👤 N V Gomyranova

To evaluate the effect of inclisiran therapy on the blood lipid profile 90 days post-injection and to describe the baseline structural and ultrasound characteristics of carotid and femoral plaques in high- and very high-risk patients who failed to achieve low-density lipoprotein cholesterol goals despite ongoing lipid-lowering treatment. This prospective observational single-center study included 22 patients (mean age 50.9±8.6 years, 50% men) with dyslipidemia and atherosclerotic plaques in peripheral arteries narrowing the lumen by 25-49%. Familial hypercholesterolemia was diagnosed in 59% of patients, and statin intolerance in 36%. Duplex scanning of the carotid and femoral arteries was performed. The gray-scale median (GSM) method is currently used for the quantitative assessment of carotid artery (CA) plaque echogenicity. Inclisiran was administered on day 1, day 90, and then every six months. Blood lipid profiles, including low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), triglycerides, and lipoprotein (a) [Lp(a)], were assessed. At baseline, median concentrations were 3.7 [2.5; 5.4] mmol/l for LDL-C, 5.4 [4.4; 6.8] mmol/l for TC, and 22.0 [5.0; 108.0] mg/dl for Lp(a). Carotid artery evaluation showed a median of 4.0 [2.0; 4.0] plaques, total stenosis of 110% [63.8; 118.8], and a GSM of 38.6 [28.6; 52.4], with a predominance of heterogeneous plaques (59%). Femoral artery assessment revealed a median of 2.0 [2.0; 3.0] plaques, 75% [42.5; 111.3] total stenosis, and a minimum echogenicity of 41.5 [33.4; 57.4] gray-scale units, with 65% heterogeneous plaques. Ninety days post-initiation of inclisiran, LDL-C was reduced by 65% (to 1.3 [1.2; 2.9] mmol/L, p<0.01), TC by 30% (p<0.01), triglycerides by 35%, and Lp(a) by 33%. Inclisiran demonstrated high efficacy in reducing LDL-C levels in patients at high and very high risk of cardiovascular disease who failed to reach targets with standard therapy. The identified plaque characteristics indicate a high risk of atherothrombosis in this cohort. The dynamics of these structural plaque changes will be assessed after completing the one-year follow-up. Show less

Familial hypercholesterolemia (FH) is a prevalent hereditary disorder, with its monogenic form linked to an elevated risk of early-onset ischemic heart disease. Evaluating the prevalence and penetrance of pathogenic and likely pathogenic variants associated with this disorder would provide valuable information supporting routine FH screening of the general population. Such informed screening would facilitate early identification of at-risk individuals, enabling timely intervention and management. We analyzed genetic data from 4,856 individuals with various cardiovascular conditions for pathogenic and likely pathogenic variants in the PCSK9, APOB, and LDLR genes. The evaluation included comprehensive clinical assessments, instrumental examinations, and laboratory tests. All genetic data were obtained through the whole-genome sequencing of blood leukocytes. A total of 1.77% of participants carried pathogenic or likely pathogenic variants in the LDLR or APOB genes, and none in the PCSK9 gene. After adjusting for sex and age, the risk of ischemic heart disease was 1.3 times higher in carriers of pathogenic or likely pathogenic variants [95% CI 1.18-1.46; FH remains significantly underdiagnosed. Only 10.5% of carriers of pathogenic or likely pathogenic variants in the LDLR and APOB genes had a prior diagnosis of FH. Our findings suggest low diagnostic rates for this disorder in Eastern European populations and highlight the need for routine genetic screening of younger individuals. However, further research is needed to assess the clinical applicability and cost-effectiveness of such screening programs. Show less