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

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

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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