Homozygous Familial Hypercholesterolemia in Spain Prevalence and Phenotype-Genotype Relationship

Background— Homozygous familial hypercholesterolemia (HoFH) is a rare disease characterized by elevated plasma levels of low-density lipoprotein cholesterol (LDL-C) and extremely high risk of premature atherosclerotic cardiovascular disease. HoFH is caused by mutations in several genes, including LDL receptor ( LDLR ), apolipoprotein B ( APOB ), proprotein convertase subtilisin/kexin type 9 ( PCSK9 ), and LDL protein receptor adaptor 1 ( LDLRAP1 ). No epidemiological studies have assessed HoFH prevalence or the clinical and molecular characteristics of this condition. Here, we aimed to characterize HoFH in Spain. Methods and Results— Data were collected from the Spanish Dyslipidemia Regist…

Two-generation cardiovascular disease prevalence in familial hypercholesterolemia

Consensus document of an expert group from the Spanish Society of Arteriosclerosis (SEA) on the clinical use of nuclear magnetic resonance to assess lipoprotein metabolism (Liposcale®)

The assessment and prevention of cardiovascular risk (CVR) that persists in patients with dyslipidaemia despite treatment and achievement of goals specific to the plasma concentration of cholesterol linked to low density (c-LDL) is a clinical challenge today, and suggests that conventional lipid biomarkers are insufficient for an accurate assessment of CVR. Apart from their lipid content, there are other lipid particle characteristics. The results of this study show that there are a number of lipoprotein compounds that determine atherogenic potential and its influence on the CVR. However, such additional characteristics cannot be analysed by the techniques commonly used in clinical laborato…

Identifying genetic risk variants for coronary heart disease in familial hypercholesterolemia: an extreme genetics approach

Mutations in the low-density lipoprotein receptor (LDLR) gene cause familial hypercholesterolemia (FH), a disorder characterized by coronary heart disease (CHD) at young age. We aimed to apply an extreme sampling method to enhance the statistical power to identify novel genetic risk variants for CHD in individuals with FH. We selected cases and controls with an extreme contrast in CHD risk from 17 000 FH patients from the Netherlands, whose functional LDLR mutation was unequivocally established. The genome-wide association (GWA) study was performed on 249 very young FH cases with CHD and 217 old FH controls without CHD (above 65 years for males and 70 years of age for females) using the Ill…

FABP4 plasma levels are increased in familial combined hyperlipidemia

The lipid profile of familial combined hyperlipidemia (FCHL) shares some characteristics with atherogenic dyslipidemia seen in diabetes, metabolic syndrome, and obesity. Adipocyte fatty acid-binding protein 4 (FABP4) appears to be a determinant of atherogenic dyslipidemia. We examined relationships between FABP4 plasma concentrations, dyslipidemia, and metabolic variables in patients with FCHL. We studied 273 unrelated FCHL patients and 118 control subjects. FABP4 was higher in FCHL than controls, with mean levels of 21.8 (10.1) microg/l and 19.2 (9.2) microg/l, respectively (adjusted P= 0.012). In FCHL, FABP4 correlated to body mass index (BMI), waist circumference, insulin levels, and hom…

Association of plasma markers of cholesterol homeostasis with metabolic syndrome components. A cross-sectional study.

Abstract Background and aims Increased plasma phytosterols, which reflect enhanced cholesterol absorption, have been related to an increased risk of cardiovascular disease (CVD). However, high CVD risk conditions, such as obesity, diabetes and the metabolic syndrome (MetS) have been associated with reduced cholesterol absorption. We investigated associations between plasma noncholesterol sterols and MetS components. Methods and results With a cross-sectional design, we related MetS components to plasma noncholesterol sterol-to-cholesterol ratios measured by gas chromatography in 674 dyslipidemic patients and 361 healthy subjects participating in a prospective cohort study. Plasma phytostero…

Registro de hipertrigliceridemias de la Sociedad Española de Arteriosclerosis

Value of the Definition of Severe Familial Hypercholesterolemia for Stratification of Heterozygous Patients

Familial hypercholesterolemia (FH) is characterized by high low-density lipoprotein (LDL) cholesterol with co-dominant transmission and high risk of cardiovascular disease (CVD), although with high variability among subjects. Currently, CVD stratification tools for heterozygous FH (HeFH) are not available. A definition of severe HeFH has been recently proposed by the International Atherosclerosis Society (IAS), but it has not been validated. Our study aims to see clinical characteristics and prevalence of CVD in subjects defined as severe HeFH by IAS criteria. Probable or definite HeFH introduced in the Dyslipidemia Registry of Spanish Arteriosclerosis Society were analyzed by the IAS crite…

Documento de consenso de un grupo de expertos de la Sociedad Española de Arteriosclerosis (SEA) sobre el uso clínico de la resonancia magnética nuclear en el estudio del metabolismo lipoproteico (Liposcale)

Resumen La evaluacion y prevencion del riesgo cardiovascular (RCV) que persiste en los pacientes con dislipidemia a pesar del tratamiento y de haber alcanzado los objetivos especificos de la concentracion plasmatica de colesterol unido a lipoproteinas de baja densidad (c-LDL) es un reto clinico en la actualidad, y sugiere que los biomarcadores lipidicos convencionales resultan insuficientes para una evaluacion precisa del RCV. Mas alla de su contenido lipidico, existen otras caracteristicas propias de las particulas lipoproteicas que determinan su potencial aterogenico y su influencia en el RCV. Sin embargo, dichas caracteristicas adicionales no pueden ser analizadas por las tecnicas utiliz…

Autosomal recessive hypercholesterolemia in Spain.

Abstract Background and aims Autosomal recessive hypercholesterolemia (ARH) is a very rare disease, caused by mutations in LDL protein receptor adaptor 1 (LDLRAP1). It is characterized by high levels of low-density lipoprotein cholesterol (LDL-C) and increased risk of premature cardiovascular disease. We aimed to characterize ARH in Spain. Methods Data were collected from the Dyslipidemia Registry of the Spanish Atherosclerosis Society. A literature search was performed up to June 2017, and all diagnostic genetic studies for familial hypercholesterolemia of Spain were reviewed. Results Seven patients with ARH were identified, 6 true homozygous and one compound heterozygous with a novel muta…

Indications of PCSK9 inhibitors in clinical practice. Recommendations of the Spanish Society of Arteriosclerosis (SEA), 2019

A group of experts convened by the Spanish Society of Arteriosclerosis (SEA) has been in charge of updating the SEA document on the indications of PCSK9 inhibitors (PCSK9i) in clinical practice that was published in 2016. This update is justified by the fact that the data from clinical trials carried out on a large scale with PCSK9i have shown that in addition to their high potency to lower atherogenic cholesterol, they reduce the risk of atherosclerotic cardiovascular disease, both in patients with stable disease, and with recent disease, and with a high degree of security. This update provides the recommendations and level of evidence for the prescription of iPCSK9 in patients with homozy…

Estándares SEA 2019 para el control global del riesgo cardiovascular

One of the main goals of the Spanish Society of Arteriosclerosis is to contribute to a wider and greater knowledge of vascular disease, its prevention and treatment. Cardiovascular diseases are the leading cause of death in our country and also lead to a high degree of disability and health expenditure. Arteriosclerosis is a multifactorial disease, this is why its prevention requires a global approach that takes into account the different risk factors with which it is associated. Thus, this document summarizes the current level of knowledge and integrates recommendations and procedures to be followed for patients with established cardiovascular disease or high vascular risk. Specifically, t…

Hipercolesterolemia familiar homocigota: adaptación a España del documento de posición del grupo de consenso sobre hipercolesterolemia familiar de la Sociedad Europea de Arteriosclerosis. Documento de Consenso de la Sociedad Española de Arteriosclerosis (SEA) y la Fundación Hipercolesterolemia Familiar (FHF).

Homozygous familial hypercholesterolaemia (HoFH) is a rare life-threatening disease characterized by markedly elevated circulating levels of low-density lipoprotein cholesterol (LDL-C) and accelerated, premature atherosclerotic cardiovascular disease (ACVD). The Consensus Panel on Familial Hypercholesterolaemia of the European Atherosclerosis Society (EAS) has recently published a clinical guide to diagnose and manage HoFH (Eur Heart J. 2014;35:2146-57). Both the Spanish Society of Atherosclerosis (SEA) and Familial Hypercholesterolaemia Foundation (FHF) consider this European Consensus document of great value and utility. However, there are particularities in our country which advise to ha…

Indicaciones de los inhibidores de PCSK9 en la práctica clínica. Recomendaciones de la Sociedad Española de Arteriosclerosis (SEA), 2019

Resumen Un grupo de expertos convocado por la Sociedad Espanola de Arteriosclerosis (SEA) se ha encargado de actualizar el documento de la SEA sobre las indicaciones de los inhibidores de PCSK9 (iPCSK9) en la practica clinica publicadas en 2016. Esta actualizacion es necesaria porque en el periodo transcurrido hasta la actualidad se han publicado los resultados de los ensayos clinicos realizados a gran escala con iPCSK9 que demuestran que, ademas de su alta potencia para disminuir el colesterol aterogenico, disminuyen el riesgo de presentar episodios de enfermedad cardiovascular aterosclerotica en los pacientes con enfermedad tanto estable como reciente, y con un alto grado de seguridad. La…

Association of selenium exposure with insulin resistance and β-cell function in middle age and older adults

Documento de consenso de la Sociedad Española de Arteriosclerosis sobre las indicaciones de los inhibidores de la PCSK9 [Consensus document of the Spanish Society of Arteriosclerosis on indications of inhibitors of PCSK9]

La SEA ha consensuado unas indicaciones médicas para el uso de los inhibidores de la PCSK9 (tabla 1), atendiendo a la relación coste/beneficio, y teniendo en cuenta que aún no se dispone de datos sobre la protección de episodios cardiovasculares.