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

Background and aims: The aim of this study was to investigate the influence of a single injection of Evolocumab on the dynamics of Lp(a), fractions of apoB100-containing lipoproteins, PCSK9, and their complexes in healthy individuals with elevated Lp(a) levels. Methods: This open-label, 4-week clinical study involved 10 statin-naive volunteers with Lp(a) >30 mg/dL, LDL-C < 4.9 mmol/L, and a moderate risk of cardiovascular events. The concentrations of Lp(a), lipids, PCSK9, circulating immune complexes (CIC), and plasma complexes of PCSK9 with apoB100-containing lipoproteins (Lp(a)–PCSK9 and LDL–PCSK9) were measured before and each week after Evolocumab (MABs) administration. Results: After a single dose injection of 140 mg of MABs, the median concentration of PCSK9 in serum increased from 496 to 3944 ng/mL; however, the entire pool of circulating PCSK9 remained bound with MABs for 2–3 weeks. LDL-C level decreased significantly from 3.36 mmol/L to 2.27 mmol/L during the first two weeks after the injection. Lp(a) concentrations demonstrated multidirectional changes in different patients with the maximal decrease on the second week. There were no positive correlations between the changes in levels of Lp(a), LDL-C, and TC. The change in the amount of circulating complex of PCSK9–Lp(a) was significantly less than of PCSK9–apoB100 (−5% and −47% after 1 week, respectively). Conclusions: A single administration of monoclonal antibodies against PCSK9 (Evolocumab) in healthy individuals with hyperlipoproteinemia(a) resulted in a decrease of Lp(a) of 14%, a 5% decrease in PCSK9–Lp(a), a 36% reduction of LDL-C, a 47% decrease in PCSK9–apoB100 and a tenfold increase in total serum PCSK9 concentration.

Familial hypercholesterolemia (FH) and elevated lipoprotein(a) [Lp(a)] level are the most common inherited disorders of lipid metabolism. This study evaluated the impact of high Lp(a) level on accuracy Dutch Lipid Clinic Network (DLCN) criteria of heterozygous FH diagnosis. A group of 206 individuals not receiving lipid-lowering medication with low-density lipoprotein cholesterol (LDL-C) >4.9 mmol/L was chosen from the Russian FH Registry. LDL-C corrected for Lp(a)-cholesterol was calculated as LDL-C − 0.3 × Lp(a). DLCN criteria were applied before and after adjusting LDL-C concentration. Of the 206 patients with potential FH, a total of 34 subjects (17%) were reclassified to less severe FH diagnosis, 13 subjects of them (6%) were reclassified to “unlike” FH. In accordance with Receiver Operating Characteristic curve, Lp(a) level ≥40 mg/dL was associated with FH re-diagnosing with sensitivity of 63% and specificity of 78% (area under curve = 0.7, 95% CI 0.7–0.8, p < 0.001). The reclassification was mainly observed in FH patients with Lp(a) level above 40 mg/dL, i.e., 33 (51%) with reclassified DLCN criteria points and 22 (34%) with reclassified diagnosis, compared with 21 (15%) and 15 (11%), respectively, in patients with Lp(a) level less than 40 mg/dL. Thus, LDL-C corrected for Lp(a)-cholesterol should be considered in all FH patients with Lp(a) level above 40 mg/dL for recalculating points in accordance with DLCN criteria.

Cardiovascular diseases are one of the main causes of mortality and disability among the population of the member countries of the Eurasian Association of Cardiology, which is directly related to the high prevalence of risk factors for atherosclerosis, among which dyslipidemia plays a leading role. The previous version of the Eurasian Recommendations for the Diagnosis and correction of lipid metabolism disorders for the prevention and treatment of atherosclerosis was presented in 2020. Over the past 5 years, approaches to risk stratification, diagnosis of subclinical atherosclerosis, and correction of dyslipidemia using various classes of lipid-lowering drugs have changed significantly. Among the initial updates, proposals should be highlighted for determining the blood lipid level in each adult or upon reaching the age of 18, using the SCORE and/or SCORE2 scales to stratify cardiovascular risk, and non-invasive imaging techniques to assess subclinical atherosclerosis. In the sections devoted to therapy, fixed combinations of lipid-lowering drugs, inclisiran, and bempedoic acid are presented. The section on the prevalence, significance and approaches to correction of hypertriglyceridemia, as well as the section on extracorporeal hemocorrection, has been expanded. A chapter on lipoprotein(a) is introduced. Sections on correction of dyslipidemia in cerebrovascular diseases, heart transplantation and HIV infection are presented. These recommendations will be useful to the phisicians of all specialties for the effective management of their patients.

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.

Aim. To evaluate the prevalence of familial hypercholesterolemia (FH) and hyperlipoproteinemia(a) (HLP(a)) in patients with premature acute coronary syndrome (ACS).Material and methods. The study included 120 patients with ACS up to 60 years (mean age, 53±7 years, 104 (87%) men) and 44 people from the comparison group without atherosclerotic cardiovascular diseases and dyslipidemia (mean age, 48±11 years, 19 (43%) men). All patients with ACS underwent coronary angiography. The lipid profile and lipoprotein(a) (Lp(a)) were determined in all patients.Results. The prevalence of HLP(a) in patients with premature manifestation of ACS was 41% (n=49), possible FH — 25% (n=30), combination of FH and HLP(a) — 13% (n=15). In the comparison group, an increased concentration of Lp(a) was detected in 14% (n=6). Based on the analysis of operating characteristic curves, Lp(a) ≥30 mg/dL had the maximum significance for ACS with a sensitivity of 40% and a specificity of 86% (area under the curve, 0,6; 95% confidence interval (CI), 0,5-0,7, p15 mg/dl was associated with two or more coronary artery lesions with a sensitivity of 67% and a specificity of 65% (area under the curve, 0,7; 95% CI, 0,6-0,7, p<0,01). On logistic regression analysis, age (odds ratio (OR). 1,1; 95% CI, 1,0-1,2, p<0,05), smoking (OR, 7,5; 95% CI, 2,5-22,0, p<0,001) and Lp(a) ≥30 mg/dl (OR, 6,7; 95% CI, 1,1-39,7, p<0,05) are independently associated with premature ACS. Only Lp(a) ≥15 mg/dL was associated with multivessel coronary artery disease in these patients (OR, 3,8; 95% CI, 1,52-9,74, p<0,01).Conclusion. Every fourth patient with premature ACS has FH, while almost every second has HLP(a), and every eighth has a combination of FH and HLP(a). HLP(a) is associated with ACS up to 60 years of age and multivessel coronary artery disease in these patients.