Arterial hypertension (AH) is a burning problem in the world. Antihypertensive pharmacological therapy combined by physical exercises is well-studied in patients with mild and moderate AH. However, studies that have investigated relaxation in patients with severe AH in addition to drug therapy are lacking. Optimization of a comprehensive treatment for patients with severe AH, by using a multicomponent rational antihypertensive pharmacotherapy (PT) with subsequent application of relaxation exercise therapy (RET). The study involved 32 male patients with severe AH. Initially, clinical-instrumental and laboratory examination, blood pressure registration and daily arterial blood pressure monitoring were carried out. Suitable PT was selected for all the patients. 3 months after starting PT the patients were divided in 2 groups. The patients of the 1st group were prescribed RET in addition to PT. The 2nd group of patients continued receiving PT alone. 3 months later, average daily blood pressure (ADBP)-syst and ADBP-diast were compared in both groups. Three months after PT both groups demonstrated a significant decrease in ADBP-syst and ADBP diast, but these indicators remained higher than normal and did not reach the target level. Three months after the inclusion of RET in the comprehensive treatment, the 1st group demonstrated a significant decrease in ADBP (systolic and diastolic), not only in comparison with the initial data, but also with the data observed three months after PT. After 6 months, ADBP-syst and ADBP-diast in the 1st group were significantly lower compared with those of patients in the 2nd group. The inclusion of RET in addition to a multicomponent antihypertensive PT is a promising treatment option for severe AH.

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Arterial hypertension (AH) is a burning problem in the world, including the Russian Federation. Medical scientists in Russia and abroad pay special attention to etiology, pathophysiology, pathogenesis, diagnosis, treatment and prognosis of AH.1-17 The prevalence of AH among the adult population is from 30–45% up to 60% and it is more frequent among people over 60 years.18,19 Throughout the world, AH also significantly affects cardiovascular complications and results in high death rate. 20 In recent years, scientists have made great progresses in the area of pharmacotherapy (PT) for patients with AH. PT helps to achieve the target level of arterial blood pressure, particularly in patients with mild and moderate AH. With a higher degree of AH (severe arterial hypertension – the 3rd degree of arterial hypertension) the effectiveness of pharmacological therapy decreases and to achieve the target level of arterial blood pressure it is necessary to use a combination of all major groups of antihypertensive medicines. Despite the use of antihypertensive medications, in clinical practice it is not always possible to reduce the blood pressure of patients with severe AH. According to current classifications, severe arterial hypertension of the 3rd degree includes a persistent increase of systolic blood pressure ≥180 and/or diastolic blood pressure ≥110 mm of mercury. For patients in this category the prospects of PT are significantly limited. Indeed, AH is known to be a systemic disease with functional and structural disorders occurring at the level of peripheral circulation with a subsequent limitation of the reserve blood flow, growth of peripheral vascular resistance and increase in severity of patients’ condition. Medicines improve the peripheral circulation at rest to the normal range of values. However, the reserve blood flow does not fully restore. One of the main factors influencing the restoring of the reserve of systemic vascular resistance is the correct selection of a motor regime for patients. Physical and rehabilitation medicine specialists on cardiac rehabilitation teams ensure that behavioral lifestyle treatments and drug therapies are applied systematically and monitor patients’ progress modifying the rehabilitative program and the motor regime.21,22 Antihypertensive pharmacological therapy combined with physical exercises is well-studied in patients with mild and moderate AH of the 1st and the 2nd degrees, who preserve exercise tolerance. With strength training, the sympatho-adrenal system (SAS) and the renin-angiotensin system (RAS) are stimulated, the heart rate and the blood pressure increase. Vice-versa, with relaxing movements, the SAS and the RAS are suppressed, the heart rate is normalized, and the blood pressure is reduced; in addition blood supply is increased due to the inclusion and the restoration of reserve capillaries - angioneogenesis.23 Since patients with a severe degree of arterial hypertension have a significantly reduced exercise tolerance because of the limited reserve of systemic vascular resistance,24 we hypothesize that relaxation exercise therapy (RET) can be a promising option for this type of patients.25 However, to our knowledge studies that have investigated relaxation in patients with severe AH in addition to drug therapy are lacking, so this study aims to investigate the efficacy and tolerability of a relaxation program performed in addition to standard PT. Indeed, aim of this study was optimization of a comprehensive treatment for patients with severe AH, by using a multicomponent rational antihypertensive PT with subsequent application of RET.

The study involved 32 male patients with severe AH, with their daily blood pressure being monitored, and average daily systolic blood pressure (ADBP-syst), average daily diastolic blood pressure (ADBP-diast), and heart rate (HR) being measured. Rational pharmacological therapy was selected for all the patients in accordance with clinical recommendations for the treatment of AH.26,27 Rational PT consisted of a multicomponent antihypertensive therapy, including ACE inhibitors, beta-blockers, calcium antagonists, angiotensin II receptor blockers, diuretics, etc. The selection of the dose of multicomponent antihypertensive therapy was made based on the control of the clinical condition, blood pressure, heart rate and subjective perceptions of the patients.

The patients received PT for 3 months. Then they were divided in 2 groups: the 1st group (average age 46.3±6.8 years) additionally to PT was prescribed RET; the 2nd group (control group, average age 43.6±7.2 years) continued to receive PT (Figure 1). All the participants signed informed consent. In addition to supportive PT, RET was individually selected for each patient from group 1 considering his individual characteristics. The selection of RET was carried out under the control of blood pressure, heart rate and clinical condition of the patient. A physical and rehabilitation medicine physician was included in the study and supervised the RET intervention. When performing RET, all the patients were engaged in exercise therapy on a daily basis for the entire observation period. All exercises were performed without strength tension. The norm group consisted of 16 practically healthy persons, average age 42.8±5.3 years. After 6 months of comprehensive treatment and 3 months from randomization, a follow-up evaluation with reassessment of cardiovascular parameters was performed. The research procedures conformed to the Declaration of Helsinki.

The data were analyzed with SAS 9.4 program (SAS Institute Inc., NC, USA) and R-Studio for Windows. The level of statistical significance was set at 95% and the statistical tests used for analysis included Student's t-test for quantitative variables (differences obtained in different groups of patients and in the course of treatment).

The results obtained after the comprehensive treatment demonstrated improvement of the subjective condition of the patients. Data presented in Table 1 indicated that at baseline the patients in both groups had significantly high ADBP-syst (P<0.001) and ADBP-diast (P<0.001).

The changes in the indicators suggested that in addition to a multicomponent antihypertensive pharmacological therapy, after 3 months: the 1st and the 2nd groups demonstrated a decrease in ADBP-syst, in the 1st group (P<0.001) and in 2nd group (P<0.001), respectively. An upward trend was observed in relation to ADBP-diast in the 1st group (P<0.001), and in the 2nd group (P<0.001), respectively (Table 2). Although, after 3 months of PT both groups demonstrated a significant decrease in ADBP, these indicators remained higher than normal and did not reach the target level. After 3 months of antihypertensive PT, RET was included in the comprehensive treatment course of the patients of the 1st group. The patients in the 2nd group continued receiving the multicomponent antihypertensive pharmacological therapy only. The results inTable 2 show that patients in the 1st group demonstrated a significant decrease in ADBP-syst after 6 months of observations and 3 months after inclusion of RET, not only in comparison with the initial data (P<0.001), but also when compared with those that were after 3 months of PT alone(P<0.001). After 6 months, the indicators of ADBP-syst and ADBP-diast in the 2nd group had a downward trend; compared with the observed results after 3 months, but the difference was unreliable. However, after 6 months ADBP-syst and ADBP-diast in the 1st group were significantly lower when compared with the same outcomes in the 2nd group.

This study showed the potential role of RET in AH management. Initially, both groups demonstrated a significant increase in ADBP-syst and ADBP-diast, compared with the normal level, without significant difference between the two group. Three months after PT both groups demonstrated a significant decrease in ADBP-syst and ADBP-diast, but these indicators remained higher than normal and did not reach the target level. Then, RET was included in the comprehensive treatment of the 1st group. Three months after the inclusion of RET in the comprehensive treatment, the 1st group demonstrated a significant decrease in ADBP (systolic and diastolic), not only in comparison with the initial data, but also with the data observed 3 months after PT. Moreover, after 6 months, ADBP-syst and ADBP-diast in the 1st group were significantly lower when compared with the values of the 2nd group, proving a significant clinical effectiveness of RET. The effects of exercise training in blood pressure levels and in its mechanisms of control are of clinical relevance and efficacy. Different exercise training modalities (aerobic, resistance, and concurrent training - combination of aerobic and resistance) contribute differently to blood pressure reduction and control. The blood pressure reduction seems not to be dependent on the type of exercise; aerobic, dynamic resistance, isometric resistance, and concurrent exercise seem equally effective in lowering baseline systolic blood pressure in comparison with control.28 Regular participation in aerobic exercise has been shown to result in a lowering of blood pressure in AH individuals.29,30. Higher-intensity aerobic exercise, up to 70% of maximal oxygen consumption, seems not to produce a greater hypotensive effect, compared with moderate-intensity aerobic exercise.30 Dynamic resistance exercise seems to be as effective as aerobic exercise in reducing blood pressure among individuals with hypertension.31 Even though no doubt remains about the importance of physical exercise for the management of hypertension, the mechanisms of the beneficial effects have not been fully elucidated. Physical exercise, in the presence of AH, seems effective in increasing the amplitude and decreasing the decay time of cytosolic calcium, suggesting a higher availability of intracellular calcium, faster removal of this ion from the cytosol, and consequently, increased cellular relaxation.

MiRNA expression can also have a role in exercise effects on AH.32 Relaxing environments (e.g., spa facilities) have been shown to contribute to the modulation of the immune system and inflammation.33-36 Inflammation cytokines have been demonstrated to play critical roles in endothelial and smooth muscle cell responses, contributing to endothelial dysfunction and the development of hypertension.37 In addition, mind-body practices that elicit the relaxation response (eight weekly individual training sessions including diaphragmatic breathing, body scan, mantra repetition, and mindfulness meditation) have been demonstrated to reduce blood pressure in essential hypertension. The response to relaxation interventions is characterized by a set of physiologic changes that include decreased oxygen consumption, decreased carbon dioxide elimination, decreased respiratory rate, increased low-frequency heart rate oscillations, and increased exhaled nitric oxide, in addition to specific changes in gene expression. Immune regulatory pathways genes have been shown to be downregulated after relaxation interventions, while glucose metabolism, cardiovascular system development, and circadian rhythm genes seemed to be upregulated.37 Only 20% of the capillary network of the human body is active at rest, while the remaining 80% of the capillaries are in a reserve state and they start working during physical activities, especially in the mode of relaxation movements. This means that the heart pump function services only 20% of the capillaries. It is known that the base of the cardiovascular system reserve is the capillary network. Therefore, for a complete recovery and preservation of the reserve of the cardiovascular system, along with supportive PT for patients with AH, the inclusion of RET appears to be promising.24, 25 Thus, it should be assumed that, since PT is not sufficient for the elimination of cellular-tissue and microcirculatory disorders in case of severe AH, it should be advisable to include RET into the multicomponent treatment, and positive changes in the indicators of the 1st group of patients after the inclusion of RET are suggestive of it.

Although these first results appear to be promising, further studies will define the number of sessions and the duration of treatment necessary to obtain a containment of blood pressure values. Another question to be investigated is the maintenance of RET after blood pressure reduction: it must be clarified if it is necessary to continue chronically the treatment for a better control of AH. The small number of patients considered necessitates further evaluation extending the trial to a larger population. The present study is not registered on a clinical trial Registry. PT with the addition of RET will also need to be considered for different grades of AH, stratifying the population according to the severity of disease. In addition, further studies may also evaluate functional tests in these patients.38 Finally, additional studies in the future should consider longer-term follow-up so as to assess the effects of combination therapy over time.

In conclusion, addition of RET into the background of a multicomponent antihypertensive PT is a promising option for severe AH. Further studies will better define the role of this intervention, even in the long term, for people with severe AH.