Predictors of the Development of Associated Clinical Conditions in Working-Age Patients With Cardiovascular Risk Factors in Conditions of High Adherence to Treatment.

AIM: To determine predictors for the development of associated clinical conditions (ACC) in patients of working age with cardiovascular risk factors (CVRFs) in the conditions of high compliance with the treatment and healthy lifestyle (HLS). MATERIAL AND METHODS: The study included 364 patients with CVRFs without target organ damage and a history of ACC. Mean age was 42.24±8.08 years. Patients were examined in consistency with the Russian Society of Cardiology (RSC) 2020 guidelines for arterial hypertension and chronic heart failure. The follow-up period was 6.45±0.42 years. 350 patients completed the study, 9 patients died during the follow-up period, and 5 were lost to follow-up. Patients were divided into two groups based on the development of ACC. The first group consisted of 56 (16%) patients with verified ACC, the second group included 294 (84%) patients without ACC. RESULTS: Regression logistic and correlation analyses confirmed the prognostic significance for the development of ACC by 12 indicators. The risk of ACC in smokers was increased more than 7 times (odds ratio (OR) 7.44, 95% confidence interval (CI): 3.42-16.21), and when type 2 diabetes mellitus (DM) developed, more than 9 times (OR 9.47, 95% CI: 4.36-20.59); with chronic kidney disease (CKD), more than 6 times (OR 6.75, 95% CI: 3.41-13, 37); with a history of COVID-19 (COronaVIrus Disease 2019) pneumonia, 7 times (OR 7.11, 95% CI: 3.04-16.58); with left ventricular hypertrophy (LVH), 6 times (OR 6, 35, 95% CI: 3.14-12.83); with CAVI index>7.2, almost 3 times (OR 2.69, 95% CI: 1.48-4.86); with PVWcf (carotid-femoral pulse wave velocity) >13 m/s, more than 5 times (OR 5.61, 95% CI: 2.79-11.28); with R-AI index (augmentation index) >1, more than 2 times (OR 2.26, 95% CI: 1.3-3.9); and with an increase in the indexed left atrial volume (ILAV) >27 ml/m2, more than 8 times (OR 8.80, 95% CI: 4.61-16.79). In the presence of polymorphisms in the form of homozygosity for the minor allele of the AGT gene (Thr174Met, rs4762), the risk of developing ACC increased 14 times (OR 14.13, 95% CI: 4.69-42.57), the APOE gene (Cys130Arg, rs429358), 11 times (OR 11.18, 95% CI: 4.18-29.93), and in the intron of the PRARα gene (rs4253778), 8 times (OR 8.11, 95% CI: 3.75-17.53). CONCLUSION: The development of ACC in patients with high compliance with treatment and a healthy lifestyle is associated with smoking, type 2 diabetes and CKD, a history of COVID-19 pneumonia, LVH, increased ILAV >27 g/m2, more pronounced arterial stiffness assessed by an increase in CAVI indices >7.2, R-AI >1, and PWVcf >13 m/s; and with the presence of polymorphism of the AGT, APOE and PPARα genes in the form of homozygosity for the minor allele.

[Russian eligibility criteria prescribing menopausal hormonal hormones therapy for patients with cardiovascular and metabolic diseases. Consensus document of the Russian Cardiological Society, Russian Society of Obstetricians and Gynecologists, Russian Association of Endocrinologists, Eurasian Association of Therapists, Association of Phlebologists of Russia].

Menopausal symptoms can disrupt the life course of women at the peak of their career and family life. Currently, the most effective treatment for these manifestations is menopausal hormone therapy (MHT). The presence of cardiovascular and metabolic diseases in itself does not exclude the possibility of prescribing MHT to relieve menopausal symptoms and improve quality of life. However, often an obstacle to the use of this type of hormonal therapy is the fear of doctors who are afraid of doing more harm to patients than good. Caution is especially important when it comes to women with underlying health conditions. Moreover, it should be recognized that there is a lack of high-quality research regarding the safety of MHT for major chronic non-infectious diseases and common comorbid conditions. The presented consensus document analyzed all currently available data obtained from clinical trials of various designs and created a set of criteria for the acceptability of prescribing MHT to women with concomitant cardiovascular and metabolic diseases. Based on the presented document, doctors of various specialties who advise women in menopause will receive an accessible algorithm that will allow them to avoid potentially dangerous situations and reasonably prescribe MHT in real practice.

[Russian Eligibility Criteria for Prescribing Menopausal Hormone Therapy to Patients With Cardiovascular and Metabolic Diseases. Consensus Document of RSC, RSOG, RAE, EUAT, RAP].

Menopausal symptoms can impair the life of women at the peak of their career and family life. At the present time, the most effective treatment for these manifestations is menopausal hormone therapy (MHT). The presence of cardiovascular and metabolic diseases in itself does not exclude the possibility of prescribing MHT to relieve menopausal symptoms and improve quality of life. However, often an obstacle to the use of this type of hormone therapy is the fear of physicians to do more harm to patients than good. Caution is especially important when it comes to women with concurrent diseases. Moreover, it should be recognized that there is a shortage of high-quality research on the safety of MHT for underlying chronic non-infectious diseases and common comorbidities. The presented consensus analyzed all currently available data from clinical trials of various designs and created a set of criteria for the appropriateness of prescribing MHT to women with concomitant cardiovascular and metabolic diseases. Based on the presented document, physicians of various specialties who advise menopausal women will receive an accessible algorithm that will allow them to avoid potentially dangerous situations and reasonably prescribe MHT in real-life practice.

Female and Male Phenotypes of Iron Deficiency in CHF. Additional analysis of the «The Prevalence of Iron Deficiency in Patients With Chronic Heart Failure in the Russian Federation (J-CHF-RF)¼ study.

Aim    To evaluate the incidence of iron deficiency (ID) in men and women with chronic heart failure (CHF) and to compare clinical and functional indexes in patient with and without ID depending on the gender.Material and methods    An additional analysis of the study "Prevalence of Iron Deficiency in Patients With Chronic Heart Failure in the Russian Federation (ID-CHF-RF)" was performed. The study included 498 (198 women, 300 men) patients with CHF, in whom, in addition to iron metabolism, the quality of life and exercise tolerance (ET) were studied. 97 % of patients were enrolled during their stay in a hospital. ID was defined in consistency with the European Society of Cardiology (ESC) Guidelines. Also, and additional analysis was performed according to ID criteria validated by the morphological picture of the bone marrow.Results    ID was detected in 174 (87.9 %) women and 239 (79.8 %) men (p=0.028) according to the ESC criteria, and in 154 (77.8 %) women and 217 (72.3 %) men (p=0.208) according to the criteria validated by the morphological picture of the bone marrow. Men with ID were older and had more severe CHF. They more frequently had HF functional class (FC) III and IV (63.4 % vs. 43.3 % in men without ID); higher concentrations of N-terminal pro-brain natriuretic peptide (NT-proBNP) and lower ET. HF FC III increased the probability of ID presence 3.4 times (p=0.02) and the probability of HF FC IV 13.7 times (p=0.003). This clinical picture was characteristic of men when either method of determining ID was used. In women, ID was not associated with more severe CHF.Conclusion    Based on the presented analysis, it is possible to characterize the male and female ID phenotypes. The male ID phenotype is associated with more severe CHF, low ET, and poor quality of life. In females of the study cohort, ID was not associated with either the severity of CHF or with ET.

[Prospects for use of Vericiguat in HFrEF: Implications of VICTORIA Trial Results. Advisory Board Summary].

In September 2021, an online meeting of the Council of Experts was held. The proposed focus of discussion was publishing the results of an international prospective, randomized, double-blind, placebo-controlled study VICTORIA. The objective of the VICTORIA study was evaluation of the efficacy and safety of supplementing a standard therapy with vericiguat at a target dose of 10 mg twice a day as compared to placebo for prevention of cardiovascular death and hospitalization for heart failure (HF) in patients with clinical manifestations of chronic HF and left ventricular ejection fraction <45% who have recently had an episode of decompensated HF. The aim of the meeting was interpretation of the VICTORIA study results on efficacy and safety of vericiguat for a potential use in a Russian population of patients after a recent episode of decompensated chronic HF with reduced ejection fraction.

[Cardiovascular effects of omega-3 polyunsaturated fatty acids: position of omega-3 polyunsaturated fatty acids in Russian and international guidelines. Council of Experts].

This Expert Council focuses on the meta-analysis of studies on the risk of atrial fibrillation (AF) in patients taking omega-3 polyunsaturated fatty acids (PUFA) and of data on the omega-3 PUFA treatment in patients with cardiovascular and kidney diseases.The major statements of the Expert Council: the meta-analysis of AF risk in patients taking omega-3 PUFA showed an increased risk of this arrhythmia. However, it should be taken into account that the risk of complications was low, and there was no significant increase in the risk of AF when omega-3 PUFA was used at a dose of ≤1 g and a standard dose of the only omega-3 PUFA drug registered in the Russian Federation, considering all AF episodes in the ASCEND study.At the present time, according to Russian and international clinical guidelines, the use of omega-3 PUFA can be considered in the following cases: • for patients with chronic heart failure (CHF) with reduced left ventricular ejection fraction as a supplement to the basic therapy (2B class of recommendations according to the 2020 Russian Society of Cardiology guidelines (RSC) and the 2022 AHA / ACC / HFSA guidelines); • for patients with hypertriglyceridemia (>1.5 mmol/l) as a part of combination therapy (IIb class of recommendations and B level of evidence according to the 2021 European guidelines on cardiovascular disease prevention, etc.); • for adult patients with stage 3-4 chronic kidney disease (CKD), long-chain omega-3 PUFA 2 g/day is recommended for reducing the level of triglycerides (2C class of recommendations). Data on the use of omega-3 PUFA for other indications are heterogenous, which can be partially explained by using different form and doses of the drugs.

[Iron deficiency in Russia heart failure patients. Observational cross-sectional multicenter study].

Aim    To evaluate the prevalence of iron deficiency (ID) in Russian patients with heart failure (HF).Material and methods    Iron metabolism variables were studied in 498 (198 women, 300 men) patients with HF. Data were evaluated at admission for HF (97 %) or during an outpatient visit (3 %). ID was determined according to the European Society of Cardiology Guidelines.Results    83.1 % of patients had ID; only 43.5 % of patients with ID had anemia. Patients with ID were older: 70.0 [63.0;79.0] vs. 66.0 years [57.0;75.2] (p=0.009). The number of patients with ID increased in parallel with the increase in HF functional class (FC). Among patients with ID, fewer people were past or current alcohol users (p=0.002), and a greater number of patients had atrial fibrillation (60.1 vs. 45.2 %, p=0.016). A multiple logistic regression showed that more severe HF (HF FC) was associated with a higher incidence of ID detection, whereas past alcohol use was associated with less pronounced ID. An increase in N-terminal pro-brain natriuretic peptide (NT-proBNP) by 100 pg/ml was associated with an increased likelihood of ID (odds ratio, 1.006, 95 % confidence interval: 1.002-1.011, p=0.0152).Conclusion    The incidence rate of HF patients is high in the Russian Federation (83.1 %). Only 43.5 % of these patients had anemia. The prevalence of ID in the study population increased with increases in HF FC and NT-proBNP.

Epidemiology of atrial fibrillation in a representative sample of the European part of the Russian Federation. Analysis of EPOCH-CHF study.

Aim    To study true prevalence of atrial fibrillation (AF) in a representative sample from the European part of the Russian Federation; to describe characteristics of patients with AF; and to provide the frequency of anticoagulant treatment.Material and methods    Cross-sectional data of the EPOCH epidemiological study (2017) were used. Data were collected in 8 constituent entities of the Russian Federation; the sample size was 11 453 people. The sample included all respondents who had given their consent for participation and were older than 10 years. Statistical tests were performed in the R system for statistical data analysis.Results    The prevalence of AF in the representative sample from the European part of the Russian Federation was 2.04 %. The AF prevalence increased with age and reached a maximum value of 9.6% in the age group of 80 to 89 years. The AF prevalence among females was 1.5 times higher than among men. With age standardization, the AF prevalence was 18.95 and 21.33 per 1,000 people for men and women, respectively. The AF prevalence increased in the presence of concurrent cardiovascular diseases (CVDs) or diabetes mellitus as well as with an increased number of comorbidities in the same person and reached 70.3 and 60.0 % in patients with 4 and 5 comorbidities, respectively. Patients with AF had a greater number of comorbidities and higher CHA2DS2VASc scores (5.0 vs. 2.0, p<0.001) compared to patients with CVDs without AF. Only 22.6 % of patients with CVD and AF took anticoagulants. Only 23.9% of patients with absolute indications for the anticoagulant treatment received anticoagulants.Conclusion    The AF prevalence in the European part of the Russian Federation was 2.04 %; it increased with age and in patients with concurrent CVDs or diabetes mellitus. Most of AF patients (93.2 %) required a mandatory treatment with oral anticoagulants.

[Left ventricular global function index as a predictor of adverse cardiovascular events in patients with acute coronary syndrome].

Aim      To evaluate the prognostic significance of the left ventricular global function index (LV GFI) in patients with acute coronary syndrome (ACS) using echocardiography (EchoCG).Material and methods             The LV GFI is an index that integrates LV cavity volumes, stroke volume, and myocardial volume. This study included 2169 patients with ACS (1340 (61.8%) men) aged 64.1±12.6 years from two observational multicenter studies, ORACLE I and ORACLE II. 1800 (83 %) cases were associated with increased concentrations of myocardial injury markers, including 826 (38.1 %) cases of ST segment elevation myocardial infarction (MI). The observation was started on the 10th day of clinical condition stabilization and lasted for one year. EchoCG was performed with evaluation of LV GFI, which was calculated as a ratio of LV stroke volume to LV global volume. The LV global volume was calculated as a sum of mean LV cavity volume (LV end-diastolic volume + LV end-systolic volume / 2) and LV myocardial volume.Results The main outcome of the study was all-cause death (n=193); recurrent coronary complications (n=253) were analyzed separately. The only EchoCG parameter indicating an adverse outcome during the one-year follow-up was a LV GFI decrease to below 22.6 % with a sensitivity of 72 % and a specificity of 60% (area under the curve, AUC=0.63). A LV GFI <22.6 % was an independent predictor of all-cause death (p=0.019) along with age (p=0.0001), history of MI (p=0.034), and presence of heart failure (HF) (p=0.044), diabetes mellitus (p=0.012), and peripheral atherosclerosis (p=0.001). The LV GFI <22.6 %, (p=0.044), heart rate upon discharge from the hospital (p=0.050), history of MI (p=0.006), presence of HF (p=0.014), and peripheral atherosclerosis (p=0.001) were also independent predictors for recurrent coronary complications. Decreased LV GFI was associated with the risk of fatal outcomes independent of the LV ejection fraction at baseline.Conclusion      In patients with ACS, the left ventricular global function index is an independent predictor for all-cause death and recurrent coronary complications and may be used for risk stratification.

Value of comparative studies of "real clinical practice" in modern cardiology. Position paper based on the expert council discussion dated 12/18/2020.

On December 18, 2020, an expert council was held with the participation of members of the Russian Society of Cardiology, the Eurasian Association of Ther-apists, the National Society for Atherothrombosis, the National Society for Evi-dence-Based Pharmacotherapy, and the Russian Heart Failure Society. The event was devoted to the discussion of the correct use of research data of "real clinical practice" in decision making.

Chronic heart failure in the Russian Federation: what has changed over 20 years of follow-up? Results of the EPOCH-CHF study.

Aim    To study the etiology and the dynamics of prevalence and mortality of CHF; to evaluate the treatment coverage of such patients in a representative sample of the European part of the Russian Federation for a 20-year period. Material and methods    A representative sample of the European part of the Russian Federation followed up for 2002 through 2017 (n=19 276); a representative sample of the population of the Nizhny Novgorod region examined in 1998 (n=1922).Results    During the observation period since 2002, the incidence of major CHF symptoms (tachycardia, edema, shortness of breath, weakness) tended to decrease while the prevalence of cardiovascular diseases has statistically significantly increased. During the period from 1998 through 2017, the prevalence of I-IV functional class (FC) CHF increased from 6.1 % to 8.2 % whereas III-IV FC CHF increased from 1.8 % to 3.1 %. The main causes for the development of CHF remained arterial hypertension and ischemic heart disease; the role of myocardial infarction and diabetes mellitus as causes for CHF was noted. For the analyzed period, the number of treatment components and the coverage of basic therapy for patients with CHF increased, which probably accounts for a slower increase in the disease prevalence by 2007-2017. The prognosis of patients was unfavorable: in I-II FC CHF, the median survival was 8.4 (95 % CI: 7.8-9.1) years and in III-IV FC CHF, the median survival was 3.8 (95 % CI: 3.4-4.2) years.

[Expert consensus regarding treatment of iron deficiency in stable and decompensated patients with heart failure].

In recent years there has been significant interest in treating iron deficiency (ID) in patients with heart failure (HF) due to its high prevalence and detrimental effects in this population. As stated in the 2020 Russain HF guidelines, Intravenous ferric carboxymaltose remains the only proven therapy for ID.This document was prompted by the results from the recent AFFIRM-AHF trial which demonstrates that treatment of ID after acute HF decompensation reduces the risk of future decompensations. Experts have concluded that in HF patients with acute decompensation, a left ventricular ejection fraction of < 50% and ID, Intravenous ferric carboxymaltose reduces future HF hospitalisations. Patients with stable HF may also benefit from treatment of ID to improve quality of life and alleviate symptoms.  It is, therefore, reasonable to screen for and treat ID in patients with HF.

[The use of diuretics in chronic heart failure. Position paper of the Russian Heart Failure Society].

The document focuses on key issues of diuretic therapy in CHF from the standpoint of current views on the pathogenesis of edema syndrome, its diagnosis, and characteristics of using diuretics in various clinical situations.

[The agreed experts' position of the Eurasian Association of Therapists on tactics of management of patients with comorbid pathology infected with SARS-Cov-2].

The agreement of experts of the Eurasian Association of Therapists (EAT) discusses pathogenesis and treatment of COVID-19. Modern data on the characteristics of cardiovascular, kidney, respiratory damage in SARS-infected CoV-2 are presented. The tactics of managing patients initially having cardiovascular diseases, diabetes mellitus, chronic obstructive pulmonary disease, bronchial asthma, chronic kidney disease are discussed in detail. The article presents data on drug interaction of drugs.

[Changes in the management of patients with acute coronary syndrome - have the disease outcomes changed?]

Aim        To analyze results of changing the management tactics in patients with acute coronary syndrome (ACS) in clinical practice from 2004 through 2018 expressed as improvement in prognosis.Material and methods        Results of two observational studies were analyzed: ORACLE I (2004-2007), which included 1193 patients with ACS (mean age, 61.1±11.69 years; men, 63.3 %) and ORACLE II (2014-2017), which included 1652 patients from 4 vascular centers (mean age, 64.61±12.67 years; men, 62.3 %).Results   Patients included into the ORACLE II study in 2014 were significantly older and the proportion of patients with diabetes mellitus was greater than in the ORACLE I study (14.7 and 22.6 %, respectively). After matching the groups by major clinical characteristics, it was found that introducing the invasive management tactics for ACS patients was associated with a reduced rate of all-cause death (from 8.2 to 6.1 % for one year), a tendency towards decreased number of coronary death cases (from 5.6 to 4.0 %), and a decrease in risk of recurrent coronary complications (from 17.4  to 7.7 %).Conclusion            Implementing the vascular program statistically significantly decreased the total death rate for at least one-year observation in comparable patient groups.

[Use of Statins, Anticoagulants, Antiaggregants and Antiarrhythmic Drugs in Patients With COVID-19. The Agreed Experts' Position of Russian Society of Cardiology, Eurasian Association of Therapists, National Society on Atherothrombosis, Societies of Experts in Urgent Cardiology, Eurasian Arrhythmology Association].

This article discusses relevant aspects in the treatment of patients with COVID-19. Up-to-date information about principles for administration of statins, antithrombotics, and antiarrhythmics is presented. The authors addressed in detail specific features of reversing heart rhythm disorders in patients with coronavirus infection and the interaction of antiarrhythmic and antiviral drugs. Recommendations are provided for outpatient and inpatient antithrombotic therapy for patients with COVID-19. Issues of antithrombotic and antiviral drug interaction are discussed.

[The Agreed Experts' Position of the Eurasian Association of Therapists on Some new Mechanisms of COVID-19 Pathways: Focus on Hemostasis, Hemotransfusion Issues and Blood gas Exchange].

The article discusses pathogenesis and treatment of COVID-19. The authors presented state-of-the-art insight into hemostatic disorders in patients with COVID-19 and clinical recommendations on prevention of thrombosis and thromboembolism in patients infected with SARS-CoV-2. The article discussed in detail a new hypothesis proposed by Chinese physicians about a new component in the pathogenesis of COVID-19, namely, about the effect of SARS-CoV-2 virus on the hemoglobin beta-chain and the formation of a complex with porphyrin, which results in displacement of the iron ion. Thus, hemoglobin loses the capability for transporting oxygen, which aggravates hypoxia and worsens the prognosis. The article stated rules of hemotransfusion safety in the conditions of COVID-19 pandemic.

[Choosing Antithrombotic Therapy in Patients with Coronary Heart Disease and Type 2 Diabetes Mellitus: How to Reduce the Risk of Death].

This review presents prevalence of type 2 diabetes mellitus (DM) in patients with ischemic heart disease (IHD), risk factors in common, and a considerable worsening of prognosis in their combination. The authors addressed pathophysiological mechanisms of platelet dysfunction and negative changes in the coagulation system in IHD patients with type 2 DM, which predetermine activation of the prothrombotic pathway of hemostasis formation. Difficulties in optimal selection of antithrombotic therapy were demonstrated for both patients with type 2 DM without a history of cardiovascular diseases and IHD patients with type 2 DM. The authors paid attention to the fact that results of randomized clinical studies (RCS) that included patients with type 2 DM and acute coronary syndrome or after coronary revascularization cannot be extrapolated to the entire population of patients with stable IHD. At present, the preferable choice of antithrombotic therapy for patients with type 2 DM and stable IHD is a combination of rivaroxaban 2.5 mg twice a day and acetylsalicylic acid 100 mg/day. This combination provides a maximal clinical benefit compared to other strategies presented in RCS.

[Atrial Fibrillation in Patients on Dialysis Therapy: Epidemiology, Prognosis and Choice of Anticoagulant Therapy].

The review presents data on the prevalence of atrial fibrillation in patients on dialysis therapy. It is shown that dialysis-dependent patients with non-valve atrial fibrillation prognosis is extremely unfavorable, significantly increased risk of death due to both ischemic and hemorrhagic complications. Scales to assess the risk of thromboembolic and hemorrhagic complications in patients with atrial fibrillation on program dialysis are not validated. The lack of data from randomized clinical trials makes it much more difficult to choose anticoagulant therapy in patients with terminal stage of chronic kidney disease on dialysis who have undergone kidney transplantation. Therefore, the need for anticoagulant therapy and the choice of drugs in patients in this category should be made on the basis of a personalized multidisciplinary approach, taking into account comorbid pathology and the patient's preferences.

EPOCHA-AH 1998­2017. Dynamics of prevalence, awareness of arterial hypertension, treatment coverage, and effective control of blood pressure in the European part of the Russian Federation.

AIM: To perform a repeated epidemiological study of a representative sample in the European part of the Russian Federation in 2017 and to compare the dynamics of arterial hypertension (AH) prevalence with the effectiveness of blood pressure (BP) control in the population compared to 1998, 2002, and 2007. MATERIALS AND METHODS: A representative sample of the European part of the Russian Federation was created in 2002 and re-examined in 2007 and 2017. In 1998, a pilot project was performed for examining a representative sample for the Nizhniy Novgorod region. RESULTS: During 19 years of follow-up, the AH prevalence increased from 35.5 to 43.3%. Te awareness and treatment coverage reached 76.9 and 79.3%, respectively, in 2017. Achievement of the target BP with a single measurement also increased among patients receiving antihypertensive medication from 14.3 to 34.9%. For the treatment of AH, medium-acting antihypertensive drugs are used, ofen at suboptimal doses. CONCLUSION: Epidemiological indices of awareness, treatment coverage, and number of effectively managed patients with AH have improved. However, the AH prevalence has increased by 7.8% for 19 years, which indicates inefciency of the primary prevention of this disease.