RU2801130C1 - Method of determining the high risk group for developing primary arterial hypertension in adolescent children - Google Patents

Abstract

FIELD: medicine, pediatrics and pediatric cardiology.

SUBSTANCE: invention is intended to determine a high risk group for developing primary arterial hypertension in adolescent children with aggravated heredity for hypertension along the 1st line of kinship. The method includes outpatient measurement of blood pressure, and at its normal level and body mass index within one standard deviation from the median value, determination of leptin, adiponectin, endothelin 1 in blood serum by enzyme immunoassay. Next, an integral indicator, the vasopressor risk index (VRI), is calculated according to the formula.

EFFECT: method provides a personalized assessment of the risk of developing primary arterial hypertension in adolescent children with normal values of blood pressure, body mass index and aggravated heredity for hypertension along the 1st line of kinship due to a more accurate determination of the development of endothelial dysfunction based on the analysis of these cytokines and adipokines.

1 cl, 1 tbl, 7 ex

Description

The invention relates to medicine, namely to pediatrics and pediatric cardiology, and can be used to determine the individual risks of developing primary arterial hypertension in adolescents requiring primary prevention. There is a way to form (determine) risk groups for developing arterial hypertension in adolescents. The risk groups for the formation of primary hypertension include children and adolescents with overweight and / or obesity (BMI (kg / m ² ) ≥ +1SDS), as well as children with symptoms potentially associated with hypertension (headaches, nosebleeds). The list of risk groups for the formation of hypertension in children is presented in the clinical guidelines "Diagnosis, treatment and prevention of arterial hypertension in children and adolescents" (2020), developed by leading specialists of the Russian Medical Society for Arterial Hypertension and the Association of Pediatric Cardiologists of Russia (Aleksandrov A.A., Kislyak O.A., Leontieva I.V. Clinical guidelines Diagnosis, treatment and prevention of arterial hypertension in children and adolescents // Systemic hypertension - 2020. - V. 17. - No. 2. - P. 7-35. https ://doi.org/10.26442/2075082X.2020.2.200126). The disadvantage of this method for determining risk groups for developing arterial hypertension are:

- the possibility of errors in determining overweight / obesity by body mass index (BMI), since this indicator does not always accurately indicate the true content of fat mass (overdiagnosis (“false” obesity) or underdiagnosis (“hidden” obesity) of obesity are possible) ;

- the possibility of registering, on the one hand, headaches without an increase in systemic blood pressure against the background of emotional lability and autonomic dysfunction, often recorded in adolescents (puberty), and on the other hand, the frequent absence of complaints of headaches against the background of increased blood pressure;

- the possibility of registering, on the one hand, episodic nosebleeds without an increase in systemic blood pressure due to mechanical damage to the vessels of the nose (sloppy toilet of the nasal passages) or pathology of the ENT organs (rhinitis, polyps, curvature of the nasal septum), and on the other hand, the frequent absence of nasal bleeding in children with systemic hypertension. It is known that in children with aggravated heredity for hypertension (AH), at the initial (functional) stage of AH formation, endothelial dysfunction develops, one of the manifestations of which is a violation of the vasomotor function of the endothelium due to increased production of vasoconstrictor cytokines (endothelium 1, angiotensin II, thromboxane A ₂ , prostaglandin H ₂ , etc.) and a decrease in vasodilators (nitric oxide, prostacyclin, endothelin depolarization factor, angiotensin I, adrenomedullin, etc.). Prolonged hyperproduction of vasoconstrictor cytokines, including by fat cells (adipocytes), contributes to the development of systemic hypertension. As is known, an excess of body fat mass (↑ adipocytes), including in “hidden” obesity, is accompanied by a change in the production of adipokines (hyperproduction of leptin and a decrease in adiponectin).

The purpose of the invention is to determine the high risk group for developing primary arterial hypertension in adolescent children with aggravated heredity for hypertension (1 line of kinship) based on the results of a laboratory integral indicator - the vasopressor risk index ((leptin / adiponectin) x endothelium 1 (arb. unit)) for the timely implementation of primary prevention of high blood pressure. The essence of the invention lies in the fact that in adolescent children with aggravated heredity for hypertension (1st line of kinship), a normal level of ambulatory blood pressure (taking into account age, height and sex) and normal values of body mass index (BMI) taking into account age and sex (BMI is within ± one standard deviation (SD) from the median value) leptin, adiponectin and endothelium 1 are determined in blood serum by enzyme-linked immunosorbent assay (ELISA) and an integral indicator (vasopressor risk index) is calculated: (leptin / adiponectin) x endothelium 1 Adolescent children with IVR 485.7 conv. units and more are classified as high-risk for the development of hypertension, requiring primary prevention.

The proposed method is carried out as follows. First, anthropometry and ambulatory blood pressure measurement with individual cuff selection are performed in adolescent children with aggravated heredity for HD (1st line of kinship). Blood pressure is measured three times and the average values of systolic and diastolic blood pressure (mm Hg) are calculated. The normal value of the mean blood pressure (systolic and diastolic) is determined within the limits of the 90th percentile, taking into account the height, age and sex of the adolescent (Alexandrov A.A., Kislyak O.A., Leontyeva I.V. Clinical recommendations. Diagnosis, treatment and prevention of arterial hypertension in children and adolescents // Systemic hypertension - 2020. - V. 17. - No. 2. - P. 7-35. https://doi.org/10.26442/2075082X.2020.2.200126). Anthropometry includes measuring height (m) and weight (kg) and calculating body mass index (BMI). Body mass index is calculated as the ratio of body weight in kilograms to the square of height in meters (kg/ ^m2 ). In accordance with WHO recommendations, a normal BMI value in adolescent children is diagnosed if BMI, taking into account age and gender, is within ± one standard deviation (SD) from the median value indicated in the normative tables (Peterkova V.A., Bezlepkina O.B. ., Bolotova N.V., Bogova E.A., Vasyukova O.V., Girsh Ya.V., Kiyaev A.V., Kostrova I.B., Malievsky O.A., Mikhailova E.G., Okorokov P.L., Petryaykina E.E., Taranushenko T.E., Khramova E.B. Clinical guidelines "Obesity in children" Problems of Endocrinology 2021;67(5):67-83 https://doi .org/10.14341/probl12802).

Then, venous blood is taken from children in a volume of 1.5-2.0 ml, it is centrifuged and blood serum is used in the work to determine adipocytokines (leptin, adiponectin, endothelium 1; Cloud-Clonecorp (USA) reagents). The study is carried out by enzyme immunoassay on a semi-automatic Dynex analyzer (USA) using the Revelation program.

According to the formula: (leptin (ng / ml) / adiponectin (pg / ml)) x endothelium 1 (fmol / ml), IVR is calculated (arb. units). The value of IVR is equal to 485.7 arb. units and more indicates the child's tendency to vasoconstriction. Adolescent children aged 10-17 years of the 2nd health group (45 girls and 45 boys) with normal values of body mass index, blood pressure and aggravated heredity for hypertension (1st line of kinship) were selected by random sampling, in whom the method was determined ELISA in blood serum adipocytokines: leptin (ng/ml), adiponectin (pg/ml) and endothelial 1 (fmol/ml). Using the quantitative values of 3 adipocytokines, the integral laboratory indicator (vasopressor risk index) was calculated using the formula: (leptin/adiponectin) x endothelium 1 (arb. units). Statistical analysis of the initial IIA data revealed 23 adolescent children with IDI ≥ 75 percentile (median IDI (108.7 arb. units)); 25th percentile IVR (42.8 arb. units); 75th percentile IVR (485.7 conventional units)), i.e. IVR value equal to or more than 485.7 arb. units

With IVR equal to 485.7 arb. units or more adolescents are considered to be at high risk for the development of arterial hypertension, requiring prophylaxis (primarily non-drug) of high blood pressure. With IVR less than 485.7 arb. units the risk of developing arterial hypertension is low: primary prevention is not carried out.

Examples. Example 1

Boy L. (11 years old) of the 2nd health group had normal baseline blood pressure indicators, taking into account age, height and sex (111/69 mm Hg), body mass index, taking into account age and sex (17.5 kg/m ² ) and aggravated heredity for hypertension (AH in the father of the child). According to the results of laboratory studies, IVR (vasopressor risk index) is 485.7 arb. units (IWR=(360.6/0.34) × 0.458=485.7 units), i.e. the child is at high risk of developing hypertension. The boy did not receive any non-drug recommendations for the prevention of arterial hypertension; no long-term drug therapy was carried out for 1 year. After 1 year, ambulatory blood pressure was 122/68 mm Hg. Art. (high normal blood pressure (HNAP)). Thus, in a boy with initially normal values of blood pressure (mm Hg. Art.), BMI (kg/m ² ) after 1 year, GNP was recorded, taking into account age, height and sex.

Example 2

Girl I. (14 years old) of the 2nd health group had normal baseline blood pressure indicators, taking into account age, height and sex (117/70 mm Hg), body mass index, taking into account age and sex (18.6 kg/m ² ) and aggravated heredity for hypertension (AH in the child's mother). According to the results of laboratory studies, IVR (vasopressor risk index) is equal to 508.6 arb. units (IVR=(118.4/0.098) × 0.421=508.6 units), i.e. the child is at high risk of developing hypertension. The girl did not receive non-drug recommendations for the prevention of arterial hypertension; no long-term drug therapy was carried out for 1 year. After 1 year, ambulatory blood pressure was 132/72 mm Hg. Art. (arterial hypertension (AH) I degree). Thus, in a girl with initially normal values of blood pressure (mm Hg) and BMI (kg/m ² ), after 1 year, AH of the first degree was recorded, taking into account age, height and sex.

Example 3

Boy A. (16 years old) of the 2nd health group had normal baseline blood pressure indicators, taking into account age, height and sex (126/75 mm Hg), body mass index, taking into account age and sex (21.4 kg/m ² ) and aggravated heredity for hypertension (AH in the father of the child). According to the results of laboratory studies, IVR (vasopressor risk index) is equal to 709.7 arb. units (IVR=(152.2/0.098) × 0.457=709.7 units), i.e. the child is at high risk of developing hypertension. The boy did not receive any non-drug recommendations for the prevention of arterial hypertension; no long-term drug therapy was carried out for 1 year. After 1 year, ambulatory blood pressure was 133/72 mm Hg. Art. (high normal blood pressure (HNP)). Thus, in a teenager with initially normal values of blood pressure (mm Hg) and BMI (kg/m ² ) after 1 year, GNP was recorded, taking into account age, height and sex.

Example 4

Boy V. (17 years old) of the 2nd health group had normal baseline blood pressure indicators, taking into account age, height and sex (121/75 mm Hg), body mass index, taking into account age and sex (21.6 kg/m ² ) and aggravated heredity for hypertension (AH in the child's mother). According to the results of laboratory studies, IVR (vasopressor risk index) is 448.9 arb. units (IVR=(226.8/0.146) × 0.289=448.9 units), i.e. the child does not belong to the high-risk group for developing hypertension. The boy did not receive any non-drug recommendations for the prevention of arterial hypertension; no long-term drug therapy was carried out for 1 year. After 1 year, ambulatory blood pressure was 120/70 mm Hg. Art. (normal blood pressure). Thus, in a teenager with initially normal values of blood pressure (mm Hg) and BMI (kg/m ² ), after 1 year, normal blood pressure was maintained, taking into account age, height and gender.

Example 5

Girl F. (17 years old) of the 2nd health group had normal baseline blood pressure indicators, taking into account age, height and sex (121/72 mm Hg), body mass index, taking into account age and sex (22.1 kg/m ² ) and aggravated heredity for hypertension (AH in the father of the child). According to the results of laboratory studies, IVR (vasopressor risk index) is equal to 118.3 conventional units. units (IVR=(164.2/0.669) × 0.482=118.3 units), i.e. the child does not belong to the high-risk group for developing hypertension. The girl did not receive non-drug recommendations for the prevention of arterial hypertension; no long-term drug therapy was carried out for 1 year. After 1 year, ambulatory blood pressure was 123/70 mm Hg. Art. (normal blood pressure). Thus, in a girl with initially normal values of blood pressure (mm Hg) and BMI (kg/m ² ), after 1 year, normal blood pressure was maintained, taking into account age, height and gender.

Example 6

Boy D. (11 years old) of the 2nd health group had normal baseline blood pressure indicators, taking into account age, height and sex (110/65 mm Hg), body mass index, taking into account age and sex (17.7 kg/m ² ) and aggravated heredity for hypertension (AH in the child's mother). According to the results of laboratory studies, IVR (vasopressor risk index) is 101.5 conventional units. units (IVR=(82.4/0.241) × 0.297=101.5 units), i.e. the child does not belong to the high-risk group for developing hypertension. The boy did not receive any non-drug recommendations for the prevention of arterial hypertension; no long-term drug therapy was carried out for 1 year. After 1 year, ambulatory blood pressure was 114/68 mm Hg. Art. (normal blood pressure). Thus, in a boy with initially normal values of blood pressure (mm Hg) and BMI (kg/m ² ), after 1 year, normal blood pressure was maintained, taking into account age, height and sex.

Example 7

Girl S. (12 years old) of the 2nd health group had normal baseline blood pressure indicators, taking into account age, height and sex (111/66 mm Hg), body mass index, taking into account age and sex (17.6 kg/m ² ) and aggravated heredity for hypertension (AH in the child's mother). According to the results of laboratory studies, IVR (vasopressor risk index) is equal to 72.23 conventional units. units (IVR=(34.7/0.098) × 0.204=72.23 units), i.e. the child does not belong to the high-risk group for developing hypertension. The girl did not receive non-drug recommendations for the prevention of arterial hypertension; no long-term drug therapy was carried out for 1 year. After 1 year, ambulatory blood pressure was 113/69 mm Hg. Art. (normal blood pressure). Thus, in a girl with initially normal values of blood pressure (mm Hg) and BMI (kg/m ² ), after 1 year, normal blood pressure was maintained, taking into account age, height and gender.

Subsequently, outpatient blood pressure measurements (after 1 year) were performed in 13 adolescent children with an initial IVR value of 485.7 arb. units and more, and in 20 - with an initial IVR of less than 485.7 arb. units Adolescent children were selected for study over time by random sampling. There were no significant differences in gender and age between the groups. Adolescent children did not receive non-drug recommendations for the prevention of arterial hypertension; no long-term drug therapy that affects the level of blood pressure was carried out.

It was found that after 1 year in adolescent children with an initial IVR value of 485.7 arb. units and more (n=13) normal blood pressure, taking into account the age, height and sex of the child was not determined: high normal systolic blood pressure (HNAP) was recorded in 7 adolescents; isolated systolic AT 1 degree - in 6 adolescents. This is evidenced by the increase in dynamics (p<0.05) of the average values of blood pressure _syst. (M±SD) (BP syst. _{initial index} =118.2±4.8 mm Hg; BP syst. _{after 1 year} =130.5±5.4 mm Hg). In dynamics (after 1 year) in adolescent children (n=20) with an initial IVR value of less than 485.7 arb. units it was found that there were no significant changes in the incidence of high normal blood pressure and hypertension (only 1 patient (5.0%) out of 20 had high normal systolic blood pressure (p>0.05), taking into account the age, height and gender of the child; Hypertension (systolic and/or diastolic) in dynamics (after 1 year) was not diagnosed (0%)).

The conjugate statistical analysis between the two indicated groups, depending on the value of IVR (equal to or more than 485.7 arb. units) using the chi-square test, confirmed the relationship between factorial (IVR) and resultant (diagnosis of high blood pressure - VNAD or AH) signs (χ ² =29.1, significance level p<0.001).

Thus, the proposed method for determining a high risk group for developing primary arterial hypertension is effective. The advantages of the proposed method are that:

1. Quantitative assessment of IVR (vasopressor risk index) makes it possible to determine the personalized risk for the development of primary hypertension in adolescent children with normal blood pressure and body mass index, but aggravated heredity for hypertension (high-risk group);

2. The establishment of a high-risk group provides the possibility of timely primary prevention (non-drug recommendations for optimizing nutrition and physical activity, psychological correction) in adolescent children, while avoiding the development of cardiovascular risks in the subsequent years of their life.

Claims (6)

A method for determining a high-risk group for the development of primary arterial hypertension in adolescent children with aggravated heredity for hypertension along the 1st line of kinship, including outpatient blood pressure measurement and characterized in that at a normal level of ambulatory blood pressure and body mass index within one standard deviation from the median leptin, adiponectin, endothelin 1 are determined in blood serum by enzyme immunoassay and the integral indicator is calculated - the vasopressor risk index (IVR) according to the formula IVR (arb. units)=(leptin/adiponectin)×endothelin 1, where leptin is the unit of measurement ng/ml; adiponectin - unit pg/ml; endothelin 1 - unit fmol/ml; at IVR 485.7 arb. units and more define a high-risk group for the development of primary arterial hypertension.