Vol 18, No 1 (2021)

Expert opinion
Expert consensus. Effect of antihypertensive therapy on cognitive functions
Ostroumova O.D., Parfenov V.A., Ostroumova T.M., Yakhno N.N., Chazova I.E., Bogolepova A.N., Galyavich A.S., Geraskina L.A., Emelin A.I., Zakharov V.V., Kislyak O.A., Kulesh A.A., Levin O.S., Podzolkov V.I., Privalova E.V., Shikh E.V.

Arterial hypertension (AH) is the major modifiable risk factor for cognitive impairment (CI), including dementia, CI in cerebrovascular and neurodegenerative diseases, including Alzheimer’s disease. By 2050, the number of people with dementia will approximately 3 times increase due to the aging population and limited opportunities for drug prevention and treatment of severe CI. In connection with the above, it seems necessary to create an expert consensus, which would summarize the evidence-based medicine data available to date on the effect of antihypertensive therapy (AHT) on cognitive function (CF). In the expert consensus, the data of prospective randomized clinical trials, observational and population studies, meta-analyzes on the effect of AHT on the risk of dementia and CI progression, including certain CF, were summarized and analyzed. The consensus considers the effect of antihypertensive drugs (AHD) on various cognitive domains. Literature data give evidence that AHT reduces the risk for dementia, including vascular dementia, reduces the risk of for dementia in Alzheimer’s disease, as well as reduces the risk and can prevent the progression of non-dementia CI. The effect of AHT on various CF has been little studied. Most meta-analyzes did not reveal the benefits of any class of AHD; however, one study demonstrated the advantage of angiotensin receptor blockers, while another study – diuretics. The consensus emphasizes that, given the high incidence of AH in the general population, AHT may be one of the most effective ways to prevent CI or delay CI progression. The effect of different classes of AHD on CF requires further study. It is necessary to conduct a larger number of well-designed randomized clinical trials that would assess the state of executive functions in patients with AH.

Systemic Hypertension. 2021;18(1):5-12
Uncontrolled arterial hypertension: main causes, features of pathogenesis and approaches to treatment
Denisova A.R., Solntseva T.D., Sivakova O.A., Chazova I.E.

Patients with arterial hypertension represent a special population group with a high risk of developing cardiovascular diseases. The most difficult to control are resistant and refractory hypertension. It is known that patients with uncontrolled hypertension have a worse prognosis, both in terms of cardiovascular events and all-cause mortality. This review presents topical issues related to the features of pathogenesis, treatment and prognosis in patients with refractory and refractory hypertension.

Systemic Hypertension. 2021;18(1):13-18
Original Article
Effects of the b-blockers on the functional state of patients with ventricular arrhythmias
Shubitidze I.Z., Tregubov V.G.

Sudden cardiac death and the heaviest arrhythmic events are connected to ventricular arrhythmias (VA). The issue of optimization of drug therapy for VA remains relevant. Given the possible multidirectional effects of antiarrhythmic drugs on the functional state, in order to determine the effectiveness of pharmacotherapy in patients with VA it is advisable to use a stepwise integrated approach.

Aim. Compare the effects of bisoprolol, nebivolol and sotalol on the functional state of patients with VA.

Materials and methods. 120 patients with VA of grade I–IV based on the В. Lown grading system, I–II groups based on J. Bigger grading system against the background of essential hypertension or its combination with coronary heart disease took part in the research, they were randomized into three groups for treatment with bisoprolol, nebivolol and sotalol. As part of combination therapy, patients were administered lisinopril, and if indicated, acetylsalicylic acid, atorvastatin. Initially and after 24 weeks of therapy the following was done: quantitative assessment of regulatory-adaptive status by cardio-respiratory synchronism test, treadmill test, six-minute walk test, subjective assessment of quality of life, all-day monitoring of blood pressure and electrocardiogram.

Results. With comparable hypotensive and antiarrhythmic effects, therapy with nebivolol had a positive effect on the regulatory-adaptive status, had a better effect on exercise tolerance in comparison with bisoprolol and sotalol, more improved the quality of life, in comparison with bisoprolol and sotalol.

Conclusion. In patients with VA against the background of essential hypertension or its combination with coronary heart disease as part of combination therapy the use of nebivolol may be preferable to bisoprolol or sotalol due to a more pronounced positive effect on the functional state.

Systemic Hypertension. 2021;18(1):19-24
Etiopathogenesis, diagnosis, and approaches to the treatment of arterial hypertension: an assessment of the physicians’ basic knowledge. Final results of the PHYSTARH project
Bontsevich R.A., Vovk Y.R., Gavrilova A.A., Kirichenko A.A., Ebzeeva E.Y., Kosmacheva E.D., Kompaniets O.G., Prozorova G.G., Nevzorova V.A., Martynenko I.M., Barysheva V.O., Ketova G.G., Maksimov M.L., Osipova O.A.

Introduction. Arterial hypertension (AH) is a syndrome accompanied by an increase in systolic blood pressure (BP)≥140 mmHg and/or diastolic BP≥90 mmHg. It is a progressive pathology that affects the adult employable population and leads to the development of deadly complications.

Aim. To compare the level of physicians’ knowledge in AH’s definition, diagnosis and treatment in different centers of Russia.

Materials and methods. In the framework of the multicenter study PHYSTARH (the full name of the project “Physicians ‘and undergraduates’ knowledge in arterial hypertension treatment”), which was launched in 2017, an anonymous survey was conducted among 425 doctors from 9 cities/regions of Russia (Belgorod Region, Moscow, Krasnodar Territory, the Republic of Adygea, Voronezh, Primorye Territory, Tatarstan, Lipetsk, Chelyabinsk).

Results. The study revealed an insufficient level of doctors’ knowledge in diagnosis and treatment of AH. Less than half of the respondents correctly answered the following questions: determining hypertension by the level of “home” monitoring of BP (36% of physicians), determining the degree of hypertension for the proposed numerical values (37% of physicians), definition and prevalence of the “refractory” hypertension (33% of physicians), definition of the “masked” hypertension (45% of physicians), the need for drug correction of high normal BP (9% of physicians), selection of the main classes of antihypertensive drugs without clinical situations (26% of physicians).

Conclusion. The physicians’ knowledge on AH is unsatisfactory, despite the prevalence of pathology and the availability of clinical guidelines, which, in our view, justifies the need for additional public education programs for doctors in different regions.

Systemic Hypertension. 2021;18(1):25-30
Clinical and functional characteristics of arterial stiffness in elderly
Murkamilov I.T., Aitbaev K.A., Fomin V.V., Murkamilova Z.A., Redzhapova N.A., Yusupov F.A.

Aim. Purpose of the study. To study the clinical and functional features of the parameters of arterial stiffness in the elderly, depending on gender differences.

Materials and methods. The study included 497 therapeutic patients aged from 60 to 74 years. The average age of the examined patients was 65.1±3.9 years. All patients underwent a comprehensive clinical and instrumental examination. The study of the parameters of arterial stiffness and central arterial pressure (BP) was carried out on the AngioScan-01 apparatus (AngioScan-Electronics, Russia). Depending on the sex differences, the entire sample was divided into two age-matched groups: women (n=287) and men (n=210).

Results. In the group of women, systolic levels (138±20 mm Hg vs 134±19 mm Hg; p=0.018), central (137±20 mm Hg vs 133±19 mm Hg; p=0.024), average (46±9 mm Hg vs 45±6 mm Hg; p=0.018), pulse BP (53±16 mm Hg vs 50±14 mm Hg; p=0.038), the value of the double product (107.4±23.5 conventional units vs 101.4±22.5 conventional units; p=0.004), augmentation index (AI) [22.1 (13.5, 31,3)% vs 15.9 (8.8; 24.9)%; p=0.005], the increase index at a pulse frequency of 75 per minute [23.2 (16.0; 30.5)% vs 15.9 (9.2; 23.5)%; p=0.005] and systole duration in percent (35.50±5.60 vs 34.24±4.53; p=0.007) were significantly higher than in the group of men. In addition, men showed a statistically significant increase in the average value of the alternative stiffness index (9.76±2.61 vs 8.17±2.03; p=0.005) and the dependence of the AI on age (p<0.05). At the same time, a statistically more significant correlation of central and peripheral hemodynamic parameters with the presence of elevated AI (p<0.05) was recorded in the group of women.

Conclusion. In older women, an increase in systolic, central, average, pulse BP is associated with an increase in AI and an increase in the magnitude of the double product. In the group of elderly men, the increase in the alternative vascular stiffness index contributes to an increase in the duration of the pulse wave. Statistically more pronounced correlation relationships between the value of the AI and clinical and hemodynamic parameters were recorded in elderly women.

Systemic Hypertension. 2021;18(1):31-36
Combined antihypertensive and psychocorrective therapy in patients with arterial hypertension and anxiety-depressive disorders: are there any advantages?
Skibitsky V.V., Ginter J.E., Fendrikova A.V., Sirotenko D.V.

Relevance. Arterial hypertension (AH) and anxiety-depressive disorders (ADD) are comorbid pathologies that are common in clinical practice. At the same time, the possibility of including an antidepressant in antihypertensive therapy for optimal control of hypertension, as well as to ensure a vasoprotective effect, has not been studied enough.

Aim. To compare the effect of traditional antihypertensive therapy and therapy, including an antidepressant, on indicators of the daily profile of blood pressure (BP), stiffness of the vascular wall and central aortic pressure (CAP), the severity of anxiety and depression, as well as on cognitive function (CF) in patients AH and ADD.

Materials and methods. The study included 90 patients with AH and ADD, who were randomized into two groups: group 1 – patients who received a fixed combination of an angiotensin II receptor blocker and a diuretic, a b-blocker and an antidepressant; group 2 – persons who took only three-component antihypertensive therapy. Before and after 24 weeks, all patients underwent a general clinical examination, 24-hour BP monitoring – ABPM (BpLab Vasotens, “Petr Telegin”, Russia) with an assessment of the daily profile of BP, CAP and vascular stiffness. In addition, testing was carried out on the HADS, CES-D scales; CF were rated according to the Montreal scale.

Results. In the group of patients treated with an antidepressant, it was noted that the target BP level was achieved more quickly when lower doses of angiotensin II receptor blockers were prescribed. After 6 months of therapy in both groups, there was a comparable positive dynamics of the main indicators of ABPM. In group 1, a statistically more pronounced decrease in both peripheral and CAP at night was recorded. In both groups of patients, a decrease in the augmentation index was noted; however, a statistically significant improvement in the parameters of the speed of propagation of the pulse wave in the aorta and the time of propagation of the reflected wave was recorded only in persons receiving antidepressant. In group 1, there was a regression of ADD, as well as a significant improvement in CF.

Conclusions. The use of sertraline as part of a combination antihypertensive therapy in patients with AH and ADD contributed to a more rapid achievement of target BP values, a significant improvement in ABPM (especially at night), vascular wall stiffness and CAP. It is also important that the appointment of sertraline was accompanied by a regression of anxiety-depressive symptoms, an improvement in CF.

Systemic Hypertension. 2021;18(1):37-42
Specificity of the effect of double fractures of the rhythmogram on the daily variability of the sinus rhythm in patients with pulmonary and arterial hypertension
Sobolev A.V., Ryabykina G.V., Kozhemyakina E.S.

Introduction. In contrast to coronary heart disease (CHD), heart failure and a number of other diseases, in arterial and pulmonary hypertension, the deterioration of the functional state of the patient is often not accompanied by a decrease in the parameters of his sinus rhythm variability (SRV) for long periods of time. Moreover, an increase in age and an increase in blood pressure in patients with hypertension may lead not to a decrease, but to an increase in the parameters of daily SRV. It is noted that with hypertension on the sinus rhythm, the number of so-called double fractures of the rhythmogram (DFR) – sequences of RR intervals «short-long-short-long» – becomes greater, which can greatly affect the daily SRV.

Aim. To study the specifics of the effect of DFR on daily SRV in arterial and pulmonary hypertension.

Materials and methods. 300 Holter ECG records were analyzed, including 67 records of healthy persons, 20 records of CHD patients with CAG-confirmed vascular damage, 126 records of patients with arterial hypertension and 87 records of patients with idiopathic pulmonary hypertension. In the analysis of daily SRV, a modification of the SRV analysis method developed at the National Medical Research Center of Cardiology, taking into account the presence of DFR, was used.

Results. It is shown that DFR reflects the processes of regulation of the sinus rhythm, which are affected differently by CHD and hypertension. In CHD, the frequency of DFR and its effect on the daily SRV significantly decreases (compared to the norm). With hypertension, the frequency of the appearance of DFR increases; there is a clear trend towards a decrease in SRV in comparison with the norm in the areas without DFR; in areas with DFR, this trend is less pronounced or absent, and at ages over 50 years, SRV increases.

Conclusion. When studying the daily SRV of patients with arterial and idiopathic pulmonary hypertension, it is necessary to take into account the effect of DFR on the increase in SRV.

Systemic Hypertension. 2021;18(1):43-49
Aspects of efficacy, safety and adherence to antihypertensive therapy with single pill combinations of valsartan, amlodipine and hydrochlorothiazide (Vamloset® and Co-Vamloset) in patients with 2 and 3 grade of arterial hypertension in the Russian clinical study VICTORY II
Chazova I.E., Martynyuk T.V., Rodnenkov O.V., Gorieva S.B., Rogoza A.N., Arkhipov M.V., Grinshtein Y.I., Ostroumova O.D., Galyavich A.S., Rotar’ O.P., Khaisheva L.A., Kameneva T.R.

Aim. To assess the efficacy and safety of Vamloset® (amlodipine/valsartan 5/80, 5/160, 10/160 mg) and Co-Vamloset (amlodipine/valsartan/hydrochlorothiazide 10/160/12.5, 10/160/25 mg) in achieving the target levels of blood pressure (BP) in patients with stage 2–3 arterial hypertension (AH). The article discusses indicators affecting adherence to antihypertensive therapy (AHT).

Material and methods. The VICTORY II Russian study in 8 clinical centers of the Russian Federation included 103 patients over 18 years of age with stage 2–3 essential AH (who haven’t been previously treated and have office systolic BP≥160 mm Hg and/or diastolic BP≥100 mm Hg or who haven’t reached the target office blood pressure with mono- or double AHT). The Full Analysis Set (FAS) for efficacy analysis included 99 patients, a FAS population with the restoration of data missed using Last Observation Carried Forward. The SF-36 questionnaire for assessing the quality of life, the effect on erectile function in men, the convenience of current therapy from the point of view of patients were analyzed after 16 weeks of treatment. The Per Protocol (PP) population included 80 patients completing the study without major protocol deviations to assess the primary parameters of efficacy. All patients with stage 2 hypertension were prescribed Vamloset® (amlodipine/valsartan 5/80 mg), with stage 3 hypertension – amlodipine/valsartan 5/160 mg. Dose titration of Vamloset® and Co-Vamloset (LLC «Krka-RUS») was carried out every 4 weeks according to the AHT schemes.

Results. The study’s active phase included 100 patients aged 59.5±10.9 years (women 59%) with AH duration of 83.4±8.4 months; 83% of patients received AHT prior inclusion in the study. In the PP population, 16 week- AHT with Vamloset® or Co-Vamloset allowed reaching the target BP in 90.0% of patients (95% confidence interval [CI] 81.2–95.6). Overall clinical efficacy was achieved in 98.8% of patients (95% CI 93.2–100.0). All treatment regimens were characterized by high patient compliance. In the total group, 50% of patients rated their AHT as more convenient than they had previously used; of them, in the stage 2 AH group – 47.8%, in the stage 3 AH group – 53.3%. Metabolic neutrality with regard to at least one indicator was observed in 100% of patients, with regard to 6 indicators – in 43.9% [33.9; 54.9]. For all 98 patients included in the analysis, changes in all SF-36 scales, except for physical functioning (p=0.339), were statistically significant (p<0.05). The effect of AHT on erectile function was rated as positive in 51.3% of men. Good tolerance data are consistent with the established drug safety profile.

Conclusion. In the VICTORY II study, high antihypertensive efficacy and an improvement in a set of indicators of optimal adherence to AHT by Vamloset® and Co-Vamloset within 16 weeks were proved in patients with stage 2–3 AH. Patient’s high rating for quality improvement in the quality of life, safety of therapy and ease of use ensured optimal compliance of Vamloset® and Co-Vamloset therapy throughout the study.

Systemic Hypertension. 2021;18(1):50-62

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