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Aim. To study genetic causes of decreased low-density lipoprotein cholesterol (LDL-C) in Russian patients.Material and methods. The study included the following Epidemiology of Cardiovascular Diseases and their Risk Factors in Regions of Russian Federation (ESSE-RF) participants: individuals with LDL-C

Aim. To study the contribution of rare and low-frequency variants of ANGPTL3, ANGPTL4, APOA5, APOB, APOC2, APOC3, LDLR, PCSK9, LPL genes in assessing the risk of coronary artery disease (CAD) in a cohort of Russian patients with various cardiovascular risks.Material and methods. The study was conducted on a sample of participants in cohort and epidemiological studies (n=2405). Targeted enrichment of coding sequences and exon-intron regions of nine genes (ANGPTL3, ANGPTL4, APOA5, APOB, APOC2, APOC3, LDLR, PCSK9, LPL) was performed. Genetic diagnostics was carried out by next generation sequencing.Results. CAD was confirmed in 267 patients (11%). After genetic diagnosis, all patients were divided into three following groups: individuals with previously described genetic variants associated with elevated levels of low-density lipoprotein cholesterol (LDL-C) and/or triglycerides (TGs); individuals with genetic variants associated with reduced levels of LDL-C and/or TGs; individuals without genetic variants associated with LDL-C and/or TG levels, or with two or more variants with opposite effects on LDL-C and/or TG levels. Kaplan-Meier method revealed that the groups significantly differ in cumulative risk of CAD (p

Aim. To monitor the scope and effectiveness of lipid-lowering therapy (LLT) in the out- and inpatient settings among people hospitalized at the National Medical Research Center for Therapy and Preventive Medicine.Material and methods. Retrospective analysis of randomly selected case records for April-May 2012, 2015 and 2022 (n=658).Results. From 2012 to 2022, the proportion of outpatients taking statins increased as follows: from 28,8 to 60,4% (from 22,2 to 73,3% for high cardiovascular risk (CVR) and from 34,8 to 91,7% for very high CVR). Patients with very high CVR were significantly more likely to be prescribed high-intensity statin therapy (from 3,8 to 45,8%). Inpatients with high CVR were prescribed statins less often (74,3%) than patients with very high CVR (93,6%). In 2022, compared to 2015, the proportion of inpatients who received combined LLT increased as follows — 8,9 vs 0,5% (p< 0,001). Target low-density lipoprotein cholesterol

Aim. The search for genetic markers of ADIPOQ, associated with the level of adiponectin and development of coronary atherosclerosis.Material and methods. To the study, patients included, who had undergone diagnostic coronary arteriography in 2011-2012 in the NMRCPM with assessment of the severity of coronary atherosclerosis. The level of adiponectin was measured in plasma with the test-system based on the immune enzyme analysis. Genetic variants rs17300539, rs182052 and rs266729 gene ADIPOQ were measured realtime (Applied Biosystems, 7500 Real Time PCR System). Alleles of the studied variants were summarized by a unified score of genetic risk (SGR).Results. To the study, 447 patients included, of those 319 males (70,7%). Median of age was 61 [55-69] y.o. All patients were selected to 2 groups by SGR (≤2 and >2, respectively). Groups differed by the level of adiponectin 7,64 vs 8,29 mcg/mL (р=0,01), total cholesterol 4,60 vs 5,00 mM/L (p=0,03), cholesterol of low density lipoproteides 2,8 vs 3,09 mM/L (p=0,03), and the rate of unstable angina development 2,15% vs 6,8% (р=0,02) and type 2 diabetes 11,8% vs 21,1% (р=0,01), respectively. There was no difference in the groups by Syntax and Gensini score.Conclusion. Genetic score based on the three variants of ADIPOQ does determine the plasmatic level of adiponectin and risk of unstable angina and diabetes, but not the grade of coronary atherosclerosis.

Aim. The aim of the present study was to evaluate the contribution of 11 singlenucleotide polymorphisms (SNPs) and production factors to the development of arterial hypertension (AH) in men in an organized workers cohort of machinebuilding plant.Material and methods. The study included men aged 20-65 years who had contact with production factors (PF) during at least 50% of the working time. Genotyping of 11 SNPs was performed using TaqMan real-time PCR. Data statistical analysis was carried out using statistica 8.0 and SAS, v. 6.12 software.Results. 583 men were included in the study, 205 of those had AH, 378 did not. The groups differed significantly in age, presence of higher education, the frequency of combination of two or more components of the metabolic syndrome and the severity of its individual components: weight, waist circumference, level of total cholesterol, triglycerides, low density lipoprotein cholesterol, glucose. As a result of genotyping, it was found that the frequency distribution of genotypes between groups with and without AH significantly differed for two SNPs — rs2932538 (p=0,0414) in the MOV10 gene and rs4373814 (p=0,0344) in the CACNB2 gene. Combining information on several SNPs in the genetic risk SCORE (GRS) it was shown that the mean value of the total GRS in the groups with and without AH was 0,0382±0,119 and 0,0195±0,111, correspondingly. The differences between the groups were significant (p=0,032). Based on the results of multivariate analysis, it was shown that the independent factors associated with the presence of AH in participants were age (OR=1,057 (1,037-1,076), p=0,0001), the presence of two or more components of the metabolic syndrome (OR=2,519 (1,621-3,914), p=0,0001) and the total GRS, consisting of 11 SNP (OR=1,479 (1,02-2,143), p=0,04). PF adjusting for the age were not associated with the presence of AH.Conclusion. In men, who had direct contact with PF at machine-building plant, GRS consisting of 11 SNPs was an independent factor influencing the presence of AH. The results show the necessity of practical USAge of genetic tests together with traditional risk factors assessment with the aim for increase of AH risk estimation precision and for carrying out individual prevention.

Aim. To estimate the effectiveness of lipid-lowering therapy (LLT) at outpatient and hospital treatment stages in patients at high and very high cardiovascular risk during 2011-2015.Material and methods. In a cross-sectional epidemiological study we analyzed LLT in hospital patients for the period April-May 2011, 2012 and 2015. All data were obtained from randomly selected case-records of patients (n=548; 20% of all hospital patients over the study period). Risk categories of patients as well as target levels of low density lipoprotein (LDL) cholesterol were determined according to the current clinical guidelines for the respective year. Outpatient LLT was administered in local out-patient clinics and hospital one – in the clinic of State Research Centre for Preventive Medicine.Results. The most commonly prescribed group of lipid-lowering drugs was statins, while combined treatment or monotherapy with other lipid-lowering agents were used only in rare cases. From 2011 to 2015 the proportion of patients taking statins before admission increased from 20% to 49.8% (from 23.1% up to 29.6% of patients at high cardiovascular risk and from 28% up to 68.5% of patients at very high cardiovascular risk, respectively). During hospitalization the proportion of individuals receiving statins increased from 49.8% to 72.9%, from 29.6% to 74% and from 68.5% to 95.3% in general group, among patients at high and very high cardiovascular risk, respectively. In 2015 LDL cholesterol target levels were achieved in 14.8% and 7.1% of patients at high and very high risk, respectively. In-hospital rate of simvastatin administration reduced from 33.6% to 0.5%, whereas prescription of atorvastatin and rosuvastatin increased from 31.4% to 64.5% and from 3.6% to 9.9%, respectively. Average dose of statins (in conversion to atorvastatin) increased from 10 mg to 20 mg in high-risk patients and from 10 mg to 40 mg – in very high risk group.Conclusion. Positive trend in frequency of LLT prescription was demonstrated in patients at high and very high cardiovascular risk during 2011-2015. Nevertheless, significant number of patients in out-patient clinics still remains under non-optimal treatment.

Currently, cardiovascular diseases (CVD) remain the main problem in the world and in Russia in particular. The study of the causes and progression of atherosclerosis is a critical moment in the fight against CVD. Adipose tissue and processes that occur in it attracts attention in recent years. The important role of adipose tissue as an endocrine and immune organ is revealed as well as its participation in the development of the inflammatory process. This leads to the development of initial manifestations of atherosclerosis a precursor of many metabolic disorders and CVD. Particular attention causes adipokines regulatory peptide hormones in the adipose tissue, as well as insulin, due to its close relationship with the adipose tissue and especially with adiponectin and leptin. Recent data on the role of adiponectin, leptin and insulin in the pathogenesis of atherosclerosis in order to identify new potential targets among peptide hormones for the treatment of atherosclerosis are presented.

Aim. To validate and evaluate the accuracy of 14 genetic risk scores (GRSs) for type 2 diabetes (T2D), created earlier in other countries, using a Russian population sample from the biobank of the National Medical Research Center for Therapy and Preventive Medicine.Material and methods. For genetic analysis, next generation sequencing data was used on a sample from the Russian population (n=1165) based on the biobank collection. The study included 14 GRSs associated with T2D.Results. The study demonstrated that the predictive power of 12 out of 14 GRSs for T2D was replicated in the Russian population. As quality metrics, we used the area under the ROC curve, which for models including only GRS varied from 54,49 to 59,46%, and for models including GRS, sex and age — from 77,56 to 78,75%.Conclusion. For the first time in Russia, a study of 14 T2D GRSs developed on other populations was conducted. Twelve GRSs have been validated and can be used in the future to improve risk prediction and prevention of T2D in Russia.

Aim. To validate and evaluate the accuracy of 15 genetic risk scores (GRSs) for obesity, created in populations of European origin in the sample of two European Russia regions. Material and methods. Genetic testing has been performed using next generation sequencing on a sample from the Russian population (n=1179). The study included 15 GRS associated with body mass index (BMI) or waist-to-hip ratio adjusted for BMI (WHRadjBMI).Results. The predictive power of 8 out of 9 GRSs for obesity based on BMI remains the same for the Russian population. The predictive power of 6 GRSs for obesity based on WHRadjBMI is lower in the Russian population than in the reference sample. GRS reproducibility increases with the size of initial samples and number of variants included in the GRS increase. The use of GRSs for obesity based on BMI in the Russian population created on European populations is justified.Conclusion. For the first time in Russia, 15 obesity GRSs developed in European populations have been validated. The data obtained on the effectiveness of the considered GRS can be used in the future to improve the obesity prediction and prevention in Russia.