Adherencia terapéutica a los anticoagulantes orales y su importancia en la enfermedad tromboembólica venosa / Adherence to oral anticoagulation drug treatment and its importance in venous thromboembolic disease

En la actualidad no existe un consenso en la definición operativa de la no adherencia a los anticoagulantes orales, no obstante, es conocido que su evaluación y las intervenciones para su mejora son aspectos fundamentales en la práctica clínica diaria. La intención de este trabajo es realizar una revisión actualizada sobre el tema de la adherencia al tratamiento con anticoagulantes orales así como de las consecuencias de la no adherencia al tratamiento en la enfermedad tromboembólica venosa. Se realizó una búsqueda bibliográfica en las bases de datos MedLine y Google y la identificación de los estudios sobre la adherencia publicados entre 2009-2015. La no adherencia ocurre en grado sustancial en la anticoagulación oral, a pesar de ser uno de los tratamientos farmacológicos sometidos a monitorización más intensa. Esta condición es una de las principales razones para suspender el tratamiento anticoagulante. La no adherencia disminuye el beneficio del tratamiento y puede afectar la estimación de su eficacia, por lo que es necesario mejorar la comprensión de la terapéutica por parte del paciente. La adherencia probablemente tiene el mayor impacto en la calidad de la anticoagulación. La mejora de la adherencia terapéutica a los anticoagulantes orales repercutiría en una mejor evolución clínica de los pacientes y en la disminución de los costos sanitarios(AU)

Nowadays there is no consensus about the operational definition of not adherence to oral anticoagulant therapy; however it is known that its evaluation and the interventions to improve it are fundamental in the daily clinical practice. The intention of this study is to realized a current review of the adherence to oral anticoagulant treatment and the consequences of the no adherence to this treatment in venous thromboembolic disease. A literature review was made on MedLine and Google and those studies about adherence to treatment published in the 2009-2015 period were found. Non-adherence to treatment significantly occurs in the oral anticoagulation in spite of being one of the drug therapies under more intensive monitoring. This condition is one of the main reasons to interrupt the anticoagulant treatment. Non-adherence reduces the benefits of treatment and may influence the assessment of its efficacy, so it is necessary to improve the understanding of therapeutics by the patient. Adherence to treatment probably has the highest impact on the quality of anti-coagulation. The improvement of adherence to oral anticoagulant treatment would have an effect in a better clinical progress of patients and in the decrease of health costs(AU)

The Impact of CDH13 Polymorphism and Statin Administration on TG/HDL Ratio in Cardiovascular Patients

PURPOSE: Adiponectin is expressed in adipose tissue, and is affected by smoking, obesity, and genetic factors, such as CDH13 polymorphism, contributing to the development of coronary vascular diseases (CVDs). MATERIALS AND METHODS: We investigated the effect of genetic variations of CDH13 (rs3865188) on blood chemistry and adiponectin levels in 345 CVD patients undergoing statin-free or statin treatment. RESULTS: Genetic variation in CDH13 was significantly correlated with several clinical factors, including adiponectin, diastolic blood pressure, triglyceride (TG), and insulin levels. Subjects with the T allele (mutant form) had significantly lower adiponectin levels than those with the A allele. Total cholesterol (TC), low-density lipoprotein cholesterol (LDLc), TG/high-density lipoprotein cho-lesterol (HDLc) ratio, and HDL3b subtype were markedly decreased in statin treated subjects regardless of having the A or T allele. TG and TG/HDL in the statin-free group with TT genotype of the rs3865188 was higher than in the others but they were not different in the statin-treated subjects. We observed a significant difference in adiponectin levels between patients with the A and T alleles in the statin-free group; meanwhile, no difference in adiponectin levels was noted in the statin group. Plasma levels of other cytokines, leptin, visfatin, interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-alpha), were not different among the CDH13 genotypes according to statin administration. Body mass index (BMI), TG, insulin, HDL3b, and TG/HDL ratio showed negative correlations with adiponectin levels. CONCLUSION: Plasma adiponectin levels and TG/HDL ratio were significantly different according to variants of CDH13 and statin administration in Korean patients with CVD.

Importancia médica del glucocáliz endotelial: Parte 2: su papel en enfermedades vasculares y complicaciones de la diabetes mellitus / Medical significance of endothelial glycocalyx: Part 2: Its role in vascular diseases and in diabetic complications

El glucocáliz endotelial es una capa constituida por glucosaminoglicanos, proteoglicanos y glucoproteínas que cubre al endotelio en su cara luminal. La participación del deterioro del glucocáliz endotelial parece esencial en los pasos iniciales de la fisiopatología de la aterosclerosis, de las complicaciones microangiopáticas de la diabetes mellitus y de la enfermedad venosa crónica. Los factores de riesgo de la aterosclerosis como la hipercolesterolemia, la hiperglucemia, la inflamación, el exceso de sodio y las fuerzas de tensión alteradas causan deterioro del glucocáliz. Esto provoca disfunción endotelial y permite la filtración de lipoproteínas (LDL) y de leucocitos al espacio subendotelial, iniciando la formación de la placa de ateroma. En la diabetes el glucocáliz adelgazado, principalmente por estrés oxidativo, posibilita la filtración de proteínas (albuminuria) y el trastorno endotelial de la microangiopatía. La hipertensión venosa crónica altera las fuerzas de tensión y daña el glucocáliz, lo que permite la filtración de leucocitos a las partes más profundas de la pared venosa, iniciando la inflamación y el deterioro morfológico y funcional de las venas que lleva a la enfermedad venosa crónica. El tratamiento con glucosaminoglicanos (sulodexida) logra prevenir o revertir el daño al glucocáliz endotelial y algunas de sus consecuencias; es eficaz en la enfermedad venosa crónica, especialmente con úlceras venosas. También ha sido útil en aterosclerosis obliterante de miembros inferiores y en la nefropatía diabética con albuminuria.

Endothelial glycocalyx is a layer composed by glycosaminoglycans, proteoglycans and glycoproteins attached to the vascular endothelial luminal surface. Shredding of glycocalyx appears as an essential initial step in the pathophysiology of atherosclerosis and microangiopathic complications of diabetes mellitus, as well as in chronic venous disease. Atherosclerosis risk factors, as hypercholesterolemia (LDL), hyperglycemia, inflammation, salt excess and altered shear stress can damage glycocalyx. This lead to endothelial dysfunction and allows LDL and leukocytes to filtrate to the subendothelial space initiating atheroma plaque formation. Degradation of glycocalyx in diabetes mellitus is mainly due to oxidative stress and enables protein filtration (albuminuria) and endothelial disorder of microangiopathy. Chronic venous hypertension brings to altered shears stress which results in shredded glycocalyx, this allows leukocytes to migrate into venous wall and initiate inflammation leading to morphologic and functional venous changes of the chronic venous disease. Treatment with glycosaminoglycans (sulodexide) prevents or recovers the damaged glycocalyx and several of its consequences. This drug improves chronic venous disease and promotes healing of chronic venous ulcers. It has also been useful in peripheral arterial obstructive disease and in diabetic nephropathy with albuminuria.

Evaluación de efecto vasoprotector del consumo de curcumina en ratas macho Sprague-Dawley con dieta hipercolesterolémica / Evaluation of the curcumin vasoprotective effect in Sprague-Dawley male rats with a hypercholesterolemic diet

INTRODUCCIÓN: El hígado graso no alcohólico puede abarcar desde una simple esteatosis hasta una cirrosis hepática. Los mecanismos fisiopatológicos que modulan el estrés oxidativo, la actividad inflamatoria y profibrótica, deberían ser cruciales en su mayor o menor agresividad hepática y vascular. Un compuesto derivado de la Cúrcuma longa L, la curcumina, poseería propiedades vasoprotectoras. OBJETIVO: Comparar en situaciones de dieta hipercolesterolémica los cambios vasculares entre ratas macho Sprague Dawley que consumen curcumina y las que no consumen. MATERIAL Y MÉTODO: Estudio analítico, experimental, longitudinal y prospectivo en ratas macho Sprague-Dawley expuestas a condiciones de hígado graso no alcohólico e hígado graso no alcohólico adicionando curcumina, durante 4 meses. Sacrificadas, se realizó protocolo de función vascular en arteria mesentérica superior aislada (respuesta a acetilcolina, N nitro-L-arginina metil éster y nitroprusiato) y medición de presión portal por punción directa. Los resultados fueron expresados en promedios junto a la desviación estándar de la media. Lasdiferencias entre los grupos fueron probadas mediante t de Studenty test de Mann-Whitney. RESULTADOS: La medición de presión portal no mostró diferencias significativas entre ambos grupos. No hubo diferencias significativas en las pruebas con Nnitro-L-arginina metil éster ni nitroprusiato; diferencia que sí existió con acetilcolina entre la dilatación de la arteria mesentérica superior de hígado graso no alcohólico y las de hígado graso no alcohólico más curcumina. DISCUSIÓN: La curcumina mejoró la respuesta vasodilatadora a acetilcolina, lo que sugiere que el posible efecto antioxidante sería mejorando la función endotelial. Se sugiere su futuro uso terapéutico.

INTRODUCTION: Nonalcoholic fatty liver disease can range from simple steatosis to cirrhosis. The pathophysiological mechanisms that modulate oxidative stress, inflammatory and profibrotic activity should be crucial in the liver injury and vascular aggressiveness. Curcumin, a compound derived from Curcuma longa L, possesses vasoprotectives properties. OBJECTIVE: To compare in hypercholesterolemic diet situations the vascular changes between Sprague-Dawley male rats who consume curcumin and who do not consume. MATERIAL AND METHOD: Analytical, experimental, prospective and longitudinal study in Sprague-Dawley male rats exposed to conditions of Nonalcoholic fatty liver with and without curcumin, for four months. After the sacrifice, a vascular function protocol was performed on an isolated superior mesenteric artery (response to acetylcholine, L-NGNitroarginine Methyl Ester and nitroprusside) and measurement of portal pressure by direct puncture. The results were expressed as average and the standard deviation of the central tendency. The differences between the groups were tested using Student's t-test and Mann-Whitney test. RESULTS: The portal pressure measurement showed no significant differences between groups. There was no significant difference in the nitroprusside test, in the other hand, exist a difference with acetylcholine between arteries of nonalcoholic fatty liver group against nonalcoholic fatty liver plus curcumin group. DISCUSSION: Curcumin improved the vasodilator response in response to acetylcholine, suggesting a possible antioxidant effect which improves endothelial function. It is suggested for future therapeutic use.

Uso de parâmetros microcirculatórios para a avaliação de tratamento clínico da desordem venosa crônica (DVC) / Use of microcirculatory parameters to evaluation of clinical treatment in chronic venous disorder

Objetivos: Avaliar mudanças na microangiopatia cutânea em estágio iniciais de pacientes com desordem venosa crônica depois do uso de Cirkan® [droga venotônica contendo Ruscus aculeatus (extrato de planta), hesperidina methylchacone (flavonóide) e vitamina C], meio elástica de média compressão ou nenhum tratamento durante quatro semanas. Pacientes e Métodos: Cinquenta e cinco pacientes do sexo feminino, (85 pernas), entre 25 e 57 anos, com pelo menos um membro classificado como C2,s o C2,3,s (da classificação CEAP), foram alocadas consecutivamente, de acordo com a ordem de entrada nesses três grupos. Cinco mulheres sem doença venosa, com idades semelhantes foram também investigadas. Utilizando-se a técnica de luz polarizada ortogonal (método não-invasivo), medidas da densidade capilar funcional (DCF, número de capilares com fluxo sanguíneo/mm2), morfologia capilar (MC, % de capilares anormais/mm2) e diâmetros (um) da papila dérmica (DPD), no novelo capilar (DNC) e do capilar da perna (DC) foram obtidos na região peri-maleolar medial e mais tarde analisada utilizando-se o Sofware CapImage. Resultados e conclusão: Pacientes com DVC mostraram mudanças significativas no diâmetro e na morfologia capilar comparada com mulheres saudáveis, em concordância com nossos achados prévios (J Vasc Surg 43:1037-1044, 2006). Em pacientes tratados com Cirkan® durante quatro semanas, houve diminuição do diâmetro capilar em ambas as pernas e melhora da morfologia na perna esquerda, sugerindo melhora da hipertensão venosa crônica. Nenhuma mudança significativa pôde ser detectada nos outros grupos de pacientes. Esses resultados confirmam a existência de disfunção microcirculatória nos estágios iniciais da DVC, provavelmente devido à hipertensão pós-capilar e apóiam a ação do venotônico Cirkan®.

Objetives: To evaluate changes on cutaneous microangiopathy in chronic venous disorder (CVD) after use of Cirkan® [venotonic drug containing Ruscus aculeatus (plant extract), hesperidine methilchacone (flavonoid) and vitamin C], elastic compression stockings (ECS) or no treatment for four weeks. Patients and Methods: Fifty-five female patients (85 legs), 25 to 57 years, with at least one limb classified as C2,s of C2,3,s (CEAP classification), were allocated consecutively, according to entrance order, in these three groups. Ten healthy women age-matched were also investigated. Using orthogonal polarization spectral technique (noninvasive method), measurements of functional capillary density (FCD, number of capillaries with flowing red blood cells/mm2), capillary morphology (CM, 5 of abnormal capillaries/mm2) and diameters (um) of dermal papilla (DDP), capillary bulk (DCB) and capillary limb (CD) were obtained on the medial perimalleolar region and later analyzed using CapImage software. Results and conclusions: CVD patients showed significant changes on CD and CM compared to healthy subjects in agreement with our previous findings (J Vasc Surg 43:1037-1044, 2006). On Cirkan®-treated patients, after 4 weeks, CD decreased on both limbs and CM improved on the left one, suggesting an amelioration of the chronic venous hypertension. No significant changes could be detected on other patient groups. These results confirm the exixtence of microcirculatory dysfunction in early stages of CVD, probably due to post-capillary hypertension, and further support the venotonic action of Cirkan®.

Randomized trial of atorvastatin in improving endothelial function in diabetics without prior coronary disease and having average cholesterol level.

OBJECTIVE: The aim of this study was to determine whether HMGCoA reductase inhibitor with atorvastatin can modulate endothelial function in type II diabetics having average cholesterol and no prior cardiovascular disease. MATERIAL AND METHOD: Type II diabetics, with no prior cardiovascular events and total cholesterol at admission of < or = 200 mg/dl or LDL < or = 140 mg/dl, were randomized to placebo (n = 20) or atorvastatin 20 mg daily (n = 22) for 30 weeks. Brachial artery endothelium-dependent dilatation or flow-mediated dilatation (FMD) and endothelium-independent dilatation or nitroglycerine-mediated dilatation (NTGMD) were measured at baseline and after thirty weeks of treatment. RESULTS: Baseline clinical characteristics were similar at admission in both groups. After thirty weeks of treatment, the FMD did not significantly change in either the atorvastatin or placebo group (4.11 +/- 1.05% to 3.01 +/- 1.27% vs 5.75 +/- 1.93% to 6.45 +/- 1.41%, respectively; p = 0.46 by analysis of covariance). Similarly, the NTGM did not change in either group. CONCLUSION: The addition of HMGCoA reductase inhibitor with atorvastatin did not improve endothelial function in type 2 diabetes having average cholesterol with no prior cardiovascular disease, despite an improvement of the lipid profile.

Síndrome hepatopulmonar / Hepatopulmonary syndrome

El Síndrome hepatopulmonar (SHP) es una entidad clínica reconocida por vez primera en 1884 por Flückiger, sin embargo fue hasta 1977 cuando Kennedy y Knudson la consideraron como un síndrome, el cual se caracteriza por una tríada conformada por insuficiencia hepática, vasodilatación pulmonar e hipoxemia. Entre las causas de esta entidad clínica se encuentra la insuficeincia hepatica, ya sea aguda o crónica. El factor relajante del endotelio es aparentemente la principal causa de las alteraciones vasculares pulmonares. La sintomatología es la producida por la insuficiencia hepática per se como ascitis, ictericia, eritema palmar, varices esofágicas, hemorragia del tubo digestivo, y por el componente pulmonar como son, ortodeoxia, hipocratismo digital y cianosis. Los mecanismos de hipoxemia en el SHP son alteraciones de la ventilación perfusión, cortos circuitos y trastornos de la difusión. El diagnóstico se realiza con base en diferentes estudios, como son la radiografía de tórax, el gammagrama perfusorio, la ecocardiografía contrastada bidimensional y la angiografía. Hasta el momento, no hay un tratamiento conocido que sea totalmente efectivo, no obstante el trasplante hepático ha sido considerado como la mejor opción, aunque otros como la embolización y terapia farmacológica pueden ser utilizados

Ectasia vascular del antro (EVA) o watermelon stomach (WS): poco frecuente causa de anemia / Gastric vascular ectasia (GAVE) or wartemelon stomach (WS): unfrequent cause of anemia

La ectasia vascular del antro (EVA) o watermelon stomach (WS) es una causa poco frecuente de anemia o hemorragia digestiva alta manifesta en pacientes de edad avanzada. Presentamos 5 apcientes, todas mujeres, edad promedio 79 años, 4 anémicas de larga evolución y 1 con melena. Tres tenían endoscopía típica de WS, 2 tenían patente difusa. Las 5 con anatomía patológica positiva: ectasias vasculares y/o microtrombos fíbrinosos y proliferación fibromuscular en la l mina propria. La biopesia esdoscópica es tan fiel como el estudio de la pieza de antrectomía. Ninguna tenía hipertensión portal, aunque la EVA sería una entidad diferente a la gastropatía vascular del cirrótico. El tratamiento conssitió en electrocoagulación monopolar de las lesiones tras fracaso del tratamiento médico en 1 caso, corticoterpia mas ferroterapia en 3, mientras que el restante no requiere tratamiento por el momento. Conclusiones: la EVA debe tenerse presente en pacientes anémicos crónicos sien diagnóstico, de edad avanzada. Las im genes endoscópicas no siempre son las típicas del estómago en sandía (WS). Se debe biopsiar el antro gastrico ante la duda. Si no responden al tratamiento con corticoides y/o hierro, el tratamiento de elección es el laser o el "heat electrocoagulación monopolar o la esclerosis. La cirurgía es el último recurso a aplicar.

Thrombolytic therapy in 1995.

In summary, the amount of research in the field of thrombolysis done in patients with acute myocardial infarction has shown the enormous benefit not only for mortality but other cardiovascular events. Its benefit over other non cardiac conditions are accumulating. Several large-scale studies are underway and expected to give us answers for which conditions will benefit from thrombolytic therapy.