Autosomal Recessive Hypercholesterolemia Long-Term Cardiovascular Outcomes

BACKGROUND Autosomal recessive hypercholesterolemia (ARH) is a rare lipid disorder characterized by premature atherosclerotic cardiovascular disease (ASCVD). There are sparse data for clinical management and cardiovascular outcomes in ARH. OBJECTIVES Evaluation of changes in lipid management, achievement of low-density lipoprotein cholesterol (LDL-C) goals and cardiovascular outcomes in ARH. METHODS Published ARH cases were identified by electronic search. All corresponding authors and physicians known to treat these patients were asked to provide follow-up information, using a standardized protocol. RESULTS We collected data for 52 patients (28 females, 24 males; 31.1 +/- 17.1 years of age…

Is complying with the recommendations of sodium intake beneficial for health in individuals at high cardiovascular risk? Findings from the PREDIMED study

Background: Excess sodium intake is associated with high blood pressure, a major risk factor for cardiovascular disease (CVD). It is unknown whether decreasing sodium intake to ,2300 mg/d has an effect on CVD or all-cause mortality. Objective: The objective was to assess whether reductions in sodium intake to ,2300 mg/d were associated with either an increased or a decreased risk of fatal and nonfatal CVD and all-cause mortality. Design: This observational prospective study of the PREvencicon DIeta MEDiterr� (PREDIMED) trial included 3982 participants at high CVD risk. Sodium intake was evaluated with a validated food- frequency questionnaire and categorized as low (,1500 mg/d), in- termedi…

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…

Management of Dyslipidemia in the Metabolic Syndrome

In order to characterize the metabolic syndrome it becomes necessary to establish a number of diagnostic criteria. Because of its impact on cardiovascular morbidity/mortality, considerable attention has been focussed on the dyslipidemia accompanying the metabolic syndrome. The aim of this review is to highlight the fundamental aspects of the pathophysiology, diagnosis, and the treatment of the metabolic syndrome dyslipidemia with recommendations to clinicians. The clinical expression of the metabolic syndrome dyslipidemia is characterized by hypertriglyceridemia and low levels of high-density lipoprotein-cholesterol (HDL-C). In addition, metabolic syndrome dyslipidemia is associated with hi…

Prevalence of plasma lipid abnormalities and its association with glucose metabolism in Spain: The di@bet.es study

Abstract Introduction Dyslipidemia is a significant contributor to the elevated CVD risk observed in type 2 diabetes mellitus. We assessed the prevalence of dyslipidemia and its association with glucose metabolism status in a representative sample of the adult population in Spain and the percentage of subjects at guideline-recommended LDL-C goals. Material and methods The di@bet.es study is a national, cross-sectional population-based survey of 5728 adults. Results A total of 4776 subjects were studied. Dyslipidemia was diagnosed in 56.8% of subjects; only 13.2% of subjects were treated with lipid lowering drugs. Lipid abnormalities were found in 56.8% of Spanish adults: 23.3% with high LDL…

Practical guidance for combination lipid-modifying therapy in high- and very-high-risk patients: A statement from a European Atherosclerosis Society Task Force

International audience; Background and aimsThis European Atherosclerosis Society (EAS) Task Force provides practical guidance for combination therapy for elevated low-density lipoprotein cholesterol (LDL-C) and/or triglycerides (TG) in high-risk and very-high-risk patients.MethodsEvidence-based review.ResultsStatin-ezetimibe combination treatment is the first choice for managing elevated LDL-C and should be given upfront in very-high-risk patients with high LDL-C unlikely to reach goal with a statin, and in primary prevention familial hypercholesterolaemia patients. A proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor may be added if LDL-C levels remain high. In high and very-h…

The use of statins in people at risk of developing diabetes mellitus: Evidence and guidance for clinical practice

Reducing low-density lipoprotein cholesterol (LDL-C) levels using statins is associated with significant reductions in cardiovascular (CV) events in a wide range of patient populations. Although statins are generally considered to be safe, recent studies suggest they are associated with an increased risk of developing Type 2 diabetes (T2D). This led the US Food and Drug Administration (FDA) to change their labelling requirements for statins to include a warning about the possibility of increased blood sugar and HbA1c levels and the European Medicines Agency (EMA) to issue guidance on a small increased risk of T2D with the statin class. This review examines the evidence leading to these clai…

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

Abstract Background Autosomal recessive hypercholesterolemia (ARH) is a rare lipid disorder characterized by premature atherosclerotic cardiovascular disease (ASCVD). There are sparse data for clinical management and cardiovascular outcomes in ARH. Objectives Evaluation of changes in lipid management, achievement of low-density lipoprotein cholesterol (LDL-C) goals and cardiovascular outcomes in ARH. Methods Published ARH cases were identified by electronic search. All corresponding authors and physicians known to treat these patients were asked to provide follow-up information, using a standardized protocol. Results We collected data for 52 patients (28 females, 24 males; 31.1 ± 17.1 years…

EU-wide cross-sectional observational study of lipid-modifying therapy use in secondary and primary care: the DA VINCI study

Abstract Aims To provide contemporary data on the implementation of European guideline recommendations for lipid-lowering therapies (LLTs) across different settings and populations and how this impacts low-density lipoprotein cholesterol (LDL-C) goal achievement. Methods and results An 18 country, cross-sectional, observational study of patients prescribed LLT for primary or secondary prevention in primary or secondary care across Europe. Between June 2017 and November 2018, data were collected at a single visit, including LLT in the preceding 12 months and most recent LDL-C. Primary outcome was the achievement of risk-based 2016 European Society of Cardiology (ESC)/European Atherosclerosis…

Familial hypercholesterolaemia is underdiagnosed and undertreated in the general population: guidance for clinicians to prevent coronary heart disease: Consensus Statement of the European Atherosclerosis Society

AIMS: The first aim was to critically evaluate the extent to which familial hypercholesterolaemia (FH) is underdiagnosed and undertreated. The second aim was to provide guidance for screening and treatment of FH, in order to prevent coronary heart disease (CHD).METHODS AND RESULTS: Of the theoretical estimated prevalence of 1/500 for heterozygous FH, <1% are diagnosed in most countries. Recently, direct screening in a Northern European general population diagnosed approximately 1/200 with heterozygous FH. All reported studies document failure to achieve recommended LDL cholesterol targets in a large proportion of individuals with FH, and up to 13-fold increased risk of CHD. Based on prev…

Lipid-lowering therapy and low-density lipoprotein cholesterol goal achievement in patients with acute coronary syndromes: The ACS patient pathway project

Background and aims: Post-acute coronary syndrome (ACS) patients are at very high risk for recurrent events and mortality, despite the availability of effective pharmacological approaches. Aim of this survey was to evaluate the compliance to ESC/EAS guidelines during the management of ACS patients and the effectiveness of secondary prevention in seven European countries.Methods: By means of an online questionnaire, data on 2775 ACS patients (either acute case or follow-up patients) were collected, including data on lipid profile, medications, follow-up visit planning, screening for familial hypercholesterolemia.Results: Lipid profiles were obtained for 91% of ACS patients in the acute phase…

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…

Remarkable quantitative and qualitative differences in HDL after niacin or fenofibrate therapy in type 2 diabetic patients

Abstract HDL-increasing drugs such as fenofibrate and niacin have failed to decrease the cardiovascular risk in patients with type 2 diabetes. Drug-mediated quantitative and qualitative HDL modifications could be involved in these negative results. To evaluate the quantitative and qualitative effects of niacin and fenofibrate on HDL in patients with type 2 diabetes, a prospective, randomised controlled intervention trial was conducted. Thirty type 2 diabetic patients with low HDL were randomised to receive either fenofibrate (FFB) or niacin + laropiprant (ERN/LPR) as an add-on to simvastatin treatment for 12 weeks according to a crossover design. At the basal point and after each interventi…

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…

Response to treatment and occurrence of cardiovascular (CV) complications in patients with autosomal recessive hypercholesterolemia (ARH): A retrospective analysis

Homozygous familial hypercholesterolaemia: new insights and guidance for clinicians to improve detection and clinical management. A position paper from the Consensus Panel on Familial Hypercholesterolaemia of the European Atherosclerosis Society

Item does not contain fulltext AIMS: Homozygous familial hypercholesterolaemia (HoFH) is a rare life-threatening condition characterized by markedly elevated circulating levels of low-density lipoprotein cholesterol (LDL-C) and accelerated, premature atherosclerotic cardiovascular disease (ACVD). Given recent insights into the heterogeneity of genetic defects and clinical phenotype of HoFH, and the availability of new therapeutic options, this Consensus Panel on Familial Hypercholesterolaemia of the European Atherosclerosis Society (EAS) critically reviewed available data with the aim of providing clinical guidance for the recognition and management of HoFH. METHODS AND RESULTS: Early diagn…

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.