Vol 15, No 4 (2018)

Combining treatments with antihypertensive, lipid lowering, antidiabetic and antiplatelet effects into a single pill significantly increases adherence to treatment, provides multiple control of risk factors and reduces the risk of cardiovascular diseases and fatal events. At the same time, there is still no convincing evidence that the using polypill in cardiology instead of the standard treatment strategy leads to a greater reduction in the incidence of primary end points (total mortality, fatal myocardial infarction, stroke, etc.)

Background. To improve the prognosis and quality of life of patients with essential hypertension, it is necessary to search for combinations of antihypertensive drugs that can affect all parameters of blood pressure (BP) and restrict remodeling of target organs. Aim. To study the effect of free and fixed combination of angiotensin converting enzyme inhibitor (perindopril arginine) and dihydropyridine calcium antagonist (amlodipine) on BP parameters, target organs damage criteria and quality of life of hypertensive patients. Materials and methods. The study included 92 patients suffering from arterial hypertension (AH) II and III stages. The 1st group included patients who received within 12 months treatment in a free combination of an angiotensin converting enzyme inhibitor (perindopril arginine) and amlodipine, in the 2nd group - in a fixed combination. The changes in BP indices were compared, including BP variability, criteria for target organs remodeling and quality of life assessed using the SF-36 questionnaire. Results. The results of office and 24-hour BP monitoring at the study stages demonstrated better control of all BP indices in patients of the 2nd group, reduction of short-, medium- and long-term BP variability. Against the background of treatment with a fixed combination of amlodipine and perindopril arginine, there were significantly more significant changes in 3 parameters of target organs remodeling: glomerular filtration rate, microalbuminuria, ankle-brachial index, and restoration of diastolic function of the left ventricle. At the same time, different positive dynamics of the quality of life indicators of patients of both study groups were noted. Conclusion. Fixed combined full-dose antihypertensive therapy with amlodipine and perindopril arginine allows achieving BP targets (including BP variability) in the majority of patients with AH II and III stages with high and very high risk of cardiovascular complications. High adherence to therapy allowed not only to maintain all parameters of blood pressure at the target level within a year, but also significantly improve the parameters of target organs remodeling and the quality of life of patients

Achievement of target blood pressure levels is one of the main issues in antihypertensive pharmacotherapy. The article presents updated 2018 European Guidelines recommendations on target blood pressure levels in antihypertensive therapy and combined antihypertensive pharmacotherapy advantages. Modern fixed combinations including those with three active agents are discussed. A review of studies that show effectiveness and safety of long acting dihydropyridine calcium channel blocker amlodipine, thiazid-like diuretic indapamide, and angiotensin-converting enzyme inhibitor perindopril arginine fixed combination is presented

Purpose. To evaluate the efficiency of combination antihypertensive therapy with valsartan and amlodipine in patients with arterial hypertension (AH) and obesity, depending on the polymorphisms of the CYP2C9 and CYP11B2 genes. Materials and methods. In research included 80 obese patients (body mass index ≥30 kg/m2) and AH 1-2 disease blood pressure (BP) ≥140/90 mm Hg and <180/110 mm Hg against the background of previous antihypertensive therapy) uncontrolled medication. The patients included in the research received a fixed combination of valsartan and amlodipine at doses of 80-160/5-10 mg/day. All patients were measured office BP, implementambulatory blood pressure monitoring (ABPM) with the definition of central aortic systolic pressure (CASP) and stiffness indicators vascular wall at baseline and after 16 weeks of therapy. Venous blood samples were taken from all patients, followed by DNA extraction from leukocytes by the method of phenol-chloroform extraction. Determination of polymorphic variants of the researched genes was performed by amplification in real time on the amplifier Rotor Gene Q. We used sets of primers and probes (“Sintol”, Russia) and the Taq Man method (allele discrimination). Results. It was shown that patients with *1/*2 and *1/*3 variants more often reached the target level of office BP than with polymorphism *1/*1 (respectively 92.8 and 90.1% vs 43.7% cases, p<0.05). At the same time, in patients with polymorphisms *1/*2 and *1/*3 compared with persons who had the option *1/*1, a more expressed decrease in most indicators of ABPM and positive changes in the CASP and stiffness of the vascular wall (p<0.05) were found. When analyzing the effeciency of treatment with regard to polymorphic variants of the CYP11B2 gene, significantly more frequent achievement of the target level of BP was observed with mutant polymorphism *2/*2, than with polymorphism *1/*2 (76.5% vs 50%). When comparing the degree of change in ABPM, CASP, and vascular wall stiffness, depending on the polymorphic variant of the CYP11B2 gene, a more pronounced positive dynamics of most parameters in polymorphism carriers *2/*2 was found than in persons with *1/*1 and *1/*2. It was also found that among persons with the most frequent polymorphism of the CYP2C9 gene - *1/*1, reached the target level of BP as a result of 16-week therapy, there was a significant predominance of the polymorphism *2/*2 of the CYP11B2 gene over its other variants. Conclusion. Obtained during our study data on the relationship of the effectiveness of therapy with valsartan and amlodipine with different polymorphisms of the CYP2C9 and CYP11B2 genes can be used and taken in to account in the individualized selection of antihypertensive therapy patients with AH and concomitant obesity. It can also be assumed that genetic testing preceding the correction of treatment, as one of its personalization options, will help increase the effectiveness of pharmacotherapy in patients with AH and obesity

Objective. To study effectiveness and safety of generic bosentan use for 24 weeks in patients with pulmonary arterial hypertension (PAH). Materials and methods. The study included 42 patients. In 22 patients Bosentan therapy (Bosenex®, Sotex, Russia) was used for the first time. In 20 patients switching therapy from original bosentan (Tracleer, Аctelion Pharmaceuticals Ltd., Switzerland) was performed. The patients were followed up for 24±2 weeks. Results. After 24 weeks of treatment percent of patients with functional class (FC) III decreased from 55 to 30%, percent of patients with FC II increased from 45 to 55%, some patients (15%) achieved FC I, and the 6-minute walk distance increased on 52.1 meters. In the group of therapy change heart failure FC stabilization was observed, 6-minute walk distance increased on +14.8 meters (р>0.05). Echocardiography in the first group showed significant decrease of pulmonary artery systolic pressure (PASP) at -4 mm Hg and of right atrium area on 0.9 cm2. In the switched therapy group the difference was not significant. According to chest X-ray examination change of cardio-thoracic ratio, Murray and Lupi indexes was not significant in both groups. According to results of right heart catheterization improvement of mean pulmonary arterial pressure (-6.7 mm Hg), mean right atrial pressure (-1.6 mm Hg with reference value reached), and pulmonary vascular resistance (-293.2 dynes×sec/cm-5) was achieved; р<0.05. Bosenex therapy was tolerated well and development of clinically significant adverse effects was not observed. Conclusion. Use of first generic bosentan for 24 weeks resulted in improvement of clinical and haemodynamic parameters as well as in improvement of functional ability of patients with PAH of II-III FC (World Health Organization). Switching from original medication to Bosenex® was not followed by patients’ clinical status impairment or with adverse effects development. Patients who used Bosenex® developed only adverse effects that typically occur in this medications class use, the frequency of adverse effects development did not exceed the claimed one

Epicardial fat (EF) is thought to be a cardiovascular risk factor, it has attracted a great interest from researchers and is relevant to study. The article presents a review on EF influence on cardiovascular system and metabolic parameters, as well as new therapeutic approaches to modify EF volume. There are no established methods for EF parameters measurement at present. The use of transthoracic echocardiography which is a simple, accessible, and informative procedure is suggested as one of these methods

Obesity plays a key role in the epidemic of type 2 diabetes mellitus (DM), cardiovascular and cerebrovascular diseases. Most studies confirm the association of increased arterial stiffness with obesity. However, the interrelation of various fat depots with one of the main indicators of vascular wall stiffness - the cardiovascular vascular index (CAVI) is currently not clear. The purpose of this study is to assess arterial stiffness in people with abdominal obesity without metabolic syndrome (MS) and with MS, the connection of fat depots (visceral, subcutaneous, perivascular, epicardial fat) with the stiffness parameter CAVI. Materials and methods. 68 people with abdominal obesity (AO) at the age of 18-45 years. The study included height, weight, BMI, waist circumference, and biochemical blood tests (fast glucose and glucose tolerance, uric acid, creatinine, GFR - MDRD, lipid profile, insulin, HOMA-IR). 24-hour blood pressure monitoring, computed tomography (Aquilion One Vision Edition, Toshiba, Japan) with the definition of subcutaneous, visceral, perivascular, epicardial fat, and also calculated the ratio subcutaneous to visceral fat. It was determined CAVI on the VaSera 1000 unit (Fukuda Denshi, Japan) to assess arterial stiffness. Abdominal obesity was derteming by cut off waist circumference >80 cm for women and >94 cm for men. As a result, we were formed 2 groups: persons with abdominal obesity and the presence of no more than one additional risk factor (metabolically healthy) - group 1, persons with MS (abdominal obesity in combination with 2 and more extra risk factors) - group 2, the control group consisted of healthy individuals (n=15) without obesity - group 0. Results. There was no statistically significant difference between CAVI groups. Correlations of CAVI with age r=0.340 (p=0.005), with daytime mean systolic blood pressure - SBPm average (r=0.280, p=0.021) and with mean diastolic blood pressure - DBPm average (r=0.329, p=0.006), with night SBPm average (r=0.233, p=0.014) and with DBPm average (r=0.297, p=0.014), with the volume of periaortic fat (r=0.218, p=0.074) were found. An inverse correlation was found between CAVI and BMI (r=-0.279, p=0.021), with subcutaneous fat depot (r=-0.285, p=0.019) and with the ratio of subcutaneous to visceral fat (r=-0.303, p=0.012). According to the multivariate regression analysis, the most significant impact on CAVI is exerted by age, daytime SBPm, BMI, and the volume of periaortic fat

The review focuses on the main strategies of antihypertensive therapy set out in the 2018 ESC/ESH recommendations. The basis of antihypertensive therapy consists of five main classes of antihypertensive drugs, which should form the basis of the combined drug antihypertensive therapy in most patients. The single pill strategy is to take advantage of fixed combinations as a starting antihypertensive therapy for most patients. Among the fixed combinations, the combination of an ACE inhibitor with a diuretic (Noliprel®) remains one of the most preferred for antihypertensive therapy, since In addition to its antihypertensive potential, it has the ability to prevent renal, coronary complications and cerebrovascular events, to influence the progression of atherosclerosis, the occurrence of new cases of diabetes and to achieve a statistically significant reduction in total mortality