Las guías de práctica clínica de manejo de la dislipemia. Una visión transatlántica.Clinical Practice Guidelines for the Management of Dyslipidemia. Transatlantic Perspectives

Situación de la dislipemia en España. Las guías de práctica clínica (GPC) se han convertido en un instru- mento fundamental en nuestra actividad asistencial. La revisión deta- llada de la evidencia científica disponible permite la elaboración de documentos de recomendaciones diagnósticas y terapéuticas avala- dos por las principales instituciones científicas. A pesar de que habi- tualmente están basadas en los mismos estudios y, por lo tanto, se redactan a partir de los mismos resultados, pueden existir diferentes interpretaciones y distintos enfoques, como ha sucedido reciente- mente en las principales GPC que abordan el manejo de las dislipe- mias. En el año 2011 la Sociedad Europea de Cardiología (ESC) y la European Atherosclerosis Society (EAS) publicaron la Guía ESC/EAS para el manejo de las dislipemias1, con unas recomendaciones que se mantienen vigentes y la mayoría de las sociedades científicas de nuestro entorno respaldan. A finales de 2013, el American College of Cardiology (ACC) y la American Heart Association (AHA) hicieron pública su guía sobre el tratamiento del colesterol sanguíneo para reducir el riesgo cardiovascular aterosclerótico en adultos2. Aunque persiguen la misma finalidad, que es la reducción del riesgo cardio- vascular mediante el tratamiento de la dislipemia, lo hacen con una orientación completamente distinta que ha generado un gran debate en el último año y ha hecho correr ríos de tinta, no solo en la literatura médica, sino también en la prensa generalista. En este número de REVISTA ESPAÑOLA DE CARDIOLOGÍA SUPLEMENTOS se revisarán detalladamente ambas GPC, sus fortalezas y sus debilidades. Como sucede la mayoría de las veces, habrá aspectos positivos en una y otra, y no necesariamente debemos elegir entre las dos, sino que tenemos la oportunidad de conocer la visión de las sociedades impli- cadas y hacer un análisis constructivo de sus recomendaciones. En lo que sí hay un acuerdo total en las GPC del manejo de dislipemia es que el tratamiento debe basarse, además de en medidas de estilo de vida, en la utilización de estatinas como fármacos hipolipemiantes de elección cuando esté indicado, en prevención primaria según el nivel de riesgo y siempre en prevención secundaria, salvo contraindicación. Se ha demostrado rotundamente la eficacia de las estatinas en la disminución del colesterol plasmático, con una reducción proporcional de la morbimortalidad cardiovascular. Las estatinas, por su mecanismo de acción, no solo reducen el colesterol plasmático, sino que también poseen otros efectos extrali- pídicos; estas acciones pleotrópicas se están estudiando en diferentes escenarios, tanto clínicos como experimentales, con la finalidad de establecer posibles beneficios de las estatinas más allá de su capacidad hipolipemiante. Este aspecto, así como la utilización de las estatinas en el síndrome coronario agudo y el manejo de la dislipemia de pacientes con cardiopatía isquémica, diabéticos y otros grupos de riesgo, también se abordará en esta monografía. A lo largo de los seis artículos que la componen, expertos en el manejo de la enfermedad cardiovascular en nuestro país ofrecen una puesta al día sobre el manejo de la dislipemia

Type 1 diabetic mellitus patientswith increased atherosclerosisriskdisplay decreased CDKN2A/2B/2BAS gene expression in leukocytes

Background: Type 1 diabetes mellitus (T1DM) patients display increased risk of cardiovascular disease (CVD) and are characterized by a diminished regulatory T (Treg) cell content or function. Previous studies have shown an association between decreased CDKN2A/2B/2BAS gene expression and enhanced CVD. In the present study the potential relationship between CDKN2A/2B/2BAS gene expression, immune cell dysfunction and increased cardiovascular risk in T1DM patients was explored. Methods: A cross-sectional study was performed in 90 subjects divided into controls and T1DM patients. Circulating leukocyte subpopulations analysis by flow cytometry, expression studies on peripheral blood mononuclear cell by qPCR and western blot and correlation studies were performed in both groups of subjects. Results: Analysis indicated that, consistent with the described T cell dysfunction, T1DM subjects showed decreased circulating CD4+CD25+CD127- Treg cells. In addition, T1DM subjects had lower mRNA levels of the transcription factors FOXP3 and RORC and lower levels of IL2 and IL6 which are involved in Treg and Th17 cell differentiation, respectively. T1DM patients also exhibited decreased mRNA levels of CDKN2A (variant 1 p16Ink4a), CDKN2A (p14Arf, variant 4), CDKN2B (p15Ink4b) and CDKN2BAS compared with controls. Notably, T1DM patients had augmented pro-atherogenic CD14++CD16+-monocytes, which predict cardiovascular acute events and enhanced common carotid intima-media thickness (CC-IMT). Conclusions: Decreased expression of CDKN2A/2B/2BAS in leukocytes associates with increased CC-IMT atherosclerosis surrogate marker and proatherogenic CD14++CD16+ monocytes in T1DM patients. These results suggest a potential role of CDKN2A/2B/2BAS genes in CVD risk in T1DM

Novel Immune Features of the Systemic Inflammation Associated with Primary Hypercholesterolemia: Changes in Cytokine/Chemokine Profile, Increased Platelet and Leukocyte Activation

Primary hypercholesterolemia (PH) is associated with a low grade systemic inflammation that is likely the main driver of premature atherosclerosis. Accordingly, we characterized the immune cell behaviour in PH and its potential consequences. Whole blood from 22 PH patients and 21 age-matched controls was analysed by flow cytometry to determine the percentage of leukocyte immunophenotypes, activation, and platelet-leukocyte aggregates. Plasma markers were determined by Enzyme-Linked ImmunoSorbent Assay (ELISA). The adhesion of platelet-leukocyte aggregates to tumor necrosis factor-α (TNFα)-stimulated arterial endothelium was investigated using the dynamic model of the parallel-plate flow chamber. PH patients presented greater percentage of Mon 3 monocytes, Th2 and Th17 lymphocytes, activated platelets, and leukocytes than controls. The higher percentages of circulating platelet-neutrophil, monocyte and lymphocyte aggregates in patients caused increased platelet-leukocyte adhesion to dysfunctional arterial endothelium. Circulating CXCL8, CCL2, CX3CL1, and IL-6 levels positively correlated with key lipid features of PH, whereas negative correlations were found for IL-4 and IL-10. We provide the first evidence that increased platelet and leukocyte activation leads to elevated platelet-leukocyte aggregates in PH and augmented arterial leukocyte adhesiveness, a key event in atherogenesis. Accordingly, modulation of immune system behavior might be a powerful target in the control of further cardiovascular disease in PH

LDL particle size and composition and incident cardiovascular disease in a South-European population: The Hortega-Liposcale Follow-up Study.

The association of low-density lipoprotein (LDL) particle composition with cardiovascular risk has not been explored before. The aim was to evaluate the relationship between baseline LDL particle size and composition (proportions of large, medium and small LDL particles over their sum expressed as small-LDL %, medium-LDL % and large-LDL %) and incident cardiovascular disease in a population-based study. Methods: Direct measurement of LDL particles was performed using a two-dimensional NMR-technique (Liposcale®). LDL cholesterol was assessed using both standard photometrical methods and the Liposcale® technique in a representative sample of 1162 adult men and women from Spain. Results: The geometric mean of total LDL particle concentration in the study sample was 827.2 mg/dL (95% CI 814.7, 839.8). During a mean follow-up of 12.4 ± 3.3 years, a total of 159 events occurred. Medium LDL particles were positively associated with all cardiovascular disease, coronary heart disease (CHD) and stroke after adjustment for traditional risk factors and treatment. Regarding LDL particle composition, the multivariable adjusted hazard ratios for CHD for a 5% increase in medium and small LDL % by a corresponding decrease of large LDL % were 1.93 (1.55, 2.39) and 1.41 (1.14, 1.74), respectively. Conclusions: Medium LDL particles were associated with incident cardiovascular disease. LDL particles showed the strongest association with cardiovascular events when the particle composition, rather than the total concentration, was investigated. A change in baseline composition of LDL particles from large to medium and small LDL particles was associated with an increased cardiovascular risk, especially for CHD

Alteración de los lípidos plasmáticos en las obstrucciones de las vías biliares / Juan Francisco Gimilio Ascaso ; dirigido por Rafael Cármena Rodríguez

Tesis - Universidad de Murcia.MEDICINA ESPINARDO. DEPOSITO. MU-Tesis 4

Inhibición de la proproteína convertasa subtilisina/kexina tipo 9 (PCSK9) en el tratamiento de la hipercolesterolemia.

Se diapome de un nuevo grupo de fármacoshipocolesterolemiantes potentes y bien tolerados, para completar las opciones terapéuticas en sujetos de alto o muy alto riesgo cardiovascular, especialmente con hipercolesterolemia genética, que con el tratamiento habitual, estatinas y asociaciones con ezetimiba o resinas, no consigan llegar a los objetivos propuestos o en aquellos con intolerancia a estatinas y necesidad de disminuir los concentraciones de cLDL por su alto riesgo cardiovascula

Consenso Delphi sobre el manejo de la dislipidemia en pacientes con alteración del metabolismo de la glucosa: estudio Diana. [Delphi consensus on management of dyslipidaemia in patients with impaired glucose metabolism: Diana study].

Objetivos: El objetivo de este estudio fue desarrollar un consenso multidisciplinar mediante el sistema Delphi para establecer recomendaciones clínicas en torno al manejo de la dislipidemia cuando hay una alteración del metabolismo de la glucosa, y la importancia de los factores que se valoran al prescribir y realizar el seguimiento del tratamiento con estatinas. Métodos: El cuestionario formulado por el comité científico incluyó 4 bloques de preguntas alrededor del paciente dislipidémico con alteración del metabolismo de la glucosa, de los que aquí presentaremos los resultados de los 2 primeros: a) manejo de la dislipidemia; y b) factores que se valoran al prescribir y realizar el seguimiento del tratamiento con estatinas. Resultados: Con un porcentaje superior al 90% se consensuó entre los 497 expertos participantes en el estudio que debía realizarse un cribado de dislipidemia a pacientes con diabetes o prediabetes, y/o con enfermedad cardiovascular o con antecedentes familiares y/u obesidad abdominal y/o hipertensos. En presencia de dislipidemia existe un elevado grado de acuerdo en que la estatina es el tratamiento hipolipidemiante de elección, en cambiarla cuando aparecen efectos secundarios, en la elección de dosis y tipo de estatina según la concentración de colesterol LDL basal del paciente y el objetivo a alcanzar, así como la posible interacción con otros fármacos Conclusiones: El cribado de la dislipidemia se realiza principalmente en pacientes con enfermedad cardiovascular o algún factor mayor de riesgo cardiovascular. Al prescribir una estatina los médicos encuestados valoraron fundamentalmente la capacidad de reducción del colesterol LDL y el riesgo de interacciones medicamentosas. OBJECTIVES: The aim of the present study was to develop a multidisciplinary consensus based on the Delphi system to establish clinical recommendations for the management of dyslipidaemia when hyperglycaemia is present, and the relevant factors that should be taken into consideration when prescribing and monitoring treatment with statins. METHODS: The questionnaire developed by the scientific committee included four blocks of questions about dyslipidaemia in patients with impaired glucose metabolism. The results of the first two blocks are presented here: a) management of dyslipidaemia; b) relevant factors that should be taken into consideration when prescribing and monitoring treatment with statins. RESULTS: Among the 497 experts who participated in the study, an agreement of over 90% was attained for recommending screening for dyslipidaemia in patients with diabetes or pre-diabetes and/or cardiovascular disease or a family history and/or abdominal obesity and/or hypertension. There was a high degree of agreement that a statin is the lipid-lowering treatment of choice, and that it should be switched when side effects develop. Also, the choice of statin and dose should be made according to baseline LDL cholesterol levels, the target to achieve, and the possible drug-drug interactions. CONCLUSIONS: The screening of dyslipidaemia is primarily conducted in patients with cardiovascular disease, or any major cardiovascular risk factor. When prescribing a statin, physicians mainly focus on the ability to reduce LDL cholesterol and the risk of drug interactions

Indicaciones de los inhibidores de PCSK9 en la práctica clínica. Recomendaciones de la Sociedad Española de 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 homozygous and heterozygous familial hypercholesterolemia, with atherosclerotic cardiovascular disease, and in primary prevention in patients with very high cardiovascular risk. These recommendations have been established taking into account the concentration of LDL-C, the clinical situation of the patient, the additional risk factors and the cost-effectiveness of their use

COSMIC project: consensus on the objectives of the metabolic syndrome in clinic

Metabolic syndrome (MetS), a disorder with a high and growing prevalence, is a recognized risk factor for cardiovascular disease (CVD) and type 2 diabetes. It is a constellation of clinical and metabolic risk factors that include abdominal obesity, dyslipidemia, glucose intolerance, and hypertension. Unfortunately, MetS is typically underrecognized, and there is great heterogeneity in its management, which can hamper clinical decision-making and be a barrier to achieving the therapeutic goals of CVD and diabetes prevention. Although no single treatment for MetS as a whole currently exists, management should be targeted at treating the conditions contributing to it and possibly reversing the risk factors. All this justifies the need to develop recommendations that adapt existing knowledge to clinical practice in our healthcare system. In this regard, professionals from different scientific societies who are involved in the management of the different MetS components reviewed the available scientific evidence focused basically on therapeutic aspects of MetS and developed a consensus document to establish recommendations on therapeutic goals that facilitate their homogenization in clinical decision-making

Consensus on the Statin of Choice in Patients with Impaired Glucose Metabolism : Results of the DIANA Study

Altres ajuts: Laboratorios del Dr. Esteve, S.A.U. has supported the scientific committee to undertake the fieldwork of the Delphi survey for this study, without participating in the design, data analysis or drafting of this articleDespite the recognized clinical benefit of statins on cardiovascular prevention, providing correct management of hypercholesterolaemia, possible adverse effects of their use cannot be disregarded. Previously published data shows that there is a risk of developing diabetes mellitus or experiencing changes in glucose metabolism in statin-treated patients. The possible determining factors are the drug characteristics (potency, dose), patient characteristics (kidney function, age, cardiovascular risk and polypharmacy because of multiple disorders) and the pre-diabetic state. In order to ascertain the opinion of the experts (primary care physicians and other specialists with experience in the management of this type of patient) we conducted a Delphi study to evaluate the consensus rate on diverse aspects related to the diabetogenicity of different statins, and the factors that influence their choice. Consensus was highly significant concerning aspects such as the varying diabetogenicity profiles of different statins, as some of them do not significantly worsen glucose metabolism. There was an almost unanimous consensus that pitavastatin is the safest statin in this regard. Factors to consider in the choice of a statin regarding its diabetogenicity are the dose and patient-related factors: age, cardiovascular risk, diabetes risk and baseline metabolic parameters (which must be monitored during the treatment), as well as kidney function