COMPARATIVE ANALYSIS OF THE EFFICACY OF FIXED-DOSE COMBINATIONS OF AMLODIPINE/LISINOPRIL AND BISOPROLOL/HYDROCHLORTHIAZIDE IN PATIENTS WITH ESSENTIAL ARTERIAL HYPERTENSION COMBINED WITH OBESITY AND OVERWEIGHT

Aim. To study the characteristics of the daily profile of blood pressure (BP) and heart damage in patients with essential hypertension (HT), depending on the presence of obesity as well as the antihypertensive and organoprotective effects of fixed-dose combinations of amlodipine/lisinopril and bisoprolol/hydrochlorothiazide in hypertensive patients with obesity or overweight.Material and methods. 60 patients with untreated HT, stage II, degree 1-2 (51.7% of men, aged 53.6±0.8 years) were examined. 24-hour BP monitoring and transthoracic echocardiography with calculation of myocardial stiffness parameters were performed in all patients. Hypertensive patients with obesity and overweight were randomized into groups treated with fixed-dose combinations amlodipine/lisinopril (n=25) or bisoprolol/hydrochlorothiazide (n=30). Doses of drugs were titrated until the target BP was achieved. The follow-up was 12 weeks.Results. Patients with HT and obesity (n=28) compared with hypertensive patients without obesity (n=32) had greater systolic BP (SBP) variability at night (p<0.05) and a morning surge in SBP (p<0.01), end systolic volume (p<0.05), systolic volume (p<0.01),right ventricle anterior-posterior dimension (p<0.001), right atrium volume (p<0.01), the thickness of the interventricular septum (p<0.01) and the posterior wall (p<0.001) of the left ventricle (LV), significantly lower LV global longitudinal systolic 2D-strain (p<0.001), coefficient of diastolic and end-systolic LV elastance (p<0.05 for both). At the end of the follow-up period patients in the amlodipine/lisinopril group compared to patients in the bisoprolol/hydrochlorothiazide group had a greater decrease in the mean daily pulse BP (-10.8 vs -5.4 mm Hg, respectively; p<0.05) and variability of SBP in daytime (-2.8±0.8 vs -0.9±0.3 mm Hg, respectively; p<0.05). Only patients in the amlodipine/lisinopril group had a significant decrease in the variability of SBP (from 12.2±0.8 to 10.9±0.5 mm Hg; p<0.05) and diastolic BP (from 9.3±0.5 to 8.4±0.4 mm Hg; p<0.001) at night. Patients in the amlodipine/lisinopril group compared to patients in the bisoprolol/hydrochlorothiazide group had a greater increase in the left atrium strain (p<0.01), 2D-strain of LV and a greater decrease in the LV end diastolic stiffness (-21.39±2.45 vs -3.54±1.57 mm Hg/ml, respectively; p<0.001), the LV end systolic elastance (-16.15±2.14 vs -12.85±1.37 mm Hg/ml, respectively; p<0.05), and LV myocardial mass index (-13.2±0.9 vs -8.4±0.7 g/m2, respectively; p<0.01), the thickness of the interventricular septum and the posterior wall of the LV.Conclusion. Untreated hypertensive obese patients in comparison with hypertensive patients without obesity have higher BP level variability during the night and early morning SBP surge, greater sizes of the heart chambers and LV myocardial wall thickness, higher LV myocardium stiffness. In obese or overweight patients with HT, a fixed-dose combination of amlodipine/lisinopril, compared with the fixed-dose combination of bisoprolol/hydrochlorothiazide, resulted in a more significant decrease in pulse BP and variability of systolic and diastolic BP at night, contributed to a more pronounced improvement in the elastic properties of the left atrium and LV myocardium and decrease in LV hypertrophy

Effect of the Single-Pill Amlodipine/Valsartan Combination on Hypertrophy and Myocardial Deformation Characteristics in Middle-Aged Patients with Essential Arterial Hypertension

Aim. To investigate the impact of amlodipine/valsartan single-pill combination (A/V SPC) on left ventricular hypertrophy (LVH) and left ventricular (LV) myocardial strain and stiffness parameters in naїve middle-aged patients with stage II grade 1-2 essential arterial hypertension (EAH).Material and methods. A group of patients with stage II grade 1-2 EAH who had not previously received regular antihypertensive treatment (AHT) [n=38; mean age 49.7±7.0 years] was retrospectively formed. All the patients were treated with A/V SPC and all of them achieved target office blood pressure (BP) (less than 140/90 mm Hg). And after 12 weeks follow-up (since the time of reaching the target BP) the AHT effectiveness assessment, its impact on LVH and LV myocardial strain and stiffness parameters (general clinical data, ambulatory blood pressure monitoring, conventional and 2D-speckle tracking echocardiography) were performed in all included patients.Results. The number of patients with LVH significantly (p=0.039) decreased from 25 individuals (65.8%) at baseline to 15 patients (39.5%) at the end of follow-up. Among patients with LVH at baseline after the treatment with A/V SPC significantly decreased (p<0.001 for all) interventricular septum thickness (from 1.36±0.19 to 1.28±0.18 cm), LV posterior wall thickness (from 1.08±0.09 to 0.97±0.11 cm) and the LV myocardial mass index (from 123.3±19.3 to 110.8±20.8 g/m2). At the end of follow-up end-systolic elastance significantly (p<0.001) decreased from 4.01±1.12 to 3.46±0.88 mm Hg/ml. In the subgroup of patients with reduced (in absolute value) LV longitudinal 2D-strain (n=27) at baseline, there was a significantly (p=0.005) increasing in this parameter at the end of the study (from -16.14±2.21% to -17.30±2.13%, Δ%=8.45±13.35).Conclusion. In naive patients 40-65 years old with stage II grade 1-2 EAH AHT with A/V SPC provides effective 24 hours BP control, significantly reduced LVH and improves LV strain parameters, which indicates decreasing of LV myocardial stiffness

High sympathetic tone in development of the left ventricle hypertrophy and beta-blockers for regression

The review is focused on clinical significance of the left ventricle hypertrophy (LVH) — presentation of heart lesion as a target organ for systemic hypertension (SH). Various LVH development mechanisms are presented, and special attention is paid to sympathic nervous system and β-adrenoreceptors in pathogenesis. Fundamental methods of diagnostics are described for LVH, in comparison. The pathology is classified from the perspective of recent guidelines on echocardiographic diagnostics. Epidemiology provided. Taken current evidence, the prognostic role of LVH is described as a factor increasing the risk of fatal and non-fatal cardiovascular, cerebrovascular and renal complications in SH patients. Trials data presented that points on LVH regression with highly selective β1-blocker bisoprolol treatment. Pathophysiology of LVH regression is discussed for β1-blocker treatment

The Biosynthetic Pathways for Shikimate and Aromatic Amino Acids in Arabidopsis thaliana

The aromatic amino acids phenylalanine, tyrosine and tryptophan in plants are not only essential components of protein synthesis, but also serve as precursors for a wide range of secondary metabolites that are important for plant growth as well as for human nutrition and health. The aromatic amino acids are synthesized via the shikimate pathway followed by the branched aromatic amino acid metabolic pathway, with chorismate serving as a major branch point intermediate metabolite. Yet, the regulation of their synthesis is still far from being understood. So far, only three enzymes in this pathway, namely, chorismate mutase of phenylalanine and tyrosine synthesis, tryptophan synthase of tryptophan biosynthesis and arogenate dehydratase of phenylalanine biosynthesis, proved experimentally to be allosterically regulated. The major biosynthesis route of phenylalanine in plants occurs via arogenate. Yet, recent studies suggest that an alternative route of phynylalanine biosynthesis via phenylpyruvate may also exist in plants, similarly to many microorganisms. Several transcription factors regulating the expression of genes encoding enzymes of both the shikimate pathway and aromatic amino acid metabolism have also been recently identified in Arabidopsis and other plant species