Implementation of a biochemical, clinical, and genetic screening programme for familial hypercholesterolemia in 26 centres in Spain: The ARIAN study.

Background: Familial hypercholesterolemia (FH) is clearly underdiagnosed and undertreated. The aim of this present study is to assess the benefits of FH screening through a joint national program implemented between clinical laboratories and lipid units. Methods: All clinical laboratory tests from 1 January 2017 to 31 December 2018 were reviewed, and those with LDL cholesterol (LDL-C) levels >250 mg/dl were identified in subjects >18 years of age of both sexes. Once secondary causes had been ruled out, the treating physician was contacted and advised to refer the patient to an LU to perform the Dutch Lipid Clinic Network score and to request genetic testing if the score was ≥6 points. Next Generation Sequencing was used to analyse the promoter and coding DNA sequences of four genes associated with FH (LDLR, APOB, PCSK9, APOE) and two genes that have a clinical overlap with FH characteristics (LDLRAP1 and LIPA). A polygenic risk score based on 12 variants was also obtained. Results: Of the 3,827,513 patients analyzed in 26 centers, 6,765 had LDL-C levels >250 mg/dl. Having ruled out secondary causes and known cases of FH, 3,015 subjects were included, although only 1,205 treating physicians could be contacted. 635 patients were referred to an LU and genetic testing was requested for 153 of them. This resulted in a finding of sixty-seven pathogenic variants for FH, 66 in the LDLR gene and one in APOB. The polygenic risk score was found higher in those who had no pathogenic variant compared to those with a pathogenic variant. Conclusion: Despite its limitations, systematic collaboration between clinical laboratories and lipid units allows for the identification of large numbers of patients with a phenotypic or genetic diagnosis of FH, which will reduce their vascular risk. This activity should be part of the clinical routine.

Implantación de un programa de cribado bioquímico y genético de hipercolesterolemia familiar. Colaboración entre el laboratorio clínico y las unidades de lípidos: diseño del Proyecto ARIAN / Implantation of a biochemical and genetic screening programme for family hypercholesterolaemia. Collaboration between the clinical laboratory and lipid units: Design of the ARIAN Project

Introducción y objetivo: La hipercolesterolemia familiar (HF) es el trastorno genético más frecuente asociado con enfermedad coronaria prematura debido a la presencia de cLDL incrementado desde el nacimiento. Se encuentra infradiagnosticada e infratratada. El objetivo primario del proyecto ARIAN es determinar el número de pacientes diagnosticados de HF tras implantar un nuevo procedimiento de cribado desde el laboratorio. Material y métodos: Este proyecto se ha diseñado como un análisis retrospectivo mediante consulta al sistema informático. Se seleccionaron de las bases de datos de laboratorio aquellas muestras de suero de pacientes ≥ 18 años con cLDL directos o calculados > 250 mg/dl, desde el 1 de enero del 2017 hasta el 31 de diciembre del 2018. Una vez descartadas causas secundarias, se comunicó al médico de Atención Primaria solicitante la sospecha de que su paciente pudiera portar una HF y gestionar una cita prioritaria en la unidad de Lípidos. Todos aquellos pacientes con una puntuación ≥ 6 puntos de los criterios de las Clínicas holandesas se les propuso un estudio genético. Resultados: El protocolo se presentó a 55 laboratorios de forma individualizada. Hasta el día 30 de diciembre del 2020, el número centros que han remitido resultados es de 24. El número de muestras analizadas hasta ese momento fue de 3.266.341, lo que representa un 34% de la población atendida en esas áreas de salud (9.727.434). Conclusiones: La identificación de nuevos sujetos con HF mediante esta nueva estrategia desde el laboratorio y su remisión a las unidades de Lípidos debe incrementar el número de pacientes tratados en las unidades de Lípidos y permitir iniciar cribados en cascada familiar.(AU)

Introduction and objective: Familial hypercholesterolaemia (FH) is the most common genetic disorder associated with premature coronary artery disease due to the presence of LDL-C cholesterol increased from birth. It is underdiagnosed and undertreated. The primary objective of the ARIAN project was to determine the number of patients diagnosed with FH after implementing a new screening procedure from the laboratory. Material and methods: This project was designed as a retrospective analysis by consulting the computer system. We selected from databases serum samples from patients ≥ 18 years with direct or calculated LDL-C>250mg/dL from 1 January 2017 to 31 December 2018. Once secondary causes had been ruled out, the requesting primary care physician was notified that their patient might have FH and to arrange a priority appointment in the lipid unit. All patients with a score of ≥ 6 points according to the Dutch Lipid Clinic Criteria were proposed for a genetic study. Results: By December 30th, 2020, 24 centres out of the initial 55 had submitted results. The number of patients analysed up to that point was 3,266,341, which represents 34% of the population served in those health areas (9,727,434). Conclusions: The identification of new subjects with FH through this new strategy from the laboratory and their referral to lipid units should increase the number of patients treated in lipid units and initiate familial cascade screening.(AU)

Implantation of a biochemical and genetic screening programme for family hypercholesterolaemia. Collaboration between the clinical laboratory and lipid units: Design of the ARIAN Project. / Implantación de un programa de cribado bioquímico y genético de hipercolesterolemia familiar. Colaboración entre el laboratorio clínico y las unidades de lípidos: diseño del Proyecto ARIAN.

INTRODUCTION AND OBJECTIVE: Familial hypercholesterolaemia (FH) is the most common genetic disorder associated with premature coronary artery disease due to the presence of LDL-C cholesterol increased from birth. It is underdiagnosed and undertreated. The primary objective of the ARIAN project was to determine the number of patients diagnosed with FH after implementing a new screening procedure from the laboratory. MATERIAL AND METHODS: This project was designed as a retrospective analysis by consulting the computer system. We selected from databases serum samples from patients ≥ 18 years with direct or calculated LDL-C>250mg/dL from 1 January 2017 to 31 December 2018. Once secondary causes had been ruled out, the requesting primary care physician was notified that their patient might have FH and to arrange a priority appointment in the lipid unit. All patients with a score of ≥ 6 points according to the Dutch Lipid Clinic Criteria were proposed for a genetic study RESULTS: By December 30th, 2020, 24 centres out of the initial 55 had submitted results. The number of patients analysed up to that point was 3,266,341, which represents 34% of the population served in those health areas (9,727,434). CONCLUSIONS: The identification of new subjects with FH through this new strategy from the laboratory and their referral to lipid units should increase the number of patients treated in lipid units and initiate familial cascade screening.

Physicochemical Properties of Lipoproteins Assessed by Nuclear Magnetic Resonance as a Predictor of Premature Cardiovascular Disease. PRESARV-SEA Study.

Some lipoprotein disorders related to the residual risk of premature cardiovascular disease (PCVD) are not detected by the conventional lipid profile. In this case-control study, the predictive power of PCVD of serum sdLDL-C, measured using a lipoprotein precipitation method, and of the physicochemical properties of serum lipoproteins, analyzed by nuclear magnetic resonance (NMR) techniques, were evaluated. We studied a group of patients with a first PCVD event (n = 125) and a group of control subjects (n = 190). Conventional lipid profile, the size and number of Very Low Density Lipoproteins (VLDL), Low Density Lipoproteins (LDL), High Density Lipoproteins (HDL) particles, and the number of particles of their subclasses (large, medium, and small) were measured. Compared to controls, PCVD patients had lower concentrations of all LDL particles, and smaller and larger diameter of LDL and HDL particles, respectively. PCVD patients also showed higher concentrations of small dense LDL-cholesterol (sdLDL), and triglycerides (Tg) in LDL and HDL particles (HDL-Tg), and higher concentrations of large VLDL particles. Multivariate logistic regression showed that sdLDL-C, HDL-Tg, and large concentrations of LDL particles were the most powerful predictors of PCVD. A strong relationship was observed between increased HDL-Tg concentrations and PCVD. This study demonstrates that beyond the conventional lipid profile, PCVD patients have other atherogenic lipoprotein alterations that are detected by magnetic resonance imaging (MRI) analysis.

Maternally inherited hypercholesterolemia does not modify the cardiovascular phenotype in familial hypercholesterolemia.

BACKGROUND AND AIMS: Familial hypercholesterolemia (FH) is a codominant autosomal disease characterized by a high risk of cardiovascular disease when not in lipid-lowering treatment. However, there is a large variability in the clinical presentation in heterozygous subjects (HeFH). Maternal hypercholesterolemia has been proposed as a cardiometabolic risk factor later in life. Whether this phenotype variability depends on the mother or father origin of hypercholesterolemia is unknown. The objective of this study was to analyze potential differences in anthropometry, superficial lipid deposits, comorbidities, and lipid concentrations depending on the parental origin of hypercholesterolemia within a large group of HeFH. METHODS: This is a cross-sectional observational, multicenter, nation-wide study in Spain. We recruited adults with HeFH to study clinical differences according to the parental origin. Data on HeFH patients were obtained from the Dyslipidemia Registry of the Spanish Atherosclerosis Society. RESULTS: HeFH patients were grouped in 1231 HeFH-mother-offspring aged 45.7 (16.3) years and 1174 HeFH-father-offspring aged 44.8 (16.7) years. We did not find any difference in lipid parameters (total cholesterol, triglycerides, LDLc, HDLc, and Lp(a)), nor in the comorbidities studied (cardiovascular disease prevalence, age of onset of cardiovascular disease, obesity, diabetes, and hypertension) between groups. Lipid-lowering treatment did not differ between groups. The prevalence of comorbidities did not show differences when they were studied by age groups. CONCLUSIONS: Our research with a large group of subjects with HeFH shows that a potential maternal effect is not relevant in FH. However, due to the size of our sample, potential differences between genders cannot be completely ruled out. This implies that severe maternal hypercholesterolemia during pregnancy is not associated with additional risk in the FH affected offspring.

Triglicéridos, colesterol HDL y dislipidemia aterogénica en la guía europea para el control de las dislipidemias 2019 / Triglycerides, HDL cholesterol and atherogenic dyslipidaemia in the 2019 European guidelines for the management of dyslipidaemias

En general, las guías de práctica clínica tanto europeas con americanas han abordado el control de la dislipidemia aterogénica de forma poco convincente e incluso superficial, en gran medida por las limitaciones terapéuticas disponibles. En consecuencia, esta dislipidemia está infradiagnosticada, infratratada e infracontrolada. Dada la reciente aparición de la guía 2019 de la European Atherosclerosis Society y de la European Society of Cardiology sobre el control de las dislipidemias, parece oportuno examinar su posicionamiento con respecto a la dislipidemia aterogénica y/o sus principales componentes, el aumento en las lipoproteínas ricas en triglicéridos y la disminución del colesterol de las lipoproteínas de alta densidad

In general, both European and American clinical guidelines have addressed the management of atherogenic dyslipidaemia in an unconvincing and even superficial way, largely because of the available therapeutic limitations. Consequently, this type of dyslipidaemia is underdiagnosed, under-treated, and under-controlled. Given the recent presentation of the 2019 guidelines of the European Atherosclerosis Society and the European Society of Cardiology on the management of dyslipidaemias, it seems appropriate to examine its position with respect to atherogenic dyslipidaemia and/or its main components, the increase in triglyceride-rich lipoproteins, and the decrease of high-density lipoprotein cholesterol

Incidencia de eventos cardiovasculares y cambios en el riesgo estimado y en el tratamiento de la hipercolesterolemia familiar: registro SAFEHEART / Incidence of cardiovascular events and changes in the estimated risk and treatment of familial hypercholesterolemia: the SAFEHEART registry

INTRODUCCIÓN Y OBJETIVOS: El estudio SAFEHEART se diseñó para analizar la situación y mejorar el conocimiento de la hipercolesterolemia familiar heterocigota (HFH) en España. Nuestro objetivo es determinar la tasa de incidencia de eventos cardiovasculares, el riesgo estimado de sufrir un evento y su modificación, el empleo de tratamiento hipolipemiante y la consecución de objetivos de colesterol unido a lipoproteínas de baja densidad en pacientes con HFH. MÉTODOS: El SAFEHEART es un estudio prospectivo de cohorte, abierto, multicéntrico, de escala nacional, con seguimiento protocolizado a largo plazo en una población de HFH caracterizada molecularmente. Se analizó a los pacientes mayores de 18 años con seguimiento completo. RESULTADOS: El análisis en este estudio se hizo con 2.648 pacientes con HFH. La mediana de seguimiento fue de 6,6 (4,8-9,7) años. La tasa de incidencia general de eventos cardiovasculares fue de 1,3 eventos/100 pacientes-año. El riesgo estimado de sufrir un evento cardiovascular a 10 años se redujo en el seguimiento, y pasó del 1,6 al 1,3% (p <0,001). En el último seguimiento, el 20,6 y el 22,2% de los pacientes en prevención primaria y secundaria consiguieron un colesterol unido a lipoproteínas de baja densidad <100 y <70 mg/dl respectivamente. CONCLUSIONES: En este estudio se muestra la tasa de incidencia de eventos cardiovasculares, el riesgo estimado de sufrir un evento cardiovascular en la mayor población de pacientes con HF en España, así como su modificación, la consecución de objetivos en colesterol unido a lipoproteínas de baja densidad y su tratamiento. Aunque el riesgo cardiovascular de la HFH es elevado, un adecuado tratamiento reduce la probabilidad de sufrir un evento

INTRODUCTION AND OBJECTIVES: The SAFEHEART study was designed to analyze the situation of familial heterozygous hypercholesterolemia (FHH) and improve knowledge of this disease in Spain. Our objective was to determine the incidence rate of cardiovascular events, the estimated risk of developing an event and its modification, the use of lipid-lowering treatment, and the achievement of low-density lipoprotein cholesterol targets in patients with FHH. METHODS: SAFEHEART is a prospective, open, multicenter, nationwide cohort study, with long-term protocol-based follow-up in a population of individuals with molecularly-characterized FHH. We analyzed patients older than 18 years with complete follow-up. RESULTS: We included 2648 patients with FHH. The median follow-up was 6.6 (4.8-9.7) years. The overall incidence rate of cardiovascular events was 1.3 events/100 patient-years. After the follow-up, the 10-year estimated risk of developing a cardiovascular event was reduced from 1.6% to 1.3% (P <.001). In the last follow-up, 20.6% and 22.2% of the patients in primary and secondary prevention achieved low-density lipoprotein cholesterol values <100mg/dL and <70mg/dL, respectively. CONCLUSIONS: This study was performed in the largest population of patients with FHH in Spain. We identified the incidence rate of cardiovascular events, the estimated risk of developing a cardiovascular event and its modification, the achievement of low-density lipoprotein cholesterol targets, and the therapeutic management in this population. Although the cardiovascular risk of FHH is high, appropriate treatment reduces the likelihood of an event

Dislipidemia aterogénica 2019. Documento de consenso del Grupo de Dislipidemia Aterogénica de la Sociedad Española de Arteriosclerosis / Atherogenic Dyslipidaemia 2019. Consensus document of the Atherogenic Dyslipidaemia Group of the Spanish Arteriosclerosis Society

No disponible

Incidence of cardiovascular events and changes in the estimated risk and treatment of familial hypercholesterolemia: the SAFEHEART registry.

INTRODUCTION AND OBJECTIVES: The SAFEHEART study was designed to analyze the situation of familial heterozygous hypercholesterolemia (FHH) and improve knowledge of this disease in Spain. Our objective was to determine the incidence rate of cardiovascular events, the estimated risk of developing an event and its modification, the use of lipid-lowering treatment, and the achievement of low-density lipoprotein cholesterol targets in patients with FHH. METHODS: SAFEHEART is a prospective, open, multicenter, nationwide cohort study, with long-term protocol-based follow-up in a population of individuals with molecularly-characterized FHH. We analyzed patients older than 18 years with complete follow-up. RESULTS: We included 2648 patients with FHH. The median follow-up was 6.6 (4.8-9.7) years. The overall incidence rate of cardiovascular events was 1.3 events/100 patient-years. After the follow-up, the 10-year estimated risk of developing a cardiovascular event was reduced from 1.6% to 1.3% (P <.001). In the last follow-up, 20.6% and 22.2% of the patients in primary and secondary prevention achieved low-density lipoprotein cholesterol values <100mg/dL and <70mg/dL, respectively. CONCLUSIONS: This study was performed in the largest population of patients with FHH in Spain. We identified the incidence rate of cardiovascular events, the estimated risk of developing a cardiovascular event and its modification, the achievement of low-density lipoprotein cholesterol targets, and the therapeutic management in this population. Although the cardiovascular risk of FHH is high, appropriate treatment reduces the likelihood of an event. CLINICAL TRIAL REGISTRATION: http://www.clinicaltrials.gov. Identifier: NCT02693548.

Triglycerides, HDL cholesterol and atherogenic dyslipidaemia in the 2019 European guidelines for the management of dyslipidaemias. / Triglicéridos, colesterol HDL y dislipidemia aterogénica en la guía europea para el control de las dislipidemias 2019.

In general, both European and American clinical guidelines have addressed the management of atherogenic dyslipidaemia in an unconvincing and even superficial way, largely because of the available therapeutic limitations. Consequently, this type of dyslipidaemia is underdiagnosed, under-treated, and under-controlled. Given the recent presentation of the 2019 guidelines of the European Atherosclerosis Society and the European Society of Cardiology on the management of dyslipidaemias, it seems appropriate to examine its position with respect to atherogenic dyslipidaemia and/or its main components, the increase in triglyceride-rich lipoproteins, and the decrease of high-density lipoprotein cholesterol.

Non-HDL cholesterol as a therapeutic goal. / Colesterol-no HDL como objetivo terapéutico.

Although cholesterol linked to low-density lipoproteins (c-LDL) is well established as a risk factor for cardiovascular disease, there is often a more complex dyslipidaemia pattern that contributes to the formation of atherosclerotic plaque. Non-HDL cholesterol (c-NO-HDL) is used to estimate the total amount of atherogenic lipoproteins in plasma, some of which are not usually determined in daily clinical practice. c-NO-HDL is easily calculated from the subtraction of total plasma cholesterol from the cholesterol content carried by high density lipoproteins. The c-NO-HDL has a predictive value superior to that of C-LDL to estimate the risk of major cardiovascular events in epidemiological studies. Genetic studies by analysis of the complete genome, together with those based on Mendelian randomisation, point to the aetiological character of c-NO-HDL on ischaemic heart disease (IHD). Intervention studies, and the meta-analyses derived from them, close the causal circle between c-NO-HDL and IHD, by demonstrating that any intervention that decreases the concentrations of the former reduces the incidence of arteriosclerotic heart disease. The European ESC/EAS 2016 guide for the management of dyslipidaemia considers c-NO-HDL as a therapeutic target with a Class IIa recommendation (should be performed) Level B (data from a single randomised clinical trial [RCT]) or from several non-RCTs), and sets its target at less than 100 or 130mg/dL for those patients with very high risk or high risk, respectively. These achievable c-NO-HDL values are easily calculated by adding 30mg/dL to the c-LDL targets.

Colesterol-no HDL como objetivo terapéutico / Non-HDL cholesterol as a therapeutic goal

Aunque el colesterol unido a las lipoproteínas de baja densidad (c-LDL) está bien establecido como un factor de riesgo de las enfermedades cardiovasculares; existe frecuentemente un patrón dislipidémico más complejo que contribuye a la formación de la placa arteriosclerótica. El colesterol no HDL (c-NO-HDL) se utiliza para la estimación de la cantidad total de lipoproteínas aterogénicas en plasma, algunas de las cuales no son determinadas habitualmente en la práctica clínica diaria. El c-NO-HDL se calcula fácilmente a partir de la sustracción de la cifra de colesterol total plasmático el contenido de colesterol vehiculizado por las lipoproteínas de alta densidad. El c-NO-HDL presenta una superioridad predictora sobre el c-LDL para estimar el riesgo de eventos cardiovasculares mayores en los estudios epidemiológicos. Los estudios genéticos mediante análisis del genoma completo, junto a los basados en la aleatorización mendeliana, apuntan al carácter etiológico del c-NO-HDL sobre la cardiopatía isquémica (CI). Los estudios de intervención, y los metaanálisis de ellos derivados, cierran el círculo causal entre c-NO-HDL y CI al demostrar que cualquier intervención que haga disminuir las concentraciones del primero aminora la incidencia de la cardiopatía arteriosclerótica. La guía europea ESC/EAS 2016 para el manejo de las dislipidemias contempla al c-NO-HDL como una diana terapéutica con una recomendación clase iia (debería realizarse), nivel B (datos de un único RCT o de varios no RCT), y fija su objetivo en menor de 100 o 130 mg/dl para aquellos pacientes con muy alto riesgo o alto riesgo, respectivamente. Estos valores a lograr de c-NO-HDL se calculan fácilmente añadiendo 30 mg/dl a los objetivos c-LDL

Although cholesterol linked to low-density lipoproteins (c-LDL) is well established as a risk factor for cardiovascular disease, there is often a more complex dyslipidaemia pattern that contributes to the formation of atherosclerotic plaque. Non-HDL cholesterol (c-NO-HDL) is used to estimate the total amount of atherogenic lipoproteins in plasma, some of which are not usually determined in daily clinical practice. c-NO-HDL is easily calculated from the subtraction of total plasma cholesterol from the cholesterol content carried by high density lipoproteins. The c-NO-HDL has a predictive value superior to that of C-LDL to estimate the risk of major cardiovascular events in epidemiological studies. Genetic studies by analysis of the complete genome, together with those based on Mendelian randomisation, point to the aetiological character of c-NO-HDL on ischaemic heart disease (IHD). Intervention studies, and the meta-analyses derived from them, close the causal circle between c-NO-HDL and IHD, by demonstrating that any intervention that decreases the concentrations of the former reduces the incidence of arteriosclerotic heart disease. The European ESC/EAS 2016 guide for the management of dyslipidaemia considers c-NO-HDL as a therapeutic target with a Class IIa recommendation (should be performed) Level B (data from a single randomised clinical trial [RCT]) or from several non-RCTs), and sets its target at less than 100 or 130mg/dL for those patients with very high risk or high risk, respectively. These achievable c-NO-HDL values are easily calculated by adding 30 mg/dL to the c-LDL targets

Riesgo cardiovascular residual de origen lipídico. Componentes y aspectos fisiopatológicos / Residual cardiovascular risk of lipid origin. Components and pathophysiological aspects

Es indudable la relación del cLDL y el riesgo cardiovascular, así como de los beneficios del tratamiento con estatinas. Una vez conseguido el objetivo de cLDL, son notables las evidencias que demuestran la persistencia de un elevado riesgo cardiovascular, concepto denominado riesgo residual. El riesgo residual de origen lipídico se fundamenta en la dislipidemia aterogénica, caracterizada por un aumento de triglicéridos y de las lipoproteínas ricas en triglicéridos, un descenso del cHDL y alteraciones cualitativas de las partículas LDL. Las medidas más utilizadas para identificar esta dislipidemia se basan en la determinación de colesterol total, triglicéridos, HDL, colesterol no HDL y colesterol remanente, además de las apolipoproteínas B100 y la lipoproteína(a) en determinados casos. El tratamiento de la dislipidemia aterogénica se basa en la pérdida de peso y ejercicio físico. En cuanto al tratamiento farmacológico, no tenemos evidencia del beneficio cardiovascular con los fármacos dirigidos al descenso de triglicéridos y cHDL; el fenofibrato parece tener eficacia en situaciones de dislipidemia aterogénica

There is no doubt about the relationship between LDL-c and cardiovascular risk, as well as about the benefits of statin treatment. Once the objective of LDL-c has been achieved, the evidences that demonstrate the persistence of a high cardiovascular risk, a concept called residual risk, are notable. The residual risk of lipid origin is based on atherogenic dyslipidemia, characterized by an increase in triglycerides and triglyceride-rich lipoproteins, a decrease in HDL-c and qualitative alterations in LDL particles. The most commonly used measures to identify this dyslipidemia are based on the determination of total cholesterol, triglycerides, HDL, non-HDL cholesterol and remaining cholesterol, as well as apolipoprotein B100 and lipoprotein (a) in certain cases. The treatment of atherogenic dyslipidemia is based on weight loss and physical exercise. Regarding pharmacological treatment, we have no evidence of cardiovascular benefit with drugs aimed at lowering triglycerides and HDL-c, fenofibrate seems to be effective in situations of atherogenic dyslipidemia

Residual cardiovascular risk of lipid origin. Components and pathophysiological aspects. / Riesgo cardiovascular residual de origen lipídico. Componentes y aspectos fisiopatológicos.

There is no doubt about the relationship between LDL-c and cardiovascular risk, as well as about the benefits of statin treatment. Once the objective of LDL-c has been achieved, the evidences that demonstrate the persistence of a high cardiovascular risk, a concept called residual risk, are notable. The residual risk of lipid origin is based on atherogenic dyslipidemia, characterized by an increase in triglycerides and triglyceride-rich lipoproteins, a decrease in HDL-c and qualitative alterations in LDL particles. The most commonly used measures to identify this dyslipidemia are based on the determination of total cholesterol, triglycerides, HDL, non-HDL cholesterol and remaining cholesterol, as well as apolipoprotein B100 and lipoprotein (a) in certain cases. The treatment of atherogenic dyslipidemia is based on weight loss and physical exercise. Regarding pharmacological treatment, we have no evidence of cardiovascular benefit with drugs aimed at lowering triglycerides and HDL-c, fenofibrate seems to be effective in situations of atherogenic dyslipidemia.

Los fibratos en la prevención primaria de la enfermedad cardiovascular. Comentarios a los resultados de una revisión sistemática de la Colaboración Cochrane / Fibrates in primary prevention of cardiovascular disease. Comments on the results of a systematic review of the Cochrane Collaboration

Los fibratos son un grupo de hipolipidemiantes que reducen los triglicéridos, elevan las lipoproteínas de alta densidad y disminuyen la fracción de partículas de LDL pequeñas y densas. Recientemente, se han publicado los resultados de un estudio de la Colaboración Cochrane sobre su eficacia y seguridad en la prevención primaria de la enfermedad cardiovascular. Este estudio incluye una revisión sistemática y un metaanálisis de 6 estudios (16.135 pacientes) que evalúan, en personas en prevención primaria, los beneficios clínicos de los fibratos comparados con el uso de un placebo o de otros hipolipidemiantes. Concluyen que, comparados con placebo, los fibratos son útiles para reducir en un 16% el combinado muerte por enfermedad cardiovascular, infarto de miocardio no fatal o accidente cerebrovascular no fatal (NNT: 112) y que disminuyen la morbimortalidad coronaria un 21% (NNT: 125). Complementariamente, los fibratos podrían reducir la retinopatía diabética previamente establecida. Sin embargo, no influyen en la mortalidad total ni en la de origen no cardiovascular. Tampoco su empleo conjunto con estatinas beneficia a pacientes sin enfermedad cardiovascular establecida, comparado con el uso de estatinas en monoterapia. Los fibratos son seguros, aunque pueden elevar los niveles séricos de creatinina

Fibrates are drugs that reduce triglycerides, elevate high-density lipoproteins, as well as decrease small, dense LDL particles. The results of a study have recently been published by the Cochrane Collaboration on fibrates efficacy and safety in the primary prevention of cardiovascular disease. This study includes a systematic review and a meta-analysis of 6 studies (16,135 patients) that evaluated the clinical benefits of fibrates compared to placebo use or other lipid-lowering drugs. This review showed evidence of a protective effect of the fibrates compared with placebo as regards a reduction 16% of a compound objective of death due to cardiovascular disease, non-fatal myocardial infarction, or non-fatal cerebrovascular accident (NNT: 112), and that reduce coronary morbidity and mortality by 21% (NNT: 125). In addition, fibrates could reduce previously established diabetic retinopathy. However, fibrates do not influence total mortality, or non-cardiovascular mortality. Its joint use with statins does not benefit patients without established cardiovascular disease, compared to the use of statins in monotherapy. Fibrates are safe, although they can elevate serum creatinine levels

Fibrates in primary prevention of cardiovascular disease. Comments on the results of a systematic review of the Cochrane Collaboration. / Los fibratos en la prevención primaria de la enfermedad cardiovascular. Comentarios a los resultados de una revisión sistemática de la Colaboración Cochrane.

Fibrates are drugs that reduce triglycerides, elevate high-density lipoproteins, as well as decrease small, dense LDL particles. The results of a study have recently been published by the Cochrane Collaboration on fibrates efficacy and safety in the primary prevention of cardiovascular disease. This study includes a systematic review and a meta-analysis of 6 studies (16,135 patients) that evaluated the clinical benefits of fibrates compared to placebo use or other lipid-lowering drugs. This review showed evidence of a protective effect of the fibrates compared with placebo as regards a reduction 16% of a compound objective of death due to cardiovascular disease, non-fatal myocardial infarction, or non-fatal cerebrovascular accident (NNT: 112), and that reduce coronary morbidity and mortality by 21% (NNT: 125). In addition, fibrates could reduce previously established diabetic retinopathy. However, fibrates do not influence total mortality, or non-cardiovascular mortality. Its joint use with statins does not benefit patients without established cardiovascular disease, compared to the use of statins in monotherapy. Fibrates are safe, although they can elevate serum creatinine levels.

Fibrates in the secondary prevention of cardiovascular disease (infarction and stroke). Results of a systematic review and meta-analysis of the Cochrane collaboration. / Los fibratos en la prevención secundaria de la enfermedad cardiovascular (infarto e ictus). Resultados de una revisión sistemática y metaanálisis de la colaboración Cochrane.

Fibrates are a group of drugs that are known mainly for reducing triglycerides, increasing high density lipoproteins (HDL), and reducing the fraction of small, dense LDL particles. The results of a Cochrane Collaboration study have recently been published on their efficacy and safety in the secondary prevention of severe cardiovascular accidents, including coronary and cerebrovascular disease. The study included randomised clinical trials in which the fibrate was compared with placebo or with no treatment. Clinical trials comparing two different fibrates were excluded. The clinical trials evaluated included a total of 16,112 patients (13 trials). The meta-analysis (including all the trials with fibrates) showed evidence of a protective effect of the fibrates compared with placebo as regards a compound objective of non-fatal stroke, non-fatal myocardial infarction, and death of cardiovascular origin (hazard ration of 0.88, with a 95% confidence interval of 0.83 to 0.94; in 16,064 individuals included in 12 studies). Thus, the results showed, with a moderate level of evidence, that fibrates could be effective in secondary prevention considering a compound objective of non-fatal stroke, non-fatal myocardial infarction, and death of cardiovascular origin.

Los fibratos en la prevención secundaria de la enfermedad cardiovascular (infarto e ictus). Resultados de una revisión sistemática y metaanálisis de la colaboración Cochrane / Fibrates in the secondary prevention of cardiovascular disease (infarction and stroke). Results of a systematic review and meta-analysis of the Cochrane collaboration

Los fibratos son un grupo de fármacos que se caracterizan principalmente por reducir los triglicéridos, elevar las lipoproteínas de alta densidad (HDL) y reducir la fracción de partículas de LDL pequeñas y densas. Se ha publicado recientemente los resultados de un estudio de la Colaboración Cochrane sobre su eficacia y seguridad en la prevención secundaria de accidentes cardiovasculares graves, incluyendo enfermedad coronaria y cerebrovascular. El estudio incluye ensayos clínicos aleatorizados en los que el fibrato se compara con placebo o con no tratamiento. Se excluyen ensayos clínicos comparando 2 fibratos diferentes. Los ensayos clínicos evaluados incluyen un total de 16.112 pacientes (13 ensayos). El metaanálisis (incluyendo todos los ensayos con fibratos) muestra la evidencia de un efecto protector de los fibratos comparados con placebo en lo relativo a un objetivo compuesto de ictus no fatal, infarto de miocardio no fatal, y muerte de origen cardiovascular (tasa de riesgo de 0,88, con intervalo de confianza (95%) de 0,83 a 0,94; en 16.064 individuos incluidos en 12 estudios). Por tanto, los resultados muestran con una evidencia de grado moderado que los fibratos pueden ser efectivos en la prevención secundaria considerando un objetivo compuesto de ictus no fatal, infarto no fatal, y muerte de origen cardiovascular (AU)

Fibrates are a group of drugs that are known mainly for reducing triglycerides, increasing high density lipoproteins (HDL), and reducing the fraction of small, dense LDL particles. The results of a Cochrane Collaboration study have recently been published on their efficacy and safety in the secondary prevention of severe cardiovascular accidents, including coronary and cerebrovascular disease. The study included randomised clinical trials in which the fibrate was compared with placebo or with no treatment. Clinical trials comparing two different fibrates were excluded. The clinical trials evaluated included a total of 16,112 patients (13 trials). The meta-analysis (including all the trials with fibrates) showed evidence of a protective effect of the fibrates compared with placebo as regards a compound objective of non-fatal stroke, non-fatal myocardial infarction, and death of cardiovascular origin (hazard ration of 0.88, with a 95% confidence interval of 0.83 to 0.94; in 16,064 individuals included in 12 studies). Thus, the results showed, with a moderate level of evidence, that fibrates could be effective in secondary prevention considering a compound objective of non-fatal stroke, non-fatal myocardial infarction, and death of cardiovascular origin (AU)

Dislipemia aterogénica en las guías de práctica clínica de lípidos. ¿Una asignatura pendiente? / Atherogenic dyslipidaemia in clinical practice guidelines on lipids. A pending issue?

Las guías de práctica clínica (GPC) se posicionan en relación con la dislipemia aterogénica (DA) de forma desigual. El objetivo de este estudio fue revisar las GPC específicas de DA y el posicionamiento de las GPC de dislipemias comparando sus recomendaciones con las específicas de DA. Se realizó una búsqueda de GPC en MEDLINE, Biblioteca Virtual en Salud y National Guidelines Clearinghause. Se utilizaron como palabras clave: dislipemia, hipercolesterolemia, tratamiento de la dislipemia, dislipemia aterogénica, triglicéridos, cHDL, cLDL y prevención cardiovascular. Se limitó la búsqueda a 10 años para GPC de DA. Para GPC de dislipemia, se activaron los filtros: guía de práctica clínica, consensos y fecha de publicación del 1 de enero de 2015 al 2 de febrero de 2017. Se seleccionaron 5 GPC de DA y 10 GPC sobre tratamiento de las dislipemias. Se registraron y analizaron los siguientes parámetros: definición, riesgo residual, colesterol no-HDL, diagnóstico y tratamiento, comparándolos con las recomendaciones sobre la DA. Se observó una caracterización global de la DA en las guías específicas. Todas las GPC de dislipemias recogen el colesterol no-HDL como objetivo secundario de control lipídico. Las recomendaciones más concordantes con las especificadas de DA son las de la European Society of Cardiology y la European Atherosclerosis Society, la National Lipid Association, la American Association of Clinical Endocrinologists y el American College of Endocrinology, y la guía de la Canadian Cardiovascular Society. Aunque ha mejorado, las GPC de dislipemia todavía abordan de forma insuficiente la DA (AU)

Clinical practice guidelines (CPG) adopt distinct approaches to atherogenic dyslipidaemia (AD). The aim of this study was to review CPG specifically on AD and those on dyslipidaemia and to compare their recommendations. A search for CPG was conducted in MEDLINE, Biblioteca Virtual en Salud and National Guidelines Clearinghouse, using the following key terms: dyslipidaemia, hypercholesterolaemia, dyslipidaemia treatment, atherogenic dyslipidaemia, triglycerides, HDLc, LDLc and cardiovascular prevention. For CPG on AD, the search was restricted to the last 10 years. For CPG on dyslipidaemia, the following filters were used: clinical practice guideline, consensus, and publication date between January 1, 2015 and February 2, 2017. We selected 5 CPG on AD and 10 CPG on the treatment of dyslipidaemia. The following parameters were registered and analysed: definition, residual risk, non-HCL-cholesterol, diagnosis and treatment. These parameters were compared with recommendations on AD. A global classification of AD was observed in AD-specific guidelines. Non-HDL-cholesterol was a secondary target of lipid control in all CPG on dyslipidaemia. The recommendations most in agreement with those of CPG on AD were those of the European Society of Cardiology and the European Atherosclerosis Society, the National Lipid Association, the American Association of Clinical Endocrinologists and the American College of Endocrinology, and the guideline of the Canadian Cardiovascular Society. Although CPG on dyslipidaemia have improved, their approach to AD continues to be deficient (AU)