Antonio Hernández Mijares

Oxidative stress, endothelial dysfunction and atherosclerosis.

This review focuses on the role of oxidative processes in atherosclerosis and the cardiovascular diseases (CVD) that can arise as a result. Atherosclerosis represents a state of heightened oxidative stress characterized by lipid and protein oxidation in the vascular wall. Overproduction of reactive oxygen species (ROS) under pathophysiologic conditions forms an integral part of the development of CVD, and in particular atherosclerosis. Endothelial dysfunction, characterized by a loss of nitric oxide (NO) bioactivity, occurs early on in the development of atherosclerosis, and determines future vascular complications. Although the molecular mechanisms responsible for mitochondria-mediated disease processes are not clear, oxidative stress seems to play an important role. In general, ROS are essential to the functions of cells, but adequate levels of antioxidant defenses are required in order to avoid the harmful effects of excessive ROS production. In this review, we will provide a summary of the cellular metabolism of reactive oxygen species (ROS) and its role in pathophysiological processes such as atherosclerosis; and currently available antioxidants and possible reasons for their efficacy and inefficacy in ameliorating oxidative stress-mediated diseases.

Management of Dyslipidemia in the Metabolic Syndrome Recommendations of the Spanish HDL-Forum

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 high levels of apolipoprotein (apo) B-100-rich particles of a particularly atherogenic phenotype (small dense low-density lipoprotein-cholesterol [LDL-C]. High levels of triglyceride-rich particles (very low-density lipoprotein) are also evident both at baseline and in overload situations (postprandial hyperlipidemia). Overall, the ‘quantitative’ dyslipidemia characterized by hypertriglyceridemia and low levels of HDL-C and the ‘qualitative’ dyslipidemia characterized by high levels of apo B-100- and triglyceride-rich particles, together with insulin resistance, constitute an atherogenic triad in patients with the metabolic syndrome.The therapeutic management of the metabolic syndrome, regardless of the control of the bodyweight, BP, hyperglycemia or overt diabetes mellitus, aims at maintaining optimum plasma lipid levels. Therapeutic goals are similar to those for high-risk situations because of the coexistence of multiple risk factors. The primary goal in treatment should be achieving an LDL-C level of <100 mg/dL (or <70 mg/dL in cases with established ischemic heart disease or risk equivalents). A further goal is increasing the HDL-C level to ≥40 mg/dL in men or 50 mg/dL in women. A non-HDL-C goal of 130 mg/dL should also be aimed at in cases of hypertriglyceridemia.Lifestyle interventions, such as maintaining an adequate diet, and a physical activity program, constitute an essential part of management. Nevertheless, when pharmacologic therapy becomes necessary, fibrates and HMG-CoA reductase inhibitors (statins) are the most effective drugs in controlling the metabolic syndrome hyperlipidemia, and are thus the drugs of first choice. Fibrates are effective in lowering triglycerides and increasing HDL-C levels, the two most frequent abnormalities associated with the metabolic syndrome, and statins are effective in lowering LDL-C levels, even though hypercholesterolemia occurs less frequently. In addition, the combination of fibrates and statins is highly effective in controlling abnormalities of the lipid profile in patients with the metabolic syndrome.

Significance of High Density Lipoprotein-Cholesterol in Cardiovascular Risk Prevention

In the approach to lipid-related risk factors for cardiovascular diseases, serum high density lipoprotein-cholesterol (HDL-C) levels bear a particular significance as this lipoprotein is considered to be an antiatherogenic factor mainly, but not only, because of its influence and impact on reverse cholesterol transport. Hence the need and requirement to consider serum HDL-C levels for both primary and secondary prevention of cardiovascular disease. A particularly important aspect is the association of the ‘low HDL syndrome’ with the metabolic syndrome.These factors force us to consider serum HDL-C level as a therapeutic target by itself, or even in association with low density lipoprotein-cholesterol (LDL-C) levels when the latter are increased. This review stresses the aspects connecting serum HDL-C levels and cardiovascular risk, and looks at the populations that should be considered amenable to therapeutic management because of low serum HDL-C levels.We review therapeutic strategies, both pharmacological and nonpharmacological. The aim of this review is to present therapeutic management recommendations for correcting the proportion of cardiovascular risk that is attributable to changes in HDL-C. Serum HDL-C levels of >40 mg/dL must be a therapeutic target in primary and secondary prevention. This goal is particularly important in patients with low serum HDL-C levels and ischemic heart disease (IHD) or its equivalents, even if the therapeutic target for serum LDL-C levels (<100 mg/ dL) has been achieved. The first choice for this clinical condition is fibric acid derivates. The same therapeutic option should be considered in patients without IHD with low serum HDL-C levels and high cardiovascular risk (>20%), hypertriglyceridemia, type 2 diabetes mellitus, or metabolic syndrome.

Prevalencia de malnutrición entre ancianos institucionalizados en la Comunidad Valenciana

Fundamento Conocer la prevalencia de malnutricion en poblacion anciana institucionalizada estratificada por percentiles de edad y sexo. Pacientes y metodo Se estudiaron un total de 615 ancianos institucionalizados, con una edad media (DE) de 79,33 (9,07) anos. Los parametros antropometricos medidos fueron peso, talla, distancia rodilla-talon, pliegues tricipital y subescapular, y perimetro del brazo y de la cintura. Se calcularon el perimetro y el area muscular del brazo y la masa grasa. Los parametros bioquimicos determinados fueron colesterol, trigliceridos, albumina, prealbumina, transferrina, proteina fijadora de retinol, C3 y recuento de linfocitos. Se diagnostico malnutricion cuando al menos dos de los parametros estudiados eran patologicos, inferiores al percentil 25, y determinaciones analiticas inferiores a la normalidad. Resultados La prevalencia de malnutricion fue del 26,87% (IC del 95%, 23,15–30,86): del 29,08% (IC del 95%, 22,82–35,97) en varones y del 25,59% (IC del 95%, 25,1–30,61) en mujeres. Los parametros antropometricos estudiados se encuentran reducidos en todos los casos en los pacientes con malnutricion. Sin embargo, los parametros bioquimicos no presentan, en general, diferencias significativas entre estos pacientes y los sujetos con buen estado nutricional si se comparan de forma bivariante, pero si ofrecen diferencias significativas si se aplica un analisis multivariante controlando los parametros edad y sexo. Conclusion En nuestro estudio encontramos una prevalencia de malnutricion elevada en un rango inferior de lo esperado, segun los estudios realizados con grupos de edad similar. Los parametros antropometricos se encuentran asociados con malnutricion en ancianos, y de los datos bioquimicos destaca el descenso de la prealbumina.

Disfunción eréctil como marcador de vasculopatía en la diabetes mellitus tipo 2 en España. Estudio DIVA

BACKGROUND AND OBJECTIVES Erectile dysfunction (ED) is a sign of vascular disease in type 2 diabetic patients. The present subanalysis of the DIVA Registry, whose main objective was to estimate the prevalence of clinical vascular disorder and silent vascular disorder, as well as risk factors in type 2 diabetic patients treated in Spain, aims to analyze the relationship between those data and the prevalence of ED in these patients. PATIENTS AND METHODS A total of 2444 type 2 diabetic patients (56% male; mean age 65.2 years) attended by 387 cardiologists and endocrinologists at ambulatory care were included. RESULTS Coronary heart disease was present in 37% of the patients, cerebrovascular disease in 12%, and peripheral arterial disease in 13%. Forty percent of male patients had ED (according to the IIEF criteria), although in this group, as compared to those patients without ED, the prevalence of cardiovascular disease and signs of subclinical vascular disorder (microalbuminuria and abnormal ankle/brachial index (ABI)) was higher. The only independent predictor of ED was left ventricular hypertrophy (OR 5.2; 95% CI: 1.1-24.1; P=.03), with the ABI <0,9 being of borderline significance (OR 5.9; 95% CI: 0.9-39.9; P=.06). Poor glycemic and lipemic control (P<.05 in both cases) as well as cerebrovascular and peripheral arterial disease (P<.01 in both cases) and renal dysfunction (P<.001) were all more frequent among patients with severe ED. CONCLUSIONS Forty percent of diabetic patients suffer from ED. The results of this study suggest that ED may be considered as an atherosclerosis marker and could be included in algorithms for risk stratification and subclinical vascular disorder detection.

Síndrome metabólico en pacientes con cardiopatía isquémica. Resultados obtenidos con la utilización de diferentes criterios

Carecemos de un criterio unico para definir el sindrome metabolico, considerado como aglutinador del riesgo cardiovascular. Con objeto de comparar su prevalencia en pacientes con cardiopatia isquemica, utilizando los criterios del Grupo Europeo de Resistencia a la Insulina y los del National Colesterol Education Program, se diseno un estudio observacional, transversal, de los factores integrantes del sindrome metabolico en pacientes con cardiopatia isquemica. Se estudio a 169 pacientes (129 varones y 40 mujeres) con edades entre 35 y 79 anos. La prevalencia del sindrome metabolico con los criterios del grupo europeo fue del 43,7% y con los del grupo americano, del 40,8% (sin diferencias significativas). La prevalencia del sindrome metabolico entre pacientes con cardiopatia isquemica es elevada. Los criterios diagnosticos utilizados son similares y sin diferencias significativas entre ellos, aunque la concordancia diagnostica fue del 50%.

Estudio REALIST (REsiduAl risk, LIpids and Standard Therapies): Un análisis del Riesgo Residual dependiente del perfil lipídico en el síndrome coronario agudo

The R3i Foundation (Residual Risk Reduction Initiative), an independent, multinational and academic organization, is conducting the REALIST (Residual Risk, Lipids and Standard Therapies) study in 40 centers in different countries. This is a retrospective epidemiological study, designed to provide new data on the residual risk of major coronary events attributable to lipid abnormalities in patients receiving the current standard treatment. The initial results are expected in mid 2010, and the overall results at the end of 2010.

Diagnóstico de síndrome metabólico. Adecuación de los criterios diagnósticos en nuestro medio

La asociación de factores de riesgo cardiovascular es conocida desde hace muchos años. En 1923, Kylin describió la asociación de hipertensión arterial, hiperglucemia y gota. En 1936, Himsworth propuso la existencia de dos tipos de diabetes, la sensible y la resistente a la insulina. En 1956, Vague describió un tipo de obesidad androide asociada a hiperuricemia y riesgo cardiovascular. Los estudios epidemiológicos, como el realizado en la población de Framingham, han demostrado que los factores de riesgo cardiovascular en la mayoría de las ocasiones se presentan agrupados. En 1988, Reaven expuso la asociación de intolerancia a la glucosa, hipertensión, hipertrigliceridemia y disminución del colesterol de las lipoproteínas de alta densidad (cHDL) con el nombre de síndrome X, destacando su impacto en la morbilidad y mortalidad cardiovascular. Posteriormente, se han añadido otros componentes como la microalbuminuria, la esteatosis hepática no alcohólica, alteraciones procoagulantes y proinflamatorias, la hiperferritinemia y la hiperhomocisteinemia, entre otras. Sin embargo, ha sido la obesidad visceral el componente que se ha incorporado como más definitorio. El síndrome ha recibido diferentes acepciones, como síndrome de resistencia a la insulina, síndrome plurimetabólico, cuarteto de la muerte, síndrome dismetabólico cardiovascular y más recientemente, propuesto por la Organización Mundial de la Salud (OMS), síndrome metabólico (SM). Su importancia clínica y epidemiológica es la de ser un precursor identificable y corregible de la diabetes tipo 2 y de la enfermedad cardiovascular1. El SM es complejo, poligénico, multifactorial en su origen, y los criterios de definición distan de estar internacionalmente consensuados. En un reciente informe conjunto de la American Diabetes Association (ADA) y la European Association for the Study of Diabetes (EASD), se efectúa una serie de puntualizaciones sobre el concepto de SM2. Este informe recuerda que el término “síndrome” abarca un conjunto de síntomas y signos que conforman un proceso morboso y suelen obedecer a un proceso fisiopatológico único, y cuya combinación confiere un riesgo diferente del ocasionado por su suma. En relación con estos aspectos, establece determinadas críticas al reconocimiento como entidad del denominado SM y al valor clínico de su diagnóstico:

Factores de riesgo cardiovascular en pacientes con obesidad mórbida: influencia de la pérdida de peso

Fundamento Analizar la presencia de factores de riesgo cardiovascular (FRCV) en pacientes conobesidad morbida y la influencia de la reduccion ponderal mediante intervencion dietetica sobreestos FRCV. Asimismo, valorar la influencia del sexo en la presencia de FRCV y en la respuestaa la intervencion dietetica. Pacientes y metodo A todos los pacientes con obesidad morbida (23 varones y 36 mujeres) seles efectuo una valoracion antropometrica y de los FRCV (fibrinogeno, presion arterial, estudiodel metabolismo hidrocarbonado mediante la realizacion de sobrecarga oral de glucosa, perfillipidico completo, presencia de sindrome de apneas del sueno), antes y despues de una intervenciondietetica alternando dietas de muy bajo contenido calorico con dietas hipocaloricasconvencionales. Se compararon los resultados antes y despues de la intervencion dietetica mediantela prueba de la t de Student para muestras apareadas (tras comprobar que se cumplianlas condiciones de aplicacion). Resultados Se consiguio una reduccion ponderal muy significativa, principalmente en varones(reduccion de 33,4 kg; intervalo de confianza (IC) del 95%, 26,9-39,8), que se acompano deuna reduccion de los FRCV asociados, especialmente en el sexo masculino, en el que mejorode forma significativa la distribucion de grasa (reduccion de cintura de 24,8 cm; IC del 95%,18,4-36,5) y el perfil lipidico: trigliceridos (IC del 95%, 25,4-90), colesterol HDL y apoproteinaB100. Conclusiones En pacientes con obesidad morbida existe una elevada presencia de FRCV asociados.Con la reduccion ponderal obtenida mediante intervencion dietetica durante un ano hemosconseguido una reduccion significativa de los mismos. Esta mejoria es especialmente importanteen los varones.BACKGROUND: We studied the presence of cardiovascular risk factors in patients with morbid obesity and analyzed the influence of weight loss achieved through diet on these factors. We also evaluated the influence of gender on the presence of cardiovascular risk factors and on its response to diet. PATIENTS AND METHODS: An anthropometric evaluation was performed in patients with morbid obesity (23 men and 36 women). The presence of cardiovascular risk factors was evaluated (fibrinogen, blood pressure, glucose metabolism determination by means of oral glucose tolerance test, complete lipid profile, sleep apnea syndrome), before and after following, on an alternative fashion, very-low calorie and low-calorie diets. The comparison was made with the t-test for paired samples. RESULTS: A very significant weight loss was achieved in our patients, particularly in men (decrease of 33.4 kg, 95% CI: 26.9 to 39.8). This was accompanied by a reduction in the presence of cardiovascular risk factors, particularly in men, in whom the body fat distribution improved significantly (decrease in waist: 24.8 cm, 95% CI 18.4 to 36.5), as well as the lipid profile including triglycerides, VLDLc, HDLc and B100 apoprotein. CONCLUSIONS: Patients with morbid obesity have a high prevalence of cardiovascular risk factors. A significant reduction of this prevalence can be achieved with diet during one year. This improvement is particularly significant in men.

Metabolic Syndrome in Patients With Coronary Heart Disease. Results of Using Different Diagnostic Criteria

A unified definition of metabolic syndrome, considered a common feature of cardiovascular risk, is lacking. The aim of this study was to compare the prevalence of this syndrome in patients with ischemic heart disease using two diagnostic criteria: the European Group of Resistance to Insulin and the National Cholesterol Education Program. We designed an observational, crosssectional study of the factors that make up metabolic syndrome in subjects diagnosed with coronary heart disease. A total of 169 patients aged 35 to 79 years were studied (129 men and 40 women). With the European group criterion the percentage of patients with metabolic syndrome was 43.7%, whereas the American group criterion yielded a prevalence of 40.8% (no significant difference). The prevalence of metabolic syndrome among patients with ischemic heart disease is high. The diagnostic criteria used are similar and do not differ significantly, although diagnostic concordance was only 50%.