Rational Pharmacotherapy in Cardiology

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Vol 16, No 1 (2020)
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4-9 599

Aim. To reveal the statistically significant determinants of the coronary artery (CA) stenosis ≥70% in patients with chronic stable CA disease receiving drug therapy.

Material and methods. The study included 68 patients (aged 59.6±6.4 years) with stable CA disease and optimal cardioactive therapy. Coronary angiography was performed in all patients. Basic serum parameters of carbohydrate and lipid metabolism were evaluated; serum concentration of cytokines, adipokines and high sensitive C-reactive protein (hsCRP) were determined by ELISA. The epicardial adipose tissue (EAT) thickness was measured by B-mode echocardiography.

Results. The patients’ classification model was created. It allowed to determine probability P for CA stenosis of 70% or more for each patient using formula Р, where L=0.89-1.09×gender+ 0.51×triglycerides–0.28×HDL+0.24×hsCRP (HDL – high density lipoproteins). If calculated P value falls into interval (0; 0.228) the patient should be classified into the group with the risk of CA stenosis ≥70%, while if calculated P value falls into interval (0.228; 1), the patient should be classified into group with CA stenosis below 70%. Even though EAT thickness was indistinguishable determinant of CA stenosis ≥70% in our study, its inclusion into the model as a fifth variable allowed to increase the model quality: area under ROC-curve (AUC) in the model without EAT thickness constituted 0.708 (p=0.009), and increased up to 0.879 (p=0.011) after EAT thickness inclusion.

Conclusions. Male sex, level of triglycerides, HDL and hsCRP are statistically significant determinants of CA stenosis ≥70%. The presence of the triglycerides level in the created model underscores an important contribution of this lipid fraction, even when elevated only up to the moderate values, into modulation of the residual cardiovascular risk in patients receiving statins.

10-18 602

Aim. To study the efficacy, safety, and adherence to therapy with new oral anticoagulants in patients older than 75 years with atrial fibrillation.

Material and methods. Patients (n=431) over 75 years old (82.7±3.4 years) with various types of atrial fibrillation/flutter (AF) were included in a nonrandomized observational study of new oral anticoagulants (NOAC) in real clinical practice. A history of cardiac surgery was in 27.6% of patients. All patients had >3 risk factors for ischemic stroke (CHA2DS2-VASс 4.81±0.4 points) and >1 risk factor for bleeding (HAS-BLED 3.01±0.2 points). The duration of the observation study was from 12 to 42 (26.9±4.9) months. Dabigatran was taken in 38.5% (n=166) of patients, rivaroxaban – in 41.3% (n=178), apixaban – in 20.2% (n=87) of patients.

Results. The incidence of new cases of myocardial infarction was 0.8% per year, surgical revascularization – 0.9% per year, cardiovascular death – 0.8% per year. The frequency of ischemic stroke was 1.1% per year, transient ischemic attacks – 0.4% per year, all thromboembolic episodes – 1.77% per year. The incidence of intracranial hemorrhage was 0.2% per year, of minor bleeding – 4.4% per year, of the combined cardiac point (the total frequency of all strokes, major bleeding, myocardial infarction, mortality from cardiovascular causes, revascularization procedures) – 4.2% per year. Significant differences in the frequency of endpoints depending on the drug of NOAC taken by patients were not found. Violations of the regimen and doses were more often observed with twice daily intake (63.9% for dabigatran and 59.8% for apixaban) than with a single dosage regimen per day (45.5% for rivaroxaban). The leading causes of non-adherence to NOAC therapy in patients over 75 years of age included skipping the next scheduled dose (43.6%) and changing the frequency of the drug taking (16.9%). For NOAC with a double dose per day, dabigatran and apixaban, the frequency of administration was violated in 27.7% and 28.7%, respectively, and with a single dose per day, rivaroxaban – in 1.1%.

Conclusion. Therapy with NOAC in patients older than 75 years with AF is effective and safe. There were no statistically significant differences in the incidence of thromboembolic or hemorrhagic events during three NOACs treatment in patients with AF older than 75 years. The incidence of non-adherence was less  

19-23 716

Aim. To study the frequency of prescribing anticoagulant therapy in outpatients with AF in accordance with clinical guidelines.

Material and methods. Control Of Anticoagulation Therapy in Atrial Fibrillation (COAT-AF) observational study was conducted at the Saint Joasaph Belgorod Regional Clinical Hospital from January 1, 2016 to December 31, 2017. Patients with AF represented 15.5% of all patients admitted to cardiology department N1. 429 patients were included into the study: 203 women, 226 men; aged of 62.55±11.12 years. Exclusion criteria were mitral stenosis, mechanic prosthetic valve, first episode of AF. CHA2DS2-VASc score was used in all patients for calculation the risk of ischemic stroke and systemic thromboembolism. For patients that were treated by warfarin international normalization ratio (INR) was assessed at admission and discharge from the hospital.

Results. From 429 patients 35 had 1 point according to the CHA2DS2-VASc scale, 393 (91.6%) patients had ≥2 points. Only 1 patient had 0 point. Therefore, most patients had absolute indications to anticoagulant therapy. At admission 60 (14%) patients received new oral anticoagulants (NOACs), 213 (49.6%) – warfarin, 156 (36.4%) – did not take any oral anticoagulant. Among patients receiving warfarin only 36 (8.4%) had target INR at admission. Therefore, effective anticoagulant therapy was observed only in 22.4% of patients in real clinical practice. Analyzing anticoagulant therapy in 2016 and 2017 we found a significant increase in NOAC prescription from 10.4% in 2016 to 18.9% in 2017 (p=0.0193).

Conclusion. Our data reflects important gaps of anticoagulant therapy in real clinical practice. We compare our results with other Russian registries that included AF-patients. Data at admission and discharge suggests that there are great possibilities for optimization of anticoagulant therapy mainly with NOACs.

24-32 908

Aim. To study the prevalence of familial hypercholesterolemia (FH), the characteristics of the clinical features and treatment of the disease in selected regions of the Russian Federation, this article describes the design and initial characteristics of patients included in the study.

Material and methods. The study participants were selected among those included in the study “Epidemiology of cardiovascular risk factors and diseases in the regions of the Russian Federation” (ESSE-RF) in different regions of the Russian Federation. The study included individuals with lowdensity lipoprotein cholesterol (LDL-C) levels >4.9 mmol/l or LDL-C levels >1.8 mmol/l, but ≤4.9 mmol/l during statin therapy, according to the data obtained in the ESSE-RF study. These persons are invited for examination and questioning by experts in the field of FH diagnostics. On the basis of the survey data and provided medical documentation, the following information is collected: age, sex, smoking status, presence of hypertension, history of coronary artery disease, stroke, atherosclerosis of cerebral and peripheral arteries, LDL-C level, type, volume and duration of lipid-lowering therapy throughout life, presence and dates of secondary causes of hyperlipidemia, information about the family history of development of early cardiovascular diseases and atherosclerotic diseases, increased levels of LDL-C in relatives of the 1st and 2nd degree of kinship. All patients are examined for the presence of tendon xanthomas (Achilles, metacarpal, elbow, knee tendons) and Corneal arcus. During the visit, blood is taken for subsequent biobanking, measurement of current blood lipid levels, elimination of secondary forms of hypercholesterolemia (for subsequent determination of liver enzymes, thyroid stimulating hormone) and genetic testing. The diagnosis of FH is based on Dutch Lipid Clinical Network Criteria (DLCN). Besides, all participants in the study are tested for compliance with the diagnosis of FH according to Simon Broome criteria. All patients with a definite or probable diagnosis of FH according to DLCN or Simon Broome criteria are subjected to ultrasound examination of carotid, femoral arteries and heart and molecular genetic testing for LDLR, APOB and PCSK9 gene variants.

Results. Out of 16 360 participants of the ESSE-RF study in 10 regions, 1787 people (10,9%) met the criteria for inclusion in this study. Among them, men accounted for 35.4%, of which 1150 (7%) patients had a LDL-C level >4.9 mmol/l and 637 (3,9%) had a LDL-C level from 1,81 mmol/l to 4.9 mmol/l during lipid-lowering therapy. When compared to the original cohorts of participants from the 10 regions as compared to 3 previously surveyed regions and selected sub-groups within these cohorts we observed significant differences in several parameters such as age, total cholesterol level, triglycerides, LDL-C, the frequency of cardiovascular diseases, that may indicate regional differences in FH prevalence.

Conclusion. The analysis of clinical data of the participants of the ESSE-RF study shows that more than 10% of individuals require an additional examination to verify the FH diagnosis, and regional differences in the FH prevalence are possible.


33-39 439

Aim. To study the effects of proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor, alirocumab, on lipid levels in patients who receive secondary prevention of cardiovascular diseases (CVD) and require enhanced lipid-lowering therapy.

Material and methods. The study included 49 patients (aged of 61.53±1.14 years; 31 [63.3%] men) receiving alirocumab who did not reach the target low density lipoprotein cholesterol (LDL-C) concentrations despite the ongoing optimal lipid-lowering therapy. In all patients, the initial level of lipids was evaluated, as well as their parameters after subsequent alirocumab injections.

Results. LDL-C serum level significantly decreased after the first injection compared to the initial level from 2.92±0.22 to 1.65±0.19 mmol/L (p<0.001; Δ45.31±3.61%) and down to 1.74±0.17 mmol/L for the entire study period (p<0.001; Δ41.52±2.69%). The change in LDL-C level between injections did not show statistically significant differences (p=0.141). A direct strong statistically significant correlation between the LDL-C level after the first injection and its average values for the entire observation period was found (r=0.958, p<0.001).

Conclusion. The results of the study indicate that the PCSK9 inhibitor, alirocumab, in patients who need secondary prevention of CVD shows a significant additional decrease in the concentration of LDL-C after the first injection. At the same time, approximately half of the patients were able to achieve the recommended levels of LDL-C. The persistence of the achieved low LDL-C levels over time demonstrated that the average concentration of LDL-C during the observation corresponded to the values after the first injection. This finding shows that there is no need for constant monitoring of lipid metabolism parameters when prescribing such therapy.

40-45 788
The one of the main aims in modern clinical pharmacology is to provide safe and effective therapy considering a frequent administration of several drugs having different drug-drug interactions. Warfarin belongs to the number of popular anticoagulants which along with its efficiency not infrequently alters anticoagulant characteristics when administered with other drugs and food products. A case of a decrease in the efficacy of warfarin in a patient with mitral stenosis while taking a combined choleretic drug is presented in the article. The components of this choleretic drug (dry animal bile, dry garlic extract, dry nettle extract, activated charcoal) could impair the absorption of warfarin, increase intestinal absorption of vitamin K, and have a negative effect on the anticoagulant effect of warfarin. Management of patients receiving anticoagulants should be performed in accordance with clinical recommendations. Prescription of drugs, including multicomponent ones, without proven efficacy, for such patients should be considering the potential drug interaction.
46-50 726

This article presents a clinical case of a 62-year-old man with a long history of coronary heart disease and smoking, whose main complaint upon admission to the hospital was voice hoarseness and atypical pain syndrome in the chest. During a preliminary medical examination, attention was paid to the clinical picture, atypical for a coronary heart disease – voice hoarseness was identified as a manifestation of the recurrent nerve compression, or cardio-vocal syndrome. Given the lack of connection between the chest pain and physical exertion, a high index of a smoking person as well as signs of the recurrent nerve compression syndrome, a multi-spiral computer tomography with contrasting of the chest organs was performed (in line with official recommendations of the Russian Associations of Oncologists and Otolaryngologists). The results revealed a proliferative lesion of the mediastinum and multiple focal lesions of both lungs. A subsequent thoracoscopy and biopsy confirmed the mediastinal form of a lung cancer. Promptly initiated poly-chemotherapy allowed stabilizing the patient’s condition and significantly improving his prospects. In this context, the article discusses the complexity of a timely diagnosis of a primary lung cancer and emphasizes the need to focus on specific and unique features of the disease course as well as on a broader clinical picture. Tactics of a multidisciplinary approach allows making a diagnosis in a timely manner, significantly improving the effectiveness of therapy and patient’s survival prognosis.


51-58 608

Aim. To study the clinical manifestations and factors associated with the presence of chronic heart failure (CHF) in patients with early rheumatoid arthritis (RA) prior to anti-inflammatory therapy. Material and methods. The study included 74 patients with valid diagnosis of RA (criteria ACR/EULAR, 2010), 56 women (74%), median age – 54 [46;61] years, disease duration – 7 [4;8] months; seropositive for IgM rheumatoid factor (87%) and/or antibodies to cyclic citrullinated peptide (100%) prior to taking disease modifying anti-rheumatic drugs and glucocorticoids. CHF was verified in accordance with actual guidelines. The assessment of traditional risk factors for cardiovascular diseases, echocardiography, tissue Doppler imaging, carotid artery ultrasound, were carried out before the start of therapy in all patients with early RA. The concentration of NT-proBNP was determined by electrochemiluminescence. The normal range for NT-proBNP was less than 125 pg/ml.

Results. CHF was diagnosed in 24 (33%) patients: in 23 patients – CHF with preserved ejection fraction, in 1 patient – CHF with reduced ejection fraction. 50% of patients with RA under the age of 60 were diagnosed with CHF. NYHA class I was found in 5 (21%) patients, class II – in 15 (63%), class III – in 1 (4%). Positive predictive value of clinical symptoms did not exceed 38%. All patients with early RA were divided into two groups: 1 – with CHF, 2 – without CHF. Patients with RA+CHF compared with patients without CHF were older, had higher body mass index, frequency of carotid atherosclerosis, of ischemic heart disease (IHD), hypertension, C-reactive protein (CRP) levels and intima media thickness. Independent factors associated with the presence of CHF were identified by linear regression analysis: abdominal obesity, CRP level, systolic blood pressure, dyslipidemia, carotid intima thickness, IHD. The multiple coefficient of determination was R2=57.1 (R-0.76, p<0.001). Level of NT-proBNP in RA patients with CHF (192.0 [154.9; 255.7] pg/ml) was higher than in RA patients without CHF (77 [41.1; 191.2] pg/ml) and in control (49.0 [33.2; 65.8] pg/ml), p<0.0001 and p=0.01, respectively. To exclude CHF in patients with early RA, the optimal NT-proBNP level was 150.4 pg/ml (sensitivity – 80%, specificity – 79%), the area under the ROC curve = 0.957 (95% confidence interval 0.913-1.002, p<0.001).

Conclusion. CHF was detected in a third of RA patients at the early stage of the disease. Factors associated with the presence of CHF were abdominal obesity, CRP level, systolic blood pressure, dyslipidemia, intima media thickness, IHD.


59-68 709

Aim. To evaluate the structure of multimorbidity, outcomes and the potential effect of dapagliflozin in patients with a combination of cardiovascular disease (CVD) and type 2 diabetes in Russian clinical practice.

Material and methods. The data of 10 registries with the inclusion of 22957 people, including 4370 with type 2 diabetes in 6 regions of the Russian Federation, were analyzed. Scenarios for reducing mortality from all and cardiovascular causes and hospitalizations for CVD were simulated among groups of patients with diabetes combined with myocardial infarction (MI) and diabetes combined with heart failure with reduced ejection fraction (HFrEF) based on data from the Federal Registry of diabetes, the RECVASA and REGION registries, relative risks associated with analyzed adverse events from the DECLARE study.

Results. When analyzing the data of all 22957 patients with CVD included in the registries, it was found that the proportion of patients with comorbid diabetes was on average 19.0%. Of the various diagnoses of CVD, the combination with diabetes was most often recorded in patients that had MI – 2.0%, stroke – 22.5% and heart failure – 24.0%. In the RECVASA registry (Ryazan) for 4 years of follow-up of 699 patients with a combination of CVD and diabetes mortality from all causes was 20.9%, and from cardiovascular causes – 15.6%. The simulated number of potentially prevented cardiovascular deaths with dapagliflozin taking in patients with diabetes combined with MI for 4 years in Russia will be 39124, and 37440 cardiovascular hospitalizations. The number of potentially preventable deaths from all causes among patients with diabetes combined with HFrEF will be 4543, cardiovascular deaths in 1995, and the number of prevented cardiovascular hospitalizations will be 7072.

Conclusion. According to data from the registries of CVD patients in 6 regions of the Russian Federation, it was revealed that in real clinical practice the proportion of people with comorbid diabetes averaged 19% both at the outpatient and hospital stages. These subgroups of multimorbid patients have both the highest risk of developing fatal and non-fatal cardiovascular complications, and the largest number of indications for prescribing drugs that affect the prognosis due to effects on both CVD and diabetes.

69-74 561

Aim. To analyze the associations of health care system resources utilization and temporary disability (TD) with the main cardiovascular risk factors (RF) at the population and individual level in working age population based on ESSE-RF study data.

Material and methods. The analysis was based on ESSE-RF study data. Standard epidemiological survey methods and evaluation criteria were used. Analysis of probability and number of outpatient visits, hospitalizations, ambulance calls and TD was conducted by using hurdle model. Hypertension, obesity, hypercholesterolemia, hyperglycemia and tobacco consumption were independent variables.

Results. A total of 21923 individuals aged 25-64 years were included: men – 8373 (38%) and women – 13550 (62%). The probability of outpatient visits significantly determined in group with tobacco consumption and with hypercholesterolemia for men, and for women – in the smoking group, with obesity and with hyperglycemia. Numbers of outpatient visits has doubled for patient with hyperglycemia. The numbers of outpatient visits were higher among women smokers compared to non-smokers. Chance to be hospitalized significantly associate with smoking, obesity, hypercholesterolemia for men and with obesity, hyperglycemia – for women. Hypercholesterolemia was associated with a smaller number of inpatient treatment cases among men. The probability of ambulance calls increased for smoking men, for male group with hypertension, hypercholesterolemia, obesity and with hyperglycemia, at the same time, the likelihood increased in female group with hypertension, hyperglycemia, smoking and with obesity. In addition, numbers of ambulance calls were higher in 1.55 times for women with obesity (p<0.05).

Conclusion. So, there is a significant association of probability of using and consumption level of healthcare recourse with the RF depending on the type of medical care, sex and RF.


75-81 473

Aim. To assess the quality of therapy in stable coronary heart disease (CHD) patients, who first sought consultation in the specialized cardiology department of the research center, and try to adjust the therapy in accordance with current clinical guidelines, paying special attention to achieving the target levels of blood pressure, low-density lipoprotein cholesterol (LDL), and glycosylated hemoglobin (in patients with diabetes mellitus), increasing exercise tolerance and improving the quality of life (QL).

Material and methods. The ALIGN study is an integral part of the PROFILE outpatient registry. ALIGN study included all patients with verified coronary heart disease who came for consultation to the specialized institution for the first time or for the first time in more than the last 3 years. Patients have been recruited from December 01, 2017 to December 31, 2019. The study consisted of 4 visits: the first-time visit – inclusion in the study (V0), when drug therapy, QL, and adherence were evaluated, and therapy correction was made in accordance with clinical guidelines. In 3 months (V1) the target values of clinical and laboratory parameters were estimated. The third visit (V2) was planned to take place 1 year after the first visit with reevaluation of QL and patients' adherence to treatment, and effectiveness of the therapy. The fourth visit (V3)/telephone contact was planned in 2 years after the first visit to assess life status, get information about complications and therapy.

Results. 389 people were included in the PROFILE registry for the specified period of time, 79 had a verified diagnosis of CHD, and 71 patients were included in the ALIGN study: 55 men (aged of 68.7±8.96 years) and 16 women (aged of 67.5±8.08 years). Arterial hypertension was registered in 90.1% of patients, stable angina class I-III – in 62%, 47.9% of patients had a history of acute myocardial infarction (AMI), 52.1% had percutaneous coronary intervention, 15.5% of patients had coronary artery bypass graft, chronic heart failure was detected in 40.8%, diabetes mellitus – in 21.1%, atrial fibrillation – in 15.5% of patients. Lipid-lowering drugs were taken by 53 (74.6%) patients, but only 21 (29.6%) achieved the target values of LDL cholesterol. Angiotensin-converting enzyme inhibitors were taken by 34 patients (47.9%), and angiotensin receptor blockers by 15 (21%) of patients, 47 (66.2%) patients took beta-blockers, antiplatelet agents were taken by 61 people, and anticoagulants by 10 patients. Patients who had a history of AMI had been prescribed BB in 88%, statins – in 90%, and renin-angiotensin-aldosterone system (RAAS) blockers – in 80% of cases.

Conclusions. Initial quality of therapy for patients with stable CHD did not fully match the clinical guidelines: a quarter of patients did not receive lipidlowering therapy, and target levels of LDL cholesterol were achieved only in one third of patients. Among patients who had a history of AMI, every fifth patient did not receive RAAS blockers.


82-93 757

Arterial hypertension (AH) is one of the most common diseases in the elderly. It has been proven that lowering blood pressure (BP) is effective in preventing stroke and cardiovascular complications in patients even at the age of ≥80 years. On the other hand, there is evidence that a significant decrease in BP can be harmful to older people and may lead to a higher risk of overall mortality. Therefore, existing guidelines for the treatment of AH determine specific approaches for managing patients of older age groups, where the target BP levels are determined not only by age and concomitant diseases, but also by the presence of frailty. Moreover, there is a need to monitor the dynamics of frailty indicators (social, functional, cognitive and mental status of the patient), since their deterioration may require changes in the tactics of antihypertensive therapy (dose reduction, drug withdrawal or replacement) and changes in target BP levels. In this regard, in recent years, the possibility/necessity of a planned and controlled process of dose reduction, drug withdrawal or replacement, if this drug can be harmful and/or does not bring benefits (deprescribing), has attracted attention. This article is a review of current literature, which presents the design and main characteristics of randomized clinical trials (RCTs) and systematic reviews on the deprescribing of antihypertensive drugs in elderly patients with AH and frailty. An analysis of these studies showed the benefits of deprescribing of antihypertensive drugs for elderly patients with frailty, which avoids potential harm to their health, improves the quality of life and reduces the economic cost of treatment. Therefore, deprescribing of antihypertensive drugs can be used as an additional tool to achieve the necessary target BP values in patients of an older age group. However, for the development of deprescribing of antihypertensive drugs schemes and its introduction into clinical practice, the results of large specially planned RCTs are needed to study this issue.

94-98 482

Blood pressure (BP) is a highly variable physiological indicator. Most people have BP changes within 40-50 mmHg during the day. Various external factors (from the patient’s position during BP measurement to poor adherence to therapy and abuse of short-acting antihypertensive drugs) affect the assessed indicators. Evaluation of the average daily, intra-visit, as well as long-term ("from visit to visit") BP variability is used in clinical practice. In the past twenty years a number of major studies demonstrated that increased BP variability is an independent prognostic factor that increases the risk of cardiovascular complications. The largest meta-analysis of 41 studies showed that an increase in long-term BP variability was associated with 15% and 18% increase in total and cardiovascular mortality, respectively. According to the IDHOCO project, the threshold coefficient of variation for day-today variability is >11.0/12.8. Different groups of antihypertensive drugs have an uneven effect on BP variability. Consistent data from ASCOT-BPLA, X-CELLENT and ACCOMPLISH studies indicate that among the main groups of antihypertensive drugs, calcium antagonists, mainly amlodipine, have the greatest potential for the variability reduction. A decrease in BP variability, as shown in a post-hoc analysis of CAMELOT and PREVENT studies, has a positive effect on the incidence of major adverse cardiac events (MACE). Thus, the BP variability is an important indicator that reflects the prognosis in hypertensive patients. BP variability reduction can be considered as one of the independent goals of therapy. Calcium antagonists can be considered as first-line drugs for patients with high BP variability.

99-107 781

Arterial thrombosis is a result of complex interaction between blood cells, soluble coagulation factors in plasma and vessel wall. Antiplatelet drugs do not always provide the necessary antithrombotic effect of sufficient strength, because their influence does not extend to all three factors involved in this process. Low doses of direct oral inhibitors of thrombin are able to potentiate antithrombotic effect of antiplatelet therapy. The combination of rivaroxaban in a dose of 2.5 mg and standard double antiplatelet therapy turned out to be the most promising for clinical use, since studies with dabigatran and apixaban at the II and III stages of the trials were found to be unsuccessful due to the unacceptably high frequency of bleeding. Studies of the combination of rivaroxaban at a dose of 2.5 mg and standard antiplatelet therapy conducted in previous years among patients with acute myocardial infarction showed a decrease in the frequency of complications of atherothrombosis associated with their ischemic nature, while at the same time there was a slight increase in hemorrhagic complications. In the COMPASS study the combination of rivaroxaban (2.5 mg) plus aspirin reduced the risk of the primary endpoint (myocardial infarction, ischemic stroke, cardiovascular death) more significantly than aspirin alone in patients with stable ischemic heart disease and ischemic brain disease. The pathophysiological rationales for the use of low doses of rivaroxaban when added to dual antiplatelet therapy are considered, and the significance of recent studies in patients with acute coronary syndrome, stable ischemic heart disease and in the prevention of ischemic stroke is discussed.

108-117 677

Currently, the number of obese people in the world is constantly increasing. Obesity has a direct negative impact on the heart and blood vessels, which can be considered not only as an appropriate response to an increase in the volume of circulating blood due to an increase in body weight, but also as a side tissue reaction of the myocardium to hormonal and metabolic changes inherent in obesity. Our review is devoted to the description of the mechanisms of influence of obesity on the structural and functional parameters of the heart, which create prerequisites for the development of cardiovascular diseases, as well as the existing contradictions. Currently, the accumulated data suggest that an excessive amount of adipose tissue, in addition to metabolic disorders, including insulin resistance, imbalance of adipokines and inflammation markers, leading to the development of lipotoxicity, can directly penetrate the myocardium and cause violations of its contractile properties, as well as affect the conduction of excitation pulses and provoke the development of rhythm and conduction disorders. The development of endothelial dysfunction in obesity ultimately leads to the development of atherosclerosis and coronary heart disease. In addition, obesity contributes to the emergence of risk factors for hypertension, diabetes, atrial fibrillation, chronic heart failure, obstructive sleep apnea syndrome. Given the differences in the literature on the effect of obesity on long-term outcomes in patients with cardiovascular diseases, it is important to conduct prospective studies on the role of individual factors and their combinations that affect the mortality of patients with cardiovascular diseases.

118-125 667

Atrial fibrillation (AF) is the most common arrhythmia. It is diagnosed in more than 33 million people worldwide and is the leading cause of hospitalization for arrhythmias. AF is characterized by fast and irregular atrial activation without discrete P-waves at a surface electrocardiography. AF pathophysiological mechanisms are very complex and include the dynamic interaction between arrhythmia substrate and triggers. Consequently, the clinical search for effective therapeutic targets should include the entire process of the onset and progression of the disease: from the first paroxysms to the development of a stable permanent form of AF.

126-132 482

The new international guidelines on hypertension management have been issued in the past few years. The AHA (2017) and ESH (2018) Guidelines are similar in many key aspects. However, they differ substantially in the area of blood pressure (BP) measurement methodology. In this article, we aim to explain the ESC Guidelines position, specifically the conservative BP thresholds and a wider use of ambulatory BP measurement methods. In our opinion, the main reason behind this position is the introduction and a relatively widespread use of automatic office BP measurement (AOBP). On one hand, this method has questioned the results of the SPRINT trial – the key evidence source for the AHA Guidelines. On the other hand, AOBP has challenged the concept of “traditional office BP measurement”. Therefore, it is important to be aware of the current multiplicity of BP measurement methods and respective threshold values recommended for each method. It is essential to perform the office BP measurement correctly and thoroughly. Throughout all stages of the hypertensive patient management (diagnosis, antihypertensive treatment choice, and long-term observation), the use of out-of-clinic BP measurement is strongly advisable.

133-138 449

This work represents literature review data regarding the study of the effect of surgical myocardial revascularization on the processes of electrical myocardial instability underlying the onset of life-threatening ventricular arrhythmias, as well as the possibilities for its non-invasive assessment by studying the heart rhythm variability and turbulence. Analyzed data demonstrated that, relying only on the presence of a viable myocardium, it is often impossible to predict the positive effect of revascularization on the prognosis in patients, especially those with reduced myocardial contractility. Considering the well-studied relationship between myocardial remodeling and neurohormonal activation, such non-invasive methods for assessing vegetative regulation of cardiac activity, as heart rate variability and turbulence may provide additional diagnostic information. The literature data indicate that heart failure, ventricular arrhythmias and recurrences of angina and myocardial infarction are the main problems that determine an unfavorable outcome in the postoperative period. There is important evidence that violations of the vegetative regulation of the heart, the heterogeneity of repolarization processes in the myocardium are integral indicators of the morphofunctional changes occurring in the process of coronary heart disease (CHD) progression. The role of indicators of heart rate variability and turbulence as predictors of sudden cardiac death was proved, mainly due to fatal ventricular heart rhythm disorders and cardiovascular mortality. Along with this, changes in these indicators, and their prognostic role in patients with CHD in revascularization are the subject of discussion, which determines the relevance of further studies on the effect of various methods of revascularization on the electrical instability of the myocardium, as one of the most important factors in the development of life-threatening ventricular arrhythmias that are predictors of sudden cardiac death, especially in patients who previously had acute myocardial infarction. Besides it is important to study the effect of myocardial revascularization on the indicators of cardiac autonomic regulation and the possibility of their use as prognostic criteria before and after surgery.


139-146 849

Effective and safe treatment of patients with polymorbidity is an urgent task of modern healthcare. Of particular difficulty is the treatment of patients with cardiovascular comorbidity, which requires an integrated approach to the treatment and development of a special, so-called patient-oriented approach. Modern scientific evidence proposes the use of levocarnitine, as part of complex therapy to increase its effectiveness. So, it was shown that levocarnitine can have a beneficial effect on blood pressure in patients with hypertension, especially those who are overweight and obese. Levocarnitine is also effective in the treatment of heart failure, which has been studied in several clinical studies, which demonstrated its ability to increase the ejection fraction of the left ventricle, stroke volume of blood and other indicators. Optimization of the bioavailability of nitrogen oxide (NO) and a decrease in systemic oxidative stress while taking levocarnitine plays an important positive role in complex therapy in patients with coronary artery disease: exertional angina and post-infarction cardiosclerosis, reducing the number of anginal attacks. Since levocarnitine has powerful antioxidant effects, it also has the neuroprotective effect found in in vitro studies in animal experiments. In case of impaired renal function, due to accelerated elimination and impaired reabsorption, a deficiency of levocarnitine in the body tissues develops, and therefore the US Food and Drug Administration (US FDA) decided on the possibility of using levocarnitine in patients on hemodialysis. Thus, taking into account the positive effects of levocarnitine in a number of frequently combined diseases, it can be considered as the drug of choice in the treatment of patients with polymorbidity.


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The Russian Federation is among countries with high cardiovascular risk. Hypercholesterolemia is a leading risk factor for the development of atherosclerotic cardiovascular diseases. To achieve low-density lipoprotein cholesterol (LDL-C) targets, such approaches as lifestyle changes and pharmacological correction, based on the use of statins, are applied. At the same time, a significant proportion of the population has moderate hypercholesterolemia and is characterized by low or moderate cardiovascular risk. Although first-line recommendations should be followed, a healthy lifestyle alone is not enough to achieve target levels of LDL-C, which means that even people with low to moderate risk may end up with the prospect of lifelong therapy with lipid-lowering drugs. These individuals do not have an indication for lipid-lowering therapy, and they are usually recommended a change in diet and supplementation. Innovative nutritional strategies have been developed to manage dyslipidemia. They were based either on changing some “risky” food components or on encouraging the consumption of “healthy” functional foods and/or nutraceuticals. Nutraceuticals (registered as food supplements in Russia) is an innovative way to help control LDL-C at low and moderate risk individuals without lipid-lowering drugs and as nutritive support for the cholesterol-lowering diet. Red yeast rice (RYR) based preparations have been already developed and available at the moment. RYR based preparations can be considered in patients with low and moderate cardiovascular risk, who have not reached the target level of LDL-C and have no indications for statin therapy or have statin intolerance. RYR based preparations contains a statin-like substance monacolin K in a dose of 3 mg. In randomized clinical trials, it was proved that the use of high-quality RYR nutraceutical leads to a decrease in LDL-C by an average of 20% without increasing the risk of side effects like for statins. Evaluation of dietary supplements and functional foods should necessarily include not only evidence of beneficial effects with respect to effects on the lipid profile and atherosclerosis, but also proven good tolerability. The manufacturing standard for these products is also important, guaranteeing component standardization and quality. RYR analogues should guarantee the absence of mycotoxin in their composition. In Russia, programs are needed for the primary prevention of atherosclerotic cardiovascular diseases with effects on hypercholesterolemia at the population level.



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