ApoB100 remodeling and stiffened cholesteryl ester core raise LDL aggregation in familial hypercholesterolemia patients.

Patients with familial hypercholesterolemia (FH) exhibit a significant residual cardiovascular risk. A new cardiovascular risk factor is the susceptibility of individual LDL particles to aggregation. This study examined LDL aggregation and its relationship with LDL lipid composition and biophysical properties in patients with FH compared to controls.

Homozygous familial hypercholesterolemia in Spain. Data from Registry of the Spanish Atherosclerosis Society.

Unlabelled: Homozygous familial hypercholesterolemia (HoFH) is a rare disease characterized by the presence of two pathogenic variants in the LDLR, APOB, PCSK9 or LDLRAP1 genes, which cause very high levels of LDL cholesterol and premature atherosclerotic cardiovascular disease (ASCVD).The objective of this study is to analyze the current situation regarding diagnosis, cardiovascular disease, lipid-lowering treatment and degree of control of lipids in patients with HoFH in the National Dyslipidemia Registry of the Spanish Atherosclerosis Society.

Methods: Subjects with HoFH, confirmed by the presence of two pathogenic variants in the genes mentioned above, included in the registry from 2013 to June 2023 with an updated review were analyzed.

Novel protocol for the transcriptomic analysis of endothelial extracellular vesicles in atherosclerosis.

Introduction: Despite the key role of the endothelium in atherosclerosis, there are no direct techniques for its analysis. The study of extracellular vesicles of endothelial origin (EEVs), might lead to the identification of molecular signatures and early biomarkers of atherosclerosis. The aim of this work was to set up the methods for EEVs separation and transcriptomic analysis.

PCSK9 inhibitors on the management of primary and secondary cardiovascular prevention.

Background: Proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) have represented an important change in the management of hypercholesterolemia, although, until now, they have barely been used. Without PCSK9i, many patients with atherosclerotic cardiovascular disease (CVD) or those at very high risk do not reach their therapeutic LDLc objectives.

Objective: The analysis aimed to examine the clinical and biochemical characteristics of subjects receiving PCSK9i treatment in the Dyslipidemia Registry of the Spanish Atherosclerosis Society.

Extracellular vesicles in atherosclerosis: Current and forthcoming impact?

Atherosclerosis is the main pathogenic substrate for cardiovascular diseases (CVDs). Initially categorized as a passive cholesterol storage disease, nowadays, it is considered an active process, identifying inflammation among the key players for its initiation and progression. Despite these advances, patients with CVDs are still at high risk of thrombotic events and death, urging to deepen into the molecular mechanisms underlying atherogenesis, and to identify novel diagnosis and prognosis biomarkers for their stratification.

APOE and familial hypercholesterolemia.

Purpose Of Review: Autosomal dominant hypercholesterolemia is a common cause of cardiovascular disease. In addition to the classic genes that cause hypercholesterolemia, LDLR, APOB and PCSK9 , a new locus has emerged as a candidate to be the cause of this hyperlipidemia, the p.(Leu167del) mutation in the APOE gene.

Consensus on lipoprotein(a) of the Spanish Society of Arteriosclerosis. Literature review and recommendations for clinical practice.

The irruption of lipoprotein(a) (Lp(a)) in the study of cardiovascular risk factors is perhaps, together with the discovery and use of proprotein convertase subtilisin/kexin type 9 (iPCSK9) inhibitor drugs, the greatest novelty in the field for decades. Lp(a) concentration (especially very high levels) has an undeniable association with certain cardiovascular complications, such as atherosclerotic vascular disease (AVD) and aortic stenosis. However, there are several current limitations to both establishing epidemiological associations and specific pharmacological treatment.

Higher Parametric Thyroid Feedback Quantile-based Index Is a Predictor of Type 2 Diabetes in a German Population Sample.

Context: Type 2 diabetes has been described to be associated with hypothyroidism but we recently found that a decrease in pituitary sensitivity to thyroid hormone is associated with diabetes, obesity, and metabolic syndrome.

Objective: We aimed to assess the longitudinal nature of this association in the population-based Study of Health in Pomerania (SHIP) in Germany.

Methods: Among a population-based sample of 4308 participants aged 20 to 79 years, 77% were followed for a period of 5 years.

OptiMo-LDLr: An Integrated In Silico Model with Enhanced Predictive Power for LDL Receptor Variants, Unraveling Hot Spot Pathogenic Residues.

Familial hypercholesterolemia (FH) is an inherited metabolic disease affecting cholesterol metabolism, with 90% of cases caused by mutations in the LDL receptor gene (LDLR), primarily missense mutations. This study aims to integrate six commonly used predictive software to create a new model for predicting LDLR mutation pathogenicity and mapping hot spot residues. Six predictive-software are selected: Polyphen-2, SIFT, MutationTaster, REVEL, VARITY, and MLb-LDLr.

Factors associated with the presence of tendon xanthomas in familial hypercholesterolemia.

Introduction And Objectives: Tendon xanthomas (TX) are lipid deposits highly specific to familial hypercholesterolemia (FH). However, there is significant variability in their presentation among FH patients, primarily due to largely unknown causes. Lipoprotein(a) is a well-established independent risk factor for atherosclerotic cardiovascular disease in the general population as well as in FH.

Impact of conducting a genetic study on the management of familial hypercholesterolemia.

Background: Clinically diagnosed familial hypercholesterolemia (FH) may require a genetic test (GT) to confirm diagnosis. GT availability/accessibility is resource-dependent and usually restricted to specialized clinics. While GT has a diagnostic value, it has not yet defined its impact on long-term management and prognosis of FH.

Atherogenic dyslipidaemia in type 2 diabetes mellitus: The PREDISAT study.

Extremely variable prevalence rates of atherogenic dyslipidaemia (AD) in type 2 diabetes (T2DM) subjects have been reported. The primary aim was to assess AD prevalence in Spanish T2DM subjects. Secondary objectives were to evaluate the differential clinical characteristics between T2DM subjects with and without AD, to describe lipid profile evolution and use of lipid-lowering treatment in clinical practice by the Spanish Lipid Units.

Absence of the influence of the APOE gene on the incidence of type 2 diabetes mellitus in a cohort of workers: Effect of diet and shift work.

Background: APOE gene encoded a multifunctional protein in lipid metabolism, also associated with inflammatory markers. Type 2 diabetes (T2D) is a complex metabolic disease related to increased blood glucose, triglycerides and VLDL and associated with different dyslipidaemias. The aim of this study was to analyze whether the APOE genotype could determining the risk of developing T2D in a large cohort of workers.

Contribution of Genetic Variants to Dyslipidemia.

Background: apo (apolipoprotein) E has crucial role in lipid metabolism. The genetic variation in gene is associated with monogenic disorders and contributes to polygenic hypercholesterolemia and to interindividual variability in cholesterol. rare variants may be involved in the phenotype of genetic hyperlipidemias.

Functional foods and nutraceuticals in the treatment of hypercholesterolemia: Statement of the Spanish Society of Arteriosclerosis 2023.

In the management of hypercholesterolemia, besides advising a healthy, plant-based diet, it may be useful to recommend functional foods or nutraceutical with cholesterol-lowering properties. Given the progressive increase in the number of these products and their rising use by the population, the Spanish Society of Arteriosclerosis (SEA) has considered it appropriate to review the available information, select the results of the scientifically more robust studies and take a position on their usefulness, to recommend to health professionals and the general population their potential utility in terms of efficacy and their possible benefits and limitations. The following clinical scenarios have been identified in which these products could be used and will be analyzed in more detail in this document: (1) Hypolipidemic treatment in subjects with statin intolerance.

An elevated parametric thyroid feedback quantile-based index is associated with atrial fibrillation.

Introduction: Atrial fibrillation is associated with hyperthyroidism. Within the euthyroid range, it is also associated with high thyroxine (fT4), but not with thyrotropin (TSH). We aim to describe differences in thyroid regulation, measured by the Parametric Thyroid Feedback Quantile-Based Index (PTFQI), between patients with atrial fibrillation and the general population.

Diagnosis of Familial Dysbetalipoproteinemia Based on the Lipid Abnormalities Driven by APOE2/E2 Genotype.

Background: Familial dysbetalipoproteinemia (FDBL) is a monogenic disease due to variants in APOE with a highly variable phenotype. Current diagnostic lipid-based methods have important limitations. The objective is twofold: to define characteristics of dysbetalipoproteinemia (DBL) based on the analysis of APOE in patients from a lipid unit and in a sample from the general population, and to propose a screening algorithm for FDBL.

Genotypes Modulate Inflammation Independently of Their Effect on Lipid Metabolism.

The association between genotypes and cardiovascular disease (CVD) is partially mediated by LDL-cholesterol concentration but persists after adjusting for lipid levels and other cardiovascular risk factors. Data from the Aragon Workers Health Study (AWHS) (n = 4159) and the Lipid Unit at the Hospital Universitario Miguel Servet (HUMS) (n = 3705) were used to investigate the relationship between C-reactive protein (CRP) levels and genotype. Lipoprotein particle and GlycA concentrations were analyzed in a subsample from AWHS.

A mechanism-based operational definition and classification of hypercholesterolemia.

In contrast to strong evidence-based clinical recommendations for lipid-lowering treatment, there is no analogous definitive diagnostic definition of hypercholesterolemia and its various subtypes. For many clinicians, guideline indications for hypolipidemic treatment can become broadly conflated with hypercholesterolemia in a non-specific sense. In this statement, we propose a unified definition and mechanism-based classification of hypercholesterolemia, which in turn should help to stratify patients and guide efficient diagnosis without interfering with the current strategies of ASCVD risk reduction.

A Cross-Sectional Study Examining the Parametric Thyroid Feedback Quantile Index and Its Relationship with Metabolic and Cardiovascular Diseases.

The usual inverse correlation between thyrotropin (TSH) and thyroid hormone disappears in syndromes of central resistance to thyroid hormone, where both are high. TSH and thyroid hormone are also simultaneously high when there is an elevation of the set point of the thyroid regulation axis. This can be estimated with indices, such as the Parametric Thyroid Feedback Quantile-based Index (PTFQI), which was designed for the general population.

Triglyceride Metabolism Modifies Lipoprotein(a) Plasma Concentration.

Background: Lipoprotein(a) (Lp(a)) is a significant cardiovascular risk factor. Knowing the mechanisms that regulate its concentration can facilitate the development of Lp(a)-lowering drugs. This study analyzes the relationship between triglycerides (TGs) and Lp(a) concentrations, cross-sectionally and longitudinally, and the influence of the number and composition of TG-rich lipoproteins, and the APOE genotype.