Background: Arterial hypertension (AH) remains the most common cardiovascular (CV) risk factor worldwide. Methods: Seventy five moderate-to-severe hypertensive patients with abdominal obesity aged from 48 to 66 years (45/30 men and women respectively) were selected from the entire cohort (n = 375) according to the inclusion and exclusion criteria. The patients were divided into two subgroups depending on the arm of antihypertensive therapy lines. The first subgroup of patients (n = 36) received a non-fixed combination of oral antihypertensive agents: perindopril (4-8 mg daily), indapamide (1.25-2.5 mg daily) and amlodopine (5-10 mg daily). The second subgroup of patients (n=39) received fixed-dosed combination of these antihypertensive agents aforementioned in the ranged doses (4 mg/1.25mg/5 mg; 4 mg/1.25mg/10 mg; 8 mg/2.5 mg/5 mg; 8 mg/2.5mg/10 mg) in the same manner. The examinations of the clinical status, office, and ambulatory blood pressure values were carried out at baseline in 3 and 6 months after study entry. Results: The frequencies of BP target levels after treatment were higher in the fixed-dose combination group than in the non-fixed combination (at 3 months: 80% versus 58%, p<0.05 and at 6 months: 85% versus 53%, p<0.05). The adherence to triple fixed-dose combination was also higher in comparison with one to non-fixed combination (at 3 months: 82% versus 64%, p<0.05 and at 6 months: 87% versus 61%, p<0.05). It has been established that low-dose of perindopril/indapamide/amlodopine (4mg/1.25/10mg and 8mg/2.5/5mg) were used frequently in fixed-dose combination cohort of patients than in non-fixed combination (15% versus 0%, P<0.05, and 33% versus 19%, p<0.05, respectively). At the same time, maximum doses of these agents (8mg/2.5mg/10mg) were required for achieving target BP levels in a significantly lower proportion of patients receiving fixed-dose combination as compared to patients receiving non-fixed combination (52% versus 81%, p<0.05). Additionally, the triple fixed-dose combination has proved to be better in restoring ambulatory blood pressure monitoring profile than non-fixed combination. Conclusion: Achievement of target blood pressure levels in patients with uncontrolled arterial hypertension and abdominal obesity was possible at lower doses of perindopril, indapamide, and amlodipine when used as a fixed-dose combination rather than non-fixed (free) combination. Key words: abdominal obesity, antihypertensive therapy, arterial hypertension, fixed-dose combination of antihypertensive agents, non-fixed combination of antihypertensive agents Cite this article : Koval S M, Snihurska I O, Starchenko T G, Penkova M Y, Mysnychenko O V, Yushko K O, Lytvynova O M, Vysotska O, Berezin A E. Efficacy of fixed dose of triple combination of perindoprilindapamide-amlodipine in obese patients with moderate-to-severe arterial hypertension: an open-label 6-month study. Biomed. Res. Ther.; 6(11):3501-3512. 3501 History •

Background. The angiotensin-(1-7) is a new component of the renin-angiotensin system, the product of the degradation of angiotensin II and its functional antagonist, but its role in hypertension with type 2 diabetes (T2D) is not clear. The aim of the study was to investigate the levels of angiotensin-(1-7) in patients with hypertension and T2D and determine its relations to hemodynamic and cardiac structural and functional parameters. Material and methods. We examined 70 patients with hypertension and T2D. Investigation protocol included physical examination, standard transthoracic echocardiography and determination of the angiotensin-(1-7) blood levels by ELISA. Control group consisted of 16 healthy volunteers. Results. The angiotensin-(1-7) levels in observed patients were significantly lower than in volunteers [105.51 (89.13;121.17) ng/L vs. 132.75 (125.06; 142.87) ng/L, p < 0.001]. The levels of the angiotensin-(1-7) significantly negatively correlated with duration of hypertension (r = -0.29, p < 0.05), systolic blood pressure (BP) (r = -0.38, p < 0.05), diastolic BP (r = -0.36, p < 0.01), average BP (r = -0.32, p < 0.01), left ventricular (LV) internal dimension at end-diastole (r = -0.37, p < 0.01), LV mass (r = -0.40, p < 0.001), LV mass index (r = -0.41, p < 0.001). In patients with LV hypertrophy, angiotensin-(1-7) levels were significantly lower than in patients without LV hypertrophy [101.9 (88.2; 117.7) ng/L vs. 129.3 (117.5; 136.8) ng/L, p < 0.01] and in patients with diastolic LV dysfunction -lower than in the patients with normal diastolic function [101.1 (87.9; 116.6) ng/L vs. 121.1 (105.5; 128.9) ng/L, p < 0.01]. Conclusions. The angiotensin-(1-7) can be considered as an important pathogenetic factor in the development of hypertension with T2D, a BP regulator and a cardioprotective agent that prevents the development of remodeling and diastolic dysfunction of the LV.

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The aim: To study the association between T344C single nucleotide polymorphism (SNP) of aldosteronesynthase (ALS) gene CYP11B2 (rs1799998) with anthropometric, clinical, haemodynamic, structural and metabolic parameters of patients with arterial hypertension (AH) and abdominal obesity (AO).Materials and methods: 112 patients with AH II stage, 2–3 degrees with AO aged 45–69 years were surveyed. Control group is composed of 28 healthy city residents of the appropriate age and gender. Haemodynamicparameters, blood glucose levels, glucose tolerance test, the expanded lipid spectrum, aldosterone levels wereevaluated. Genotyping of T344C SNP of ALS gene CYP11B2 was performed by polymerase chain reaction inreal-time. Statistical data processing was carried out using SPSS packages.Results: The distribution of T344C SNP genotypes of ALS gene CYP11B2 among healthy individuals andpatients with AH and AO does not significantly differ and is similar to that in the European population. Theserum level of HDL-C in patients with TT genotype was significantly higher than in patients with TC genotype(p = 0.01). The association between TT + TC genotypes of ALS gene CYP11B2 and left ventricular hypertrophy(LVH) (p < 0.05) in the examined patients was shown. The significant direct correlations between «hypertensive» T allele of aldosterone synthase gene frequency and the duration of AH and the severity of LVH werefound.Conclusions: The associations between TT + TС genotypes T344C SNP of ALS gene, and the presence ofLVH as well as between TT genotypes and elevated serum level HDL-C in AH patients with AO were established.

Objective:Study the ambulatory blood pressure monitoring (ABPM) parameters in patients with arterial hypertension (AH) with abdominal obesity (AO) in the dynamics of antihypertensive therapy.Design and method:60 AH patients with AO were examined. All patients were prescribed a fixed combination of drugs: olmesartan and amlodipine once a day in the morning at doses: 20 mg / 5- 40 /10 mg. ABPM was performed according to the standard method before and after 6 months of treatment.Results:24-hour systolic BP (SBP) and diastolic BP (DBP) in patients were 150 (140–159) / 98 (82–105) mm Hg. 24-hour pulse BP - 58 (50–64) mm Hg. Daytime SBP variability in patients was 19 (12–25) mm Hg, daytime DBP variability was 15 (9–19) mm Hg. SBP variability at night was 15 (9–17) mm Hg, DBP variability at night was 13 (8–15) mm Hg. As a result of treatment, the target BP level was achieved in 80% of patients according to the office BP and in 60% -according to the ABPM. The number of patients with pathological variability of BP decreased from 49% to 23% (p < 0.05). An excessive morning rise in SBP at the beginning of the study was noted in 32% of patients, and at the end of the observation - in 11% (p < 0.05). The number of patients with nocturnal hypertension decreased from 42% to 15% after 6 months of treatment (p < 0.001). The distribution of patients by BP profiles revealed that at the beginning of the study «dipper» was in 40% of the patients, «over-dipper» - in 12%, «non-dipper» - in 38%, and «night-picker»- in 6%. After 6 months of treatment the number of patients with the «dipper» profile of ABPM increased to 88%, and with «over-dipper» decreased to 6%. The number of patients with unfavorable «non-dipper» and «night-picker» profiles of ABPM decreased to 5%(p < 0.05) and 1% (p > 0.05), respectively.Conclusions:The fixed combination of olmesartan/ amlodipine led to the normalization of parameters of the ABPM profile in hypertensive patients with AO.