Introduction: Nowdays the analysis of gene candidates polymorphisms and formation of genetic risk scores are actively being used in diagnostic and preventive management in arterial hypertension (AH). Hypothesis: The purpose of the research was to analyze and compare the proportion of modified candidate genes (CG) of AH in different age groups by calculating the gene modification index (GMI) for confirmation of the hypothesis of modified genes accumulation through generations. Methods: 182 patients with AH were examined, mean age 44,3 [18-75], m/f=95/87, (ESC/ISH 2018). Patients were divided into 3 groups depending on age: 1st group - from 18 to 30 y.o. (n=48, m/f=27/21); 2nd group - from 31 to 55 y.o. (n=74, m/f=34/40); 3rd group - from 56 to 75 y.o. (n=60, m/f=28/32). Patients were analysed on the the following CG by PCR: ADD1: 1378, AGT: 704, AGT: 521, AGTR1: 1166, AGTR2: 1675, CYP11B2: - 344, GNB3: 825, NOS3: -786 , NOS3: 894. The GMI which represents the percentage of "pathological" genotypes. The GMI from 0 to 20% was considered as low genetic risk (GR), from 21 to 40 % - moderate GR, from 41 to 70% - high GR, from 71 to 100% - very high GR. Results: In 1 group the average GMI was 64,7% [CI 95%, 29-74], with low GR in 2 (4,2%), moderate GR - in 10 (20,8%), high GR - in 22 (45,8%), very high GR - in 14 (29,2%) patients. In 2 group the average GMI was 56,2% [CI 95%, 18-72], 12 (16,2%) patients had low GR, moderate GR was in 20 (27,1%), high GR - in 26 (35,1%), very high GR - in 16 (21,6%) patients. In 3 group the average GMI was 42,4% [CI 95%, 16-71], low GR was in 16 (26,7%), moderate GR - in 22 (36,7%), high GR - in 14 (23,3%), very high GR - in 8 (13,3%) patients. Analyzing data between the groups, a strong significant difference in GMI was between 1 and 3 groups (64,7% vs 42,4%, p=0,002), high significant differences were also between the 1 and 3 groups, especially in the proportion of patients with high GR (45,8% vs 23,3%, p=0,001) and very high GR (29,2% vs 13,3%, p=0,008) in the group of young patients. Conclusions: It was revealed in the research the accumulation of pathological genetic polymorphisms in the population of hypertensive patients through generations. It was found the strong significant difference in the proportion of "pathological" GP between young and older patients.

The high prevalence of arterial hypertension (AH) and concomitant obesity in young patients is not only a medical but also a social problem. It is important to develop additional modern approaches to the management of young patients with AH and obesity, which will increase the effectiveness of existing antihypertensive (anti-AH) medical therapy and prevent early damage of target organs and complications. The purpose of the research was to evaluate the antihypertensive efficacy of the proposed complex treatment and its impact on quality of life in young patients with AH and obesity (or overweight). Material and methods 123 patients with AH (ESC 2018), of young age 18–44 (mean age 32.81±0.58) y.o. were examined, among them the overweight was in 40 patients, obesity - in 42 patients. The average BMI was (28.34±0.45) kg/m2. All patients were divided into 2 groups depending on the treatment: Group 1 – standard anti-AH treatment, Group 2 – modified combined therapy, which included on the background of standard anti-AH medications the dosed controlled physical exercises with its obligatory registration, a modified DASH diet with increased intake of Ca-containing products and Metformin in the presence of insulin resistance according to the HOMA index (with correction of dose depending on BMI). In dynamics the patients were performed daily blood pressure monitoring (BPM) was performed and the SF-36 questionnaire was used to assess the quality of life (QOL). Results and discussion According to BPM data in the Group 1 the average 24-hour value of SBP decreased by 12.5% (p=0.01), in Group 2 – by 20.2% (p=0.001), DBP - by 11.2% (p=0.03) and by 18.8% (p=0.01) respectively (the difference between the groups for SBP and DBP was p=0.032 and p=0.041, respectively). Assessing the degree of nocturnal blood pressure decreasing, in the Group 1 the percentage of patients with insufficient nocturnal blood pressure decreasing (non-dipper) and stable increasing (night peaker) decreased non-significantly (p=0.086), unlike the Group 2, where there was a significant (p=0.02) positive dynamics in relation to these unfavorable types of blood pressure profile. Evaluating the indicators of QOL according to SF-36, the physical component of health in the Group 1 increased by 16.7%, in Group 2 – by 33.4% (p=0.001), the mental component of health – by 13.5% and 28.9%, respectively (p=0.001). Thus, the additional use of the proposed treatment complex with the inclusion of dosed registered exercises, increased consumption of Ca-containing products and correction of insulinresistance significantly increases the effectiveness of antihypertensive medical therapy and has a positive effect on physical and mental components of QOL in young patients with AH and obesity or overweight. Funding Acknowledgement Type of funding sources: None.

The concept of evolutionary accumulation of candidate gene polymorphisms in the realization of the hypertensive phenotype becomes promising in understanding of arterial hypertension (AH). A large amount of data about genetic polymorphisms in population have been accumulated and perspective approaches to their integrative assessment are being formulated for practical management. The purpose of the research was to analyze and compare the proportion of modified candidate genes (CG) in the group of hypertensive patients with and without obesity with the group of non-hypertensive patients by calculating the gene modification index (GMI) for the assessment of possible usage of genetic stratification in the management of AH. Methods 106 patients with AH and obesity (age 46.2 [24–72], m/f 79/27), (group 1), 96 hypertensive patients without obesity (age 48.3 [26–75], m/f 72/24), (group 2) and 98 non-hypertensive patients (age 41.6 [26–69], m/f 39/59), (group 3) (ESC/ISH 2018, WHO 1997) were examined. The analysis of polymorphisms of the following CG by PCR was perfomed: ADD1: 1378, AGT: 704, AGT: 521, AGTR1: 1166, AGTR2: 1675, CYP11B2: −344, GNB3: 825, NOS3: −786, NOS3: 894. The GMI which represents the percentage of “pathological” genotypes was formed and calculated by the formula: GMI = (N/13.5) × 100, where N is the sum of points of present GP (“pathological” homozygous was 1,5 points, heterozygous – 1 point, “normal” genotype – 0 points); 13.5 – maximum number of points. The GMI from 0 to 20% was considered as low genetic risk (GR), from 21 to 40% – moderate GR, from 41 to 70% – high GR, from 71 to 100% – very high GR. Results In patients with AH and obesity, a low GR was in 4 (3.8%), in the group of hypertensive patients without obesity – 13 (13.5%), in normotensive patients – in 81 (82.7%) (p1–3 = 0.0001, p2–3 = 0.0001, p1–2 = 0.02). Moderate GR was observed in 21 (19.8%) patients of the 1st group, in 25 (26%) patients of the 2nd group and in 12 (12.2%) patients of the 3rd group (p1–3 = 0.07, p2–3 = 0.01, p1–2 = 0.02). 54 (50.9%) patients of group 1, 41 (42.7%) patients of group 2 and 5 (5.1%) of patients of group 3 had a high GR (p1–3 = 0.0001, p2–3 = 0.0001, p1–2 = 0.08); a very high GR was in 27 (25.5%) patients of the 1st group, in 17 (17.8%) of the 2nd group and was absent in the patients of the 3rd group (p1–3 = 0.0001, p2–3 = 0.0001, p1–2 = 0.02). The average GMI in group 1 was 66.2% [CI 95%, 20–78], in group 2 – 56.4% [CI 95%, 18–72], in group 3 – 22% [CI 95% 5–41], (p1–3 = 0.0001, p2–3 = 0.0001, p1–2 = 0.04). Conclusions It was revealed a strong significant predominance of the proportion of modified CG in hypertensive patients with and without obesity compared with non-hypertensive patients. There was a moderate significant difference between hypertensive patients, depending on the presence of obesity. Evaluation of GMI is a perspective direction in the diagnosis and prevention of AH and can be used in practical management. Funding Acknowledgement Type of funding source: None