International Journal of Psychosocial Rehabilitation, Vol. 24, Issue 05, 2020
ISSN: 1475-7192
DOI: 10.37200/IJPR/V24I5/PR2020213
Received: 12 Mar 2020 | Revised: 28 Mar 2020 | Accepted: 06 Apr 2020
5055
Abstract---
The study of vitamin D - dependent risk factors for the formation of essential arterial hypertension
(EAH) based on the assessment of serum levels of calcidiol (25 (OH) D), calcium and vasoconstrictor factor
endothelin-1-21 in 132 students aged 13 to 16 years (average age 14.64 ± 0.19 years) with normal, high normal
blood pressure and essential arterial hypertension (EAH) established the priority effect of vitamin D supply on the
level of diastolic blood pressure in the group of children with labile arterial hypertension and in the group of
children with stable on the parameters of systolic blood pressure. In the mechanism of EAH formation in children,
an interdependence between vitamin D deficiency and the severity of endothelial dysfunction by the level of
endothelin -1-21 was revealed. The following vitamin D were determined by diagnostic efficiency - dependent risk
factors for the formation of EAH in children in decreasing importance: endothein-1-21> 0.41fmol / ml; vitamin D
<20ng / ml; Ca <2.22 mmol / L.
Keywords---
Essential Arterial Hypertension, School Children, Blood Pressure, Vitamin D (25 (OH) D),
Endothelin-1-21.
I.
I
NTRODUCTION
Essential arterial hypertension (EAH) is one of the leading problems of modern medicine, being a significant
cause of early disability and death in people of working age, the origins of which lie in childhood [1, 2]. In the
structure of all registered diseases of the circulatory system in the Republic of Uzbekistan, the leading role belongs
to diseases characterized by elevated levels of pressure (33.6-37, 8% in the country) [3]. It is generally recognized
that the cardiovascular system is the leading effector system in the process of postnatal adaptation, through which
the reactions of many regulatory systems of the div are mediated. The prevalence of EAH in childhood and
adolescence is significant - from 2.4% to 20% or more [4, 5]. In recent years, there has been a tendency toward an
increase in the frequency of EAH among schoolchildren, which is the result of an increase in the proportion of
children with obesity and a behavioral stereotype that is far from a healthy lifestyle [6]. In children with blood
pressure (BP) exceeding the norm, the tendency to its further increase increases with age and remains increased in
33-42% of them, and in 17-26% of children arterial hypertension (AH) progresses. In 50% of children, hypertension
is asymptomatic, which makes it difficult to identify and, accordingly, timely treatment. Often, already in childhood,
Akhmedova Firuza Mirzakirovna, Tashkent Pediatric Medical Institute, Tashkent, Uzbekistan.
Agzamova Shoira Abdusalamovna, Tashkent Pediatric Medical Institute, Tashkent, Uzbekistan.
Akhmedova Dilorom Ilxamovna, Tashkent Pediatric Medical Institute, Tashkent, Uzbekistan.
Tashpulatova Fatima Kudratovna, Tashkent Pediatric Medical Institute, Tashkent, Uzbekistan.
Vitamin D - Dependent Risk Factors of Formation
of Essential Arterial Hypertension at School
Children of Tashkent City
Akhmedova Firuza Mirzakirovna,
Agzamova Shoira Abdusalamovna,
Akhmedova Dilorom Ilxamovna and
Tashpulatova Fatima Kudratovna
International Journal of Psychosocial Rehabilitation, Vol. 24, Issue 05, 2020
ISSN: 1475-7192
DOI: 10.37200/IJPR/V24I5/PR2020213
Received: 12 Mar 2020 | Revised: 28 Mar 2020 | Accepted: 06 Apr 2020
5056
target organ damage occurs: left ventricular hypertrophy, detected in 38-41% of children with hypertension [7, 8]. In
this regard, the problem of prevention of modifiable risk factors in children and adolescents is a priority in pediatrics
and pediatric cardiology.
To date, it has been irrefutably proven that vitamin D, as a hormone with the formation of its “hormone-like axis:
calcidiol-calcitriol-VDR (vitamin D receptor),” is closely interconnected not only with parathyroid hormone and
calcitonin, but also with the biological effects of insulin, estrogen, neurotrophic factors and cytokines [9, 10]. In this
regard, it is possible to imagine the consequences of insufficient levels of vitamin D in the human div, ranging
from growth retardation to a wide range of chronic diseases that take hundreds of millions of adults' lives [11, 12].
Evidence of the beneficial effects of vitamin D has stimulated the development and adoption of nationwide
recommendations to address its deficiency in Poland (2009, 2013) [13, 14], Hungary (2012) [15], Germany, Austria
and Switzerland (2012) [ 16], Russian Federation (2018) [17], USA (2011) [18]. In 2012, the European Food Safety
Authority issued revised vitamin D levels (upper limits) for all relevant populations [19]. The level of calcidiol - 25
(OH) D in serum is accepted as a standard biomarker of vitamin D supply for the div. This metabolite is quite
stable (half-life is 2-3 weeks), reflects the intensity of vitamin D synthesis in the skin and food intake [17, 20].
A meta-analysis of 11 placebo-controlled studies (5660 patients aged 6 months to 75 years) confirmed the
protective effect of vitamin D intake against respiratory tract infections (influenza, pneumonia, acute respiratory
infections) [17, 24]. Higher serum vitamin D levels correlated with improved lung function in patients with cystic
fibrosis [25], with a 43% reduction in the risk of type 2 diabetes and metabolic syndrome (meta-analysis of 28
studies in 99,745 patients) [14].
Various studies have established a relationship between serum 25 (OH) D levels and blood pressure [21, 22, 23].
A meta-analysis of 7 cohort studies involving more than 43 thousand people established a relationship between a
low level of 25 (OH) D and a high frequency of arterial hypertension (AH) for 7–8 years [26]. S. Pilz et al. in a
randomized controlled study, it was recorded that taking vitamin D helps to reduce systolic blood pressure by 2-6
mm Hg. [27]. According to the results of a large-scale study of NHANES (National Health and Nutrition
Examination Survey 2001-2004) in the USA, 61% of adolescents 12-19 years old (out of 4666) had insufficient
levels of vitamin D (15-29 ng / ml) and 9% deficient (<15 ng / ml). These vitamin levels were associated with high
systolic blood pressure and low levels of high density lipoproteins [28].
Low levels of vitamin D are associated with cardiac ventricular hypertrophy, endothelial dtsfunction, and
activation of the renin-angiotensin system (RAS). It has been proven that in vitro the active form of the vitamin
suppresses RAS, and the renin gene in the promoter region has a D-sensitive element, through which the vitamin has
a direct regulatory effect on its transcription and renin production [29, 30, 31].
No relationship was found between vitamin A and vitamin D risk factors in children according to available
literature data, which requires further research.
One of the main risk factors for EAH is endothelial dysfunction (ED). Given the main functions of the
endothelium, it is possible to distinguish vasomotor, hemostatic, angiogenic and adhesive forms of ED. With
vasomotor ED, the synthesis of vasoactive substances is disrupted, and as a result, the vasomotor activity of the
International Journal of Psychosocial Rehabilitation, Vol. 24, Issue 05, 2020
ISSN: 1475-7192
DOI: 10.37200/IJPR/V24I5/PR2020213
Received: 12 Mar 2020 | Revised: 28 Mar 2020 | Accepted: 06 Apr 2020
5057
endothelium is reduced. Markers of endothelial vasomotor dysfunction are blood levels of nitric oxide (NO) and
endothelin-1, prostacyclin and thromboxane A2 [32, 33].
Endothelin-1 (E-1) is the strongest vasoconstrictor peptide synthesized in the div. Its vasoconstrictor potential
is 10 times higher than that of angiotensin II and is considered as a marker of ED in cardiovascular diseases. E-1 is
synthesized during stimulation of the endothelium by various factors - adrenaline, thrombin, angiotensin,
vasopressin. The concentration of E-1 in the blood normally does not exceed 0.1-1.0 mmol / ml or may not be
determined at all [34]. Currently, 3 endothelin isoforms consisting of 21 amino acid residues have been isolated: E-
1, E-2 and E-3. They are identified in the tissues of the lungs, kidneys of the brain, placenta, etc. E-1, unlike E-2 and
E-3, is produced by the endothelium [35, 36].
Thus, vitamin D deficiency refers to modifiable risk factors for many diseases. Insufficient vitamin supply is
associated with a risk of developing pathology of the cardiovascular, bone, endocrine, immune and other systems.
Vitamin D is becoming one of the most cost-effective supplements that can improve population health and reduce
the cost of preventing non communicable diseases in both childhood and adulthood. In children, the data on the role
of vitamin D and its relationship with ED in the occurrence and progression of EAH are sporadic, which is of
interest for further scientific research.
Purpose of the Study
To study vitamin D-dependent risk factors for the formation of EAH in schoolchildren based on serum levels of
calcidiol - 25 (OH) D, calcium and endothelin 1-21.
II.
M
ATERIAL
A
ND
M
ETHODS
We examined 132 schoolchildren aged 13-16 years (average age 14.64 ± 0.19) in Tashkent, selected by
randomization. In the groups of children observed, there were 86 boys (65.2 ± 4.1%) and girls, respectively, 46 (34.8
± 4.1%). The distribution by gender and age was uniform.
The examinations were carried out using standard research methods (questioning, collection of ante- and
postnatal history, heredity, environmental factors, clinical and paraclinical studies (blood pressure (BP));
anthropometry according to WHO criteria (2009); determination of puberty according to Tanner's scheme (1962),
etc.) The WHO recommendations and the Russian recommendations (second revision, 2009) [37, 38] were taken as
a criterion for high blood pressure and establishing a diagnosis of EAH.
Criteria for Inclusion in a Clinical Trial
Children with essential grade I arterial hypertension (EAH) without target organ damage and children with
normal and high normal blood pressure, without exacerbation of chronic foci of infection for 6 months. The
inclusion criteria were: normal blood pressure - SBP and DBP, the level of which is ≥10th and <90th percentile of
the distribution curve of blood pressure in the population for the corresponding age, gender and height; high normal
blood pressure - average values of SBP and / or DBP at three visits of ≥90th percentile, but <95th percentile for a
given age, gender and height, or ≥120 / 80mm Hg. (even if this value is <90th percentile. AH, I degree - average
levels of SBP and / or DBP from three dimensions equal to or greater than the 95th percentile established for this
International Journal of Psychosocial Rehabilitation, Vol. 24, Issue 05, 2020
ISSN: 1475-7192
DOI: 10.37200/IJPR/V24I5/PR2020213
Received: 12 Mar 2020 | Revised: 28 Mar 2020 | Accepted: 06 Apr 2020
5058
age group, provided that they exceed the 99th percentile no more than 5 mm Hg (Russian recommendations, 2009)
[37] Provided that the elevated blood pressure during dynamic observation is not constantly recorded, the diagnosis
of labile hypertension is made. Children are 13-16 years old.
Exclusion Criteria from a Clinical Trial
Exclusion criteria were congenital malformations of the kidneys, endocrine pathology, secondary or
symptomatic hypertension, stage II EAH, somatic pathology in the acute stage.
In accordance with the goal, the distribution of children into groups was carried out taking into account blood
pressure indicators: group 1 - children with normal blood pressure (BP) (control group) (n = 43), group 2 - children
with high normal blood pressure (HNBP) (comparative - group 2) - 42, 2 main groups: group 3 - children with labile
arterial hypertension (LAH) - 25 and group 4 - children with stable arterial hypertension (SAH) - 22.
The level of calcium was determined in blood serum using a Minray BS-200 biochemistry analyzer (China)
using commercial Human kits (Germany). Serum concentrations of endothelin-1-21 and 25 (OH) D in blood serum
were determined using commercial BIOMEDICA kits (Austria) for endothelin-1-21 (the reference value for
endothelin-1-21 (for adults) was on the median 0.26 fmol / ml) and DIA source (Belgium) for 25 (OH) D using a
Stat Fax 2100 analyzer (Israel) using ELISA.
The interpretation of the level of 25 (OH) D in the blood serum of children was carried out according to the
National Vitamin D Provision Program, which was presented by I.N. Zakharova at the XX Congress of Russian
Pediatricians with international participation, February 16, 2018 [17]. But vitamin D deficiency <10 ng / ml was
characterized as “pronounced vitamin D deficiency” according to the 2017 classification. This interpretation is
presented in table 1.
Table 1: Interpretation of Concentrations of 25 (OH) D (Zakharova I.N., 2018., RF)
Classification
25 (OH) D in blood
Vitamin D deficiency
<20 ng / ml (<50 nmol / L)
Vitamin D insufficiency
21-30 ng / ml (51-75 nmol / l)
Adequate Vitamin D levels > 30 ng / ml (> 75 nmol / L)
In the statistical analysis, the mean values (M) were calculated, their standard error (m), and the 95% confidence
interval (CI). The statistical significance of the differences was evaluated by Student's t criterion for dependent and
independent samples, while the difference was considered significant at p <0.05. An analysis of the relationship of
variables was carried out with the calculation of the Spearman correlation coefficient. For the clinical and prognostic
assessment of the risk of developing EAH in children, we calculated the values of the relative risk RR (relative risk -
RR = Ie / Io = [a / (a + b)] / [c / (c + d)]). Potentially adverse effects of vitamin D-dependent factors during critical
assessment of the risk of EAH formation in children calculated the values of sensitivity (sensitivity, Sе, Sе = a / (a +
s)) and specificity (specificity, Sр, Sр = d / (b + d) ) diagnostic tests. For an integrated assessment of the diagnostic
effectiveness of the analyzed factors, the validity indicators (Validity = Se (%) + Sp (%) - 100%) and the diagnostic
efficiency index (Diagnostic efficiency = (a + d) / (a + b + c + d)) were calculated [39].
International Journal of Psychosocial Rehabilitation, Vol. 24, Issue 05, 2020
ISSN: 1475-7192
DOI: 10.37200/IJPR/V24I5/PR2020213
Received: 12 Mar 2020 | Revised: 28 Mar 2020 | Accepted: 06 Apr 2020
5059
III.
R
ESULTS
A
ND
D
ISCUSSION
The frequency of occurrence of various levels of vitamin D provision for children depending on blood pressure
parameters is presented in table 2.
Table 2: Frequency of Occurrence of Various Levels of Vitamin D Provision for Tashkent School Children
Depending on Blood Pressure (abs /%, ng / ml)
25(ОН)D
3
level
Control group
n=43
High normal
blood pressure
n=42
labile arterial
hypertension
n=25
stablearterialhypertensionn=22
Abs %
Abs
%
Abs
%
Abs
%
Adequate Vitamin
D levels
20
46,5±7,6 -
-
-
-
-
-
Vitamin D
insufficiency
21
48,8±7,6 17
40,5±7,6
3
12,0±6,5
***
1
4,5±4,4
***
Vitamin D
deficiency
2
4,7±3,2
19
45,2±7,7
***
11
44,0±9,9
***
10
45,5±10,6
***
Severe vitamin D
deficiency <10 ng /
ml
-
-
6
14,3±5,4
11
44,0±9,9
^^
11
50,0±10,6
^^
The average level
of vitamin D, ng /
ml
27,4±0,92
16,3±1,2***
12,35±1,1***
11,8±1,1***
Note: the significance of differences in indicators at *** - p <0.001, relative to the control; ^ - p <0,01 in relation
to the group with high normal blood pressure
According to the table, it can be seen that the frequency of insufficient vitamin D content in children of the main
groups was significantly lower than in the control group (p <0.001 and p <0.001, respectively, in the 1st and 2nd
main groups). The same trend, but with the opposite vector, was also noted in relation to the frequency of
occurrence of vitamin D deficiency, starting with the comparison group with respect to the control. Severe
deficiency or vitamin deficiency was diagnosed only in children with high normal blood pressure and AH, with a
significantly high frequency in the main groups in relation to the comparison group.
Adequate vitamin D was only present in children in the control group. At the same time, the average
concentration of 25 (OH) D in children of this group was evaluated as insufficient (Fig. 1).
Significantly low values of 25 (OH) D in children in the comparison groups (p <0.001) and the main (p <0.001
and p <0.001, respectively, in the 1st and 2nd main groups) with respect to the control, tended to be deficient.
An analysis of the vitamin D supply for schoolchildren depending on blood pressure indicators established a
significantly high frequency of deficient vitamin D content in children with high normal blood pressure (p <0.001)
and AH (p <0.001) in relation to children with a normal level of blood pressure. The diagnostic test, as vitamin D
deficiency for the comparison group and the 1st main one, had 90% (Se = 0.90 = 90%) sensitivity, 68% (Sp = 0.68 =
68%) specificity and relative risk RR = 11, 25, for the 2nd main, 89% (Se = 0.89 = 89%) and 70% (Sp = 0.70 =
70%) of sensitivity, specificity, and RR = 10.0, respectively.
A pronounced deficiency was noted in children with high normal blood pressureand AH with a significant high
frequency in the main groups in relation to the comparison group p <0.01 and p <0.01, respectively, in the 1st, (Se =
International Journal of Psychosocial Rehabilitation, Vol. 24, Issue 05, 2020
ISSN: 1475-7192
DOI: 10.37200/IJPR/V24I5/PR2020213
Received: 12 Mar 2020 | Revised: 28 Mar 2020 | Accepted: 06 Apr 2020
5060
0.75, Sp = 0, 61, RR = 3.0) and in the 2nd, (Se = 0.75, Sp = 0.65, RR = 3.3,) main groups.
Figure 1: The Average Level of Vitamin D in the Analyzed Groups, ng / ml
A comparative analysis of the average parameters of serum calcium levels in children with different blood
pressure levels is presented in figure 2.
Figure 2: Averaged Serum Calcium Levels in Children of the Analyzed Groups
From the data of the figure it follows that the compared parameters of the level of calcium did not go beyond the
normative range. But the average values of serum calcium concentration in children with high normal blood pressure
(p <0.05), with stable hypertension (p <0.05) and with labile hypertension (p <0.05) were significantly low
compared to healthy children.
Endothelin-1-21 (E-1) is the most powerful vasoconstrictor factor, the main activators of the synthesis of which
are hypoxia and local ischemia. E-1 enhances the production of cytokines and thereby initiates the inflammatory
process [40].
As a rule, to realize its function, E-1 binds to two types of receptors: type A, localized on smooth muscle cells
27.4
16.3
12.35
11.8
0
5
10
15
20
25
30
Control
group
High Normal
Blood
Presure
LAH
SAH
ng/ml
р<0,001
р<0,001
р<0,001
2.15
2.2
2.25
2.3
2.35
2.4
Control group
High normal
blood pressure
LAH
SAH
2.36
2.3
2.25
2.22
Ca mmol/L
p<0,05
p<0,05
p<0,05
International Journal of Psychosocial Rehabilitation, Vol. 24, Issue 05, 2020
ISSN: 1475-7192
DOI: 10.37200/IJPR/V24I5/PR2020213
Received: 12 Mar 2020 | Revised: 28 Mar 2020 | Accepted: 06 Apr 2020
5061
(SMC) of blood vessels, and type B, localized on endothelial and SMC, the activation of these receptors causes a
vasoconstrictor and mitogenic effect. The question of what place E-1 occupies in the pathogenesis of EAH in
children and adolescents remains a controversial issue, which determines the relevance of further research in this
area.
Our studies on the level of vasoconstrictor factor endothelin - 1-21 (E-1) in 78 schoolchildren showed an
increase in its values in blood serum in groups with high normal blood pressure and AH (Figure 3).
Figure 3: Comparative Analysis of the Level of Endothelin 1-21 in Children in the Analyzed Groups
According to the data presented, it was found that in children of the control group the level of E-1-21 did not
exceed the reference values (<0.26 fmol / ml), whereas in children with HNBP (0.27 ± 0.05 fmol / ml, p < 0.05)
LAH (0.42 ± 0.1 fmol / ml, p <0.05) and SAH (0.59 ± 0.1 fmol / ml, p <0.001) this level was significantly high
compared to the control (0.13 ± 0.02 fmol / ml).
The frequency of occurrence of high levels of e-1-21 depending on blood pressure in the analyzed groups is
presented in table 3. According to the table it is clear that the frequency of indicators of e-1-21> 0.26 and> 1.0 fmol
/ ml in children with SAH was 2.4 and 1.6, respectively, times higher (OS = 2.4; RR = 1.5 and OS = 1.6; RR = 1.5,
respectively) than in children with LAH. But in children with HNBP, the frequency of indicators of the level of E-1-
21> 0.26 fmol / ml was identical compared to the group of children with SAH (60.0 ± 10.9%, against 61.1 ± 11.5%,
respectively), which indicated early signs of ED in children with high normal blood pressure. This test has 100%
sensitivity and 0% specificity in the early diagnosis of ED with EAH.
0.13
0.27
0.42
0.59
Endothelin-1-21 (fmol/ml)
Control
group
HNBP
LAH
SAH
р<0,001
р<0,05
р<0,05
International Journal of Psychosocial Rehabilitation, Vol. 24, Issue 05, 2020
ISSN: 1475-7192
DOI: 10.37200/IJPR/V24I5/PR2020213
Received: 12 Mar 2020 | Revised: 28 Mar 2020 | Accepted: 06 Apr 2020
5062
Table 3: The Frequency of Occurrence of High Levels of Endothelin level -1-21 Depending on Blood Pressure (abs
/%, fmol / ml)
The level of endothelin is 1-21,
fmol / ml
I group
Normal blood
pressure
(control group)
n = 20
II group
HNBP
(comparison
group)
n = 20
III group
LAH
(1st main
group)
n = 20
IV groups
SAH
(2nd main
group)
n = 18
Abs
%
Abs
%
Abs
%
Abs
%
<0,26
24
100,0
8
40,0±10,9
9
45,0±11,1
3
16,7±8,8
>0,26; <1,0
-
-
12
60,0±10,9
8
40,0±10,9
11
61,1±11,5
>1,0
-
-
-
-
3
15,0±7,9
4
22,2±9,8
We obtained results are comparable with literature data. In the studies of G. Aflyatumova et al. (2017) the level
of E-1-21 in adolescents with a stable form of EAH was significantly higher than in the labile version (1.67 ± 0.12
versus 1.14 ± 0.13 fmol / ml, respectively) [41]. Also, the levels of E-1-21 in children with labile hypertension were
significantly higher than in the control (1.38 ± 0.13 versus 0.8 ± 0.08 fmol / ml, respectively, p <0.001).
It was found that in physiological concentrations E-1 acts on endothelial receptors, causing the release of
relaxation factors, and at higher levels it activates receptors on SMCs, causing their persistent vasoconstriction and
proliferation of media. Thus, using the same factor, two opposite vascular reactions (dilatation and constriction) are
controlled by the feedback mechanism [42].
The results form the basis for the development of measures for effective non-drug and drug therapy based on
antagonists of E-1-21 receptors, which is especially important for children and adolescents with HNBP and AH as a
way to prevent EAH and its complications in the adult period.
In our work, to identify causal relationships between factors providing vitamin D and levels of calcium,
endothelin-1-21 in blood serum and physical development parameters in the formation of EAH in children,
depending on the level of blood pressure, a mathematical correlation analysis was performed between the above
values (Fig. 4).
According to Figure 3, it is seen that between the vitamin D level and endothelin -1-21, strong negative
correlation relationships were established in the comparison groups (r = -0.80, p <0.001) and two main (r = -0.66, p
< 0.01 and r = -0.79, p <0.001, respectively, in groups of children with LAH and SAH), which indicates the
relationship between vitamin D deficiency and the severity of endothelial dysfunction.
Our results are comparable with published data. Kodensovoy V.M. et al. (2017), an association was established
between the lack of vitamin D in the div and the occurrence of three mutually influencing processes: oxidative
stress, inflammation, endothelial dysfunction [20].
The level of vitamin D provision had a positive associative relationship of medium strength with physical
development parameters (with growth values: r = 0.45, p <0.05; weight: r = 0.62, p <0.01; BMI: r = 0 , 47, p <0.05)
in children of the control group. But these interdependencies lost strength and reliable values in groups of children
with HNBP and hypertension.
International Journal of Psychosocial Rehabilitation, Vol. 24, Issue 05, 2020
ISSN: 1475-7192
DOI: 10.37200/IJPR/V24I5/PR2020213
Received: 12 Mar 2020 | Revised: 28 Mar 2020 | Accepted: 06 Apr 2020
5063
Figure 4: Features of the Correlation between the Level of Vitamin D and the Values of Ca, Endothelin -1-21 in the
Blood Serum, the Parameters of Physical Development, Systolic and Diastolic Blood Pressure in the
Analyzed Groups
Between the parameters of blood pressure and level 25 (OH) D, multidirectional correlation relationships were
established, where the relationship between high blood pressure values and low levels of vitamin D in children of
the main groups is logically traced.
In the control group (Fig. 4) of children, there was a direct correlation of weak strength between blood pressure
(r = 0.40, p> 0.05 and r = 0.48, p <0.05, respectively, for SBP and DBP) .
A rather specific dynamics of the connections is monitored in relation to the values of SBP and DBP in groups of
children with HNBP, LAH and SAH. In the group of children with HNBD, a direct dependence of the level of
diastolic blood pressure on the degree of provision with vitamin D appears (r = 0.63, p <0.01). A change in the
polarity of the bonds was noted in the relationships between the level of vitamin D and the values of SBP and DBP
in the main groups: the priority influence of vitamin D supply on the level of DBP (r = -0.64, p <0.01) in the group
of children with LAH, but in group of children with SAH, this effect was directed to the parameters of systolic blood
pressure (r = -0.6, p <0.01).
A single reliable relationship was found between the levels of vitamin D and Ca (r = 0.66, p <0.01) in the group
of children with HNBP. In the control (r = 0.41, p> 0.05) and main (r = 0.34, p> 0.05 and r = 0.03, p> 0.1) groups of
children, the described similar relationship was absent.
0.41
0.66
0.34
0.03
-0.05
-0.8
-0.66
-0.79
0.62
0.17
0.44
0.23
0.48
0.63
-0.64
-0.5
-1
-0.8
-0.6
-0.4
-0.2
0
0.2
0.4
0.6
0.8
Control group
HNBP
LAH
SAH
Са
E-1
Height
Weight
Body mass index
Systolic blood pressure
р<0,001
р<0,001
р<0,001
р<0,01
р<0,001
International Journal of Psychosocial Rehabilitation, Vol. 24, Issue 05, 2020
ISSN: 1475-7192
DOI: 10.37200/IJPR/V24I5/PR2020213
Received: 12 Mar 2020 | Revised: 28 Mar 2020 | Accepted: 06 Apr 2020
5064
The only reliable relationship between the level of endothelin-1-21 and the values of Ca (r = -0.68, p <0.01) in
the blood serum with a negative vector in the second main group of children was revealed.
Potentially adverse effects of vitamin D - dependent factors in a critical assessment of the risk of EAH formation
in children calculated the values of sensitivity (Se) and specificity (Sp) of diagnostic tests. Indicators of Ce and Sp
of the analyzed vitamin D - dependent factors in diagnosing the risk of EAH formation are presented in table 4.
Table 4: The Values of Sensitivity (Se) and Specificity (Sp) Analyzed Diagnostic Tests
№
Analyzed Factors
Children with HNBP Children with SAH
S
e
%
S
p
%
S
e
%
S
p
%
1
Deficiency Vit. D <20 ng / ml
90,0
68,0
89,0
70,0
2
0.17 <Endothelin 1-21 <0.41 fmol / ml 48,0
67,0
72,0
67,0
3
Endothelin 1-21> 0.41 fmol / ml
33,3
82,7
100
82,7
4
Са<2,22mmol/L
50,0
67,4
51,2
67,4
The results indicate that a potentially adverse effect of the factor, such as a deficient vitamin D content in the
blood, in diagnosing the risk of EAH in children has a fairly high sensitivity of 90%. Therefore, in 10% of cases, it
is likely that people with a very high risk of developing the disease will be classified as low.
Moreover, this factor has moderate specificity, i.e. in 68% of cases, positive test results can correctly diagnose a
very high risk of disease formation.
For an integrated assessment of the diagnostic effectiveness of the analyzed factors, the validity indices and the
diagnostic efficiency index were calculated. Validity and diagnostic efficacy indicators of the analyzed vitamin D -
dependent factors in diagnosing the risk of EAH formation are presented in table 5.
Table 5: Validity and Diagnostic Effectiveness of the Analyzed Diagnostic Tests
№
Analyzed Factors
Validity Assessment Diagnostic efficiency
HNBP
SAH
HNBP
SAH
1
Deficiency Vit. D <20 ng / ml
50,3
67,4
75,3
83,7
2
0.17 <Endothelin 1-21 <0.41 fmol / ml 16,2
39,5
58,8
69,8
3
Endothelin 1-21> 0.41 fmol / ml
16,0
82,7
62,0
87,8
4
Са<2,22mmol/L
17,4
18,6
58,8
59,3
An integral assessment of the factor - deficient vitamin D in the blood when diagnosing the risk of EAH
formation showed moderate validity (67.4%) and a fairly high diagnostic efficiency (83.7).
Consequently, a critical assessment of potentially unfavorable vitamin D-dependent risk factors for the formation
of essential arterial hypertension in children established the following diagnostic tests for diagnostic effectiveness in
decreasing importance: endothelin 1-21> 0.41 fmol / ml - 87.8; vitamin D deficiency <20 ng / ml - 83.7; 0.17
<Endothelin 1-21 <0.41 fmol / ml - 69.8; Ca <2.22 mmol / L - 59.3.
IV.
C
ONCLUSIONS
1.
An analysis of the availability of vitamin D for schoolchildren, depending on blood pressure, established a
significantly high frequency of deficient vitamin D in children with HNBP (p <0.01) and hypertension (p
<0.01) in relation to children with normal blood pressure. The diagnostic test, as vitamin D deficiency for
the comparison group and the 1st main one, had 90% (Se = 0.90 = 90%) sensitivity, 68% (Sp = 0.68 =
International Journal of Psychosocial Rehabilitation, Vol. 24, Issue 05, 2020
ISSN: 1475-7192
DOI: 10.37200/IJPR/V24I5/PR2020213
Received: 12 Mar 2020 | Revised: 28 Mar 2020 | Accepted: 06 Apr 2020
5065
68%) specificity and relative risk RR = 11, 25, for the 2nd main, 89% (Se = 0.89 = 89%) and 70% (Sp =
0.70 = 70%) of sensitivity, specificity, and RR = 10.0, respectively. A pronounced deficiency was noted in
children with HNBP and AH with a significant high frequency in the main groups in relation to the
comparison group p <0.01 and p <0.01, respectively, in the 1st, (Se = 0.75, Sp = 0, 61, RR = 3.0) and in the
2nd, (Se = 0.75, Sp = 0.65, RR = 3.3,) main groups.
2.
Studies on the level of endothelium-dependent vasoconstrictor factor endothelin-1-21 (E-1-21) showed a
significant increase in its values in blood serum in children with high normal blood pressure (0.27 ± 0.05
fmol / ml, p <0.05) and arterial hypertension (0.42 ± 0.1 fmol / ml, p <0.05 and 0.59 ± 0.1 fmol / ml, p
<0.001, respectively, in groups of children with LAH and SAH) compared with the control (0.13 ± 0.02
fmol / ml).
3.
In the mechanism of EAH formation in children, the relationship between vitamin D deficiency and the
severity of endothelial dysfunction in terms of endothelin levels of -1-21 (r = -0.79, p <0.001), as well as
the priority effect of vitamin D provision on the DBP level (r = -0.64, p <0.01) in the group of children with
LAH, but in the group of children with SAH this effect was directed to the parameters of systolic blood
pressure (r = -0.6, p <0.01).
4.
A critical assessment of potentially unfavorable vitamin D-dependent risk factors for the formation of
essential arterial hypertension in children has established the following diagnostic tests for diagnostic
effectiveness in decreasing importance: endothelin 1-21> 0.41 fmol / ml - 87.8; vitamin D deficiency <20
ng / ml - 83.7; 0.17 <Endothelin 1-21 <0.41 fmol / ml - 69.8; Ca <2.22 mmol / L - 59.3.
R
EFERENCES
[1]
Alexandrov A.A., Rozanov V.B., Pugaeva H.S., Ivanova E.I. The prognostic value of high blood pressure
in children and adolescents (32 - year long-term follow-up).
Cardiovascular therapy and prevention.
2018;
17 (4): 12-18.
[2]
Arsentiev VG, SergeevYu.S., SeredaYu.V., Tikhonov VV High blood pressure in children and adolescents:
an emphasis on diagnostic issues.
Pediatrics.
2018; 97 (3): 119-124.
[3]
TursunovD.Sh. The effectiveness of organizational forms of prevention and treatment of arterial
hypertension in primary health care. Abstract. diss. Ph.D. Tashkent. 2012.23 s.
[4]
Flynn J.T., Kaelber D.C., Baker-Smith C.M. et al. Clinical practice Guideline for screening and
management of High Blood pressure in Children and Adolescents.
Pediatrics.
2017.140 (3) e20171904.
[5]
Williams B., Mancia G., Spiering W., AgabitiRosei E. et al. 2018 ESC / ESH Guidelines for the
management of arterial hypertension:
the task Force for the management of arterial hypertension of the
European Society of Cardiology and the European Society of Hypertension. Eur. Heart J.
2018. Sept. 1; 39
(3): 3021-3104. Doi: 10.1093 / eurheartj / ehy339.
[6]
Agzamova Sh. A., Hasanova G.M. Obesity in children: frequency of occurrence and features of thickness
of epicardial fat depending on indicators of div weight index and lipid spectrum.
International Journal of
Psychosocial Rehabilitation
Vol. 24, Issue 05, 2020. p. 434-442. DOI: 10.37200 / IJPR / V24I5 /
PR201709
[7]
Jurko A. J., Minarik M., Jurco T., Tonhajzerova I. White coat hypertension in pediatrics.
Ital. J. Pediatrics.
2016; 42: 4.
[8]
Litwin M., Feber J., Ruzicka M. Vascular Aging: Lessons From Pediatric Hypertension. Canadian Journal
of Cardiology. Volume 32. 2016.
[9]
Dreval A.V., Kryukova I.V., Barsukov I.A. TevosyanL.Kh. Extra-bone effects of vitamin D (literature
review).
Russian medical journal.
2017; 1: 53-56.
[10]
Bikle DD. Extraskeletal actions of vitamin D. Ann. N. Y. Acad. SCI. 2016; 1376: 29-52.
International Journal of Psychosocial Rehabilitation, Vol. 24, Issue 05, 2020
ISSN: 1475-7192
DOI: 10.37200/IJPR/V24I5/PR2020213
Received: 12 Mar 2020 | Revised: 28 Mar 2020 | Accepted: 06 Apr 2020
5066
[11]
Bergman P., Lindh A.U., Bjorkhem-Bergman L., Lindh J.D. Vitamin D and respiratory tract infections:
a
systematic review and meta-analysis of randomized controlled trials. Plos one.
2013; 8 (6): e65835.
[12]
Zittermann A., Pilz S., Hoffmann H., Marz W. Vitamin D and airway infections: A European perspective.
European J. of Medical Research.
2016: 21 (1): doi: 10.1186 / s40001-16-0208-y.
[13]
Charzewska J., Chlebna-Sokol D., Chybicka A. et al. Prophylaxis of Vitamin D deficiency-Polish
recommendation 2009.
Endocrinol.
Pol. 2010; 61: 228-232.
[14]
Pludowski P., Karczmarewicz E., Bayer M., Carter G., Chlebnasokop D. et al. Practical guidelines for the
supplementation of vitamin D and the treatment of deficits in Central Europe - recommended vitamin D in
takes im the general population and groups at risk of vitamin D deficiency. 30-50 ng of vitamin D in
optimal - Central Europe consensus. Sept. 2013. EndocrinologiaPolska. 2013; 64 (4): 319-27. Doi: 10/5603
/ EP2013.0012.
[15]
Takacs I., Benko I., Toldy E. et al. Hungarian consensus regarding the role of vitamin D in the prevention
and treatment of diseases. Orv. Hetil. 2012; 153 (Suppl.): 5-26.
[16]
German Nutrition Society. New reference values for vitamin D. Ann. Nutr. Metab. 2012; 6: 214-246.
[17]
Symposium "D-hormone - the opening of the XXI century". Review of I.N. Zakharova, L.Ya. Klimova,
V.A. Kuryaninova, I.L. Nikitina et al. Pediatrics
(Addendum to Journal of Consilium Medicum).
2018: 1:
23-30.
[18]
IOM (Institute of Medicine): Dietary reference intakes for calcium and vitamin D. Washington (DC):
National Academies Press (US); 2011.
[19]
Holick M.F., Binkley N.C., Bischoff-Ferrari H.A., Gordon C.M. et al. Endocrine Society Evaluation
treatment, and prevention of vitamin D deficiency: An Endocrine Society clinical practice guideline.
J.
Clin. Endocrinol. Metab. 2011
; 96: 1911-1930.
[20]
Kodentsova V.M., Mendel O.I., Khotimchenko S.A., Baturin A.K., Nikityuk D.B., Tutelyan V.A.
Physiological need and effective doses of vitamin D to correct its deficiency.
The current state of the
problem. Nutrition issues.
2017.V. 86. No. 2. S. 47-62.
[21]
Karonova T.L., Andreeva A.T., Zlotnikova E.K., Grineva E.N. Vitamin D deficiency and hypertension:
what is common?
Arterial hypertension.
2017; 23 (4): 275-281.
[22]
Nikitina I.L., Todeva M.M., Ilyina M.N., Budanova M.V. et al. Vitamin D treatment experience: is it
possible to influence the metabolic and cardiovascular risk factors for obese children.
Arterial
hypertension.
2015; 21 (4): 426-435.
[23]
Agzamova S. A., Akhmedova F, Shamansurova E. A., Evaluation of potentially removable risk factors of
arterial hypertension in chiloren of Uzbekistan.
European science review.
No. 7 - 8. 2018. July-August: p.
72-75
[24]
Bergman P., Lindh A.U., Bjorkhem-Bergman L., Lindh J.D. Vitamin D and respiratory tract infections:
a
systematic review and meta-analysis of randomized controlled trials. Plos one.
2013; 8 (6): e65835.
[25]
Pashkevich A.A., Borisenko T.S., Kaystrya I.V., Orlov A.V. et al. Vitamin D deficiency in children with
cystic fibrosis.
Treatment and prevention.
2018; 8 (1): 5-12.
[26]
Wang L., Song Y., Manson J.E., Pilz S. Circulating 25-hydroxyvitamin D and risk of cardiovascular
disease: A meta-analysis of prospective studies. Circ. Cardiovas
. Qual. Outcomes.
2012; 1; 5: 819-829.
[27]
Pilz S, Gaksh M., Kienreich K., Grubler M. et al. Effects of vitamin D on blood pressure and
cardiovascular risk factors:
a randomized controlled tried. Hypertension
2015; 65 (6): 1195-120.
[28]
Kumar J., Muntner P., Kaskei F.J., Hailpern S.M. MLM Prevalence and associations of 25- hydroxyvitamin
D deficiency in US children.
NHANES
2001-2004. Pediatrics. 2009; 124: 362-370.
[29]
Dubova A.V., Pshenichnaya E.V., Bordyugova E.V., Onoprienko Z.S. The effect of vitamin D on the
occurrence and progression of cardiovascular pathology in adults and children.
(Literature review). Bulletin
of emergency and reconstructive surgery.
2016; 1 (2): 292-298.
[30]
Yakovleva L.V., Zeid S.S.K., Melititskaya A.V. The relationship between vitamin D levels, renin, and
div mass index in adolescent children with primary hypertension.
Medical Bulletin of Bashkortostan.
2017; T. 12. No. 5 (71): 65-69.
[31]
Dudinskaya E.N., Tkacheva O.N. The role of vitamin D in the development of arterial hypertension //
Kariovascular therapy and prevention.
- 2012 .-- 11 (3). - S.77-81.
[32]
Mayanskaya S. D., Grebenkina I. A. Structural and functional remodeling of the vessel wall in patients with
a history of arterial hypertension.
Cardiology.
2015.2.27-31.
[33]
Samolyuk MO, GrigoryevaN.Yu., Assessment of endothelial dysfunction and the possibility of its
correction at the present stage in patients with cardiovascular diseases.
Cardiology. Study of.
Implementation. Practice.
2019. №3. S. 4-9.
International Journal of Psychosocial Rehabilitation, Vol. 24, Issue 05, 2020
ISSN: 1475-7192
DOI: 10.37200/IJPR/V24I5/PR2020213
Received: 12 Mar 2020 | Revised: 28 Mar 2020 | Accepted: 06 Apr 2020
5067
[34]
Sergeeva E.V., Sadykova D.I. Endothelin-1 as a marker of endothelial dysfunction in various forms of
essential hypertension in adolescents.
Russian Bulletin of Perinatology and Pediatrics.
2016.4.17-177
[35]
Mikashinovich Z.I., NagornayaP.Yu., Kovalenko T.D. Biochemical indicators of endothelial damage of
inflammatory genesis in adolescents with arterial hypertension.
Kuban Scientific Medical Bulletin.
2012; 2:
123-125.
[36]
Plotnikova I.V., Kovalev I.A., Suslova T.E., Bezlyak V.V. The relationship of endothelial dysfunction with
the development of essential hypertension in adolescence.
Cardiology.
2015; 3: 21-26.
[37]
Diagnosis, treatment and prevention of hypertension in children and adolescents. Russian recommendations
(second revision).
Appendix 1 to the journal Cardiovascular Therapy and Prevention.
2009; 8 (4): 32 s.
[38]
Global
Status
Report
on
noncommunicable
diseases
2013
[http://apps.who.int/iris/bitstream/10665/148114/1/9789241564854_eng.pdf?ua=1]
[39]
Kelmanson I.A. Principles of evidence-based pediatrics. - St. Petersburg: Tome, 2004.-240s.
[40]
RyabchenkoA.Yu., Dolgov A.M., Denisov E.N. et al. Role of nitric oxide and endothelin-1 in the
development of ischemic disorders of cerebral circulation.
Neurological Bulletin.
2014. No1. S. 34-37.
[41]
Aflyatumova G.N., Sadykova D.I., Nigmatullina R.R., Chibireva M.D. The nature of endothelial
dysfunction in essential arterial hypertension in adolescents (clinical and experimental study).
Arterial
hypertension.
2017; 23 (2): 131-140.
[42]
Golivets T.P., Dubonosova D.G., Osipova O.A., Petrova G.D. et al. Effects of endothelin-1 in the
development and progression of metabolic syndrome and other socially significant non-infectious diseases
(literature review).
Scientific reports of Belgorod State University.
Series: Medicine. Pharmacy. 2017.
Electronic resource. https: // cyberleninka / article / n / effect ...
