Aim. To study of the relationship between gene polymorphisms (FGA, ITGA2, PAI1) and pulmonary embolism (PE).

Material and methods. We examined 120 patients with pulmonary embolism, who made up the main group (mean age, 63,22±3,16 years). There were 66 men (mean age, 60,24±3,17 years) and 54 women (mean age, 6,19±3,67 years). The control group consisted of 200 people (mean age, 64,92±3,50 years). The DNA Bank of the Research Institute of Internal and Preventive Medicine was formed during a series of population screenings. All patients signed written informed consent to participate in the molecular genetic study. The work involved the calculation of the following output data: standard deviation; mean square; Pearson chi-squared test; likelihood ratio; Fisher's exact test and linear relationship.

Results. The probability of PE among women carriers of ID genotype of FGA gene rs35496957 polymorphism in the group with PE is 2,08 times higher than that in the control group (95% confidence interval (CI), 1,06-4,09; p=0,32); among women carriers of the TT genotype of ITGA2 gene rs1126643 polymorphism in the group with PE — 3,08 times compared to the control group (95% CI, 1,36-6,97; p=0,006).

Conclusion. The study of genetic factors in the development of pulmonary embolism (FGA, ITGA2, PAI-1) is necessary to create a personalized approach to patient management at all stages.

Aim. To evaluate the association of the nucleotide sequence variant rs1799752 (I/D) of the angiotensin-converting enzyme (ACE) gene with acute coronary syndrome (ACS) in patients after a coronavirus disease 2019 (COVID-19).

Material and methods. The study included 100 patients (women — 50, men — 50) with ACS and prior COVID-19, verified by a polymerase chain reaction (PCR), hospitalized in the regional vascular center № 7 of the City Clinical Hospital № 2 city of Novosibirsk. The mean age of women and men was 59,5±7,2 years and 53,5±9,3 years, respectively. The diagnosis of ACS was established according to a set of criteria proposed and established by the Russian Society of Cardiology and in accordance with the updated 2020 guidelines. Patients underwent examinations, coronary angiography with stenting, as provided for in the standards of care and guidelines. In patients, the nucleotide sequence variant rs1799752 of the ACE gene was determined using PCR. The comparison group consisted of 200 patients with ACS without COVID-19 (no positive PCR or antibodies). Statistical analysis was carried out using the SPSS 17.0.5 software package.

Results. When comparing the frequencies of rs1799752 genotypes of the ACE gene in groups with ACS with COVID-19 and ACS without COVID-19, significant differences were obtained (p=0,013). In the group with ACS and COVID-19, carriage of the heterozygous genotype was less common (p=0,005) and there was an accumulation of carriers of the homozygous DD genotype (1,6 times higher; 26% vs 16%; p=0,044).

Conclusion. The nucleotide sequence variant rs1799752 (I/D) of the ACE gene is associated with ACS in patients after COVID-19.

Aim. To determine the associations of allelic variants of the CYP2C19 gene with coronary atherosclerosis and ischemic events in patients with myocardial infarction (MI) living in the Khanty-Mansi Autonomous Okrug — Yugra.

Material and methods. This prospective observational study included 203 patients with acute MI who underwent percutaneous coronary intervention. Patients also underwent genetic testing using real-time polymerase chain reaction to determine allelic variants of the CYP2C19 gene. Using biostatistical analysis methods, associations were established between the genotypes of patients with MI, their clinical characteristics and major ischemic events over 7-year follow-up.

Results. Significant associations were identified between allelic variants of CYP2C19*2 (*1/*2 and *2/*2) and smoking, right ventricular volume and glomerular filtration rate (GFR). The presence of the allelic variant CYP2C19*3 (*3/*3) was associated with GFR ³90 ml/min/1,73 m² and impaired glucose tolerance. A significant association was established between the CYP2C19*17 alleles (*1/*17, *17/*17) with coronary atherosclerosis, smoking, levels of troponin T, aspartate aminotransferase, total cholesterol, left ventricular posterior wall thickness, and a history of myocardial infarction. Data from multivariate analysis showed a clear association of allelic variants of CYP2C19*2 (*1/*2 and *2/*2) with the composite endpoint of 7-year follow-up (death, recurrent myocardial infarction, stent/bypass thrombosis, myocardial revascularization). A significant influence of CYP2C19*17 genotypes (*1/*17 and *17/*17) on myocardial revascularization in patients in the post-infarction period was also determined.

Conclusion. CYP2C19*2 genotypes (*1/*2 and *2/*2) in MI patients living in Khanty-Mansi Autonomous Okrug — Yugra are clearly associated with ischemic events during a 7-year follow-up. CYP2C19*17 genotypes (*1/*17 and *17/*17) are clearly associated with coronary atherosclerosis and myocardial revascularization in the long-term post-infarction period.

Aim. To identify and rank factors predisposing to angina relapse in Buryat patients who underwent percutaneous intervention for acute coronary syndrome.

Material and methods. The study included 142 Buryat patients who underwent coronary stenting for acute coronary syndrome. All patients received clopidogrel. The CYP2C19*2 and CYP2C19*3 alleles were determined. Efficacy endpoints were assessed according to the Academic Research Consortium-2 criteria. Laboratory parameters and concomitant omeprazole therapy were assessed.

Results. This study examined in detail a group of patients with short-term angina relapse without formal signs of unstable angina. A logistic regression model was obtained that makes it possible to identify and rank independent risk factors for recurrent angina in Buryat patients. Risk factors were ranked as follows: carriage of CYP2C19*2 and/or CYP2C19*3 alleles (coefficient b1=3,489, 95% confidence interval (CI) (3,096-346,213)), treatment with omeprazole (b2=2,816, 95% CI (2,745-101,616)), male sex (b3=2,749, 95% CI (1,425-163,458)) and blood glucose level (b4=0,354, 95% CI (1,141-1,779)).

Conclusion. Thus, angina pain relapse in Buryat patients is facilitated by signs significant for recurrent myocardial infarction. This study suggests that patients with recurrent angina pain without electrocardiographic deterioration and biomarker elevation may require more careful personalization of therapy.

Aim. To identify predictors of heart failure in patients with dilated cardiomyopathy (DCM) and ischemic myocardial dilatation (IMD).

Material and methods. In total, we examined 221 patients with cardiomyopathies: DCM and IMD. The mean age of the patients was 55,30±9,69 years (minimum — 20 years, maximum — 77 years). From the total number of patients, a group of patients with DCM (idiopathic origin) (group 1) was identified in the amount of 111 people, of which 99 were men (89,2%) and 12 women (10,8%). The mean age of patients with DCM was 51,73±9,74 years, for men — 51,00±8,96 years, for women — 57,75±3,71 years. The median age in DCM patients was 53,00 [48,00; 58,00], for men — 53,00 [46,00; 57,00], in women — 59,50 [49,00; 68,75]. Patients with IMD (ischemic origin) consisted of 110 people (group 2), of which 100 were men (91,5%) and 10 women (8,5%). The mean age of patients with IMD was 58,68±8,38 years, for men — 58,29±8,46 years, for women — 62,90±6,29 years. The median age in patients with IMD was 58,00 [53,50; 63,50], in men — 58,00 [52,00; 63,00], in women — 61,50 [59,25; 66,00]. Biological material (venous blood) was taken from all patients for molecular genetic analysis. To isolate the DNA structure, the phenol-chloroform extraction was used. Using the polymerase chain reaction, genotyping of gene  polymorphisms was carried out, followed by analysis of restriction fragment length polymorphisms.

Results. To assess the left ventricular systolic function, the ejection fraction was assessed. Heart failure and its severity are most often associated with a decrease in left ventricular (LV) systolic function. In our study, in the group of patients with DCM, the mean LV ejection fraction (EF) was 25,105±6,76, while in IMD group — 20,255±4,49 (p=0,0001). This confirms that these two groups have severe heart failure associated with impaired LV systolic function — a decrease in EF <30%. In patients with NYHA class III heart failure with IMD, there was a significant predominance of the heterozygous genotype (6a/5a) of the MMP3 gene polymorphism compared to the control group (66,7% vs 12,5%, p=0,023).

Conclusion. The heterozygous genotype of the MMP3 gene polymorphism can be considered as a predictor of the development of HF in patients with IMD for the purpose of early diagnosis and prevention of heart failure. In the group of patients with DCM, no differences were found during a comparative analysis with gene polymorphism.

Aim. To study the effectiveness of the calcium channel blocker amlodipine in the treatment of salt-sensitive hypertension (HTN) and compare it with the genotypes of patients.

Material and methods. The study involved 96 patients aged 42,7±5,2 years. There were following inclusion criteria: diagnosis — grade 1, stage 1 hypertension with low risk of cardiovascular events (CVEs). Before inclusion in the study, patients had not taken regular antihypertensive therapy for 3 months. Next, all patients underwent assessment of salt sensitivity of blood pressure according to the M. H. Weinberger method and, based on it, the participants were divided into salt-sensitive and salt-resistant. Regardless of the result, all patients were recommended to have a low-salt diet of 3-5 g/day, with subsequent 24-hour ambulatory blood pressure monitoring (ABPM) during the diet. In patients with ineffective diet, amlodipine was prescribed on day 26 at a dose of 2,5-5 mg once a day. The effectiveness of the drug was assessed by repeated ABPM. In addition, a genetic study was performed on 4 polymorphic variants of the genes AGT (T704C), AGT (C521T), AGTR1 (A1166C), AGTR2 (G1675A), ADD1 (G1378T), CYP11B2 (C344T), GNB3 (C825T), NOS3 (T786C), NOS3 (G894T), to determine their association with the effectiveness of a low-salt diet and amplodipine therapy.

Results. In patients with grade 1, stage 1 hypertension with low risk of CVEs, the effectiveness of a low-salt diet and amlodipine monotherapy at a dose of 2,55 mg/day was revealed. The results of the study were confirmed by achieving target values of office blood pressure and ABPM. In hypertensive patients not sensitive to salt, amlodipine monotherapy was ineffective. The genotyping revealed a relationship between antihypertensive therapy with amlodipine in salt-sensitive patients and carriage of the GG polymorphism of the AGTR2 gene.

Conclusion. The effectiveness of amlodipine and a low-salt diet in salt-sensitive patients with grade 1 hypertension, stage 1, low risk of CVEs with carriage of the GG genotype of the AGTR2 gene.

Aim. To assess the possibility of familial hypercholesterolemia (FH) detection among patients with early coronary artery disease (CAD) in practice in comparison with data from different populations. Patients with early manifestations of CAD are a promising group for identifying a proband with FH and subsequent cascade screening. The question remains open about the sufficiency of clinical criteria for diagnosing this disease.

Material and methods. We examined 651 patients with CAD manifestations aged £55 years in men and £60 years in women. FH was diagnosed according to the Dutch Lipid Clinic Network (DLCN) criteria, and cardiovascular risk was assessed using the Montreal-FH-SCOR E. In 35 phenotype-positive patients with FH, as well as 5 with lowdensity lipoprotein cholesterol levels ³5,5 mmol/l and 23 with age of manifestation of coronary artery disease £35 years, the coding sequence of the genes for apolipoprotein B (APOB), low-density lipoprotein receptor (LDLR), low-density lipoprotein receptor adapter protein 1 (LDLRAP1), proprotein convertase subtilisin/kexin type 9 (PCSK9).

Results. Definite FH was in 8 (1,2%), probable in 27 (4.2%), possible in 339 (52,1%) patients, while 277 (42,5%) patients had DLCN score of <3 points; 31 (88,6%), of 35 phenotype-positive patients had a high Montreal-FH-SCORE risk. Six carriers of pathogenic variants were identified, 2 of which were among phenotype-negative patients. A meta-analysis of 16 studies with 13065 patients (2012-2023) showed that the incidence of FH is 5,22 (4,848-5,619)% (fixed model) and 5,93 (4,528-7,515)% (random model).

Conclusion. The use of existing diagnostic scales does not provide guaranteed detection of FH among patients with early CAD. It is likely that DLCN modification by additional gradation of the criterion for the age of CAD manifestation will help increase its diagnostic value.

Wolff-Parkinson-White syndrome (WPW) is a syndrome with early ventricular excitation due to the abnormal electrical conduction through an accessory atrioventricular pathway, and is usually accompanied by supraventricular tachycardia. There is a proven genetic component in the development of this syndrome. This review presents current literature data on the association of nucleotide sequence variants of the PRKAG2 and PRKAG3 genes in patients with WPW.

Clonal hematopoiesis is a common age-dependent state accompanied by the expansion of mutant hematopoietic stem cells as a result of somatic mutations and is associated with a high risk of hematopoietic neoplasms and cardiovascular diseases. Clonal hematopoiesis in human ontogenesis occurs asymptomatically, and the fraction of mutant clones can exceed more than 2% of the total pool of circulating nucleated blood cells by age 70. Due to the variability of the accumulation rate of mutant clones, signs of clonal hematopoiesis can be observed at a younger age. Clonal hematopoiesis may act as a benign, precancerous condition and a strong factor for acute cardiovascular events such as myocardial infarction and stroke. Current evidence indicates that somatic mutations in driver genes of clonal hematopoiesis significantly increase the risk of acute conditions such as acute myeloid leukemia and acute myocardial infarction. The high mortality and morbidity of cardiovascular and cancer diseases, and their strong association with clonal hematopoiesis, make it of indeterminate potential worthy of close attention.

The most important task in providing care to patients with myocardial infarction is maintaining myocardial contractility. The article discusses issues related to the influence of genetic characteristics of patients on the repair of infarcted myocardium, the remodeling process, and restoration of left ventricular systolic and diastolic function. One approach to improving the predictive ability of genetic testing is to combine information about many nucleotide sequence variants into a single risk score, often called a polygenic risk score. The article examines recent publications on the creation and use of polygenic risk scores. The use of genetic methods during examination, further consideration of the individual characteristics of each patient when choosing therapy and prescribing a course of rehabilitation will allow for an individual approach to each patient, which in turn should have a positive impact on the disease prognosis.

Aim. To describe the antihypertensive efficacy of triple fixed­dose combination of amlodipine/indapamide/perindopril and assess the predictors of efficacy in young patients (<50 years).

Material and methods. The TRICOLOR study (NCT03722524) is an observational prospective study (n=1247) that demonstrated high antihypertensive effectiveness and good tolerability of the triple single­pill combination (SPC) of amlodipine/ indapamide/perindopril. This subgroup analysis was performed on 199 patients aged <50 years (16% of the total population), and the comparison group consisted of 925 patients (82,3% of the total population) aged 50 years or older.

Results. In young patients, during triple therapy with SPC amlodipine/indapa­ mide/perindopril, a positive trend in blood pressure (BP) reduction was observed compared to the baseline: an average decrease in BP after 12 weeks was 32,6 (11,0)/14,8 (8,5) mm Hg (p<0,0001), comparable to patients over 50 years of age in terms of reduction in systolic blood pressure (SBP) and diastolic blood pressure (DBP) after 2, 4 and 12 weeks of follow­up. A greater number of young patients achieved a reduction in blood pressure <140/90 mm Hg after 2 weeks of therapy compared to patients 50 years of age and older (49,7% vs 38,8%, p=0,004), and blood pressure <130/80 mm Hg – after 4 and 12 weeks (51,3% vs 43,5% (p=0,041) and 74,9% vs 67,5% (p=0,038), respectively). Left ventricular hypertrophy was a significant negative predictor of SBP reduction by 12 weeks of therapy, and the presence of grade 2 hypertension (HTN) and statin use, on the contrary, were positive predictors of changes in SBP by the end of observation. More adherent younger patients were significantly more likely to have a decrease in DBP by 12 weeks of follow-up. In addition, in young patients, male sex and the presence of dyslipidemia significantly increased the chances of blood pressure control at the end of observation. Waist circumference, body mass index, and grade 2 HTN were negative predictors of achieving the target blood pressure level.

Conclusion. Thus, in young patients, good antihypertensive effectiveness of amlodipine/indapamide/perindopril was observed, comparable in the degree of blood pressure reduction with the older age group of 50 years and older.

HMG-CoA reductase inhibitors (statins) are a key class of drugs for the treatment and prevention of atherosclerosis and its complications. This class of drugs has become firmly established in Russian and international guidelines with a high level of evidence. However, the use of these drugs in practice is not yet optimal. A significant proportion of patients at very high cardiovascular risk, taking initial doses of statins, do not achieve target levels of low-density lipoprotein cholesterol. The article is devoted to the analysis of international and Russian guidelines for statin monotherapy optimization, including their prescription in primary prevention using cardiovascular risk reclassification, coronary calcium score, carotid Doppler ultrasound and lipoprotein(a) levels.

Aim. To describe demographic and clinical laboratory characteristics, concomitant diseases and drug therapy of outpatients with heart failure (HF) in the Russian Federation.

Material and methods. An interim analysis of a prospective observational multicenter registry study of patients with chronic heart failure in the Russian Federation ("PRIORITET-CHF") was performed. The study included outpatients with HF followed by a general practitioner or cardiologist.

Results. Data from 6255 patients were analyzed (31,3% of the study sample; median age, 65 years; men, 65%). HF with reduced ejection fraction (HFrEF) was diagnosed in 42,4%, HF with preserved EF — in 31,9%. In addition, 57,4% of patients were characterized by NYHA class II HF. The most common causes of HF were hypertension, coronary artery disease, and atrial fibrillation or flutter. Of the concomitant diseases, doctors most often reported chronic kidney disease (CKD) (43,2%), obesity (37,8%) and diabetes (26,7%) in HF.

Conclusion. In the Russian Federation, among outpatients with HF, there was domination of men, HFrEF phenotype, NYHA class II. The relatively young mean age and frequent associations of HF with cardiovascular risk factors and diseases underscore the importance of timely prevention initiatives. The identified high proportion of patients with CKD requires special attention and separate analysis. Despite the relatively high prescription rate of certain classes of diseasemodifying therapy for HF, the prescription of optimal quadruple therapy and electrophysiological treatments for HFrEF is insufficient.

Russian Society of Cardiology (RSC)

Developed with the special contribution of the Russian Functional Diagnostics Association, Russian Holter Monitoring and Non-invasive Electrophysiology Society, Russian Pediatric Cardiology Association.