Vascular endothelial growth factor and pulmonary hypertension in children with beta thalassemia major

Alkholy, Usama M.; Mohamed, Soma Abdalla; Elhady, Marwa; Attar, Shahinaz El; Abdalmonem, Nermin; Zaki, Ahmed

doi:10.1016/j.jped.2018.05.003

Brasil

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Original articles • J. Pediatr. (Rio J.) 95 (5) • Sep-Oct 2019 • https://doi.org/10.1016/j.jped.2018.05.003 linkcopy

Vascular endothelial growth factor and pulmonary hypertension in children with beta thalassemia major^☆

Authorship SCIMAGO INSTITUTIONS RANKINGS

Abstract

Objective: The purpose of this study was to illustrate the association between vascular endothelial growth factor level and pulmonary artery hypertension in children with β-thalassemia major.

Method: This case-control study was conducted on 116 children with β-thalassemia major; 58 of them had pulmonary artery hypertension. They were compared to 58 healthy children who were age and sex-matched (control group). Serum levels of vascular endothelial growth factor and echocardiographic assessment were done for all children.

Results: Vascular endothelial growth factor serum level was significantly higher in children with β-thalassemia major with pulmonary artery hypertension than in those without pulmonary artery hypertension, as well as in control groups (p < 0.001). Vascular endothelial growth factor serum level had a significant positive correlation with pulmonary artery pressure and serum ferritin, as well as a significant negative correlation with the duration of chelation therapy. Logistic regression analysis revealed that elevated vascular endothelial growth factor (Odd Ratio = 1.5; 95% Confidence Interval, 1.137-2.065; p = 0.005) was an independent risk factor of pulmonary artery hypertension in such children. Vascular endothelial growth factor serum level at a cutoff point of >169 pg/mL had 93.1% sensitivity and 93.1% specificity for the presence of pulmonary artery hypertension in children with β-thalassemia major.

Conclusion: Elevated vascular endothelial growth factor serum level is associated with pulmonary artery hypertension in children with β-thalassemia.

KEYWORDS Pulmonary hypertension; Vascular endothelial growth factor; β-Thalassemia

Variables	Thalassemia with PAH (n = 58)	Thalassemia without PAH (n = 58)	Healthy children Control (n = 58)	Independent t test/ANOVA/Chi-squired test		LSD
				t/F/χ²	p-value
Age (years)	11.344 ± 1.044	10.986 ± 0.945	11.357 ± 1.026	1.26	0.288
Sex (n, %)
Male	38 (65.5%)	32 (55.2%)	34 (58.6%)
Female	20 (34.5%)	26 (44.8%)	24 (41.4%)	0.65	0.722
Duration of chelation therapy	3.96 ± 1.9	4.6 ± 2.8	NA	4.16	0.018 Sig
Laboratory data
Hb (g/dL)	6.58 ± 1.38	6.44 ± 1.25	11.66 ± 0.70	186.94	<0.0001HS
PCV %	24.89 ± 7.93	23.32 ± 19.40	37.9 ± 1.99	8.32	<0.0001HS
WBCs (10³/mm³)	10.09 ± 3.59	8.61 ± 3.46	8.24 ± 2.01	2.82	0.065
Platelet (10³/mm³)	437.44 ± 286.56	455.93 ± 220.88	297.60 ± 62.46	10.95	<0.0001HS
Ferritin (ng/mL)	2,977.60 ± 986.95	1,843.74 ± 519.01	73.75 ± 24.67	145.07	<0.0001 HS
VEGF (pg/mL)	208.5 ± 57.982	156.275 ± 12.661	141.118 ± 14.403	28.55	<0.0001 HS	<0.0001^a a Thalassemia with PH vs thalassemia without PH. <0.0001^b b Thalassemia with PH vs control. 0.110^c c Thalassemia without PH vs control.
Echocardiographic data
Pulmonary Pressure (mmHg)	40.55 ± 7.59	19.48 ± 1.52	18.14 ± 3.33	190.54	<0.0001 HS
LVEDD (mm) z score	1.37 ± 0.82	0.92 ± 0.66	0.23 ± 0.84	23.47	<0.0001 HS
LVESD (mm) z score	1.42 ± 0.79	0.86 ± 0.55	0.52 ± 0.80	15.17	<0.0001 HS
EF%	71.31 ± 5.39	69.27 ± 4.45	69.71 ± 4.73	1.39	0.254
FS%	39.07 ± 4.52	37.96 ± 3.57	38.32 ± 4.02	0.55	0.575
Sep (mm) z score	1.35 ± 0.68	0.63 ± 0.19	0.45 ± 0.67	6.61	0.003 Sig
PW (mm) z score	1.22 ± 0.57	0.73 ± 0.85	5.07 ± 0.94	5.79	0.005 Sig
RV (mm) z score	1.20 ± 0.66	0.93 ± 0.63	0.43 ± 0.64	10.25	<0.0001 HS
RA (mm) z score	0.57 ± 0.32	0.53 ± 0.35	0.47 ± 0.25	0.35	0.703
AO (mm) z score	0.32 ± 0.18	0.33 ± 0.17	0.32 ± 0.14	1.62	0.204

	VEGF serum level
	R	p-value
Age of onset (months)	-0.142	0. 283
Duration of illness (years)	0.093	0.482
Hemoglobin (g/dL)	-0.047	0.752
Serum ferritin (ng/mL)	0.399	0.002 Sig
Pulmonary pressure (mmHg)	0.706	<0.0001 HS
Duration of chelation therapy (years)	-0.392	0.002 Sig

	B	S.E.	Wald	p-value	Odd ratio	95% CI for odd ratio
	B	S.E.	Wald	p-value	Odd ratio	Lower	Upper
VEGF	0.427	0.152	7.843	0.005	1.532	1.137	2.065
Age of onset	-0.537	0.158	11.495	0.001	0.584	0.428	0.797
Duration of illness	0.455	0.281	2.631	0.105	1.577	0.910	2.733
Hemoglobin	0.086	0.203	0.179	0.672	1.090	0.732	1.622
Serum ferritin	0.002	0.001	11.209	0.001	1.002	1.001	1.004
Duration of chelation therapy	-0.183	0.138	1.745	0.186	0.833	0.635	1.092
Splenectomy	-1.353	0.572	5.584	0.018	0.258	0.084	0.793

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