Despite the advances in lipidology over the past decade, the control of dyslipidemia at the population level in Russia, as in a number of European countries, remains unsatisfactory. The need for novel organizational approaches to solving the problem at the regional and federal levels is obvious. This publication provides an overview of the implemented projects and the successful practical experience of lipid centers in Russia, as well as the prospects for the development of novel models that will optimize the care provision for patients with lipid metabolism disorders at the population level.

Project of the Russian National Atherosclerosis Society

In 2016, Guidelines on the medical care organization to the patients with hereditary atherogenic lipid disorders in the regions of Russia were published, which described and presented the principles of routing patients with hereditary dyslipidemia and the organization of medical care for them within the current regulatory documents. In December 2018, the Russian Ministry of Health approved clinical guidelines for the diagnosis and treatment of familial hypercholesterolemia. Thus, persons with a severe hereditary dyslipidemia were able to get free medication with expensive lipid-lowering drugs and receive apheresis. Following the European ones, the Russian guidelines on the management of lipid metabolism disorders were updated: lower target low density lipoprotein cholesterol levels were adopted. In the Russian population, there is a high prevalence of hypercholesterolemia, including familial monogenic and polygenic types. Therefore, timely detection and routing to a lipid center or an office to a specialist (cardiologist, lipidologist), adequate and modern prescription of lipid-lowering therapy will make an important contribution not only to secondary, but also to primary prevention of atherosclerotic cardiovascular complications.

Aim. To study the production of reactive oxygen species (ROS) by platelets in patients with coronary artery disease (CAD) before and after coronary artery bypass grafting (CABG), depending on their sensitivity to acetylsalicylic acid (ASA) as a part of ASA monotherapy and dual antiplatelet therapy (DAPT) (ASA+clopidogrel).

Material and methods. The study included 104 patients with CAD (ASA monotherapy, 64 patients; DAPT, 40 patients). From day 1 after CABG, they took 100 mg a day of enteric-coated ASA. In the DAPT group, clopidogrel was prescribed for 2-3 days after CABG. All measurements were performed before surgery, on the 1st day and days 8-10 after surgery. Control group consisted of 36 healthy donors. Resistance to ASA was determined at a level of optical platelet aggregation with arachidonic acid >20% at least at one observation point. The spontaneous and ADP-induced chemiluminescence (CL) of platelets with luminol and lucigenin was assessed according to the following parameters: time to maximum intensity (Tmax), maximum intensity (Imax), area (S) under the CL curve, and the ratio of ADP-induced CL S to spontaneous CL S.

Results. Throughout the study, 71 patients with CAD were sensitive to ASA (sASA) (ASA monotherapy, 46 patients; DAPT, 25 patients), three patients — resistant (rASA) (ASA monotherapy, 1; DAPT, 2). Sensitivity of other 30 patients (ASA monotherapy, 17; DAPT, 13) changed in different follow-up periods. Compared to the control group, sASA patients had increased values of platelet CL parameters throughout the study, while in the rASA group (ASA monotherapy), Tmax was higher before CABG, and in the rASA group (ASA therapy+clopidogrel), Imax and S were higher on the first day after CABG, while Imax — on days 8-10 after CABG. Compared to sASA, the values of S and Imax before CABG, Imax after CABG, as well as Imax and S on the days 8-10 after CABG in rASA (ASA monotherapy) were significantly lower, while in rASA (ASA therapy+clopidogrel), only the Tmax values were lower on the 8-10 days after CABG.

Conclusion. In patients with CAD, depending on the sensitivity to ASA and antiplatelet therapy after CABG, the metabolic activity of platelets in terms of ROS production differs. In sASA patients, ROS synthesis is higher than in healthy individuals, while, in rASA patients (ASA monotherapy), platelets produce ROS levels lower than in sASA. CABG surgery and the addition of clopidogrel to ASA therapy leads to increased ROS production in rASA patients in the postoperative period.

Aim. To study the relationships between phenotypes of extracranial arteries' plaques (stable/unstable), their calcification and its causes, in particular, vascularization.

Material and methods. The study included 88 patients: patients (n=44) with ischemic stroke and those (n=44) with chronic brain ischemia. In all subjects, the parameters of systemic mineral homeostasis were assessed (total and ionized calcium, phosphate, total protein, albumin, and calcification propensity). Atherosclerotic plaques have been obtained during carotid endarterectomy, fixed in formalin, postfixed in 1% osmium tetroxide, stained in 2% osmium tetroxide, dehydrated in ascending ethanol series and acetone, stained with 2% alcoholic uranyl acetate and embedded into epoxy resin with its further polymerization. Epoxy resin blocks were grinded, polished, counterstained with Reynolds' lead citrate and sputter coated with carbon. Sample visualization was performed employing backscattered scanning electron microscopy. Number and area of calcium deposits and neointimal vessels were quantified using ImageJ. Statistical analysis was carried out using Mann-Whitney U-test and Spearman's rank correlation coefficient.

Results. It was found that area of neointimal calcification, but not number of calcium deposits, was associated with the stable plaque phenotype. The stabilizing effect of calcification was manifested in retarding stenosis associated with plaque rupture and stroke. Calcification extent directly correlated with total and local plaque vascularization, which have been associated with unstable and stable plaque phenotype, respectively. In addition, plaque calcification negatively correlated with total protein and albumin, thereby reflecting the impaired systemic mineral homeostasis.

Conclusion. Atherosclerotic plaque calcification and active local vascularization reduce stenosis extent and stabilize plaque. In contrast, total plaque calcification contributes to the atherosclerosis progression and promotes major acute cardiovascular events.

Aim. To assess the individual and complex prognostic value of various blood biochemical parameters (biomarkers) in the non-invasive diagnosis of coronary artery (CA) atherosclerosis.

Material and methods. The study included 216 patients (men, 115; women, 101) aged 24 to 87 years (mean age, 61,5±10,7 years), who underwent indicated coronary angiography. All patients underwent a biochemical blood tests to determine the parameters of lipid, carbohydrate and nitrogen metabolism, the hemostatic system, inflammatory markers, as well as the creatinine level as an indicator of renal function.

Results. Analysis revealed biomarkers, the deviations in the level of which contribute to the diagnosis and determination of the coronary involvement. These biomarkers include glucose, creatinine, C-reactive protein, and adiponectin. Using these biochemical parameters, a multivariate model (MVM) was constructed, which was significant for the diagnosis of coronary atherosclerosis and determination of its severity. With the help of ROC-analysis, the cutoff point of MVM of 2 was found. MVM >2 with a sensitivity of 72% indicate CA atherosclerosis of any severity, as well as with a specificity of 62,5%, it can be ruled out. Using MVM data and a cutoff point of 2, a binary logistic regression model was built, according to which, with a MVM >2, the odds for detecting CA atherosclerosis of any degree is 2,1 times higher (95% confidence interval (CI), 1,2-3,8; p=0,010), severe CA — 4,7 times (95% CI, 1,9-12,0; p=0,001) compared with individuals with MVM ≤2, who have 2,8 times (95% CI, 1,4-4,9; p=0,002) a higher chance of detecting intact CAs.

Conclusion. Thus, the total MVM score of 0-2 indicates the absence of coronary atherosclerosis, while 3-4 points -CA atherosclerosis of any severity.

Aim. To optimize the upper gastrointestinal bleeding (UGIB) risk scale in patients Material and methods. The UGIB risk scale was developed based on the with chronic coronary artery disease (CAD) receiving long-term antiplatelet therapy. prospective REGistry of long-term AnTithrombotic TherApy-1 REGATTA-1(ClinicalTrials.gov Identifier: NCT04347200). The registry includes 934 patients with stable CAD (men, 78,6%; median age, 61±10,7 years), 76% of whom were included after elective percutaneous coronary interventions and received dual antiplatelet therapy for 6-12 months. After a UGIB episode, patients were prescribed proton pump inhibitors. The 2015 European Society of Cardiology (ESC) scale was used for assessing the UGIB risk. In addition, we evaluated the ultrasound data on atherosclerotic burden (abdominal aorta and peripheral arteries).

Results. The median follow-up was 2,5 years [1,1-14,7 years]. The incidence of UGIB was 1,9 cases per 100 patient/years. Recurrent UGIB episodes and thrombosis was recorded in 13,7% and 31,4%, respectively. Based on the results of a multivariate logistic regression, a novel scale for assessing the UGIB risk (REGATTA) has been developed. In accordance with the odds ratio, points were assigned for each independent risk factor (RF): age ≥80 years — 3 points, prior gastric erosion, peptic ulcer disease or UGIB — 3 points for each RF, anticoagulation therapy — 4 points, non-steroidal antiinflammatory drug therapy — 2 points. The atherosclerotic burden (peripheral atherosclerosis and/or abdominal aortic aneurysm; 2 points) and heart failure (in most cases after a myocardial infarction; 2 points) were marked as a new independent predictor. The cutoff value (≥4 points) was determined, reflecting the high UGIB risk (sensitivity, 80,4%; specificity, 84,5%). The REGATTA scale was more powerful than the traditional 2015 ESC scale: AUC of 0,88, (95% confidence interval, 0,86-0,9) vs AUC of 0,79, (95% confidence interval, 0,760,82) (p=0,04).

Conclusion. The identified UGIB predictors (atherosclerotic burden and heart failure) and the developed REGATTA scale made it possible to improve the prognosis and prevention of UGIB in patients with stable CAD receiving long-term antiplatelet therapy.

Aim. To determine the relationship between vascular age (VA) and atherosclerosis-related cardiovascular diseases in patients with hypertension and hyperlipidemia.

Material and methods. The study involved 241 residents of Baku. The mean age was 58,7±10,9 years. There were 119 women (49,4%) and 122 (50,6%) men. The mean body mass index was 27,77±4,19 kg/m². Data on family history, smoking, obesity, diabetes, chronic kidney disease, revascularization, peripheral arterial disease, angina pectoris, drug intake, lipid profile, systolic and diastolic blood pressure were analyzed. Patient VA was estimated using an online calculator.

Results. The patient VA was on average 78,0±15,1 years. Pearson's correlation analysis showed a positive correlation between biological age (BA) and estimated VA (0,719; 95% confidence interval: 0,651-0,775; p<0,001). Pearson's chi-squared test with Monte Carlo simulation showed that within 10-month followup, myocardial infarction (MI) in presented sample was more common in age subgroups of 50-59 (10,0%) and 60-69 (8,3%) years. At the same time, in the group defined by VA, myocardial infarction was more common in the age subgroup of 70-79 (7,0%) and >80 years (13,3%). MI+stroke+revascularization in the group defined by BA was more common in age subgroups of 50-59 (12,0%) and 60-69 (14,5%) years, and in the group defined by VA, MI+stroke+revascularization was more common in age subgroups of 70-79 (11,6%) and >80 years (19,9%).

Conclusion. A significant positive correlation was found between BA and VA. In case of VA >70 years, the incidence of MI+stroke+revascularization increases approximately 3-5 times. Thus, the assessment of VA is an effective clinical tool that allows to inform the patient about possible cardiovascular events and to develop preventive measures.

Aim. Based on clinical parameters and diagnostic investigations, to create a complex model of personalized selection of patients with heart failure (HF) for cardiac resynchronization therapy (CRT). To establish the diagnostic value of the created model in predicting 5-year survival.

Material and methods. The study included 141 patients with HF (men, 77,3%; women, 22,7%). The mean age of patients at the time of implantation was 60,0 [53,0; 66,0] years. All patients had New York Heart Association (NYHA) class II-IV HF, left ventricular ejection fraction (LVEF) ≤35%, and QRS ≥130 ms. Patients were randomly divided into training (n=95) and test (n=36) samples, which were comparable in main clinical and functional characteristics.

Results. The index included parameters that had a significant relationship with 5-year survival according to the Cox regression: male sex, prior myocardial infarction, hypertension, QRS <150 ms, no left bundle branch block, PR ≥200 ms with sinus rhythm/absence of radiofrequency ablation in atrial fibrillation, NYHA class III, IV HF, LVEF <30%, left ventricular end-diastolic volume ≥235,0 ml, NT-proBNP ≥2692,0 ng/ml. All variables were scored based on the в-coefficients. In the training sample, a value ≥45 points demonstrated a sensitivity of 82,4% and a specificity of 67,2% in predicting 5-year survival (AUC, 0,873; p<0,001). The index use on the test sample showed comparable results (AUC, 0,718; p=0,020; sensitivity — 71,4%, specificity — 62,5%). Also, in the training sample, the index ≥45 points was associated with1-year survival (sensitivity — 84,6%, specificity — 58,1%, AUC, 0,811; p<0,001).

Conclusion. An index of personalized selection for CRT has been created, which makes it possible to accurately predict the 5-year survival rate, as well as the 1-year survival rate, regardless of the current selection criteria.

Aim. To analyze inhospital outcomes of carotid endarterectomy (CE) in the acute period (within 3 days from the onset) of ischemic stroke.

Material and methods. This retrospective multicenter study for the period from January 2008 to August 2020 included 357 patients who underwent CE in the acute period of stroke. An interdisciplinary commission defined the revascularization timing. There were following inclusion criteria: 1. Mild neurological disorders: NIHSS stroke of 3-8; modified Rankin Scale score <2; Bartel index >61; 2. Indications for CE according to the current national guidelines; 3. Brain ischemic focus <2,5 cm in diameter. There were following exclusion criteria: 1. Presence of contraindications to CE. The endpoints were such unfavorable cardiovascular events as death, myocardial infarction (MI), stroke/transient ischemic attack (TIA), silent stroke, silent hemorrhagic transformations, Bleeding Academic Research Consortium (BARC) type >3b bleeding, internal carotid artery thrombosis, composite endpoint (death + all strokes/TIA + MI). Silent strokes were those strokes, established according to control multi-slice computed tomography angiography, without symptoms.

Results. During the in-hospital follow-up period, 8 deaths (2,24%), 5 MIs (1,4%), 6 strokes/TIAs (1,7%), 15 silent ischemic strokes (4,2%), 13 hemorrhagic transformations (3,6%), 26 silent hemorrhagic transformations (7,3%), and 6 BARC type >3b bleeding (1,7%) were recorded. Thus, the combined endpoint was 20,4% (n=73).

Conclusion. Due to the high incidence of cardiovascular events, CE is not a safe operation for patients in the acute period of ischemic stroke. The stroke + mortality rate exceeding 3% demonstrates the ineffectiveness of this method of treatment.

Heart failure (HF) significantly worsens the patient quality of life and leads to the disability of their significant part, as well as increases the risk of death, which in turn causes economic damage.

Aim. To assess the annual socio-economic impact of HF in Russia.

Material and methods. To assess the socio-economic impact of HF, a model was developed, which assessed the number of HF patients seeking medical care (data from the epidemiological studies), the number of those with disabilities and the mortality rate among them. We also evaluated the costs of drug therapy (data from the government procurement reports) and hospitalization (data from the compulsory health insurance tariffs), social benefits due to disability, and death impact on the gross domestic product. Data on the prescription rate, hospitalizations and mortality was obtained from Russian registries of patients with cardiovascular diseases. Using the foreign study, the costs of family caregiving were also calculated.

Results. According to modeling data, there are 7,1 million people with HF seeking medical care in Russia. In this case, the annual economic impact of HF in the context of government spending, is RUB 81,86 billion, including medical costs of RUB 18,6 billion, direct nonmedical costs of RUB 47,1 billion, and indirect costs of RUB 16,2 billion. The impact of family caregiving is RUB 72,4 billion. In the structure of medical expenses, 73,6% is hospitalization costs, while the main costs of drug therapy are borne by patients, since only a part of them (19,6%) receive the necessary medications within assistance programs. In patients with HF with reduced ejection fraction, medical costs are 56% higher than in patients with HF with preserved ejection fraction.

Conclusion. HF causes significant economic burden to the state. Improving the healthcare system for this category of patients, including preferential drug provision, will reduce HF-related mortality, the healthcare system costs and, accordingly, reduce the economic impact on the state and society.

Aim. To analyze and compare the clinical, echocardiographic characteristics and serum N-terminal pro-brain natriuretic peptide (NT-proBNP) levels depending on the central cardiometabolic risk factors, with a focus on obesity, in patients with heart failure (HF) with mid-range ejection fraction (HFmrEF).

Material and methods. The study included 111 patients with old myocardial infarction and HFmrEF (men, 100%; mean age, 60 years) predominantly of NYHA class II. Echocardiography and blood sampling for NT-proBNP were performed with sinus rhythm. Left atrial volume (LAV) and left ventricular mass (LVM) were indexed to body surface area (BSA) and height raised to a power.

Results. Type 2 diabetes, overweight and obesity were diagnosed in 25%, 19%, 38% of cases, respectively, and were associated with greater changes in the morphologic and functional left ventricular parameters. There were no intergroup differences among patients with and without obesity in the LAV and LVM indexed to BSA. However, in patients with a body mass index (BMI) ≥30 kg/m², the LAV indexed to height squared and LVM indexed to height^2,7 were higher (p<0,05 for all). In 11% of obese patients, there were no changes in the criterion LAV or LVM values indexed to BSA, but the values indexed to height raised to a power exceeded the standard values. In 20% of patients with clinical manifestations of stable HFmrEF and structural and functional echocardiographic criteria, NT-proBNP were ≤125 pg/ml. An inverse correlation was found between NT-proBNP and BMI (r=-0,29; p=0,008), and lower values of myocardial stress marker were observed in obese patients (p=0,048).

Conclusion. Considering the high incidence of obesity in patients with HFmrEF and its ability to reduce NT-proBNP, an algorithm modification is required for diagnosing HFmrEF as follows: focus on clinical and personalized echocardiography data, taking into account the obesity and, possibly, indexing the threshold natriuretic peptide values in patients with BMI ≥30 kg/m². The issues of indexation of echocardiographic parameters depending on morphometric parameters in obese patients today remain open, predetermining the limitations in diagnosis of heart failure with left ventricular ejection fraction >40%. This requires the search for optimal standardization and the development of a unified methodological approach.

Aim. To assess the correlation of fibrosis biomarkers with parameters of diastolic function (DF) in assessing global longitudinal strain in patients with ST-segment elevation myocardial infarction (STEMI) and preserved left ventricular ejection fraction (EF).

Material and methods. We examined 50 patients (100%) with primary STEMI and preserved LVEF at the end of hospitalization. On the 1st day of MI, standard diagnostic investigations were carried out. On the 12th day, the serum concentration of procollagen type I carboxy-terminal propeptide (PICP), N-terminal propeptide of procollagen type III (PIIINP), and galectin-3 was determined, as well as echocardiography was performed to assess left ventricular DF. After 1 year, all participants underwent reassessment of PICP, PIIINP, and galectin-3 serum levels. Echocardiography was also performed with an assessment of DF and LV global longitudinal strain.

Results. According to speckle-tracking echocardiography, LV global longitudinal strain was visualized in 30 patients (60%), who were included in the final analysis. In the rest of the patients (40%), the limitations did not allow the technique to be performed. During the hospitalization, signs of diastolic dysfunction (DD) were detected in 5 (16,6%) patients; after 1 year, their number increased by 7 (23,3%). During the 1-year follow-up, the total number of patients with echocardiographic signs of DD was 20 (67%). At the same time, global strain parameters indicated the presence of DD in 23 (77%) patients. However, comparison of the incidence of DD according to echocardiography and using the speckle-tracking technology did not show significant differences (p=0,283). Throughout the entire follow-up period, the concentration of the studied fibrosis markers significantly exceeded the control group values. We recorded associations of global strain parameters with biochemical markers of fibrosis and LV DF indicators.

Conclusion. Fibrosis biomarkers (PICP, PIIINP, galectin-3), assessed in the subacute period of MI in patients with preserved EF, correlated with indicators of global myocardial strain, which indicates the potential value of their determination for predicting and detecting DD in the postinfarction period.

Aim. To develop a personalized approach to the trimetazidine use in patients with coronary artery disease (CAD) based on the criteria for predicting the cytoprotective activity tested in vitro.

Material and methods. We examined 30 patients with class I-III stable effort angina with concomitant hypertension and heart failure. The patients underwent echocardiography, complete blood count, biochemical tests with determination of the lipid profile, creatine phosphokinase (CPK), CPK-MB, renal and hepatic parameters. To determine the cytoprotective activity of trimetazidine, white blood cells (WBCs) of patients were examined in vitro using an Eclipse Ti-U inverted fluorescence microscope (Nikon, Japan). Living and dead cells were determined by staining WBCs with fluorescent dyes (Calcein AM, Ethidium bromide). Cell viability index (CVI) was calculated. The statistical processing was carried out. The criteria for predicting the trimetazidine cytoprotective effect were determined using Wald statistics.

Results. When trimetazidine was injected into a WBC suspension sample, two types of cell viability changes were observed: in 60% of patients, CVI increased, on average, by 37% (from 23% to 60%, p<0,001) and in 40% of patients, CVI decreased, on average, by 30% (from 54% to 24%, p<0,05).

A number of conditions of the patient initial status were identified for the manifestation of trimetazidine cytoprotective activity: grade 1 hypertension; right ventricular end diastolic dimension up to 30 mm according to echocardiography; normal lipid profile with a total cholesterol <5,3 mmol/L, very-low-density lipoproteins <1 mmol/L and an atherogenic coefficient up to 3 CU, myocyte and cardiomyocyte destruction (total CPK >100 U/L and CPK-MB >15 U/L), normal liver function (alanine aminotransferase <25 U/L), renal dysfunction (total protein <75 g/L, urea >8 mmol/L and blood creatinine >100 pmol/L), normal thrombopoiesis (immature platelet fraction <5%) and the state of functional adaptive system resistance (blood lymphocytes <30% and neutrophils >4x109/L).

Conclusion. According to this in vitro analysis, the trimetazidine significantly increases (by an average of 37%) the cell (WBC) viability in 60% of patients with CAD. There are conditions of patient initial status, which specifies an individual pharmacodynamic target for the cytoprotective action of the drug.

The paper discusses the issues of managing uncontrolled hypertension. It is noted that in the International Classification of Diseases, 10th revision (ICD-10), there is no diagnosis “hypertensive crisis”, which complicates the epidemiological estimates. In the new Russian Society of Cardiology guidelines, instead of using the term “uncomplicated hypertensive crisis”, the term “sudden pronounced individually relevant blood pressure (BP) increase” was proposed to describe pronounced BP increase without target organ damage. Since the term “uncomplicated hypertensive crisis” is not recommended for use, but this condition is often diagnosed in practice, it is advisable to replace this term with “sharp BP increase not accompanied by target organ damage” or “sudden pronounced individually relevant BP increase”. At the same time, there is no evidence that in patients with uncomplicated hypertensive crisis, a more rapid BP decrease is more effective over the standard antihypertensive therapy in relation to the risk of complications. The drug Physiotens® lowers BP smoothly and without sudden falls, while having favorable pharmacokinetics. The issues of revising the current approaches to antihypertensive therapy in patients with frequent BP increases, as well as the use of original drugs and generics are considered.

Current guidelines for the management of patients with dyslipidemia are well known and easily accessible. Despite this, according to research data based on actual clinical practice, selection of optimal tactics for managing patients with dyslipidemia often causes difficulties and leads to a failure to achieve the target levels. Tools such as clinical decision support system (CDSS) can help clinicians follow current clinical guidelines, taking into account the diversity of phenotypic profiles and side effects. This review highlights the effectiveness of CDSS implementation in medical practice as a means for making decisions in managing patients with dyslipidemia, as well as presents the algorithm for CDSS for lipid metabolism disorders created by specialists of the Almazov National Medical Research Center and the University of Milan.

It is known that the key mediator of acute phase response and marker of inflammation is C-reactive protein (CRP), the study of the role of which in the development of not only cardiovascular, but also infectious diseases has acquired particular relevance at the present time. CRP can be involved in all stages of the atherosclerotic process, including activation of the complement system and vascular endothelial cells, thrombosis, lipid accumulation, and apoptosis.

The review describes modern concepts of the structure, biological and pathophysiological properties of CRP, its value as a cardiovascular risk predictor, as well as existing methods for reducing its blood level.

According to recent studies, cardiovascular patients who achieved lower CRP levels with drug therapy had better clinical prognosis, making CRP an attractive therapeutic target. Currently, a search is underway for approaches to correct CRP levels associated with both the development of novel drugs and therapeutic apheresis methods to remove CRP from blood plasma.