On December 18, 2022, an interdisciplinary Expert Council was held in St. Pe­ter­sburg, dedicated to the debatable issues of anticoagulation in the prevention of venous thromboembolism in pregnant women with cardiovascular and systemic diseases, at which a number of proposals and guidelines were adopted, and the results of the Highlow study were considered. Leading experts from the Russian Society of Cardiology, the Russian Society of Obstetricians and Gynecologists, the National Association of Specialists in Thrombosis, Clinical Hemostaseology and Hemorheology took part in the Expert Council.

The objective of this advisory board meeting was to discuss the place of vericiguat in the treatment algorithm for heart failure with reduced ejection fraction and the necessary requirements for its successful application in clinical practice.

Aim. To assess gene expression of enzymes of the sphingomyelinase pathway of ceramide biosynthesis and degradation in fat depots of various localization in patients with cardiovascular diseases.

Material and methods. A total of 38 patients were examined: 20 with coronary artery disease (CAD) and 18 with aortic stenosis/insufficiency. Biopsies of subcutaneous, epicardial, perivascular adipose tissue (AT) (SAT, EAT, PVAT, respectively) were obtained during surgery. The gene expression of sphingomyelinase pathway enzymes (acid and neutral sphingomyelinase SMPD1 and SMPD3) and the degradation of ceramides (acid ceramidase ASAH1; sphingomyelin synthase 1 and 2 SGMS1 and SGMS2) was assessed using a quantitative polymerase chain reaction. Analysis of the level of corresponding proteins was carried out using immunoblotting (western blotting). Statistical processing was performed using GraphPad Prism 8 (GraphPad Software).

Results. In CAD, the maximum expression of SMPD1 was observed in subcutaneous and epicardial adipocytes. In acquired heart defects (AHD), the level of SMPD1 mRNA in the SAT was higher than in the PVAT. Expression of the SMPD1 gene in the EAT of patients with CAD was more pronounced than in patients with heart defects. PVAT was characterized by minimal expression of SMPD1 regardless of disease. Expression of SMPD3 had no tissue features in studied groups, while SMPD1 was more expressed in cardiac AT adipocytes than SMPD3. ASAH1 in the EAT of patients with CAD was maximal relative to adipocytes of other localizations. Persons with AHD were characterized by a high expression of ASAH1, regardless of AT localization, exceeding the values of patients with CAD. In CAD, the level of SGMS1 in EAT was higher than in SAT and PVAT, while no differences were found in patients with AHD depending on AT location. SGMS1 gene expression in EAT of patients with CAD was higher than in the group of AHD. Expression of SGMS2 significantly exceeded SGMS1 in both study groups and was maximal in SAT and PVAT adipocytes compared to EAT in the CAD group and in PVAT in the AHD group. Coronary pathology was characterized by a higher level of SGMS2 mRNA in SAT and EAT. The level of ceramide metabolism enzymes in AT of patients corresponded to the expression of their genes.

Conclusion. In coronarogenic disease, cardiac AT (mainly epicardial) is characterized not only by increased expression of gene ceramide synthesis enzymes via the sphingomyelinase pathway, but also by activation of ceramide utilization with sphingosine formation. The observed changes may contribute to the accumulation of ceramides and sphingomyelin associated with atherosclerotic processes.

Aim. To study the factors preventing the LVDD in obese patients.

Material and methods. The study included 101 obese men who initially did not have LVDD. After 4,7±0,3 years, anthropometric parameters (body mass index (BMI), hip circumference (HC), waist circumference (WC)) and LV diastolic function were reassessed. All patients at the time of enrollment were assessed for the level of neurohumoral (leptin, adiponectin, leptin receptor), pro-inflammatory (tumor necrosis factor-α, interleukin-6, -10, C-reactive protein) and profibrotic factors (collagen type I and III, matrix metalloproteinase-3, vascular endothelial growth factor, transforming growth factor β).

Results. During 4,7±0,3 years of follow-up, 26,7% of the total number inclu­ded in the study registered a decrease in body weight. A tendency to a de­crease in epicardial fat thickness (EFT) by 0,5 mm (7,49 (6,00; 9,00) mm at the time of inclusion and 7,04 (6,00; 9,00) mm over time (p=0,13)). According to echocardiography, LVDD was detected in 20 patients (19,8% after 4,7±0,3 years). Comparative analysis of baseline anthropometric parameters, EFT and after 4,7±0,3 years in groups of patients with (DD+) and without (DD-) LVDD revealed a significant decrease in body weight (p=0,03), BMI (p=0,02), WC (p=0,04) and EFT (p=0,002) only in the DD- group. Patients who developed LVDD initially had increased tumor necrosis factor-α (p=0,02), interleukin-6 (p=0,01), free fatty acids (p=0,001), type I collagen (p=0,001), type III collagen (p=0,02) and a decrease in adiponectin level (p=0,001).

Conclusion. Thus, in patients with a decrease in weight, BMI, WC and EFT during the follow-up period of 4,7±0,3 years, LVDD did not develop, which is associated with a reduced risk of myocardial lipotoxicity against the background of epicardial obesity.

Aim. To identify sex characteristics of the prevalence of obesity and hypertension (HTN) in the adult population of the Vladimir region.

Material and methods. The study included 1350 people, men and women aged 30-69 years from 5 cities of the Vladimir region (Vladimir, Kovrov, Murom, Yuriev-Polsky and Vyazniki). The response rate was at least 80%. In total, 1174 people completed the study, including 424 men (36,1%) and 750 women (63,9%). The survey was conducted according to a standard questionnaire, including socio-demographic parameters and behavioral risk factors. In all patients, anthropometric parameters, blood pressure, heart rate and resting electrocardiography were assessed.

Results. The average body mass index among women was significantly higher
compared to men (29,9±6,2 kg/m² vs 28,3±4,7 kg/m², p<0,001), while waist circumference among men exceeded similar parameters among women (95,5±11,7 cm vs 91,9±15,3 cm, p<0,001). Sex differences in anthropometric indicators have a number of features in different cities. Every third man is obese, while among women this figure was significantly higher (33,7% vs 42,1%, p<0,001). Every second man and 2/3 of women had abdominal obesity (53,1% and 71,6%, p<0,001). The prevalence of HTN among men and women was comparable (41,5% and 39,9%, respectively). Electrocardiographic signs of left ventricular (LV) hypertrophy are detected in every third respondent, while its prevalence between men and women did not differ statistically (30,5% and 35,5%, respectively).

Conclusion. In the surveyed population of men and women of the Vladimir region, the prevalence of obesity and HTN were comparable. The prevalence of obesity and abdominal obesity has sex differences due to the greater severity among women. Hypertension is also highly likely to be associated with LV hypertrophy. Obviously, in order to correct obesity and HTN, lifestyle changes at the population level must be combined with the use of antihypertensive therapy to achieve target blood pressure levels and regress LV hypertrophy.

Aim. To study the prognostic role of neutrophil gelatinase-associated lipocalin (NGAL) as a marker of adverse cardiovascular events (CVEs) in patients with coro­nary artery disease (CAD) associated with abdominal obesity (AO).

Material and methods. This 12-month prospective study included 68 patients diagnosed with CAD who were hospitalized for elective percutaneous coronary intervention (PCI). The median age was 61 [55;65] years. Depending on the presence of obesity according to the World Health Organization (1999) criteria, patients were divided into 2 groups. The 1st group included 30 patients with AO, while the 2nd group — 38 patients without obesity. Patients were measured for waist circumference and hip circumference, and waist-to-hip ratio was calculated. Lipid profile and NGAL concentration were determined. During the study, body mass index (BMI), visceral adiposity index (VAI), triglycerides (TG)/glucose index, lipid accumulation product (LAP), metabolic index (MI), TG to high-density lipoprotein cholesterol ratio (HDL-C). During this period, data was collected on the disease course and intervention outcome. After 12 months an extended examination was performed to assess the endpoints.

Results. During the follow-up period, unfavorable cardiovascular events in the 1st group of patients were registered in 33,3% of patients, and in the 2nd group — in 26,3%. In the group of patients with obesity, higher values of anthropometric indices and NGAL were established. The concentration of NGAL has the highest correlation with BMI, MI, LAP and slightly less with total cholesterol and VAI levels. The analysis showed that NGAL >47,1 ng/ml is a predictor of adverse CVEs in patients with CAD and obesity after PCI.

Conclusion. Thus, NGAL has the highest correlation with the following indices: BMI, MI, LAP, total cholesterol, and VAI. NGAL >47,1 ng/ml is a predictor of adverse CVEs in patients with CAD and obesity after PCI. NGAL may serve as a promising marker for predicting adverse CVEs. This biomarker already at the stage of hos­pitalization can assess the risk adverse outcomes in patients with CAD and AO, including those who underwent PCI.

The article reflects modern aspects of lipid-lowering therapy, based on the as­sessment of cardiovascular risk, and the possibilities of triple therapy, including statins, ezetimibe, and inclisiran.

We present our own data on the use of the drug inclisiran in patients with lipid metabolism disorders in the framework of secondary and primary cardiovascular prevention. Low-density lipoprotein levels at different times after the injection is described. The potential of innovative lipid-lowering therapy in liver transplant recipients in the long-term postoperative period are discussed.

The addition of inclisiran to statin and ezetimibe therapy is safe and leads to a decrease in low-density lipoprotein levels by more than 50% of baseline values in the general population.

Induced hypertension (HTN) is one of the HTN types, the pathogenetic mecha­nisms of which are well studied: its main cause lies in the dysfunction of visceral adipose tissue, which leads to renin-angiotensin-aldosterone system activation, imbalance of the sympathetic and parasympathetic systems, renal involvement, and then to vascular endothelium dysfunction and, in fact, to an increase in blood pressure and HTN consolidation. However, within this HTN form, some mechanisms can be distinguished that, in obesity, play a special role. This review describes such additional mechanisms as chronic inflammation, excessive salt intake, dys­biosis, environmental factors. Understanding these HTN features in obesity has es­sential for achieving target blood pressure levels. In addition, the review pays special attention to such HTN forms in obesity as masked and nocturnal, the timely diagnosis of which is extremely important for the timely initiation of therapy and improving the prognosis.

Aim. To assess the relationship of arterial stiffness, inflammatory markers, some metabolic risk factors, including gender-specific aspects, in hypertensive (HTN) patients working in the Arctic on a rotating basis.

Material and methods. In the polar settlement of Yamburg (68^о 21’ 40" northern latitude), on the basis of the medical unit of OOO YaGD, 99 men (M) and 81 women (F) with grade 1-2 HTN (61 M and 44 F) and normotensive individuals (HTN0) were examined. Patients with HTN were comparable in terms of age (p=0,68), number of rotation work years (p=0,7701), office systolic BP (p=0,473), diastolic BP (p=0,6992), and body mass index (p=0,465). We carried out 24-hour BP monitoring, common carotid artery ultrasound with the calculation of local stiffness parameters (distensibility coefficient, stiffness index, Peterson’s elastic modulus (Ep), Young’s elastic modulus (Eу)); pulse wave velocity (PWV) was studied. In addition, biochemical blood tests with the determination of high-sensitivity C-reactive protein, homocysteine, C-peptide, insulin, cortisol, atrial natriuretic peptide, interleukins (IL-1β, IL-6, IL-8, IL-10), tumor necrosis factor (TNF-α).

Results. In groups M and F with HTN, in comparison with HTN0, higher values of following vascular stiffness parameters were revealed: group F — pulse pressure (p=0,018), intima-media thickness (p=0,0077), PWV (p<0,00001), Eу (p=0,0314); group M — PWV (p=0,0004), Eу (p=0,0024) and reduced common carotid artery strain (p=0,0131). In M with HTN, in comparison with F with HTN, intima-media thickness (p=0,0008), stiffness index (p=0,0368), Ep (p=0,051) were higher. PWV in M and F with HTN was determined significantly higher than in persons with normal BP (p=0,0007; p=0,0001). Correlation analysis revealed the relationship between PWV and 24-hour blood pressure monitoring in hypertensive men and women. An increase in PWV per unit of measurement in women increases the HTN probability by 1,7 times, in men — by 1,4 times. Compared with HTN0 group, the levels of C-peptide (p=0,032), insulin (p=0,035), IL-1β (p=0,025), cortisol (p=0,031) in M group were significantly higher, while significantly higher levels of C-peptide (p=0,015), insulin (p=0,012), IL-6 (p=0,021), TNF-α (p=0,047) were revealed in F group. Stepwise logistic regression analysis revealed following independent parameters affecting the HTN probability: M group — PWV (odds ratio (OR) 1,554 (95% confidence interval (CI): 1,058-2,281, p=0,025)), C-peptide (OR 1,186 (95% CI: 1,004-1,588, p=0,022)), IL-1β (OR 1,464 (95% CI: 0,936-2,291, p=0,099)); F group — PWV (OR 2,015 (95% CI: 1,319-3,078, p=0,001)), C-peptide (OR 2,133 (95% CI: 1,236-3,680, p=0,006)), IL-6 (OR 2,101 (95% CI: 1,003-4,400, p=0,049)) and reduced TNF-α level (OR 0,801 (95% CI: 0,668-0,959, p=0,016)).

Conclusion. Under the rotation work conditions in the Arctic, high vascular stiffness values, regardless of sex, are associated with HTN. In men, regardless of BP level, vascular stiffness parameters were higher. However, a stronger association of vascular stiffness with the HTN risk was observed in women. In hyper­tensive patients in the Arctic, an association of vascular stiffness with nonspecific immune inflammation factors was found, which was more pronounced in women. In addition to vascular stiffness and pro-inflammatory cytokines, the "northern" HTN model includes C-peptide, which is an atherosclerosis modulator.

Aim. Identification and analysis of the features of vascular stiffness, 24-hour blood pressure (BP) profile, and central aortic pressure (CAP) in patients with hyper­tension (HTN) and anxiety-depressive disorders (ADDs) during andro- and meno­pausal periods.

Material and methods. The study included 120 patients with uncontrolled hyper­tension in the andro- and menopausal periods, of which 60 patients with hyper­tension and ADDs (30 men and 30 women) with median age of 58 years (52-64 years), as well as the control group — 60 patients with hypertension without ADD (30 men and 30 women) with median age of 59 years (53-65 years). All persons included in the study underwent 24-hour ambulatory BP monitoring (ABPM) and assessed the arterial stiffness parameters and CAP.

Results. Comparative evaluation of ABPM in the group of patients with HTN and ADDs revealed more pronounced pathological changes in the 24-hour BP profile compared to those in the control group. Andro- and menopause with a combination of HTN and ADDs characterized by significantly higher ABPM parameters than HTN without ADDs (regardless of the sex). At the same time, in the group of men with HTN and ADD in andropause, unfavorable changes in the main arterial stiffness parameters and CAP were more significant than in women with HTN and ADD during menopause (p<0,05). In the control men groups, in comparison with women, more pronounced unfa­vo­-
rable changes in certain vascular stiffness indicators, CAP and ABPM were recorded.

Conclusion. In men and women in periods of andro- and menopause with HTN and ADDs, the features of arterial stiffness, CAP, and 24-hour blood pressure profile were verified in comparison with patients with HTN without ADDs. At the same time, the severity of unfavorable changes in the studied parameters in men with depression in andropause is more significant than in menopausal women.

Aim. To develop predictive models of inhospital mortality (IHM) in patients with coronary artery disease after coronary artery bypass grafting (CABG), taking into account the results of phenotyping of preoperative risk factors.

Material and methods. This retrospective study was conducted based on the data of 999 electronic health records of patients (805 men, 194 women) aged 35 to 81 years with a median (Me) of 63 years who underwent on-pump elective isolated CABG. Two groups of patients were distinguished, the first of which was represented by 63 (6,3%) patients who died in the hospital during the first 30 days after CABG, the second — 936 (93,7%) with a favorable outcome. Preoperative clinical and functional status was assessed using 102 factors. Chi-squares, Fisher, Mann-Whitney methods were used for data processing and analysis. Threshold values of predictors were determined by methods, including maximizing the ratio of true positive IHM cases to false positive ones. Multivariate logistic regression (MLR) was used to develop predictive models. Model accuracy was assessed using 3 following metrics: area under the ROC curve (AUC), sensitivity (Sens), and specificity (Spec).

Results. An analysis of preoperative status of patients made it possible to identify 28 risk factors for IHM, combined into 7 phenotypes. The latter formed the feature space of IHM prognostic model, in which each feature demonstrates the patient’s compliance with a certain risk factor phenotype. The author’s MLR model had high quality metrics (AUC-0,91; Sen-0,9 and Spec-0,85).

Conclusion. The developed data processing and analysis algorithm ensured high quality of preoperative risk factors identification and IHM prediction after CABG. Prospects for further research on this issue are related to the improvement of explainable artificial intelligence technologies, which allow developing infor­mation systems for managing clinical practice risks.

Aim. To analyze mortality from cardiovascular diseases (CVDs) and diseases associated with cognitive impairment (CI) in the regions of the Russian Federation.

Material and methods. We analyzed Rosstat mortality data in 82 Russian regions in mid-year population in one-year age groups for 2019-2021. Eleven groups of causes have been formed, standardized mortality rates (SMRs), average regional SMRs, and their changes over time was assessed.

Results. In total, SMRs from CVD and CI increased from 551,4±84,9 in 2019 to 622,6±98,5 per 100 thousand population in 2020 and decreased in 2021 to 612,6±106 per 100 thousand population. However, its proportion in all-cause mortality decreased by almost 10% (46,97±4,6 in 2021 and 55,98±4,6% in 2019). The growth of SMRs from year to year was noted in 30 regions; in other regions, unstable changes were noted. The proportion of CVD causes from all-cause mortality was 30,5±5,8% in 2019, 29,1±5,7% in 2020 and 25,95±5,56% in 2021 (p<0,0001). The largest SMRs and their proportion in the mortality structure are in group 1 (chronic coronary artery disease (CAD) — an average of 17,8±5,8% over 3 years) and group 6 (causes with unclear criteria for the disease, but associated with CI — 13,9±5,9%). The contribution of the second (acute coronary artery disease — 4,6±2,8%), the third (defects, cardiopathies, endo- and myocarditis — 4,8±2,7%) and the fifth (stroke — 6,1±1,7%) groups of causes are much smaller. The sixth place in terms of SMRs and contribution to all-cause mortality is occupied by alcohol-associated causes (1,8±1,1%). The proportion of other causes (hypertension, Alzheimer’s disease, Parkinson’s disease, other mental disorders) is small.

Conclusion. When developing and implementing programs aimed at reducing mortality, results obtained should be taken into account. Significant regional differences in the rate and changes of SMRs over time indicate the need to unify the criteria for the underlying cause of death, especially in multimorbid patients.

Aim. To analyze newly diagnosed diseases and features of the post-COVID course in patients after a coronavirus disease 2019 (COVID-19) within 12-month follow-up.

Material and methods. A total of 9364 consecutively hospitalized patients were included in the ACTIV registry. Enrollment of patients began on June 29, 2020, and was completed on March 30, 2021, corresponding to the first and second waves of the pandemic. Demographic, clinical, and laboratory data, computed tomography (CT) results, information about inhospital clinical course and complications of COVID-19 during hospitalization were extracted from electronic health records using a standardized data collection form. The design included follow-up telephone interviews with a standard questionnaire at 3, 6, and 12 months to examine the course of post-COVID period.

Results. According to the ACTIV registry, 18,1% of patients after COVID-19 had newly diagnosed diseases (NDDs) over the next 12 months. Hypertension (HTN), type 2 diabetes and coronary artery disease (CAD) prevailed in the NDD structure. Comparison of the age-standardized incidence of NDDs (HTN, CAD, diabetes) in the post-COVID period in the ACTIV registry with NDD incidence in 2019 according to Rosstat and the expected incidence of NDDs according to the EPOHA study revealed that HTN, diabetes, CAD in patients after COVID-19 were registered more often as follows: HTN by 7,0 and 4,4 times, diabetes by 7,3 and 8,8 times, CAD by 2,3 and 2,9 times, respectively. NDDs most often developed in patients aged 47 to 70 years. Comparison of the actual and expected number of cases of newly diagnosed HTN, CAD and diabetes depending on age showed that the actual number of cases in the population of patients in the ACTIV register is significantly higher than expected for patients aged 45-69 years and for patients with hypertension or diabetes and aged <45 years. Patients with NDDs, compared with patients without NDDs, had a more severe acute COVID-19 course. Statistically significant independent predictors of NDD occurrence (HTN and/or diabetes and/or CAD) within 1 year after hospital discharge were age (direct relationship), body mass index (direct relationship) and glucose levels upon admission to hospital (direct relationship).

Conclusion. Available evidence suggests that a strategy for managing COVID-19 survivors should include mandatory screening for early detection of cardiovascular disease and diabetes, which will be key to reducing the risk of further COVID-19 consequences.