EFFICACY OF "CARDIOVITIN" IN THE COMPLEX TREATMENT OF PATIENTS WITH ARTERIAL HYPERTENSION
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Authors:
Elena Vladimirovna Katamanova - Doctor of Medical Sciences, doctor of allergology-immunologist FGBNU "East-Siberian Institute of Medical-Ecological Research"
Beigel Elena Alexandrovna - Candidate of Medical Sciences, allergologist-immunologist of the Federal State Budgetary Institution "East Siberian Institute for Medical and Ecological Research".
Annotation.
Arterial hypertension is one of the most common chronic nonspecific human diseases, which according to WHO accounts for 30% of all deaths. The main indicator of the effectiveness of therapy for arterial hypertension is achieving and maintaining control of the disease (achieving the target level of blood pressure). According to statistics in Russia, at least 40% of the population suffer from arterial hypertension, of which only 48% of women and 21% of men take treatment, and the target value of blood pressure reaches only 17.5% of women and 5.7% of men. Therefore, it is urgent to search for new medications that contribute to the restoration of endothelium and normalisation of microcirculation processes. Vascular endothelium plays a key role in the control of vascular tone and blood pressure on the vascular wall, metabolic needs of the tissue area. Cardiovitin, which includes bioflavonoids derived from Siberian larch wood and vitamin C, both of which have a stimulating effect on tissue blood flow, stabilise the barrier function of microvessels, reduce the permeability of capillary walls, and thus contribute to the reduction of blood pressure, can be referred to such remedies. The aim of the study was to investigate the effectiveness of cardiovitin in the complex treatment of arterial hypertension. Methods. A total of 20 patients (17 women, mean age 64.5±8.7 years, mean weight 77.8±11.4 kg and 3 men, mean age 54.6±12.4 years, mean body weight 114±40.2 kg) participated in the study. The examination programme included questionnaire, history taking, study of risk factors of AH, ECG, general blood analysis, urine, biochemical blood tests, examination by a therapist, cardiologist before and after treatment. Statistical processing of the results was performed using the software package "Statistica 6.0" (StatSof, USA, 1999). Differences at p<0.05 were considered statistically significant. Results. After 2 months of cardiovitin administration in addition to antihypertensive therapy there was statistically significant decrease of systolic BP in the examined persons (third visit) - 120.0 (120.0-130.0) at p<0.05, decrease of total cholesterol levels - 5.6 (4.6-6.4), LDL in blood - 3.2 (3.1-3.5) at p<0.05. No adverse events were recorded during the whole treatment period. Conclusion. The results of the study indicate the effectiveness of inclusion of cardiovitin into the scheme of basal antihypertensive therapy as a source of bioflavonoids involved in the processes of vascular wall stabilisation in AH.
Key words: arterial hypertension, lipidogram, cardiovitin, treatment efficacy.
Rationale. Arterial hypertension is one of the most widespread chronic non-specific human diseases, which generally accounts, according to WHO, for 30% of all deaths. Available statistics for Russia indicate that hypertension affects at least 40% of the Russian population: 58 per cent of women and 37 per cent of men, only 48 per cent of women and 21 per cent of men are systematically treated.
48% of women and 21% of men, but the target value of blood pressure is reached in 17.5% of women and 5.7% of men [1,2].
At present, the prevalence of arterial hypertension (AH) is epidemic in nature, and the problem of AH can be regarded as a large-scale non-infectious pandemic. The need to fight AH is due to the fact that it is one of the leading causes of disability and mortality. Prolonged increase in blood pressure leads to target organ damage and development of cardiovascular complications (heart failure, myocardial infarction, brain stroke and renal failure). The main indicator of the effectiveness of therapy of arterial hypertension is the achievement and maintenance of control of the disease (achieving the target level of blood pressure). High prevalence and social and economic impact of arterial hypertension on the life of society and each patient determine the need for prevention and timely detection of risk factors, adequacy of therapy, prevention of complications [3,4].
Biologically active supplement "Cardiovitin" is a natural antioxidant, contains in one capsule Dihydroquercetin 40 mg, Acerolla extract 25% 120 mg with vitamin C content of at least 30 mg, auxiliary substances. Dihydroquercetin is known to have antioxidant, capillaroprotective, haemorheological, antiplatelet and anti-inflammatory activity [5, 6, 7, ]. Dihydroquercetin in addition to therapy with cardiovascular drugs have a positive effect on the clinical course of AH. There was noted a decrease in blood pressure, improvement of blood microcirculation, reduction of congestion, improvement of patients' well-being (decrease in the frequency of headache, noise in the head, dizziness, impaired coordination of movement) [5].
Эндотелий играет ключевую роль в контроле сосудистого тонуса, обеспечивая регуляцию просвета сосудов в зависимости от скорости кровотока и кровяного давления на сосудистую стенку, метаболических потребностей участка ткани. Поэтому крайне актуальным является поиск новых медикаментозных средств, способствующих восстановлению эндотелия и нормализации микроциркуляции. К числу таких средств можно отнести кардиовитин, в состав которого входят биофлавоноиды, получаемые из древесины сибирской лиственницы и витамин С, оба эти компонента оказывают стимулирующее действие на тканевый кровоток, стабилизирующий барьерную функцию микрососудов, снижающий проницаемость стенок капилляров и тем самым способствующий снижению застойных явлений в микроциркуляторном русле и восстановлению эндотелия [5].
Таким образом, целью настоящего исследования явилось изучение эффективности кардиовитина в комплексном лечении артериальной гипертонии.
Methods.
A total of 17 women, mean age 64.5±8.7 years, mean weight 77.8±11.4 kg and 3 men, mean age 54.6±12.4 years, mean body weight 114±402 kg participated in the study. According to WHO classification, BP-160/95-180/104 mmHg, G1AH-140/90-159/94 mmHg were accepted as criteria for stage 1 hypertension. The average history of arterial hypertension was 10.0 (5.0-10.0) years.
The examination programme included questionnaire, history taking, study of AH risk factors, ECG, general blood analysis, urine, blood biochemical examination with determination of fibrinogen levels, AST, ALT, GGT, creatinine, CRP, lipidogram parameters, examination by a general practitioner, cardiologist before and after treatment. All participants continued taking the usual standard hypotensive therapy prescribed by a doctor of a polyclinic or other medical organisation.
The questionnaire developed by the Working Group on Cardiovascular Therapy of the European Society of Cardiology (ESC) and the Russian Society of Cardiology (RSC) with the support of Servier (https://servier.ru) was used.
Systolic and diastolic blood pressure was measured on the arm using an automatic blood pressure meter (HD-505, Jawon Medical Co, Kyungsan City, Korea). Blood pressure was measured in the arm with the higher BP, in a sitting position, three times with an interval of 5 minutes. The mean of these three measurements was used in data analysis. Participants did not drink caffeinated beverages such as coffee or tea, and did not exercise, smoke or eat 2 hours before the blood pressure test.
Inclusion criteria included: having signed informed consent age 19 to 65 years; having stage I, II hypertension. Exclusion criteria were: presence of secondary hypertension; decompensation of cerebrovascular disease, cardiovascular disease, malignancy, kidney disease, liver disease, thyroid disease, active tuberculosis or other infectious diseases; diabetic patients taking insulin medication; drug or alcohol dependence; taking systemic steroid therapy or immunosuppressive therapy; taking medications that affect blood pressure, such as dep.
ECG recording was performed in the supine position with quiet breathing using standard technique on a 12-channel MAC - 1200 electrocardiograph (General Electric, USA, 2001). The procedure was carried out with maximum comfort for the patient: absence of distracting and irritating factors (noise, conversations, strangers), calm environment, normal lighting and temperature in a special medical room. Electrocardiogram was taken from three leads from the chest and limbs, with each lead recording duration equal to three minutes.
In addition, such vital functions were assessed: body temperature (measured with a thermometer in the axillary (axillary) region, 36.0-36.9°C was taken as normal values); heart rate (pulse) by palpation of the radial artery on the lateral side of the wrist, heart rate at rest - 60-80 beats per minute was considered normal parameters; respiratory movement frequency (the number of respiratory movements is calculated by the number of movements of the chest and anterior abdominal wall, 16-20 respiratory movements per minute were considered normal values).
All patients with AH included in the study were treated with Cardiovitin for 8 weeks, which is the average time between two medical consultations. Cardiovitin was prescribed 1 capsule 2 times a day, for 2 months in the complex of baseline therapy of AH. Patients took hypotensive drugs according to the unified schemes of hypotensive therapy, which are included in the first-line drugs, with dosages specified in clinical recommendations. Patients took the following groups of drugs: ACE inhibitors, beta blockers, sartans, drugs containing acetylsalicylic acid (cardiomagnil), statins, sugar-lowering drugs of biguanides and sulfonylurea derivatives group.
Statistical processing of the results was performed using the software package "Statistica 6.0" (StatSof, USA, 1999). Differences at p<0.05 were considered statistically significant. The results are presented in tables, figures and text as median (Med), upper (Q25) and lower (Q75) quartiles. Intergroup
Quantitative indicators were compared between groups using the nonparametric Wilcoxon method.
In accordance with the requirements of the Biomedical Ethics Committee the examination was conducted with written informed consent of the patients, the work did not infringe the rights and did not endanger the welfare of the research subjects in accordance with the requirements of biomedical ethics approved by the Helsinki Declaration of the World Medical Association (2000). LEC conclusion No31 dated 15.02.2019.
Results.
According to the questionnaire data, it was found that in addition to the baseline therapy for AH, 30% of the examined group took statins. 35% of the group in addition to AH suffered from diabetes mellitus type 2, took tablet forms of sugar-reducing drugs. 10% were smokers. 60% of the group responded to the question about alcohol intake that they rarely drink alcohol, 40% - 1 or 3 times a month. There was no skipping of medication in any of the patients.
In the group as a whole, elevation of baseline systolic BP (BP above 140 mmHg) at three times measurement was registered in 4 examined patients (20%), diastolic BP (above 90 mmHg) - in 1 person (5%). Pulse rate varied from 56 to 87 pulse contractions per minute, the average values for the group were within the normative values, as was the heart rate index. After 2 months of cardiovitin administration there was a statistically significant decrease in systolic BP .
Electrocardiographic picture was characterised by the following changes: sinus bradycardia was registered in 3 patients (15%), horizontal deviation of the electrical axis of the heart was observed in 15%, vertical and left deviation in 5%, metabolic disorders were registered in 10% of subjects. QRS complex prolongation (more than 100) was observed in 20%, PQ (more than 200) in 5%, P (more than 100) in 55%, RR/PP ratio exceeding 1.5 - in 10% of patients. Statistically significant changes in ECG after the course of cardiovitin therapy were not observed.
Changes in ECG parameters on cardiovitin therapy, Me(Q25-Q75)
The picture of general blood analysis was characterised by normal red blood counts (erythrocytes, haemoglobin), normal leukocyte count, eosinophilia (more than 5%) in one woman and increased COE (from 20-27 ml/min) in three examined women. Against the background of cardiovitin application, a statistically significant decrease in eosinophils from 3.0(2.0-4.0)% to 2.0(1.0-3.0)% (p=0.015) and COE level from 10.0(5.5-16.0) mm/h to 8.0(2.5-10.0) mm/h (p=0.01) in the group was observed. Indicators of general urinalysis before treatment and after therapy were within normal limits, statistically significantly did not change.
As a result of the first visit, before cardiovitin administration the following biochemical indices were established: blood creatinine was not exceeded in any examined person. Club filtration rate below 60 ml/min was registered in 29.4% of women (5 people), in men SCF before the study was within normal values. ALT levels in two women (11.7%) were above 30 U/L. ALT level in men and AST level in men and women in the group were within normal values. Increase of GGT (above 61 U/l) was registered in 5 women (29.4%), in men - there was no increase of this indicator. Fibrinogen level in the group of examination in all patients with AH was normal. Blood lipidogram parameters were characterised by increased total cholesterol (above 5.2 mmol/l) in 14 out of 17 women (82.3%) and 3 out of 3 men (100%); normal HDL, decreased LDL in 4 women (23.5%), increased LDL in 1 man (33.3%), and increased TG in 2 out of 17 (11.7%) women. The atherogenicity index was elevated in 9 women and 1 man. After 2 months of cardiovitin supplementation, a statistically significant decrease in the levels of total cholesterol and LDL in the blood was observed.
Discussion.
More than 800 scientific publications on dihydroquercetin (Taxifolin) have been published in the Medline US National Library of Medicine National Institutes of Health (PubMed) international database. In the world with this substance more than 100 researches of different levels have been carried out, analytical reviews are available, patents have been registered and dissertations have been successfully defended. Dihydroquercetin (taxifolin) has been shown to have antioxidant, capillaroprotective, haemorheological, antiplatelet and anti-inflammatory activities [9].
In our post-marketing clinical study involving 20 people with AH who took cardiovitin 1 capsule 2 times a day in addition to antihypertensive therapy for 2 months, the following results were obtained. After 2 months of Cardiovitin administration there was a statistically significant decrease in systolic BP, reduction of total cholesterol and LDL in blood, which is in full agreement with the literature data [9,10].
Speaking about the safety of Cardiovitin use, it should be noted that no adverse events were registered during the whole period of treatment. Monitoring of BP, HR and duration of the corrected QT interval on ECG at the beginning and after the end of therapy did not reveal any deviations from the initial parameters.
Conclusion.
Cardiovitin administration against the background of basal hypotensive therapy contributes to statistically significant reduction of systolic blood pressure. Cardiovitin use in complex therapy of arterial hypertension promotes normalisation of lipid metabolism, with reduction of total cholesterol and LDL.
In order to improve the effectiveness of rehabilitation of patients with arterial hypertension is recommended to prescribe cardiovitin in a dose of 1 capsule in the morning and evening with meals for 2 months.
To consolidate the achieved result of rehabilitation, it is recommended to repeat courses of cardiovitin 3 times a year for 2 months.
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