-binding proteins, Natriuretic peptide, brain, Biological markers, Pneumonia associated with heart failure, Cardiac troponin, Creatine kinase, Child

表1 2组受试儿一般临床资料比较

组别	例数	性别[例数(%)]		出生胎龄(周，±s)	出生体重(g，±s)	年龄[月，M(P₂₅～P₇₅)]
组别	例数	男	女	出生胎龄(周，±s)	出生体重(g，±s)	年龄[月，M(P₂₅～P₇₅)]
研究组	80	41(51.2)	39(48.8)	37.5±4.2	2 845±626	6(3～10)
对照组	80	40(50.0)	40(50.0)	37.0±4.8	2 984±611	6(3～10)
检验值	?	χ²＝0.025		t＝0.701	t＝1.421	Z＝0.990
P值	?	0.874		0.484	0.157	0.132

表1 2组受试儿一般临床资料比较

组别	例数	性别[例数(%)]		出生胎龄(周，±s)	出生体重(g，±s)	年龄[月，M(P₂₅～P₇₅)]
组别	例数	男	女	出生胎龄(周，±s)	出生体重(g，±s)	年龄[月，M(P₂₅～P₇₅)]
研究组	80	41(51.2)	39(48.8)	37.5±4.2	2 845±626	6(3～10)
对照组	80	40(50.0)	40(50.0)	37.0±4.8	2 984±611	6(3～10)
检验值	?	χ²＝0.025		t＝0.701	t＝1.421	Z＝0.990
P值	?	0.874		0.484	0.157	0.132

表2 2组受试儿血清GDF-15、H-FABP、BNP、cTnI及CK-MB水平比较(±s)

组别	例数	血清GDF-15水平(ng/mL)	血清H-FABP水平(ng/mL)	血清BNP水平(pg/mL)	血清cTnI水平(μg/L)	血清CK-MB水平(U/L)
研究组	80	5.01±0.73	36.2±6.2	899.8±300.3	0.31±0.10	36.2±5.3
对照组	80	0.59±0.10	1.2±0.3	21.4±4.3	0.06±0.02	18.4±2.6
t值	?	53.652	50.432	26.164	21.931	26.973
P值	?	<0.001	<0.001	<0.001	<0.001	<0.001

表2 2组受试儿血清GDF-15、H-FABP、BNP、cTnI及CK-MB水平比较(±s)

组别	例数	血清GDF-15水平(ng/mL)	血清H-FABP水平(ng/mL)	血清BNP水平(pg/mL)	血清cTnI水平(μg/L)	血清CK-MB水平(U/L)
研究组	80	5.01±0.73	36.2±6.2	899.8±300.3	0.31±0.10	36.2±5.3
对照组	80	0.59±0.10	1.2±0.3	21.4±4.3	0.06±0.02	18.4±2.6
t值	?	53.652	50.432	26.164	21.931	26.973
P值	?	<0.001	<0.001	<0.001	<0.001	<0.001

图6 肺炎合并HF患儿血清BNP水平与血清CK-MB水平的相关性分析

表3 肺炎合并HF患儿预后影响因素的Cox比例风险回归模型分析的变量含义及其赋值

自变量/因变量	变量名	赋值
预后	y	y＝0表示患儿预后良好，y＝1表示患儿预后不良
性别	x₁	x₁＝0表示患儿为男性，x₁＝1患儿为表示女性
血清GDF-15水平	x₂	x₂＝0表示血清GDF-15低表达，x₂＝1表示血清GDF-15高表达
血清H-FABP水平	x₃	x₃＝0表示血清H-FABP低表达，x₃＝1表示血清H-FABP高表达
血清BNP水平	x₄	x₄＝0表示血清BNP低表达，x₄＝1表示血清BNP高表达

表3 肺炎合并HF患儿预后影响因素的Cox比例风险回归模型分析的变量含义及其赋值

自变量/因变量	变量名	赋值
预后	y	y＝0表示患儿预后良好，y＝1表示患儿预后不良
性别	x₁	x₁＝0表示患儿为男性，x₁＝1患儿为表示女性
血清GDF-15水平	x₂	x₂＝0表示血清GDF-15低表达，x₂＝1表示血清GDF-15高表达
血清H-FABP水平	x₃	x₃＝0表示血清H-FABP低表达，x₃＝1表示血清H-FABP高表达
血清BNP水平	x₄	x₄＝0表示血清BNP低表达，x₄＝1表示血清BNP高表达

表4 肺炎合并HF患儿预后影响因素的Cox比例风险回归模型分析结果

影响因素	B	SE	Wald值	P值	HR值	HR值95%CI
性别(女性vs男性)	0.084	0.247	0.116	0.734	1.088	0.670～1.765
血清GDF-15水平(高表达vs低表达)	0.841	0.293	8.239	0.004	2.319	1.306～4.118
血清H-FABP水平(高表达vs低表达)	0.552	0.268	4.242	0.039	1.737	1.027～2.937
血清BNP水平(高表达vs低表达)	0.644	0.264	5.951	0.015	1.904	1.135～3.195

表4 肺炎合并HF患儿预后影响因素的Cox比例风险回归模型分析结果

影响因素	B	SE	Wald值	P值	HR值	HR值95%CI
性别(女性vs男性)	0.084	0.247	0.116	0.734	1.088	0.670～1.765
血清GDF-15水平(高表达vs低表达)	0.841	0.293	8.239	0.004	2.319	1.306～4.118
血清H-FABP水平(高表达vs低表达)	0.552	0.268	4.242	0.039	1.737	1.027～2.937
血清BNP水平(高表达vs低表达)	0.644	0.264	5.951	0.015	1.904	1.135～3.195

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Relationship between serum levels of growth differentiation factor-15, heart-fatty acid-binding protein, brain natriuretic peptide and prognosis in children with pneumonia associated with heart failure

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Relationship between serum levels of growth differentiation factor-15, heart-fatty acid-binding protein, brain natriuretic peptide and prognosis in children with pneumonia associated with heart failure