Edited by: Oswin Grollmuss, Université Paris-Sud, France
Reviewed by: Meena Nathan, Boston Children's Hospital and Harvard Medical School, United States; Qiuwang Zhang, St. Michael's Hospital, Canada
This article was submitted to Pediatric Cardiology, a section of the journal Frontiers in Pediatrics
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Fibroblast growth factor 23 (FGF 23), an endocrine hormone regulating the homeostasis of phosphate and vitamin D, has been shown to play a role in cardiovascular disease. Increased blood FGF 23 is found to be associated with elevated blood pressure in adults. However, measurement of FGF 23 in hypertensive children has not been documented. In this study, a total of 98 children with primary hypertension and 37 controls were recruited, and blood FGF 23 was comparatively investigated. Additionally, FGF 23 levels were compared between the subgroups of patients after hypertensive children were sub-grouped according to their cardiac geometry, hypertension stages, insulin levels, and weight. The case group had a FGF 23 level of 48.99 (16.42), expressed as the median (the interquartile range), significantly higher than the 41.72 (7.05) from the control group (
Fibroblast growth factor 23 (FGF 23), primarily produced by osteocytes and osteoblasts in bone, was originally recognized as an endocrine hormone by its canonical function to regulate the homeostasis of phosphate and vitamin D (
Pediatric primary hypertension is on the rise (
This study was approved by the Medical Research Review Board of Children's Hospital, Capital Institute of Pediatrics, Beijing, in accordance with the Declaration of Helsinki, the Code of Ethics of the World Medical Association. Written informed parental consent was obtained for all participants.
All subjects, aged 8–17 years, were recruited at our department. Children with primary hypertension formed the case group while those with normal blood pressure were included in the control group. Patients with secondary hypertension or conditions that affect kidneys or the cardiovascular, endocrine, or central nervous systems were excluded. All blood samples were obtained in the morning after overnight fasting. All blood pressure measurements were performed using the auscultation method as recommended by the Fourth Report on the Diagnosis, Evaluation, and Treatment of High Blood Pressure in Children and Adolescents, and the results were used for hypertension diagnosis and stage classification (
LVH was assessed by echocardiography. Left ventricular internal dimension (LVIDd), interventricular septal thickness (IVST) and left ventricular posterior wall thickness (LVPWT) at end-diastole were measured using the Philips iE33 Ultrasound System. Relative left ventricular wall thickness (RWT) was calculated as RWT = (IVST+LVPWT)/LVIDd; left ventricular mass (LVM) was calculated as LVM = 1.04 × 0.8 × ((LVIDd+IVST+LVPWT)3–LVIDd3)+0.6 (
Plasma FGF 23 levels were determined by an enzyme-linked immunosorbent assay using the Human FGF 23 (C-Term) ELISA Kit that measures the C-terminal fragment of FGF 23 (cFGF 23). The assay was performed and the FGF 23 level was expressed as the relative unit/ml (RU/ml) according to the manufacturer's instructions (Quidel Corporation, San Diego, USA).
Fasting insulin was measured in the diagnostic laboratory of our hospital following a routine protocol.
Data normality was determined by the Shapiro-Wilk test. Parametric continuous data were expressed as mean ± standard deviation (SD) and analyzed by two-tailed Student's
A total of 98 hypertensive and 37 normotensive children, aged 8 to 17 years, were recruited. Demographics and blood pressures of all subjects are shown in
Demographics and blood pressures of all subjects.
Age (years) | 11.8 ± 2.2 | 11.1 ± 2.2 |
Number of males (%) | 78 (79.59) | 11 (29.73) |
BMI (kg/m2) | 27.32 ± 5.36 |
18.01 ± 2.48 |
Mean systolic pressure (mmHg) | 128.33 ± 12.39 |
117.73 ± 7.03 |
Mean diastolic pressure (mmHg) | 72.69 ± 12.36 |
68.35 ± 5.58 |
All FGF 23 levels were presented in the unit of RU/ml. The FGF 23 level in the case group was significantly higher than that of the control group (
Comparison of FGF 23 levels (RU/ml) between the case and control groups.
FGF levels | 48.99 (16.42) | 41.72 (7.05) | 0.0002 |
FGF 23 levels were compared between subgroups of patients. As shown in
Comparison of FGF 23 levels (RU/ml) between subgroups of patients.
Non-obese ( |
Obese ( |
0.52 |
Stage 1 ( |
Stage 2 ( |
0.28 |
Normal insulin ( |
High insulin ( |
0.44 |
Normal cardiac geometry |
Abnormal cardiac geometry |
0.0085 |
In the present study, we comparatively investigated blood FGF 23 levels in hypertensive and normotensive children, and reported that (1) children with primary hypertension had significantly higher levels of FGF 23 than controls; (2) FGF 23 levels in patients with abnormal cardiac geometry were markedly higher than those in patients with normal cardiac geometry; and (3) there were no significant differences in FGF 23 levels between non-obese and obese hypertensive children, between patients with stage 1 and stage 2 hypertension, or between patients with normal and high insulin levels. Previous studies have shown that FGF 23 levels does not differ between genders (
FGF 23 is a protein consisting of 251 amino acids with an N-terminal region that contains the conserved FGF homology domain and a C-terminus of 71-amino acid (
As one of the most important regulators of blood phosphate, FGF 23 stimulates urinary phosphate excretion. It has been shown in both adult and pediatric patients that FGF 23 levels rise as kidney function declines (
FGF 23 has been shown to be independently associated with left ventricular mass, hypertrophy and geometry in adult patients with or without CKD (
Hypertensive children have a higher rate of obesity (
Considering that this is a small-scale study from a single center, the generalizability of our data might be limited. Additionally, the control group is about a third the size of the cases, which might limit the statistical power. Further studies in a large series and in other race and ethnic groups are needed.
All authors listed have made a substantial, direct and intellectual contribution to the work, and approved it for publication.
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.