The actual prevalence of genetic variants causing familial hypercholesterolemia (FH) in every population remains unknown. The aim of this work was to determine the spectrum of pathogenic variants in patients with acute coronary syndrome (ACS) and clinically diagnosed FH using targeted sequencing. We selected 38 patients with ACS from the sample of 2,081 participants of two multicenter observational studies (2004–2007; 2014–2016) who had a clinical diagnosis of FH based on the Dutch Lipid Clinic Network score and Simon Broome criteria. The men and women included in the study were ≤ 55 and ≤ 60 years of age, respectively. Molecular genetic screening was done by targeted next-generation sequencing. We started by sequencing 3 genes associated with FH, including LDLR, APOB, and PCSK9. If no relevant variants were detected, the panel was expanded. Of 38 patients, 24 (63.2%) were shown to have mutations that could cause clinical manifestations of FH and premature coronary artery disease. All patients were heterozygous carriers. Mutations were detected in three “classic” genes LDLR, APOB, and PCSK9 associated with FH, as well as in other genes involved in lipid metabolism, such as APOE, ABCA1, ABCG5, ABCG8, LPL, ANGPTL3, and MTTP. Five variants detected in our study sample had not been described previously: the pathogenic p.Val273_Cys313del variant of the LDLR gene, the likely pathogenic p.Arg160His variant in the APOE gene, two variants of uncertain significance p.Glu612Lys and c.*415G>A in the PCSK9 gene, and the mutant variant p.Ala776Ser in the LDLR gene. We conclude that the use of clinical diagnostic criteria in patients with ACS and FH enables identification of carriers of both “classic” mutations associated with FH and rare genetic variants that can be phenotypically expressed as FH.

Отягощенная наследственность у больных с «ранним» развитием острого коронарного синдрома Ключевые слова: отягощенная наследственность, острый коронарный синдром, семейная гиперлипидемия, молодой возраст, алкоголь, курение.

BACKGROUND: Genetic factors are essential for the pathogenesis of coronary heart disease (CHD). This study presents the role of genetic factors in a prematurely developing disease in males under 55 years old and females under 60 years old. Additionally, genetic risk factors may also be significant for CHD development in other age groups although specific genetic factors may differ. AIM: The work aimed to analyze the prevalence of hereditary genetic factors in different age groups in patients with coronary heart disease. MATERIALS AND METHODS: The study was conducted as part of the analysis of data from two observational multicenter Russian studies of acute coronary syndrome (ACS) ORACUL I (1193 patients) and ORACUL II (1803 patients) (the study was registered on ClinicalTrials.gov with an ID number NCT04068909). The average age of patients was 63.512.45 years (1875 men and 1121 women). The study of a panel of candidate genes was performed using the polymerase chain reaction method. RESULTS: In order to analyze the significance of hereditary factors in patients of different ages, groups of patients with early development of CHD (men under 55 years old, women under 60 years old) were formed (n=828). The middle-aged group included men aged 5574 years and women aged 6074 years (n=1410). The older age group consisted of patients aged 75 years and older (n=602). In the group of patients with early onset coronary heart disease, the proportion of patients with aggravated heredity was higher. In the older age group, the proportion of patients with non-burdened or unknown heredity was higher. Significant differences in the frequencies of alleles and genotypes of the polymorphic variants studied by us were revealed only for the G-2667C variant of the CRP gene (the frequency of the GG genotype was 87.3% in young patients and 77.2% in the elderly and old patients (p=0.007) and for the C804A variant of the LTA gene (frequency of the CC genotype was 52 0% in young patients, 49.4% in middle-aged patients, and 34.2% in elderly and old patients, p=0.026). CONCLUSIONS: A burdened family history is more common among patients with early onset coronary artery disease. The differences revealed in the frequencies of genetic variants of genes encoding anti-inflammatory cytokines may indicate their role in the pathogenesis of coronary heart disease in older individuals.

Transcatheter aortic valve implantation is the main treatment for severe aortic stenosis in patients with high surgical risks. There are undeniable advantages such as minimally invasive access, better portability in patients and decreased risk of postoperative complications compare to open surgery. Unfortunately, most aortic stenoses have the same etiology with coronary artery diseases and it necessitates invasive treatment. Cardiac artery catheterization and providing of stable instrument position are complications in post TAVI patients. It is not always possible to perform angioplasty from diagnostic radial access in post TAVI patient and there is an option of changing access to femoral to provide more safe and stable position of instruments during manipulation.