Elena Yu. Emelyanchik

Aim. To study the impact of ANRIL rs1333049 and LPA rs10455872 polymorphisms on the clinical status of patients with heterozygous familial hypercholesterolemia (FH) and hyperlipoproteinemia(a) (hyperLP(a)). Material and methods. A total of 171 patients aged 3 to 44 years were examined. Lipid profile, apolipoprotein B (apoB), and lipoprotein(a) (LP(a)) were determined using chemiluminescence immunoassay on the Roche Cobas 8000 automated modular analyzer. Single-nucleotide variant (SNV) carriage was determined using polymerase chain reaction (PCR) on a Rotor-Gene 6000 system with TaqMan allelic discrimination technology and Applied Biosystems fluorescent probes for LPA rs10455872 (A/G) and ANRIL rs1333049 (C/G). Genotype frequency distributions corresponded to Hardy-Weinberg equilibrium. Extracranial vessel ultrasound was assessed taking into account age-specific references. Results. A study of relationship between the ANRIL rs1333049 and LPA rs10455872 in patients with FH and hyperLA revealed that the CG genotype of ANRIL rs1333049 directly correlates with apoB levels and intima-media thickness (IMT) in both target groups. An influence of the AG genotype of LPA rs10455872 on apoB, LP(a), and IMT levels was revealed in patients with FH and hyperLA(a). The mean age at onset of coronary events was 35 years. The incidence of myocardial infarction was 2,5 times higher in the FH group than in the LP(a) group. Conclusion. In patients with FH and hyperLA(a), a predominance of the ANRIL CG genotype is associated with high apoB, IMT, and the incidence of coronary events. The AG genotype of LPA rs10455872 is associated with high LP(a) levels, increased IMT, and the risk of early myocardial infarction.

В статье представлен обзор научных исследований влияния экранного времени на основные показатели состояния сердечно-сосудистой системы у детей. Рассматривались результаты публикаций, посвященные оценке влияния экранного времени на функциональное состояние сердечно-сосудистой системы и метаболизм у детей в разных регионах мира (опубликованные в период с 2018 по 1 марта 2024 г.). Анализ результатов исследований проведен с учетом географического расположения территорий. Получены данные о негативном влиянии экранного времени на факторы сердечно-сосудистого риска: отклонения пищевого поведения, укорочение сна, низкая физическая активность, повышение артериального давления и увеличение содержания атерогенных липидов в сыворотке крови детей. В популяции школьников монголоидной расы обнаружена корреляция между «проблемным» использованием экранных медиа и ожирением, более выраженная у мальчиков.

Introduction. Analysis and comparison of clinical and functional characteristics of patients with familial hypercholesterolemia (FH) with molecular genetics data make it possible to clarify the disease nature and determine the management strategy taking into account the clinical and genetic status. Considering that biochemical criteria are the leading ones in the diagnosis of FH, the study of family cases complements the disease understanding.Brief description. An analysis of the genealogical and individual data, physical and general clinical examination of three family members, advanced lipid testing, and vascular ultrasound were performed. A two-stage molecular genetics study was conducted as follows: the first stage involved parallel sequencing of 60 genes associated with FH; the second stage involved DNA assessment by the multiplex ligation-dependent probe amplification method of the low-density lipoprotein receptor (LDLR) gene to identify large deletions.Discussion. Patients with deletions in LDLR gene exons 2-10 have the most severe clinical and laboratory abnormalities and early development of cardiovascular diseases. Families with FH have the highest concentration of genomic abnormalities that can lead to atherosclerosis lesions even in preschool children and may require non-standard lipid-lowering therapy, including biopharmaceuticals.

BACKGROUND: Considering the high cardiovascular risk in patients with familial hypercholesterolemia (FH), early diagnosis and treatment are the basis for the prevention of vascular accidents. In the absence of universal screening, the results of more targeted diagnostics are of interest — the search for lipid metabolism disorders in young relatives of patients with atherosclerotic vascular diseases. OBJECTIVE: To determine the effectiveness of targeted screening for identifying patients with FH, which will justify its widespread use in clinical practice. MATERIALS AND METHODS: At the start of the observational study, 584 patients were identified from the vascular centers of the Krasnoyarsk Regional Hospital, Krasnoyarsk Interdistrict Clinical Hospital No. 20 named after. I.S. Berzon, who had lipid profile data and early cardiovascular events (all forms of coronary heart diseases), including reconstructive vascular interventions up to 55 years in men and up to 60 years in women in the case of first-degree relatives and up to 50 years in second-degree relatives. The study examined patients’ relatives aged 44 years. To diagnose FH in participants aged 16 years, the scale developed by a network of Dutch lipid clinics was used; in participants aged 16 years, the S. Broome criteria were used. Targeted screening and lipid parameters in individuals with probable, possible, and definite FH were analyzed. Data processing was performed using Microsoft Excel and Statistica v. 12.0 (USA). Parametric (calculation of the median and 25th and 75th quartiles) and nonparametric (statistical significance of differences was determined using the Mann–Whitney and χ2 tests) methods were used. RESULTS: The study examined 70 children and 104 adults aged 44 years whose first- and/or second-degree relatives suffered premature vascular events. In the general group of participants, 42 (24.14%) patients had FH (of which 18 were 17 years old) and 37 (21.2%) had hyperlipoproteinemia (a). Definite FH was documented in 16 (9.1%) patients, probable in another 16, and possible in 9. Hyperlipoproteinemia (a) was found in 37 (21.2% of general group) patients, including 12 children (17.1% of pediatric group). CONCLUSION: Not more than 30% of the population are aware of the hereditary nature of lipid metabolism disorders and atherosclerotic diseases. Targeted screening is the least expensive and most effective tool for identifying patients with FH and hyperdipoproteinemia (a).

A clinical case of the development of portopulmonary hypertension in a child after splenorenal anastomosis is presented. The surgical intervention was performed to correct the congenital malformation — cavernous transformation of the portal vein, which led to portal hypertension and varicose veins of the esophagus and stomach. In the long-term postoperative period, pulmonary arterial hypertension, hypersplenism with bilinear cytopenia, and moderate liver failure developed. Combined therapy provided a temporary improvement of the patient status, therefore, during subsequent surgery, the size of the anastomosis was changed. This led to a sustained decrease in pulmonary artery blood pressure and clinical improvement in the boy’s condition.

Aim.To study the prevalence of elevated concentrations of lipoprotein (a) (Lp(a)) and apolipoprotein B (apoB) associated with high cardiovascular risk in a random sample of the adult Krasnoyarsk population.Material and methods.Lp(a) and apoB concentrations were determined by the immunochemiluminescent method using an automated modular Cobas 8000 platform with biochemical module c702 (Roche Diagnostic, Switzerland). We examined 263 people aged 18 to 58 who agreed to expand the standard screening by Lp(a) and apoB determination.Results.We found that high and very high levels of Lp(a) are found in 12,9% of the examined, while in women the median value was significantly higher than in men (p=0,044). In addition, 11,4% of study participants had high apoB values, regardless of sex; 3,4% of the subjects had a combination of elevated levels of ap B and Lp(a).Conclusion.Screening for Lp(a) and apoB reveals dyslipidemia associated with high cardiovascular risk in 24,3% of working-age people

A search was made for publications on modern methods for determining cardiovascular risk in young people with positive family history for early cardiovascular events. The use of various screening options allows timely identification of patients with heterozygous familial hypercholesterolemia who have a high cardiovascular risk. The most effective method is cascade screening. Cardiovascular risk assessment systems that include a family history of early cardiovascular events and lipid profiles in individuals under 40 years of age provide prevention of atherosclerosis. In the diagnosis of risk, the lipoprotein (a) is of particular clinical importance, elevated concentrations of which are associated with a high risk of vascular damage and an unfavorable course of atherosclerosis.

Objective of the study: to study the role of nitric oxide (NO) in adaptive reactions of the circulatory system in premature infants with transient myocardial ischemia (TMI). Materials and methods of research: a clinical, prospective, comparative study was carried out from 2016 to 2018. 82 infants with gestational age of 31–36 weeks who have had respiratory failure were included. Newborns were divided into groups: 1st – 14 newborns with TMI ECG criteria and troponin I (TrI) >0.139 ng/ml, 2nd – 39 newborns with TMI ECG criteria and TrI<0.139 ng/ml, 3rd – 29 children with normal ECG and TrI<0.139 ng/ml. In the early neonatal period, the clinical status, blood gas analysis, ECG, echocardiography and determination of TrI and NO were carried out. Quantitative data are presented as median, 25th and 75th percentiles; qualitative – in absolute values and %. The statistical significance was assessed by the Mann–Whitney test, the analysis of the relationship was assessed by the Spearman's rank correlation coefficient. Results: the level of NO by the 7th day of life in premature newborns of the 1st group increased 3.8 times, in the 2nd and 3rd groups – 1.7 and 2.5 times. A correlation relationship was revealed between TrI and NO on the 7th day of life (r=0.793, p=0.006), between NO and pH (r=–0.738, p=0.036), NO and pCO2 (r=0.857, p=0.006) on the 1st day. Also, on the 1st day there was a statistically significant increase in the end diastolic (EDS) and end systolic sizes (EDS) of the left ventricle (LV), the relationship of LV EDS with NO (r=0.722, p=0.042) and TrI (r=0.666, p=0.049), as well as NO with the LA size (r=0.731, p=0.038) in the 1st group. Conclusions: in premature infants with TMI and destructive changes in the myocardium, an increase in NO is probably necessary to optimize LV contractility and compensate for damage to cardiomyocytes. In children with TMI in the absence of myocardial injury, a compensatory increase in NO contributes to limiting the effects of hypoxia by functional disorders of LV, which persist by the end of the early neonatal period.

The complexity of diagnosing and predicting the course of TNF-receptor-associated periodic syndrome TRAPS determines the importance of studying the dependence of clinical manifestations on the variant of genetic mutation and the presence of modifier genes. We observed 5 children with an identified diagnosis of TRAPS. It was established that the disease onset in most cases is defined as a juvenile arthritis with systemic onset. Genetic variants with the replacement of cysteine residues are associated with an early debut and an aggressive course, the c.362G> A p.R121Q mutation is associated with an erosive damage to the spine. The case of a favorable course of TRAPS in siblings with a newly detected mutation is described. The development of urgent complications of TRAPS was revealed when basic therapy with canakinumab was canceled.

Objective of the research: to study the results of levosimendan use in young children with heart failure (HF) of functional class IV (FC). Materials and methods: the analysis of observation of patients who received levosimendan: 2 with cardiomyopathies (CMP), 12 with congenital heart defects (CHD). The drug was administered intravenously 0,2 μg/kg/min. Results: in patients with CMP, the ejection fraction doubled after administration of levosimendan, in children with CHD heart contractility increased by 18%, and pulmonary artery pressure decreased by 17 mm Hg. There were no undesirable effects. Conclusion: administration of levosimendan provides an increase in cardiac output and a decrease in pulmonary resistance in children with HF IV FC without undesirable effects.