Rational Pharmacotherapy in Cardiology

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Vol 13, No 3 (2017)
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290-300 260

Aim. To study the relationship of individual cardiovascular risk factors with arterial stiffness and subclinical atherosclerosis in young men.

Material and methods. The study is part of a 32-year prospective cohort monitoring of males, beginning with childhood (11-12 years). The study-included 303 (30.1%) representatives of the initial population sample aged 41-44 who underwent an outpatient examination at the State Research-Center for Preventive Medicine in 2015-2016. The examination included a survey by a standard questionnaire, measurement of anthropometric parameters, blood pressure (BP), pulse counting. Biochemical assays were carried out according to standard laboratory procedures. Applanation tonometry-was used to measure stiffness of the arterial wall. Intima-media thickness (IMT) and subclinical atherosclerosis signs were determined in both left and right carotid arteries by ultrasound scanning.

Results. Arterial stiffness and central pressure were significantly higher in the group with hypertension (HT). Risk of HT development depended on HT-presence in mother and did not depend on HT in father. HT was associated with obesity (79.4% vs 44.3%; p<0.001), especially of abdominal type and elevated triglycerides (1.3±0.9 vs 1.8±1.1 mmol/l; p<0.05), this indirectly reflected nutritional disorder and development of metabolic syndrome. The analysis of arterial stiffness parameters showed positive correlation with mean systolic (r=0.256) and diastolic (r=0.228) BP in the brachial artery and also with heart rate (r=0.133). A statistically significant positive correlation of central pressure in the aorta and pulse BP with indices of arterial-stiffness was noted. When comparing arterial stiffness and duplex scans, a correlation of mean IMT with the augmentation index (r=0.131) and augmentation BP (r=0.125) was obtained, but no correlation between IMT and pulse wave velocity was found. Correlation of vascular rigidity with total cholesterol level was also noted (r=0.121).

Conclusion. The arterial stiffness was closely related to HT and already developed in early stages, in a fairly young age. Arterial stiffness in men was not associated with dyslipidemia and diabetes presence. Interrelation of arterial stiffness and degree of early atherosclerotic vascular lesions was ambiguous.

301-308 204

Aim. To assess the safety of the application of high-dose atorvastatin and its effect on metabolic parameters, such as the total level of nitric oxide and homocysteine in the blood plasma in patients with ischemic heart disease during a coronary artery bypass surgery (CABG).

Material and methods. The study included 42 patients with stable effort angina II-IV functional class. A special criterion for selection was the taking atorvastatin at a dose of 20 mg/day for at least 30 days before patient was directed to surgical revascularization of the myocardium. Immediately before the intervention, the dose of atorvastatin was increased to the maximum allowed with subsequent taking of 40 mg/day. Complications after CABG, indicators of lipid metabolism and biochemical safety of statin use were analyzed. The duration of observation of results of the acute atorvastatin recapture therapy was 3 weeks during hospital period. We used modern enzymatic method for nitrogen oxides determination with the application of nitrate reductase. Determination of total homocysteine was performed by high performance liquid chromatography.

Results. It was found that atorvastatin 80 mg for 12 hours and 2 hours before CABG in patients previously treated with atorvastatin 20 mg/day is well tolerated and leads to decrease in total levels of nitric oxide by 1.6 (0.18-10.8 ) μmol/l and homocysteine by 0.9 (0.17-2.69) μmol/l (p< 0.05 for both)

Conclusion. It is assumed that the metabolic effects of high-dose therapy with atorvastatin may have a positive influence on the immediate postoperative period.

309-316 239

Aim. To study the antihypertensive and hypolipidemic effect of therapy based on perindopril, including its combinations, and rosuvastatin in real clinical practice.

Material and methods. Analysis of the medical records of patients observed for hypertension (HT) and treated with perindopril, amlodipine and rosuvastatin in the multicenter nonintervention SYNERGY study was performed. Patients with established diagnosis of HT and registered elevated cholesterol blood level were included into the study. The drugs were prescribed by doctors in different doses. Data on the disease history, physical status, blood pressure (BP) measurements, and lipid blood levels were taken from the patient's medical records.

Results. 1736 patients (53% of women) with the mean age of 58.7 years were included into the analysis. 1322 patients (76.2%) previously received antihypertensive therapy, and 807 (46.5%) – lipid-lowering therapy. Reduction in systolic and diastolic BP, low density cholesterol blood level was found at the end of the study in all study groups s (p<0.05). This demonstrated an adequate antihypertensive and lipid-lowering effect of the applied treatment regimens. The average decrease in systolic BP was from 20.5 to 41.4 mm Hg, and this in diastolic BP – from 8.8 to 22.2 mm Hg. The maximum reduction in systolic BP was found in the group of perindopril 8 mg+amlodipine 10 mg+rosuvastatin 5 mg (41.4 mm Hg), and this in diastolic BP – in the group of perindopril 8 mg+rosuvastatin 10 mg. The mean decrease in low density cholesterol blood level was from 0.74 mmol/L in the group of perindopril 4 mg+amlodipine 10 mg+rosuvastatin 5 mg up to 1.75 mmol/l in the group of perindopril 8 mg+amlodipine 10 mg+rosuvastatin 20 mg

Conclusion: Therapy with perindopril, amlodipine and rosuvastatin resulted in significant reduction in BP and low-density cholesterol blood level in all the treatment groups. The study of the efficacy of combined therapy in patients with HT and dyslipidemia in real clinical practice makes it possible to evaluate the potential contribution of pharmacotherapy in reducing the risk of cardiovascular complications.

317-322 186

Aim. To study secondary prevention of cardiovascular diseases among patients of different age groups with a history of myocardial infarction by the example of outpatient cardiology institution.

Material and methods. Retrospective pharmacoepidemiological study was conducted by analyzing the medical records of 825 patients with a history of myocardial infarction, who visited the outpatient cardiology institution for the first time in 2011. Patients were divided into two groups according to their age: younger than 60 years (n=308), and 60 years and older (n=517).

Results. The population of elderly patients was more severe: significantly more often patients had disability and comorbidities. The prevalence of the main modifiable risk factors could not be assessed fully due to the lack of information in patients’ medical records. Elderly patients were significantly less likely to receive β-blockers (80.3%) and statins (63.8%). No significant differences were found in daily doses of the main prescribed preventive drugs between two groups.

Conclusion. Secondary prevention of cardiovascular diseases among patients of different age groups could not be considered proper, as there is low level of attention to the modifiable risk factors and recommendation on their correction. A tendency to under-prescription of angiotensin converting enzyme inhibitors was revealed, as well as significantly lower number of recommendations for taking statins and β-adrenoblockers in the group of elderly patients.

323-329 207

On Behalf of the Working Groups of the Registries PROFILE and REСVASA. 

Working Group of the PROFILE Registry: Akimova A.V., Voronina V.P., Dmitrieva N.A., Zakharova A.V., Zakharova N.A., Zagrebelnyy A.V., Kutishenko N.P., Lerman O.V., Lukina Yu.V., Tolpygina S.N., Martsevich S.Y.

Working Group of the RECVASA Registry: Vorobyev A.N., Zagrebelnyy A.V., Kozminsky A.N., Lukina Yu.V., Loukianov M.M., Moseichuk K.A., Nikulina N.N., Pereverzeva K.G., Pravkina E.A., Boytsov S.A., Martsevich S.Yu., Yakushin S.S.

Aim. To assess the frequency of prescription of different combinations of the main groups of antihypertensive drugs (AHD) and their fixed combinations to patients with arterial hypertension by physicians according to two outpatient registries.

Material and methods. Hypertension was diagnosed in 3648 (98.9%) patients of the RECVASA registry and in 1230 patients of the PROFILE registry (80.3%). Data on doctor’s prescriptions reflected in the outpatient charts of patients of the both registries were analyzed. The following information of the prescribed antihypertensive therapy was studied in details: AHD, including fixed and free combinations, original and generic AHD. Data on the achievement/non-achievement of target blood pressure (BP) level in patients with hypertension were also analyzed.

Results. Women were predominated among hypertensive patients of the RECVASA registry, (71.9%). The ratio of men and women was close to 1:1 in the PROFILE registry. Patients of the registry RECVASA were older: the average age was 66.2±12.8 years compared to 63.7±11.4 years in patients of the PROFILE registry, respectively. The majority of patients in the RECVASA registry (61.4%) had hypertension of the 3rd degree, patients of the PROFILE registry revealed mostly hypertension of the 2 degree (53.3%). Fixed combinations were prescribed to 14% of patients in the registry of RECVASA and to 16% of patients in the PROFILE registry. Doctors of the PROFILE registry often prescribed original AHD; 75% of patients from RECVASA registry received generics. The most popular combinations in both registries were combinations of angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers with thiazide/thiazide-like diuretics. The target level of BP was more often achieved in the patients of the PROFILE registry: 37.6% vs 26.1% in the RECVASA registry.

Conclusion. The results of the analysis of the presented registries demonstrate the low frequency of prescribing fixed combinations in real clinical practice, the inertness of physicians in achieving the target BP levels and the low efficiency of antihypertensive therapy.

330-338 230

Aim. To study the associations of ACE, ADRA2B, ADRB1, MTHFR and e-NOS3 candidate genes of arterial hypertension with its risk factors among the indigenous and non-indigenous population of Mountain Shoriya.

Material and methods. Clinical epidemiological community-based study was conducted in hard-to-reach regions of Mountain Shoriya (villages Orton, Ust’-Kabyrza, Sheregesh in Kemerovo Region). 1178 inhabitants of the mentioned villages were examined by the continuous method, selection consisted of adult population (18 years old and above), 565 people were genotyped. All patients underwent clinical, laboratory and instrumental examination. Polymorphisms of genes ACE (I/D, rs 4340), ADRB1 (s.145A> G, Ser49Gly, rs1801252) ADRA2B (I/D, rs 28365031), MTHFR (c.677S>T, Ala222Val, rs1801133) and e-NOS3 (VNTR, 4a/4b) were tested by polymerase chain reaction.

Results. Maximum number of associations with risk factors was revealed in indigenous population for genotype D/D ACE gene, in non-indigenous representatives – for genotype D/D ADRA2B gene. In indigenous carriers of genotype D/D ACE gene, the odds ratio of hypercholesterolemia, hyper-betacholesterolemia, obesity and abdominal obesity were 11.20 (р=0.018); 4.65 (р=0.001); 2.31 (р=0.031) and 1.83 (р=0.059), respectively. In the cohort of non-indigenous ethnic group in those with genotype D/D gene ADRA2B the risk of hypercholesterolemia, hyperbetacholesterolemia, hypertriglyceridemia and carbohydrate metabolism disorders was higher in 5.11 (р=0.006), 5.41 (р=0.021), 2.73 (р=0.035) and 4.13 (р=0.005) times, respectively. In the indigenous group the genotype D/D of ACE gene was associated with obesity, hypercholesterolemia, hyperbetacholesterolemia; the genotype D/D of ADRA2B gene – with hypertriglyceridemia; the genotype 4а/4а of e-NOS3 gene – with abdominal obesity. In the group of non-indigenous ethnic group genotype D/D of АСЕ gene was associated with hypoalphacholesterolemia; genotype I/I of АСЕ gene – with carbohydrate metabolism disorders; genotype D/D of ADRA2B gene – with hypercholesterolemia, hyperbetacholesterolemia and hypertriglyceridemia, carbohydrate metabolism disorders; genotype Т/Т of MTHFR gene – with hypoalphacholesterolemia, genotype C/C of MTHFR gene – with abdominal obesity.

Conclusion. The determination of polymorphisms of candidate genes and the identification of associations with modifiable risk factors broadens the understanding of the genetic component of cardiovascular diseases and creates the prerequisites for the development of a more advanced and effective prevention program.


339-345 333

Primary angiosarcoma of the heart, constituting 33% of primary heart malignancies in adults, refers to rare diseases with a difficult diagnosis. The article describes the case of primary angiosarcoma of the right atrium, diagnosed posthumously in a patient of 45 years old. The disease debuted in a previously healthy woman 45 years, 2 months before her death. There were episodes of sudden decrease in blood pressure with pain in the chest and short-term loss of consciousness, as well as moderate manifestations of heart failure (hydrothorax, small ascites, hydropericardium, hepatomegaly, leg shunting). The patient died suddenly, a pathologic study revealed an angiosarcoma of the right atrium with invasive growth, accompanied by inferior vena cava stenosis. Angiosarcoma of the heart should be included in a differential diagnosis of patient with pericardial effusion of unspecified genesis, syndromes of vena cava obstruction, unexplained right ventricular failure, syncope with a fall in blood pressure, especially in middle-aged patients.


346-356 225

Aim. To study the pharmacological treatment of patients with acute stroke (AS) within the prospective outpatient registries.

Material and methods. In the pilot phase of the study, conducting on the base of one of the out-patient clinic in Ryazan city, 200 and 115 patients were included into the outpatient registry of patients with AS history of any remoteness (AS-AR registry), and outpatient registry of the first apply (AS-FA registry) to the out-patient clinic after stroke, respectively. The correspondence of the prescribed and actually taken drug therapy to clinical recommendations, its continuity, and the adherence of patients to treatment were assessed during the prospective observation.

Results. Most patients did not receive adequate therapy to reduce the risk of AS and other cardiovascular complications in the outpatient stage, especially in the period prior to the reference AS. Drugs with a proven beneficial effect on the prognosis in the post-stroke period were prescribed significantly (p and after 2 years – in the AS-FA registry, the frequency of the therapy was not significantly different from the frequency of prescribing at the stage of inclusion in the registers, with the exception of statins (they were taken 1.7 and 1.5 times less frequently). Prognostically significant prescriptions of the inclusion phase were performed in the long-term follow-up period in 49% and 70% of patients (on average 58%), respectively; however, the frequency of first-time therapy was 44% and 19% of the total number of prescriptions in this period, respectively. Adherence to treatment, according to the Morisky-Green questionnaire, was revealed in 17.7 and 51.7% of patients, respectively

Conclusion. The results of the pilot phase of the REGION study (AS-AR and AS-FA outpatient registries) showed that the quality of the prescribed drug therapy of patients in out-patient clinic is inadequate. A comparison of the data of AS-AR and AS-FA registries allows to make a preliminary conclusion that over the 5-year period separating the remoteness of AS development in these registries, the quality of patient treatment has significantly improved, although not enough. The proportion of previously performed prognostically significant prescriptions averaged only about 60% at the stage of the further prospective follow-up. In general, during the observation period, taking into account newly made prescriptions, the frequency of adequate drug therapy during the observation period decreased only for statins. Most patients were not sufficiently committed to pharmacological treatment according to the Morisky-Green questionnaire.


357-362 175

Aim. To investigate the presence of pulmonary hypertension (PH) in patients with viral liver cirrhosis (LC) and its impact on some indicators of portal hemodynamics, and echocardiographic parameters.

Material and methods. The study included 95 patients with viral LC. The median age was 41.7 [33.2;46] years, median disease duration – 3.9 [2.6;6.9]-years. Group 1 consisted of 72 patients without PH – systolic pulmonary arterial pressure (SPAP)<30 mm Hg., group 2 – 23 patients with SPAP3139 mm Hg., control group included 19 healthy subjects. Doppler echocardiography (DEchoCG) and tissue DEchoCG were performed, and diameter,-mean flow velocity in the portal and inferior vena cava were measured.

Results: PН was diagnosed in 24% patients with LC who had the enlargement diameter of portal, inferior vena cava veins, and reduced mean blood-flow velocity in the portal vein (p<0.001). According to the DEchoCG data, in patients with LC without PH, left ventricular remodeling occurs with an-increase in its mass and systolic volume; pulmonary artery dilatation and diastolic ventricular dysfunction are also revealed in comparison with the control-group (p<0.001). The revealed abnormalities especially increased in patients with PH, they also showed dilatation of the left atrium and decrease-in the contractility of ventricular myocardium (p <0.001). In patients with LC complicated by PH, a strong correlation was found between the diameter-of the portal vein and blood flow velocity in pulmonary artery (r=0.65, p<0.05), between the diameter of the inferior vena cava and right ventricle-rapid filling flow (r=0.93, p<0.05), between the diastolic function of the right ventricle (E/A) and the blood flow velocity in the portal vein (r=0.73;-p<0.05). The revealed correlations testify to high probability of development of collateral circulation – portal-pulmonary anastomoses.

Conclusion: Detected hemodynamic disorders in viral LC indicate an important role of PH in the development of cirrhotic cardiomyopathy.Keywords: heart, рulmonary аrtery, cirrhosis of the liver.


363-369 174

Aim. To assess influence of patients’ prehospital attendance at outpatient clinics on long-term outcomes of acute coronary syndrome (ACS).

Material and methods. Patients (n=397) hospitalized with ACS (01.11.2013-31.07.2015) were included. 19.4% of patients died in hospital (77/397).-According to their rate of attendance at outpatient clinics all survived patients (n=320) were divided into 3 groups: committed to visiting outpatient-clinics (n=139), partially committed (n=103) and not committed (n=78). Follow-up period was 14-35 months (88.44% follow-up rate). During-follow-up period 12.5% of patients died (40/320). All-cause mortality and recurrent cardiovascular diseases (nonfatal myocardial infarction and stroke,-unstable angina) were defined as the primary endpoint. Prognostic significance of separate factors and their combinations were assessed by their influence on the primary endpoint.

Results. Clinical severity of course of the disease was assessed regarding all factors that had influence on the primary endpoint. By their degree of influence on the primary endpoint each factor was given a certain score. According to the sum of all scores patients were divided into 2 groups: patients with less (n=205) and more (n=78) severe clinical course of the disease. Risk of development of primary endpoint was higher in patients with more severe clinical course of the disease (relative risk 3.997; 95% confidence interval 2.199-7.267; p <0.0001) regardless of patients’ attendance at outpatient-clinics (p>0.05).

Conclusion. Patients’ prehospital attendance at outpatient clinics did not affect long-term outcomes of acute coronary syndrome. Patients with more-severe clinical course of the disease were more likely to develop adverse outcomes during the follow-up regardless of their prehospital attendance at outpatient clinics.


370-377 283

Aim. To study the effect of sacubitril/valsartan compared with valsartan on natriuresis, diuresis, blood pressure (BP) and the level of biomarkers in hypertensive patients.

Material and methods. Hypertensive patients (n=16) received sacubitril/valsartan 400 mg QD or valsartan 320 mg QD for 7 days in a double-blind,-randomized, cross-over study. The change in 24-hour diuresis and natriuresis, fractional urinary sodium excretion, and BP level have been studied, as-well as soluble biomarkers: cyclic guanosine monophosphate (cGMP), plasma brain natriuretic peptide (BNP), mid-regional precursor of the atrial natriuretic-peptide (MR-proANP) and the N-terminal precursor of the brain natriuretic peptide (NT-proBNP).

Results. The trend toward higher levels of 24-hour natriuresis on Day 1 (21%, p=0.068) was found in the sacubitril/valsartan group compared to-valsartan one. Fractional sodium excretion was significantly higher in the sacubitril/valsartan group on Day 1 after 6 hours (50%, p=0.004) and subsequent-samples up to 12 hours; the maximum effect was achieved 2-4 hours after taking the medication (mean value 2.08, p=0.005). Sacubitril/valsartan-therapy compared with valsartan therapy was associated with a significant increase in 24-hour diuresis on Day 1 (41%, p<0.05), but not on Day 7-(15%, p=0.134). Sacubitril/valsartan therapy, in contrast to valsartan therapy demonstrated a significant increase in 24 h cGMP urinary excretion-on Day 1 (95%, p<0.001) and Day 7 (83%, p=0.001). Sacubitril/valsartan lowered BP more effectively than valsartan [on Day 7, 12 hours after-taking the drug, the differences were13.6 mm Hg (p=0.004) for systolic and6.7 mm Hg (p=0.03) for diastolic BP. The decrease in the level of-NT-proBNP and MR-proANP in plasma and the transient increase in the level of BNP were found in the sacubitril/valsartan group. Both sacubitril/valsartan and valsartan therapies were well tolerated and safe.

Conclusion. Sacubitril/valsartan therapy in hypertensive patients compared with valsartan therapy was associated with transient increase in natriuresis and diuresis, more pronounced decrease in BP and changes in biomarker levels reflecting persistent inhibition of neprilysin and decrease in myocardial wall tension.


378-382 143

Aim. To study structural changes in the myocardium of Wistar rats after a single administration of epinephrine.

Material and methods. Structural changes in male Wistar rat’s left (LV) and right (RV) ventricle myocardium after a single injection of epinephrine were studied.

Results. The density of extracellular spaces in bothLV and RV myocardium increases first after single epinephrine injection (after 2 hours), and then-decreases below reference values in the next control points. It remains so even after 1 month after a single injection of epinephrine in both theLV (3.95±0.64-vs 6.83±0.30 vol% in the control group; p<0.05) and RV (4.71±0.55 vs 6.09±0.33 vol% in the control group; p<0.05). The density of collagen-fibers in both ventricles increases in all the control points, and more significantly in the RV than in theLV after 2 and 24 hours. After 2 hours the density-of collagen fibers in the RV was 25.8±1.39 vs 19.85±1.50 vol% in theLV (p<0.05), and after 24 hours it is 1.5 times higher – 30.47±1.98 vs-18.47±1.27 vol%, respectively, (p<0.05). The cardiomyocytes density in both ventricles decreases considerably without reaching control values even-in 1 month after a single injection of epinephrine.

Conclusion. Severe structural changes develop after single administration of epinephrine in both ventricles rat’s myocardium within 2 hours and persist during the first day. At that structural remodeling of theLV and RV ventricles is asynchronous. Complete regression of morphological changes in the myocardium bothLV and RV does not occur even after 1 month after a single injection of epinephrine. The high values of collagen fibers density, that are observed in both ventricles in acute adrenergic stress model, make it possible to assume that single administration of epinephrine triggers myocardial fibrogenesis mechanisms, which are continuing despite the cessation of drug exposure.


383-390 303

An increase in the activity of the renin-angiotensin-aldosterone system is one of the most important mechanisms for the realization of the cardiovascular continuum. The role that angiotensin receptor blockers play in achieving target figures of blood pressure and reducing cardiovascular risk is discussed. The importance of pleiotropic properties of angiotensin receptor blockers (in particular, activation of peroxisome proliferator-activated receptors gamma – PPAR-γ) in the management of patients with insulin resistance, obesity, dyslipidemia is also covered. The evidence base for the use of telmisartan as a drug with pleiotropic effect in patients with arterial hypertension and associated diseases (diabetes mellitus, obesity, renal dysfunction) is discussed. 

391-397 179

The choice of antihypertensive drugs for the treatment of hypertensive patients is discussed. Modern recommendations on the use of antihyperten-sive drugs in various clinical situations (lesion of target organs and the presence of concomitant conditions) are presented. Characteristics of patients with hypertension and obesity in the postmenopausal period are presented with using authors own data. The expediency of using the last generation of calcium channel blockers in this clinical situation with an emphasis on lercanidipine is justified.

398-402 409

Review on a problem of the development of atrial fibrillation in patients with thyrotoxicosis is presented. Thyrotoxicosis is one of the most frequent endocrine diseases, conceding only to a diabetes mellitus. The most frequent reasons of hyperthyroidism are Graves’ disease and functional thyroid autonomy. The authors give an analysis of data on the cardiac effects of thyrotoxicosis, features of heart remodeling under the influence of thyroid hyperfunction, prevalence of atrial fibrillation in thyrotoxicosis, depending on age, as well as the possibility of restoring sinus rhythm in the combination of these diseases. Particular attention is paid to the effect on the heart of subclinical thyrotoxicosis, which is defined as a dysfunction of the thyroid gland, characterized by low serum concentration of thyrotropin, normal values of free thyroxine and free triiodothyronine. Subclinical hyperthyroidism is also capable of causing heart remodeling and diastolic dysfunction.

Prevalence of thyrotoxicosis in elderly people is higher in areas of iodine deficiency; it is relevant for our country due to the large territory of iodine deficiency. In elderly patients, the cardiac effects of thyrotoxicosis prevail in the clinical picture, that makes it difficult to diagnose endocrine disorders, and correction of thyrotoxicosis is critically important for the successful control of the heart rhythm. The article also discusses the problem of thyrotoxic cardiomyopathy, caused by the toxic effect of excess thyroid hormones: features of this heart disorder, factors affecting its formation, clinical significance and contribution to the development of rhythm disturbances. The greatest significance is the development of atrial fibrillation as a result of thyrotox-icosis in older patients who already have various cardiovascular diseases.

Atrial fibrillation is the most frequent heart rhythm disorder in thyrotoxicosis. The main cause of arrhythmia in hyperthyroidism is the simultaneous existence of frequent focal impulses and circular motions of the excitation wave – the mechanism re-entry. Successful treatment of atrial fibrillation in patients with thyrotoxicosis is possible only when euthyroidism is achieved. In most cases, after the elimination of thyrotoxicosis, a spontaneous restoration of the sinus rhythm is observed. The chances of sinus rhythm restoration are lower in elderly patients with concomitant organic diseases of the myocardium or long-term atrial fibrillation. Moreover, even radically cured thyrotoxicosis leads to deterioration in the life prognosis.

403-408 688

Arrhythmias are one of the most complex, insufficiently studied, and therefore one of the most urgent problems of modern cardiology. A wide spectrum of clinical manifestations of cardiac rhythm disorders (CRDs), their detection both in various diseases and in healthy people, necessitate the study of their prevalence in populations. In the majority of conducted epidemiological studies a single recording of electrocardiogram (ECG) was used. This is the most usable method for examination of large populations but a little informative for detecting arrhythmias. The small frequency of CRDs detected during ECG recording is due to the short duration of its registration. An increase in the duration of ECG recording (ECG recording for 2 minutes, continuous recording of 100 cardiocycles) leads to an increase in arrhythmias frequency. With a wide introduction in the practice of ECG monitoring by Holter as well as the use of individual recorders of electrocardiogram ("handheld ECG recording") data appeared indicating a much higher frequency of CRDs. Data obtained in numerous studies on the prevalence of arrhythmias are very contradictory and depend both on the characteristics of populations and on methodological approaches, which requires further epidemiological studies. At the same time, the main initiating point of such researches is the clinical significance of certain CRDs. However, if the clinical significance of ventricular tachyarrhythmias and atrial fibrillation does not currently cause any doubt, the clinical significance of extrasystoles is highly controversial, despite the high their prevalence, including this in prognostically unfavorable groups of patients. In recent years, the results of a number of studies have been published that allow to think about the adverse effects of both supraventricular and ventricular extrasystoles of the course of certain cardiovascular diseases. Very heterogeneous results of the performed studies, as well as data about the high clinical significance of individual CRDs, make further epidemiological studies in this field extremely urgent.

409-415 200

The ischemic heart disease (IHD) with comorbid kidney dysfunction has more severe course and worse prognosis, regardless of the chosen therapeutic strategy for the treatment of coronary disease. Traits of diagnosis and treatment of IHD in patients with renal dysfunction, including end-stage kidney disease, are discussed. The analysis of the studies showed increasing difficulties in the diagnosis of IHD, and decrease in the effectiveness of drug and invasive treatment.

Results of large randomized and observational studies can help to treat patients with IHD and comorbid renal dysfunction more effectively and safe. 


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The aim of this review is to assess the effect of genetic factors on the pharmacokinetic parameters of new oral anticoagulants. The review presents data from studies investigating the effect of gene polymorphisms that encode biotransformation enzymes and transporter proteins of new oral anticoagulants on the pharmacokinetics of these drugs. RE-LY study showed a 15% decrease in trough dabigatran concentration and 27% lower risk of bleeding in carriers of CES1 gene rs2244613 polymorphism, there was also a tendency to reduce the risk of major bleeding. Further study of CES1 gene rs8192935 polymorphism showed a 3% decrease in trough dabigatran concentration in heterozygotes and 11% in homozygotes. There was found a 2% and 3% decrease in trough concentrations in hetero- and homozygotes for the minor allele of CES1 gene rs2244613 polymorphism, respectively. There was no significant effect of ABCB1 gene rs2032582 and rs1045642 polymorphisms on dabigatran pharmacokinetics. It is known the case of gastrointestinal bleeding in the carrier of allelic variants of ABCB1 gene rs2032582 and rs1045642 polymorphisms. However, there was no significant effect of genotype on rivaroxaban pharmacokinetics in the study involving the carriers of ABCB1 gene rs2032582 and rs1045642 polymorphisms. ABCB1 gene rs4148738 polymorphism was associated with higher apixaban peak concentration. But groups of patients with acute cardioembolic stroke showed no statistically significant difference of apixaban peak concentration depending on ABCB1 gene rs1045642 polymorphism genotype. ABCB1 gene rs1045642 and SLCO1B1 gene rs4149056 polymorphisms have no effect on edoxaban pharmacokinetics. Elevation of edoxaban metabolite concentration in carriers of SLCO1B1 gene allelic variants was not clinically significant because the proportion of metabolite is about 10% of the concentration of the main substance. It is necessary to provide large population studies with control of treatment efficacy and safety to prove clinical significance of genotyping for new oral anticoagulants use.

422-426 317

The review presented the importance of carvedilol using in terms of renoprotection in renal dysfunction at the pre-dialysis stage of the disease in order to reduce the risk of progression of chronic kidney diseases (CKD) and the development of cardiovascular complications. Immune and non-immune mechanisms (proteinuria, dyslipidemia, anemia, arterial hypertension) of renal dysfunction progression in patients with CKD of inflammatory and non-inflammatory origin are described. Moreover, with the slowing down of the glomerular filtration rate in CKD, the role of non-immunefactors in the development of cardiovascular complications becomes very important. In contrast to non-selective and some β1-selective beta-blockers, the use of beta-adenoblocker with vasodilating activity, in particular carvedilol, makes it possible to prevent the onset of the terminal stage ofCKD. Carvedilol, being a lipophilic beta-adrenoblocker of the third generation with alpha-blocking properties, influences the possible mechanismsof renoprotection: antihypertensive (including in combined antihypertensive therapy), anti-inflammatory, antiproliferative, anti-apoptotic, antioxidant, antiplatelet and others. Carvedilol due to the vasodilating effect softens the stress of the parietal shear, exerting a retarding action on theprogression of CKD. Carvedilol with a pronounced vasodilating effect and a long half-life significantly reduces central arterial pressure that is also animportant renoprotective mechanism in the treatment of patients with renal dysfunction. Carvedilol has an important renoprotective mechanism in CKD inhibition of the secretion of the potent vasoconstrictor endothelin. In the metabolic syndrome, in which there is a significant risk of developing renal dysfunction, carvedilol levels the imbalance of adipokine secretion, insulin resistance, sodium and water retention, and the activation of renin-angiotensin-aldosterone and sympathoadrenal systems. Carvedilol at the early stages of CKD development shows predominantly antihypertensive action due to inhibition of the renin-angiotensin-aldosterone system activity directly in the kidneys. At the late stage of the disease, the drug is able to retain residual kidney function. That is, carvedilol can be used at all stages of CKD development, regardless of the etiology of kidney damage.

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