Регистр пациентов с семейной гиперхолестеринемией и пациентов очень высокого сердечно-сосудистого риска с недостаточной эффективностью проводимой гиполипидемической терапии (РЕНЕССАНС)

Aim. To characterize patients accessing lipid clinic and assess the efficiency of treatment in a specialized medical center.Material and methods. A retrospective analysis of the surviving medical records of outpatients who visited the lipid clinic of the National Research Center for Therapy and Preventive Medicine (Moscow, Russia) in 2011-2019 (n=675) was carried out. Cardiovascular risk (CVR) and target lipoproteins levels were evaluated in accordance with actual guidelines for the diagnostics and correction of dyslipidemias.Results. The mediana of lipid clinic patients age was 57 [46;65] years. Female persons attend lipid clinic more often (61.5%). 48.5% of patients had low density lipoprotein cholesterol (LDL-c) >4.9 mmol/L, 7.7% had triglycerides level >5.5 mmol/L. Most of the patients were diagnosed with type IIa hyperlipidemia (44,1%) or type IIb (28,0%). Inherited impaired lipid metabolism was diagnosed in 27.7% individuals. 12.7% of the patients had familial hypercholesterolemia, 57.4% – had secondary causes of impaired lipid metabolism. More than half of the patients (52.4%) had low or moderate CVR, 28.1% had a very high CVR. High or very high CVR individuals revisited the lipid clinic more often than people with lower risk (68.2% vs. 35.4%). Revisiting patients (25.4%) reached LDL-c targets more often (33.3% of very high CVR patients; 45.5% of moderate-risk people) than in ordinary outpatient practice. High-intensity statin therapy was recommended for 32% of patients, and combined lipid-lowering therapy – for 14.8%. Among very high CVR individuals, combined lipid-lowering therapy was prescribed for 38.5%. Given the lipid-lowering therapy prescribed in the lipid clinic, LDL-с<1.8 mmol/L and<1.5 mmol/L will be achieved at 40.7% and 32.9% of patients with very high СVR.Conclusion. Lipid clinic is an important part of the medical care system for long-term follow-up of patients with impaired lipid metabolism, and it is more efficient in achieving target values of lipids and correcting risk factors in comparison with the primary medical service.

ЦЕЛЬ ИССЛЕДОВАНИЯ Оценить комплаентность пациентов с гетерозиготной семейной гиперхолестеринемией (геСГХС) в течение 5-летнего периода работы регистра РЕНЕССАНС (Регистр пациентов с СГХС и пациентов очень высокого сЕрдечно-Сосудистого риска с недоСтАточной эффективНоСтью, проводимой гиполипидемической терапии). МАТЕРИАЛ И МЕТОДЫ РЕНЕССАНС является открытым, национальным, наблюдательным исследованием и включает больных с СГХС. Проводилась оценка факторов риска атеросклероза, анамнеза сердечно-сосудистых заболеваний (ССЗ), интенсивности гиполипидемической терапии (ГЛТ). Каждому пациенту определены уровни общего холестерина, триглицеридов, холестерина липопротеидов высокой плотности в сыворотке крови. Содержание холестерина липопротеидов низкой плотности (ХС ЛНП) рассчитывали по формуле Фридвальда. РЕЗУЛЬТАТЫ В исследование включено 2317 пациентов с геСГХС, из которых 58% — женщин. При включении в регистр 59% больных относились к категории высокого сердечно-сосудистого риска. Динамический визит проведен у 47% пациентов, период наблюдения составил 24 [11; 42] мес. Больные с динамическим визитом чаще имели определенный диагноз геСГХС и отягощенный наследственный анамнез по ССЗ, были моложе и им в более раннем возрасте диагностировали СГХС (p<0,05). У пациентов без динамического визита были распространены модифицируемые факторы риска (p<0,001). Среди пациентов высокого сердечно-сосудистого риска 54% больных получали ГЛТ, очень высокого — 86%. За время наблюдения в регистре доля принимающих ГЛТ пациентов увеличилась с 59 до 78%, в том числе статинами в режиме высокой интенсивности с 36 до 54%, в комбинации с эзетимибом — с 15 до 34%, ингибиторами PCSK9 — с 4 до 14% (p<0,001 для всех). Целевого уровня ХС ЛНП достигли 13% пациентов. Данные симуляционного анализа продемонстрировали, что для адекватного контроля уровня ХС ЛНП, не менее 92,5% больных с геСГХС в регистре должны получать трехкомпонентную ГЛТ со статинами, эзетимибом и ингибиторами PCSK9. ЗАКЛЮЧЕНИЕ 5-летнее наблюдение за участниками регистра РЕНЕССАНС демонстрирует увеличение использования многокомпонентных схем лечения, но недостаточное для адекватного контроля ХС ЛНП.

The literature review is devoted to circulating microRNA (small noncoding ribonucleic acid molecules) of blood plasma and serum, and potential of their use as new biomarkers of coronary artery disease (CAD) at various stages. The study results demonstrate different levels of plasma and serum microRNA expression in patients with and without CAD. In this regard, determination of microRNA expression level for minimally invasive diagnosis of CAD seems promising, as well as further prognosis of disease progression. A list of microRNAs as potential biomarkers of CAD has been compiled.

Severe hypertriglyceridemia (HTG) is genetically heterogeneous, but its genetic architecture remains incompletely characterized. We investigated the genetic determinants of severe HTG in 123 patients with triglyceride (TG) levels > 5.0 mmol/L and available NGS data. We analyzed rare variants in LPL, APOC2, APOA5, GPIHBP1, LMF1, and APOE; the ε2/ε2 APOE genotype; and TG-polygenic risk score (PRS) based on 40 variants. Major genetic determinants were identified in 65.0% of individuals, including rare variants in chylomicronemia genes (24.4%; 28 variants, including 10 novel, 53.6% in LPL), rare APOE variants or the ε2/ε2 genotype (18.7%, overlapping with chylomicronemia variants in 4.1%), and an extreme polygenic burden (35.8%; PRS > 90th percentile), including 26.0% with isolated polygenic HTG. The remaining 35.0% had moderate-to-low PRS. The cohort was categorized into familial chylomicronemia syndrome (FCS, n = 7), multifactorial chylomicronemia syndrome (MCS, n = 21), polygenic HTG (n = 32), familial dysbetalipoproteinemia (FD, n = 20), and moderate-to-low PRS (n = 43) groups based on genetic determinants. FCS had the lowest PRS percentile (median 26) and the most distinct clinical profile, with the highest TG levels (median 30.60 mmol/L) and 6–24-fold higher odds of pancreatitis compared with other groups (p < 0.05), alongside a lower body mass index (median 23.0 kg/m²) than all groups except MCS, whereas FD had the lowest TG levels (10.20 mmol/L, p < 0.05). These results further advance the understanding of the complex genetic architecture of severe HTG and demonstrate that broader genetic analysis, including APOE and TG-PRS, may increase the yield of genetic determinants in severe HTG.

Aim. To evaluate the polygenic contribution to low-density lipoprotein cholesterol (LDL-C) and total cholesterol (TC) levels in patients with familial hypercholesterolemia (FH) based on polygenic risk scores (PRS), as well as to examine the potential of predicting referential FH diagnosis in non-carriers of pathogenic variants. Material and methods . The study used the results of genetic testing of a population sample from the Ivanovo Oblast (n=1673) and patients of the National Medical Research Center for Therapy and Preventive Medicine with a diagnosis of FH (n=353). The study included three different PRSs for LDL-C and three PRSs for TC. Results. The study evaluated the PRS feasibility for the Russian population: the percentage of variance explained by PRS ranged from 4,54% to 6,23% for LDL-C and from 2,74% to 5,98% for TC. Significant (p<0,001) differences in PRS values were shown for three groups as follows: a population sample from the Ivanovo Oblast, patients with clinical FH diagnosis who are carriers and non-carriers of known pathogenic variants in the LDLR, APOB and PCSK9 genes. PRS data can be used for differential diagnostics of patients with clinical diagnosis of FH to unveil individuals with polygenic hypercholesterolemia. Conclusion. For the first time, the predictive power of PRS for LDL-C and TC in the Russian FH patients has been studied.