👤 M V Ezhov

Low-density lipoprotein cholesterol (LDL-C) is a major cardiovascular risk factor and an indicator of hypolipidemic therapy effectiveness. However, direct and calculated methods for determining "LDL-C" present the sum of the cholesterol in all apoB-containing lipoproteins, including lipoprotein(a) [Lp(a)]. There has been an ongoing debate about the correctness of LDL-C in patients with elevated Lp(a) concentrations up to now. The aim of this study was to evaluate the effect of Lp(a) concentration on the LDL-C calculated by different equations. The study included the results of fasting lipids and Lp(a) concentration of 566 measurements from 283 patients (before and after lipid-lowering therapy prescribing, after exclusion of 17 patients with incomplete data). LDL-C and LDL-C corrected for Lp(a)-cholesterol (LDL-C We assessed 566 measurements of lipids and Lp(a). The number of values reclassified to a higher risk category was 10% and 13% with Martin-Hopkins and Sampson equations compared to the Friedewald formula. The percentage of Lp(a)-cholesterol (Lp(a)-C) in the LDL-C calculated by three formulas was up to 90% or more depending on the concentration of LDL-C and Lp(a). When stratified by clinically significant LDL-C thresholds, the proportion of values LDL-C Comparison of LDL-C concentrations calculated by Friedewald, Martin-Hopkins, and Sampson equations showed high consistency in patients without elevated triglycerides. The LDLcorr is reasonable to use in patients with Lp(a) concentration ≥ 30 and ≥41 mg/dL when using the Martin-Hopkins and Sampson equations, respectively. These data may help clinicians interpret LDL-C goal attainment in patients with elevated Lp(a) and avoid misclassification driven by the Lp(a)-cholesterol component. Show less

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

Peripheral artery disease (PAD) is a major global health issue. This study investigated the relationship between lipoprotein(a) [Lp(a)], high-density lipoprotein cholesterol (HDL-C) to blood cells ratios, and PAD development. The study included 361 patients categorized into groups based on the presence of stenotic atherosclerosis in lower limb arteries (LLAs) diagnosed via duplex ultrasound. Group 1 (n = 238) had atherosclerosis at the first visit. A second visit involved 281 patients: 158 from Group 1, 32 new diagnoses (Group 2), and 91 with no atherosclerosis at either visit (Group 3). Laboratory analysis included lipid profiles, Lp(a), and complete blood counts, calculating ratios like Lp(a)/HDL-C and monocyte-to-HDL-C ratio (MHR). Showed patients with stenotic atherosclerosis had significantly higher Lp(a) (20.2 vs. 12.1 mg/dL, Show less

Background: Hypertriglyceridemia (HTG) is one of the most common forms of lipid metabolism disorders. The leading clinical manifestations are pancreatitis, atherosclerotic vascular lesions, and the formation of eruptive xanthomas. The most severe type of HTG is primary (or hereditary) hypertriglyceridemia, linked to pathogenic genetic variants in LPL, APOC2, LMF1, and APOA5 genes. Case: We present a clinical case of severe primary hypertriglyceridemia (TG level > 55 mmol/L in a 4-year-old boy) in a consanguineous family. The disease developed due to a previously undescribed homozygous deletion in the APOA5 gene (NM₀₅₂₉₆₈: c.579₅₉₂delATACGCCGAGAGCC p.Tyr194Gly*68). We also evaluate the clinical significance of a genetic variant in the LPL gene (NM₀₀₀₂₃₇.2: c.106G>A (rs1801177) p.Asp36Asn), which was previously described as a polymorphism. In one family, we also present a different clinical significance even in heterozygous carriers: from hypertriglyceridemia to normotriglyceridemia. We provide evidence that this heterogeneity has developed due to polymorphism in the LPL gene, which plays the role of an additional trigger. Conclusions: The homozygous deletion of the APOA5 gene is responsible for the severe hypertriglyceridemia, and another SNP in the LPL gene worsens the course of the disease. Show less