Fernando Villar Álvarez

Control de la colesterolemia en España, 2000. Un instrumento para la prevención cardiovascular

El documento «Control de la Colesterolemia en Espana, 2000: Un instrumento para la Prevencion Cardiovascular » revisa la evidencia existente en el campo de la prevencion cardiovascular y los avances terapeuticos producidos en los ultimos anos, con el objetivo de ayudar a tomar decisiones clinicas basadas en el riesgo cardiovascular. Las enfermedades cardiovasculares son la primera causa de muerte en Espana. Su impacto demografico, sanitario y social esta aumentando y va a continuar haciendolo en las proximas decadas. El adecuado tratamiento de la hipercolesterolemia y del resto de los factores de riesgo es fundamental para prevenir las enfermedades cardiovasculares. La estratificacion del riesgo de las personas es esencial, por cuanto condiciona la periodicidad del seguimiento y la indicacion e intensidad del tratamiento. Basandose en dicha estratificacion se han establecido unas prioridades de control de la colesterolemia y del riesgo cardiovascular derivado de la misma. En prevencion primaria en los pacientes de riesgo alto, el objetivo terapeutico se establece en un cLDL inferior a 130 mg/dl. En prevencion secundaria, el tratamiento farmacologico se instaurara con un cLDL ≥ 130 mg/dl y el objetivo terapeutico sera cLDL Las estatinas son los farmacos de primera eleccion en el tratamiento de la hipercolesterolemia. Cuando exista hipertrigliceridemia moderada-grave y cHDL bajo se emplearan los fibratos. En el sindrome coronario agudo, el tratamiento hipolipemiante, cuando este indicado, debe iniciarse precozmente.

Conformational epitopes on CYP2D6 are recognized by liver/kidney microsomal antibodies

BACKGROUND/AIMS Four linear antigenic sites have been shown on the CYP2D6 molecule that are recognized by serum positive for liver/kidney microsomal antibody (LKM) type 1. The aim of this study was to search for antibodies against CYP2D6 conformational antigenic sites in LKM-1-positive sera. METHODS The capacity of four LKM-1-positive sera, before and after absorption with synthetic peptides representing CYP2D6 linear antigenic sites, and rabbit sera against linear antigenic sites between CYP2D6 amino acids 254-271 and 373-389 to inhibit the O-demethylation of dextromethorphan by CYP2D6 was tested in vitro. RESULTS Inhibition of O-demethylation of dextromethorphan was not modified by absorption of antibodies against linear CYP2D6 antigenic sites. In addition, rabbit sera against two of these sites did not inhibit the reaction. These results strongly suggest that antibodies against CYP2D6 conformational antigenic sites were present in LKM-1-positive sera. CONCLUSIONS The autoimmune response against CYP2D6 is directed against linear and conformational antigenic sites. These results strengthen the argument that the LKM-1 response is polyclonal and antigen driven.

Antibodies to liver/kidney microsome1 in chronic active hepatitis recognize specific forms of hepatic cytochrome P-450

Anti-liver/kidney microsome1-positive sera from children with chronic active hepatitis were studied in an effort to identify the microsomal antigens selected during induction and progression of this autoimmune disease. Immunoblot analysis of sodium dodecyl sulfate gel-resolved microsomal proteins from human and rat liver using anti-liver/kidney microsome1-positive sera revealed a single polypeptide of 48 kilodaltons (human microsomes) or 50 kilodaltons (rat microsomes). Levels of the 50-kilodalton rat microsomal polypeptide were suppressed in vivo by several drugs known to modulate expression of individual forms (enzymes) of hepatic cytochrome P-450, with the largest decrease effected by phenobarbital. Dot blot analysis using a panel of 10 electrophoretically homogeneous rat liver cytochrome P-450 forms under nondenaturing conditions established that the two methylcholanthrene-inducible forms, P-450 BNF-B and P-450 ISF-G (P-450 gene subfamily IA), are selectively recognized by the anti-liver/kidney microsome1 antibodies. These findings demonstrate that sera associated with autoimmune (anti-liver/kidney microsome1) chronic active hepatitis are specifically reactive with select rat hepatic P-450 forms and suggest that these autoantibodies may be principally directed against one or more constitutive forms of the corresponding human liver cytochromes.

Comentarios del Comité Español Interdisciplinario de Prevención Cardiovascular (CEIPC) a las guías europeas de prevención cardiovascular 2012

Las guias europeas de prevencion cardiovascular contemplan dos sistemas de evaluacion de la evidencia (SEC y GRADE) y recomiendan combinar las estrategias poblacional y de alto riesgo, interviniendo en todas las etapas de la vida, con la dieta como piedra angular de la prevencion. La valoracion del RCV incorpora los niveles de HDL y los factores psicosociales, una categoria de muy alto riesgo y el concepto edad-riesgo. Se recomienda el uso de metodos cognitivo-conductuales (entrevista motivadora, intervenciones psicologicas), aplicados por profesionales sanitarios, con la participacion de familiares de los pacientes, para contrarrestar el estres psicosocial y reducir el RCV mediante dietas saludables, entrenamiento fisico, abandono del tabaco y cumplimiento terapeutico. Tambien se requieren medidas de salud publica, como la prohibicion de fumar en lugares publicos o eliminar los acidos grasos trans de la cadena alimentaria. Otras novedades consisten en desestimar el tratamiento antiagregante en prevencion primaria y la recomendacion de mantener la PA dentro del rango 130-139/80-85 mmHg en pacientes diabeticos o con RCV alto. Se destaca el bajo cumplimiento terapeutico observado, porque influye en el pronostico de los pacientes y en los costes sanitarios. Para mejorar la prevencion cardiovascular se precisa una verdadera alianza entre politicos, administraciones, asociaciones cientificas y profesionales de la salud, fundaciones de salud, asociaciones de consumidores, pacientes y sus familias, que impulse las estrategias poblacional e individual, mediante el uso de toda la evidencia cientifica disponible, desde ensayos clinicos hasta estudios observacionales y modelos matematicos para evaluar intervenciones a nivel poblacional, incluyendo analisis de coste-efectividad.

Estudio bibliométrico de los artículos originales de la Revista Española de Salud Pública (1991-2000). Parte segunda: productividad de los autores y procedencia institucional y geográfica

Fundamento: En la caracterizacion de una revista cientifica, desde el punto de vista bibliometrico, es importante conocer cuantos autores participan en los trabajos publicados, asi como la institucion y ambito geografico de procedencia. El objetivo de este articulo es analizar la distribucion del numero de autores y de las instituciones donde estos trabajan, asi como su productividad, en los articulos originales publicados en la Revista Espanola de Salud Publica durante la decada 1991-2000. Metodos: De los 290 trabajos originales publicados en la Revista Espanola de Salud Publica durante la decada estudiada se ha calculado el numero total de autores, el numero de autores ocasionales, el indice de transitoriedad, la distribucion de autores por genero, la productividad de autores y de las instituciones segun el numero de trabajos y la de los autores segun la Ley de Lotka, y la distribucion por procedencia institucional y geografica. Resultados: En los originales que se publicaron en la Revista Espanola de Salud Publica entre los anos 1991 y 2000 participo un total de 1.052 autores (1.000 espanoles y 52 extranjeros). La razon de sexos para el periodo estudiado es de 1,29 a favor de los hombres. Las Comunidades Autonomas que mas autores aportan son Comunidad de Madrid (16,3%), Andalucia (13,4%) y Comunidad Valenciana (12,5%). Las instituciones de procedencia de los autores se encuentran ubicadas preferentemente en la Comunidad de Madrid (16,5%), Comunidad Valenciana (11,3%), y Andalucia y Cataluna (10,5%). El 37,6% de los autores trabajan en centros dedicados a la atencion sanitaria, seguidos de los que trabajan en la Universidad (26,3%). Al distribuir el tipo de institucion por Comunidades Autonomas, en Madrid, la Comunidad Valenciana y Andalucia la institucion mas frecuente son los centros de atencion primaria (50%, 43,3% y 28,6% respectivamente) y en Cataluna los centros de atencion especializada (42,9%). Conclusiones: La Revista Espanola de Salud Publica es una publicacion implantada en todo el territorio nacional y en el ambito hispanoamericano. La productividad de los autores que publican en ella, la de las instituciones donde trabajan y la de las Comunidades Autonomas de las que proceden los trabajos, es similar a la de otras revistas biomedicas espanolas, y menor que cuando se estudian ambitos tematicos y territoriales en mas de una publicacion.

Dislipidemias: un reto pendiente en prevención cardiovascular. Documento de consenso CEIPC/SEA

In Spain, where cardiovascular disease (CVD) is the leading cause of death, hypercholesterolemia, one of the most prevalent risk factors in adults, is poorly controlled. Dyslipidemia should not be approached in isolation, but in the context of overall cardiovascular risk (CVR). Measurement of CVR facilitates decision making, but should not be the only tool nor should it take the place of clinical judgment, given the limitations of the available calculation methods. This document, prepared by the Interdisciplinary Spanish Committee on Cardiovascular Prevention, at the proposal of the Spanish Society of Arteriosclerosis, reviews the cardiovascular prevention activities of the regional health authorities, scientific societies and medical professionals. An initiation of a national strategy on cardiovascular prevention is proposed based on lifestyle modification (healthy diet, physical activity and smoking cessation) through actions in different settings. At the population level, regulation of food advertising, elimination of trans fats and reduction of added sugar are feasible and cost-effective interventions to help control dyslipidemias and reduce CVR. In the health setting, it is proposed to facilitate the application of guidelines, improve training for medical professionals, and include CVR assessment among the quality indicators. Scientific societies should collaborate with the health authorities and contribute to the generation and transmission of knowledge. Finally, it is in the hands of professionals to apply the concept of CVR, promote healthy lifestyles, and make efficient use of available pharmacological treatments.

Recomendaciones para el control de la colesterolemia en España

Se presentan una serie de recomendaciones sobre deteccion, evaluacion e intervencion en prevencion primaria y secundaria, abordando la hipercolesterolemia desde una perspectiva multifactorial basada en el riesgo cardiovascular. Las enfermedades cardiovasculares son la primera causa de muerte en Espana. Dentro de ellas las mas importantes son la enfermedad isquemica del corazon y la enfermedad cerebrovascular. Su impacto demografico, sanitario y social aumentara a lo largo de las proximas decadas. El control de la hipercolesterolemia, junto con la erradicacion del tabaquismo y el control de la hipertension arterial, la diabetes, la obesidad y el sedentarismo, es una de las principales estrategias para prevenir las enfermedades cardiovasculares. La estratificacion del riesgo de las personas tomando en consideracion los principales factores de riesgo cardiovascular es esencial, ya que condiciona la periodicidad del seguimiento y la modalidad e intensidad del tratamiento. Basandose en esta estratificacion se han establecido las prioridades de la actuacion preventiva cardiovascular. En prevencion primaria, en las personas de riesgo alto (riesgo igual o superior al 20% o las que presentan dos o mas factores de riesgo) el objetivo terapeutico se establece en un cLDL inferior a 130 mg/dl. En prevencion secundaria el tratamiento farmacologico se instaurara con un cLDL> 130mg/dl y el objetivo terapeutico sera cLDL <100mg/dl. Los pacientes con cardiopatia isquemica deben incluirse en programas de prevencion secunadria que aseguren, de forma continuada, un buen control clinico y de los factores de riesgo.

Posicionamiento del Comité Español Interdisciplinario de Prevención Cardiovascular y la Sociedad Española de Cardiología en el tratamiento de las dislipemias. Divergencia entre las guías europea y estadounidense

The publication of the 2013 American College of Cardiology/American Heart Association guidelines on the treatment of high blood cholesterol has had a strong impact due to the paradigm shift in its recommendations. The Spanish Interdisciplinary Committee for Cardiovascular Disease Prevention and the Spanish Society of Cardiology reviewed this guideline and compared it with current European guidelines on cardiovascular prevention and dyslipidemia management. The most striking aspect of the American guideline is the elimination of the low-density lipoprotein cholesterol treat-to-target strategy and the adoption of a risk reduction strategy in 4 major statin benefit groups. In patients with established cardiovascular disease, both guidelines recommend a similar therapeutic strategy (high-dose potent statins). However, in primary prevention, the application of the American guidelines would substantially increase the number of persons, particularly older people, receiving statin therapy. The elimination of the cholesterol treat-to-target strategy, so strongly rooted in the scientific community, could have a negative impact on clinical practice, create a certain amount of confusion and uncertainty among professionals, and decrease follow-up and patient adherence. Thus, this article reaffirms the recommendations of the European guidelines. Although both guidelines have positive aspects, doubt remains regarding the concerns outlined above. In addition to using risk charts based on the native population, the messages of the European guideline are more appropriate to the Spanish setting and avoid the possible risk of overtreatment with statins in primary prevention.

Comentarios del Comité Español Interdisciplinario de Prevención Cardiovascular (CEIPC) a las Guías Europeas de Prevención Cardiovascular 2012

Based on the two main frameworks for evaluating scientific evidence (SEC and GRADE) European cardiovascular prevention guidelines recommend interventions across all life stages using a combination of population-based and high-risk strategies with diet as the cornerstone of prevention. The evaluation of cardiovascular risk (CVR) incorporates HDL levels and psychosocial factors, a very high risk category, and the concept of age-risk. They also recommend cognitive-behavioural methods (e.g., motivational interviewing, psychological interventions) led by health professionals and with the participation of the patients family, to counterbalance psychosocial stress and reduce CVR through the institution of positive habits such as a healthy diet, physical activity, smoking cessation, and adherence to treatment. Additionally, public health interventions - such as smoking ban in public areas or the elimination of trans fatty acids from the food chain - are also essential. Other innovations include abandoning antiplatelet therapy in primary prevention and the recommendation of maintaining blood pressure within the 130-139/80-85mmHg range in diabetic patients and individuals with high CVR. Finally, due to the significant impact on patient progress and medical costs, special emphasis is given to the low therapeutic adherence levels observed. In sum, improving cardiovascular prevention requires a true partnership among the political class, public administrations, scientific and professional associations, health foundations, consumer associations, patients and their families. Such partnership would promote population-based and individual strategies by taking advantage of the broad spectrum of scientific evidence available, from clinical trials to observational studies and mathematical models to evaluate population-based interventions, including cost-effectiveness analyses.

Posicionamiento del Comité Español Interdisciplinario de Prevención Cardiovascular y la Sociedad Española de Cardiología en el tratamiento de las dislipemias: divergencia entre las guías europea y estadounidense

The publication of the 2013 American College of Cardiology/American Heart Association guidelines on the treatment of high blood cholesterol has had a strong impact due to the paradigm shift in its recommendations. The Spanish Interdisciplinary Committee for Cardiovascular Disease Prevention and the Spanish Society of Cardiology reviewed this guideline and compared it with current European guidelines on cardiovascular prevention and dyslipidemia management. The most striking aspect of the American guideline is the elimination of the low-density lipoprotein cholesterol treat-to-target strategy and the adoption of a risk reduction strategy in 4 major statin benefit groups. In patients with established cardiovascular disease, both guidelines recommend a similar therapeutic strategy (high-dose potent statins). However, in primary prevention, the application of the American guidelines would substantially increase the number of persons, particularly older people, receiving statin therapy. The elimination of the cholesterol treat-to-target strategy, so strongly rooted in the scientific community, could have a negative impact on clinical practice, create a certain amount of confusion and uncertainty among professionals, and decrease follow-up and patient adherence. Thus, this article reaffirms the recommendations of the European guidelines. Although both guidelines have positive aspects, doubt remains regarding the concerns outlined above. In addition to using risk charts based on the native population, the messages of the European guideline are more appropriate to the Spanish setting and avoid the possible risk of overtreatment with statins in primary prevention.The publication of the 2013 American College of Cardiology/American Heart Association guidelines on the treatment of high blood cholesterol has had a strong impact due to the paradigm shift in its recommendations. The Spanish Interdisciplinary Committee for Cardiovascular Disease Prevention and the Spanish Society of Cardiology reviewed this guideline and compared it with current European guidelines on cardiovascular prevention and dyslipidemia management. The most striking aspect of the American guideline is the elimination of the low-density lipoprotein cholesterol treat-to-target strategy and the adoption of a risk reduction strategy in 4 major statin benefit groups. In patients with established cardiovascular disease, both guidelines recommend a similar therapeutic strategy (high-dose potent statins). However, in primary prevention, the application of the American guidelines would substantially increase the number of persons, particularly older people, receiving statin therapy. The elimination of the cholesterol treat-to-target strategy, so strongly rooted in the scientific community, could have a negative impact on clinical practice, create a certain amount of confusion and uncertainty among professionals, and decrease follow-up and patient adherence. Thus, this article reaffirms the recommendations of the European guidelines. Although both guidelines have positive aspects, doubt remains regarding the concerns outlined above. In addition to using risk charts based on the native population, the messages of the European guideline are more appropriate to the Spanish setting and avoid the possible risk of overtreatment with statins in primary prevention.