High-fat diet promotes coagulation and endothelial activation in Sprague Dawley rats: Short-term effects of combined oral contraceptives / Dieta alta en grasas promueve la coagulación y la activación endotelial en ratas Sprague Dawley: efectos a corto plazo de los anticonceptivos orales combinados

Background Combined oral contraceptives (COCs), use in individuals are associated with increased risk of thrombotic events. This highlights the significance of assessing the impact of COC on promoting coagulation and endothelial activation in high-fat diet (HFD)-fed Sprague Dawley rats. Methods Twenty (20) five-weeks-old female Sprague Dawley rats weighing between 150 and 200g were subjected to both LFD and HFD-feeding for 8-weeks to determine its influence on basic metabolic status, hemostatic profile, hemodynamic parameters (blood pressure and heart rate), as well as selected biomarkers of coagulation (tissue factor and D-dimer) and endothelial activation (Von Willebrand factor and nitric oxide). Thereafter HFD-fed animals were treated with receive high dose combined oral contraceptive (HCOC) and low dose combine oral contraceptive (LCOC) for 6 weeks. Results Our results showed that beyond weight gain, HFD-feeding was associated with hyperglycemia, increased mean arterial pressure, and reduced nitric oxide levels when compared with LFD group (p<0.05). Interestingly, treatment with high dose of COC for 6-weeks did not significantly alter atherothrombotic markers (p>0.05). However, this study is not without limitation as regulation of these markers remains to be confirmed within the cardiac tissues or endothelial cells of these animals. Conclusion HFD-feeding orchestrate the concomitant release of pro-coagulants and endothelial activation markers in rats leading to haemostatic imbalance and endothelial dysfunction. Short-term treatment with COC shows no detrimental effects in these HFD-fed rats. Although in terms of clinical relevance, our findings depict the notion that the risk of CVD in association with COC may depend on the dosage and duration of use among other factors especially in certain conditions. ... (AU)

Antecedentes El uso de anticonceptivos orales combinados (AOC) en individuos se asocia con un mayor riesgo de eventos trombóticos. Esto resalta la importancia de evaluar el impacto de los AOC en la promoción de la coagulación y la activación endotelial en ratas Sprague Dawley alimentadas con una dieta alta en grasas (HFD). Métodos Veinte (20) ratas Sprague Dawley hembra de 5semanas de edad con un peso entre 150-200g fueron tratadas mediante una alimentación con dieta baja en grasas (LFD) y alta en grasas (HFD) durante 8 semanas para determinar su influencia en el estado metabólico básico, perfil hemostático, parámetros hemodinámicos (presión arterial y frecuencia cardíaca), así como biomarcadores seleccionados de coagulación (factor tisular y D-dímero) y activación endotelial (factor de von Willebrand y óxido nítrico). Posteriormente, los animales alimentados con HFD fueron tratados con dosis alta de anticonceptivo oral combinado (AOC-AL) y dosis baja de anticonceptivo oral combinado (AOC-BL) durante 6 semanas. Resultados Nuestros resultados mostraron que, además del aumento de peso, la alimentación con HFD se asoció con hiperglucemia, aumento de la presión arterial media y niveles reducidos de óxido nítrico en comparación con el grupo LFD (p<0,05). Curiosamente, el tratamiento con dosis alta de AOC durante 6 semanas no alteró significativamente los marcadores aterotrombóticos (p>0,05). Sin embargo, este estudio no está exento de limitaciones, ya que la regulación de estos marcadores aún debe confirmarse en los tejidos cardíacos o las células endoteliales de estos animales. Conclusión La alimentación con HFD orquesta la liberación concomitante de procoagulantes y marcadores de activación endotelial en ratas, lo que conduce a un desequilibrio hemostático y disfunción endotelial. El tratamiento a corto plazo con AOC no muestra efectos perjudiciales en estas ratas alimentadas con HFD. ... (AU)

El endotelio sano y su disfunción en el riesgo cardiovascular / Healthy Endothelium and its Dysfunction in Cardiovascular Risk

Resumen El endotelio es una monocapa formada por células aplanadas llamadas w, que revisten la parte más interna del corazón, los vasos sanguíneos y los linfáticos. Es considerado un órgano que tiene una función de barrera, pero además se encarga de regular la permeabilidad y tono vascular, hemostasia, inflamación y angiogénesis. Esta revisión se centra sobre todo en las generalidades del endotelio vascular sano y su disfunción. Se analizan los conceptos de activación y disfunción, en donde la activación se considera como un proceso autolimitado, indispensable para la hemostasia y la inflamación. La disfunción endotelial, en cambio, es un proceso patológico, de mayor duración y que se presenta cuando el endotelio ya no puede autorregularse y cambia a un fenotipo proinflamatorio y protrombótico permanente. Esta disfunción es el primer cambio que lleva a la ateroesclerosis y al aumento del riesgo cardiovascular, por esta razón se revisan los principales biomarcadores de disfunción endotelial y riesgo cardiovascular. A medida que se avance en el conocimiento básico del endotelio y su disfunción, será posible diseñar nuevas medidas preventivas o terapéuticas que puedan disminuir dicho riesgo.

Abstract The endothelium is a monolayer of flatten cells named endothelial cells that form the inner layer of the heart, blood, and lymphatic vessels. Its function is not just as a barrier, but it is a regulator of vascular permeability and tone, hemostasis, inflammation, and angiogenesis. This review is about the general aspects of vascular endothelium and endothelial dysfunction that leads to increased vascular risk. Activation and dysfunction are discussed, considering the endothelial activation as a self-limiting process, necessary to promote inflammation and hemostasis. Endothelial dysfunction is a pathological process in which the endothelium loses its ability for self-regulation and acquires a prothrombotic and proinflammation phenotype. Endothelial dysfunction is the initial step for atherosclerosis and increased cardiovascular risk, so the main biomarkers of endothelial dysfunction are reviewed. As basic knowledge about endothelium increases, preventive or therapeutic measures can be designed as treatment or prevention the risk of its dysfunction.

High-fat diet promotes coagulation and endothelial activation in Sprague Dawley rats: Short-term effects of combined oral contraceptives.

BACKGROUND: Combined oral contraceptives (COCs), use in individuals are associated with increased risk of thrombotic events. This highlights the significance of assessing the impact of COC on promoting coagulation and endothelial activation in high-fat diet (HFD)-fed Sprague Dawley rats. METHODS: Twenty (20) five-weeks-old female Sprague Dawley rats weighing between 150 and 200g were subjected to both LFD and HFD-feeding for 8-weeks to determine its influence on basic metabolic status, hemostatic profile, hemodynamic parameters (blood pressure and heart rate), as well as selected biomarkers of coagulation (tissue factor and D-dimer) and endothelial activation (Von Willebrand factor and nitric oxide). Thereafter HFD-fed animals were treated with receive high dose combined oral contraceptive (HCOC) and low dose combine oral contraceptive (LCOC) for 6 weeks. RESULTS: Our results showed that beyond weight gain, HFD-feeding was associated with hyperglycemia, increased mean arterial pressure, and reduced nitric oxide levels when compared with LFD group (p<0.05). Interestingly, treatment with high dose of COC for 6-weeks did not significantly alter atherothrombotic markers (p>0.05). However, this study is not without limitation as regulation of these markers remains to be confirmed within the cardiac tissues or endothelial cells of these animals. CONCLUSION: HFD-feeding orchestrate the concomitant release of pro-coagulants and endothelial activation markers in rats leading to haemostatic imbalance and endothelial dysfunction. Short-term treatment with COC shows no detrimental effects in these HFD-fed rats. Although in terms of clinical relevance, our findings depict the notion that the risk of CVD in association with COC may depend on the dosage and duration of use among other factors especially in certain conditions. However, additional studies are required to confirm these findings, especially long-term effects of this treatment within the cardiac tissues or endothelial cells of these animals in certain conditions relating to postmenopausal state.

New mechanisms involved in the development of cardiovascular disease in chronic kidney disease.

Chronic kidney disease (CKD) is a pathology with a high worldwide incidence and an upward trend affecting the elderly. When CKD is very advanced, the use of renal replacement therapies is required to prolong its life (dialysis or kidney transplantation). Although dialysis improves many complications of CKD, the disease does not reverse completely. These patients present an increase in oxidative stress, chronic inflammation and the release of extracellular vesicles (EVs), which cause endothelial damage and the development of different cardiovascular diseases (CVD). CKD patients develop premature diseases associated with advanced age, such as CVD. EVs play an essential role in developing CVD in patients with CKD since their number increases in plasma and their content is modified. The EVs of patients with CKD cause endothelial dysfunction, senescence and vascular calcification. In addition, miRNAs free or transported in EVs together with other components carried in these EVs promote endothelial dysfunction, thrombotic and vascular calcification in CKD, among other effects. This review describes the classic factors and focuses on the role of new mechanisms involved in the development of CVD associated with CKD, emphasizing the role of EVs in the development of cardiovascular pathologies in the context of CKD. Moreover, the review summarized the EVs' role as diagnostic and therapeutic tools, acting on EV release or content to avoid the development of CVD in CKD patients.

Posterior reversible encephalopathy syndrome in critical COVID-19 patients: Report of 2 cases.

Posterior reversible encephalopathy syndrome is an acute neurological disorder characterized by variable symptoms and radiological images characteristic of vasogenic parietal-occipital edema. It is associated with clinical conditions such as high blood pressure, infection/sepsis, or cytotoxic/immunosuppressive drugs, among others. It is characterized pathophysiologically by endothelial damage with breakdown of blood-brain barrier, cerebral hypoperfusion, and vasogenic edema. The cases are presented on 2 critical COVID-19 patients who were admitted to pneumonia requiring mechanical ventilation and who, after removing sedation, developed acute and reversible neurological symptoms consisting of epilepsy and encephalopathy, associated with hyperintense subcortical lesions on brain magnetic resonance imaging compatible with posterior reversible encephalopathy syndrome. SARS-CoV-2 coronavirus would activate an inflammatory response that would damage brain endothelium. It could be triggered by cytokine release, as well as by direct viral injury, given that endothelium expresses ACE2 receptors. It could explain the possible association between posterior reversible encephalopathy syndrome and COVID-19.

Nuevos mecanismos implicados en el desarrollo de la enfermedad cardiovascular en la enfermedad renal crónica / New mechanisms involved in the development of cardiovascular disease in chronic kidney disease

La enfermedad renal crónica (ERC) tiene una alta incidencia mundial y una tendencia ascendente que afecta principalmente a personas de edad avanzada. Cuando la ERC está muy avanzada se requiere el uso de terapias renales sustitutivas para prolongar la vida (diálisis o trasplante renal) y, pese a que la diálisis mejora muchas complicaciones de la ERC, la enfermedad no revierte de manera completa. Estos pacientes presentan un aumento del estrés oxidativo, inflamación crónica y aumento de la liberación de vesículas extracelulares (VE), que provocan daño endotelial y el desarrollo de distintas enfermedades cardiovasculares (ECV). De hecho, los pacientes con ERC desarrollan de forma prematura enfermedades asociadas a una edad avanzada, como es el caso de las ECV. Las VE desempeñan un papel muy importante en el desarrollo de ECV en pacientes con ERC, ya que su número aumenta en el plasma y su contenido se modifica. Las VE de pacientes con ERC generan disfunción endotelial, senescencia y calcificación vascular. Además, los miRNA libres o transportados en las VE junto a otros componentes vehiculados en estas VE promueven disfunción endotelial, eventos trombóticos y calcificación vascular en los pacientes con ERC, entre otros efectos. En esta revisión se describen los factores clásicos y el papel de nuevos mecanismos que intervienen en el desarrollo de la ECV asociada a la ERC, con especial hincapié en el papel de las VE en el desarrollo de enfermedades cardiovasculares en un contexto de ERC. Además, se expone el papel de las VE como herramienta diagnóstica y como diana terapéutica, actuando sobre su liberación o contenido para intentar evitar el desarrollo de ECV en enfermos renales crónicos. (AU)

Chronic kidney disease (CKD) is a pathology with a high worldwide incidence and an upward trend affecting the elderly. When CKD is very advanced, the use of renal replacement therapies is required to prolong its life (dialysis or kidney transplantation). Although dialysis improves many complications of CKD, the disease does not reverse completely. These patients present an increase in oxidative stress, chronic inflammation and the release of extracellular vesicles (EVs), which cause endothelial damage and the development of different cardiovascular diseases (CVD). CKD patients develop premature diseases associated with advanced age, such as CVD. EVs play an essential role in developing CVD in patients with CKD since their number increases in plasma and their content is modified. The EVs of patients with CKD cause endothelial dysfunction, senescence and vascular calcification. In addition, miRNAs free or transported in EVs together with other components carried in these EVs promote endothelial dysfunction, thrombotic and vascular calcification in CKD, among other effects. This review describes the classic factors and focuses on the role of new mechanisms involved in the development of CVD associated with CKD, emphasizing the role of EVs in the development of cardiovascular pathologies in the context of CKD. Moreover, the review summarized the EVs’ role as diagnostic and therapeutic tools, acting on EV release or content to avoid the development of CVD in CKD patients. (AU)

Síndrome de encefalopatía posterior reversible en pacientes críticos COVID-19: reporte de 2 casos / Posterior reversible encephalopathy syndrome in critical COVID-19 patients: Report of 2 cases

El síndrome de encefalopatía posterior reversible es un trastorno neurológico agudo caracterizado por una sintomatología variable e imágenes radiológicas características de edema vasogénico parietooccipital. Está asociado a condiciones clínicas como hipertensión arterial, infección/sepsis o fármacos citotóxicos/inmunosupresores, entre otros. Se caracteriza fisiopatológicamente por daño endotelial con rotura de la barrera hematoencefálica, hipoperfusión cerebral y edema vasogénico. Presentamos 2 casos de pacientes críticos COVID-19 que ingresaron por neumonía con necesidad de ventilación mecánica y que tras retirar la sedación desarrollaron clínica neurológica aguda y reversible consistente en epilepsia y encefalopatía, asociada a lesiones subcorticales hiperintensas en la resonancia magnética cerebral compatibles con síndrome de encefalopatía posterior reversible. El coronavirus SARS-CoV-2 activaría una respuesta inflamatoria que produciría daño en el endotelio cerebral. Este último podría ser desencadenado por la liberación de citocinas, así como por una lesión viral directa, dado que el endotelio expresa receptores ACE2. Esto podría explicar la posible asociación entre el síndrome de encefalopatía posterior reversible y la COVID-19.(AU)

Posterior reversible encephalopathy syndrome is an acute neurological disorder characterized by variable symptoms and radiological images characteristic of vasogenic parietal-occipital edema. It is associated with clinical conditions such as high blood pressure, infection/sepsis, or cytotoxic/immunosuppressive drugs, among others. It is characterized pathophysiologically by endothelial damage with breakdown of blood-brain barrier, cerebral hypoperfusion, and vasogenic edema. The cases are presented on 2 critical COVID-19 patients who were admitted to pneumonia requiring mechanical ventilation and who, after removing sedation, developed acute and reversible neurological symptoms consisting of epilepsy and encephalopathy, associated with hyperintense subcortical lesions on brain magnetic resonance imaging compatible with posterior reversible encephalopathy syndrome. SARS-CoV-2 coronavirus would activate an inflammatory response that would damage brain endothelium. It could be triggered by cytokine release, as well as by direct viral injury, given that endothelium expresses ACE2 receptors. It could explain the possible association between posterior reversible encephalopathy syndrome and COVID-19.(AU)

Gen 15 estimulado por interferón, nexo común del daño vascular en la hipertensión, la obesidad y los aneurismas aórticos / Interferon-stimulated gene 15, a common link of vascular damage in hypertension, obesity and aortic aneurysms

La hipertensión y la obesidad son importantes problemas de salud en todo el mundo con notables consecuencias sobre la morbilidad y la mortalidad. De hecho, tanto la hipertensión como la obesidad son importantes factores de riesgo para el desarrollo de enfermedades cardiovasculares. La disfunción endotelial, el remodelado vascular y las alteraciones en la mecánica vascular son aspectos comunes del daño vascular en la hipertensión, la obesidad y los aneurismas. Durante las últimas décadas, se ha demostrado la importancia de la inflamación de bajo grado en el daño vascular asociado a las enfermedades cardiovasculares. Dicha inflamación se caracteriza por la acumulación de células inflamatorias en la vasculatura, así como por el aumento de citoquinas proinflamatorias locales y circulantes. Por tanto, la identificación de nuevos mediadores inflamatorios implicados en dicho daño se ha convertido en un área de investigación muy importante.El interferón-γ (IFNγ) o el factor de necrosis tumoral-α (TNFα) son importantes citoquinas implicadas en el daño vascular asociado a la hipertensión. Además, se acepta que el TNFα es un mediador clave implicado en la resistencia a la insulina y el daño vascular observado en la obesidad. Ambas citoquinas inducen la expresión del gen 15 estimulado por interferón (ISG15), una proteína similar a la ubiquitina que induce una modificación postraducional reversible (ISGilación) y que también puede secretarse como forma libre. Las funciones de ISG15 están principalmente relacionadas con la respuesta inmune frente a infecciones, sin embargo, podría ser también una interesante nueva diana del daño cardiovascular. (AU)

Hypertension and obesity are major health problems worldwide with significant consequences on morbidity and mortality. In fact, both hypertension and obesity are important risk factors for the development of cardiovascular diseases. Endothelial dysfunction, vascular remodeling, and alterations in vascular mechanics are common aspects of vascular damage in hypertension, obesity, and aneurysms. During the last decades, the importance of low-grade inflammation in vascular damage associated with cardiovascular diseases has been demonstrated. This inflammation is characterized by the accumulation of inflammatory cells in the vasculature, as well as by the increase of local and circulating pro-inflammatory cytokines. Therefore, the identification of new inflammatory mediators involved in this damage has become a very important area of research.Interferón-γ (IFNγ) or tumor necrosis tumoral-α (TNFα) are important cytokines involved in the vascular damage associated with hypertension. Furthermore, it is accepted that TNFα is a key mediator involved in insulin resistance and vascular damage observed in obesity. Both cytokines induce the expression of interferon-stimulated gene 15 (ISG15), a protein similar to ubiquitin that induces a reversible post-translational modification (ISGylation) and that can also be secreted as a free form. The functions of ISG15 are mainly related to the immune response against infections, however, it could also be an interesting new target for cardiovascular damage. (AU)

Receptor mineralocorticoide extrarrenal. Una posible nueva diana para combatir el daño vascular / Extrarenal mineralocorticoid receptor. A potential new target against vascular damage

El receptor mineralocorticoide (MR) y su principal ligando la aldosterona juegan un papel fundamental en la regulación de la presión arterial a través de sus efectos facilitadores de la reabsorción de sodio y agua. Los antagonistas del receptor de la aldosterona son fármacos de probada eficacia, que en la actualidad se utilizan en pacientes seleccionados con hipertensión arterial resistente. Además, estos fármacos aumentan la supervivencia en diversas circunstancias como en la insuficiencia cardiaca, proporcionan protección renal en pacientes con enfermedad renal crónica y tienen efectos beneficiosos adicionales en otras patologías. Más allá de sus efectos cardiorrenales, en la actualidad sabemos que el MR se expresa en otros tejidos como células musculares lisas y endoteliales vasculares mediando efectos deletéreos tales como remodelado vascular, rigidez vascular y disfunción endotelial, los cuales son factores pronósticos de futuros eventos cardiovasculares. Además, nuevas evidencias experimentales demuestran que el MR se expresa también en células adyacentes a la vasculatura como células inmunes y adipocitos a través de los cuales podría influir en la función y estructura vascular. Entre los mecanismos responsables de dichos efectos se incluyen mecanismos genómicos y no genómicos, que facilitan la producción de especies reactivas de oxígeno de distintas fuentes, entre las que destaca la enzima NADPH oxidasa, así como de otros mediadores inflamatorios. En este artículo se revisan las evidencias experimentales y clínicas que sugieren que la activación del MR por aldosterona es un importante mediador de daño vascular a través de la producción de especies reactivas de oxígeno. (AU)

Mineralocorticoid receptor (MR) and its main ligand aldosterone, play a key role in the regulation of blood pressure through their effects increasing sodium and water reabsorption. MR antagonists are effective drugs that are currently used in selected patients with resistant hypertension. In addition, these drugs increase patients survival in specific circumstances such as heart failure, they offer renal protection in chronic kidney disease patients and they have beneficial effects in other pathologies. Besides MR cardiorenal effects, it is now accepted that MR is expressed in other tissues and cells such as vascular smooth muscle cells and endothelial cells where excessive MR activation induces deleterious effects such as vascular remodeling and stiffness and endothelial dysfunction, which are prognostic factors for future cardiovascular events. Moreover, novel evidence demonstrate that MR is also expressed in non-vascular cells adjacent to vessels such as immune cells and adipocytes that might influence vascular function and structure. Among the mechanisms responsible for these effects of MR are genomic and non genomic mechanisms that facilitate reactive oxygen species production mainly from the NADPH oxidase enzyme, as well as production of other inflammatory mediators. Here we review the experimental and clinical evidence that suggest that MR activation by aldosterone is an important mediator of vascular damage through the production of reactive oxygen species. (AU)

Especies reactivas de oxígeno: papel en la función vascular y en la disfunción endotelial asociada a la enfermedad metabólica / Reactive oxygen species: role in vascular function and in metabolic disease-associated endothelial dysfunction

El estrés oxidativo, alteración de la homeostasis REDOX en células y tejidos con un incremento de los niveles de especies reactivas de oxígeno (ROS), es un mecanismo patogénico común a múltiples patologías como las enfermedades cardiovasculares, los desórdenes neurodegenerativos, la inflamación y el cáncer, razón por la cual ha existido una investigación intensa en las últimas décadas sobre los posibles efectos protectores de las terapias antioxidantes en estas enfermedades. No obstante, la señalización REDOX juega, por otra parte, un papel crítico en la homeostasis y supervivencia celular, y las ROS son producidas en pequeñas cantidades durante la función celular normal. Las investigaciones llevadas a cabo en nuestro grupo han estado enfocadas al estudio del estrés oxidativo como factor patogénico clave en la disfunción endotelial en la obesidad y en otros estados de resistencia a la insulina. La disfunción endotelial subyace a las complicaciones vasculares de la diabetes y la obesidad, y representa un fenotipo endotelial mal adaptado con alteración de la función vasodilatadora, angiogénica y de barrera del endotelio, lo que conduce a un estado vasoconstrictor, proinflamatorio y protrombótico de la pared vascular. Debido a su capacidad de inhabilitar el óxido nítrico (NO), las ROS son en parte responsables de la disfunción endotelial. Por otra parte, nuestros estudios durante estos años han permitido caracterizar el papel clave de ROS como el H2O2 en la función endotelial de arterias de resistencia renales y coronarias, y su participación en la función vascular mediante la modulación de canales iónicos y enzimas implicados en vías de señalización de la pared arterial. (AU)

Oxidative stress, impairment of REDOX homeostasis in cells and tissues leading to increased levels of reactive oxygen species (ROS), is a pathogenic mechanism underlying numerous pathologies including cardiovascular diseases, cancer, neurodegenerative disorders and inflammation. Therefore, there has been an intensive investigation during the last decades on the potential protective effects of antioxidant therapies on these disorders. Nevertheless, REDOX signaling plays a critical role in homeostasis and cell survival, and ROS are produced in small amount during normal cell function. Investigations carried out in our group during the last decade have been focused on the study of oxidative stress as a key pathogenic factor in endothelial and vascular dysfunction of resistance arteries in obesity and other insulin resistant states. Endothelial dysfunction underlies vascular complications of diabetes and obesity, and represents a maladapted endothelial phenotype consisting of impaired vasodilatation, angiogenesis and barrier function leading to a vasoconstrictor, pro-inflammatory and pro-thrombotic state of the vascular wall. ROS are involved in endothelial dysfunction since they reduce bioavailability of nitric oxide (NO). On the other hand, our investigations have provided evidence for a key role of ROS such as hydrogen peroxide (H2O2) in the endothelial function of healthy coronary and renal resistance arteries, and its involvement in vascular function through modulation of ion channels and enzymes involved in signalling pathways of the arterial wall. (AU)

La retina, una ventana de la enfermedad cerebrovascular en la diabetes / The retina, a window of cerebrovascular disease in diabetes

La enfermedad cerebrovascular es una de las complicaciones de la diabetes mellitus de larga duración. Mientras que la estructura y función de los grandes vasos cerebrales puede ser más fácilmente estudiada, la microcirculación cerebral es difícil de evaluar. Sin embargo, con una simple exploración de fondo de ojo con un oftalmoscopio se pueden visualizar las anomalías microvasculares que caracterizan a la retinopatía diabética, que es la complicación microvascular más frecuente de la diabetes. La similitud anatómica y funcional entre ambas circulaciones justifica la hipótesis de que las alteraciones en la reactividad vascular retiniana podrían considerarse un marcador temprano de disfunción microvascular cerebral en la diabetes.El factor iniciador de las angiopatías diabéticas es la disfunción endotelial. La disfunción endotelial se traduce en una reducida biodisponibilidad de óxido nítrico (NO), como consecuencia de una disminución en su síntesis o por el incremento en la producción de radicales libres de oxígeno, secuestradores de NO. La diabetes también estimula la producción de factores contráctiles derivados de endotelio. Los aniones superóxido y los radicales hidroxilos producen un efecto contráctil, así como la endotelina y ciertos derivados de la ciclooxigenasa (COX). La activación de la COX está relacionada con un elevado nivel de estrés oxidativo. El estrés oxidativo colabora con la respuesta inflamatoria determinando la disfunción vascular diabética. (AU)

Cerebrovascular disease is one of the complications of long-term diabetes mellitus. While the structure and function of the great cerebral vessels may be more easily studied, the cerebral microcirculation is difficult to assess. However, a simple eye fundus examination with an ophthalmoscope enables to visualize the microvascular abnormalities that characterize diabetic retinopathy, which isth e most common microvascular complication of diabetes. The anatomical and functional similarity between retinal and cerebral microcirculation supports the hypothesis that alterations in retinal vascular reactivity could be considered as an early marker of cerebral microvascular dysfunction in diabetes.The initiating factor of diabetic angiopathies is endothelial dysfunction. Endothelial dysfunction results in a reduced bioavailability of nitric oxide (NO), as a consequence of decreased NO synthesis and/or increased production of free oxygen radicals that are NO scavengers. Diabetes also stimulates the production of endothelial-derived contractile factors such as superoxide anions and hydroxyl radicals, endothelin and certain cyclooxygenase (COX) derivatives. COX activation is related to a high level of oxidative stress. Oxidative stress participates in the inflammatory response involved in the diabetic vascular dysfunction. These pathogenic mechanisms have been shown in both cerebral and retinal arteries, mainly through in vitro vascular reactivity studies, suggesting that diabetes induces a profound change in microvascular regulatory mechanisms. The association between the degree of retinal perfusion, brain injuries and altered cognitive function indicates a certain parallelism in the degree of impairment of both retinal and brain circulations. In addition, prospective studies conclude that diabetic retinopathy predicts ischemic cerebrovascular disease independently of other risk factors, supporting the importance of cerebral microvascular disease in diabetics. (AU)

La retina, una ventana de la enfermedad cerebrovascular en la diabetes / The retina, a window of cerebrovascular disease in diabetes

El factor iniciador de las angiopatías diabéticas es la disfunción endotelial. La disfunción endotelial se traduce en una reducida biodisponibilidad de óxido nítrico (NO), como consecuencia de una disminución en su síntesis o por el incremento en la producción de radicales libres de oxígeno, secuestradores de NO. La diabetes también estimula la producción de factores contráctiles derivados de endotelio. Los aniones superóxido y los radicales hidroxilos producen un efecto contráctil, así como la endotelina y ciertos derivados de la ciclooxigenasa (COX). La activación de la COX está relacionada con un elevado nivel de estrés oxidativo. El estrés oxidativo colabora con la respuesta inflamatoria determinando la disfunción vascular diabética. Estas afirmaciones han sido comprobadas tanto en arterias cerebrales como retinianas, fundamentalmente a través de estudios de reactividad vascular in vitro, sugiriendo que la diabetes induce un profundo cambio en los mecanismos de regulación microvascular. La asociación entre el grado de perfusión retiniana, las lesiones cerebrales y la alteración de la función cognitiva, indican un cierto paralelismo en el grado de afectación de ambas circulaciones. Además, estudios prospectivos concluyen que la retinopatía diabética predice la enfermedad cerebrovascular isquémica independientemente de otros factores de riesgo, avalando la importancia de la enfermedad cerebral microvascular en los diabéticos. Es necesario seguir investigando las alteraciones vasculares para comprender la fisiopatología subyacente de las retinopatías y de las enfermedades cerebrovasculares en la diabetes. En un futuro cercano el uso de métodos completamente automatizados de detección de signos de retinopatía no sólo facilitará la evaluación eficiente de los cambios vasculares en la retina, sino que también colaborará en la reducción de la morbilidad y mortalidad vascular cerebral.(AU)

The initiating factor of diabetic angiopathies is endothelial dysfunction. Endothelial dysfunction results in a reduced bioavailability of nitric oxide (NO), as a consequence of decreased NO synthesis and/or increased production of free oxygen radicals that are NO scavengers. Diabetes also stimulates the production of endothelial-derived contractile factors such as superoxide anions and hydroxyl radicals, endothelin and certain cyclooxygenase (COX) derivatives. COX activation is related to a high level of oxidative stress. Oxidative stress participates in the inflammatory response involved in the diabetic vascular dysfunction. These pathogenic mechanisms have been shown in both cerebral and retinal arteries, mainly through in vitro vascular reactivity studies, suggesting that diabetes induces a profound change in microvascular regulatory mechanisms. The association between the degree of retinal perfusion, brain injuries and altered cognitive function indicates a certain parallelism in the degree of impairment of both retinal and brain circulations. In addition, prospective studies conclude that diabetic retinopathy predicts ischemic cerebrovascular disease independently of other risk factors, supporting the importance of cerebral microvascular disease in diabetics. Further research on the vascular abnormalities is needed to understand the pathogenic mechanisms underlying retinopathies and cerebrovascular disease in diabetes. In the near future, the use of fully automated methods to detect signs of retinopathy will not only facilitate the efficient evaluation of vascular changes in the retina but will also help to reduce cerebral vascular morbidity and mortality.(AU)

Gen 15 estimulado por interferón, nexo común del daño vascular en la hipertensión, la obesidad y los aneurismas aórticos / Interferon-stimulated gene 15, a common link of vascular damage in hypertension, obesity and aortic aneurysms

La hipertensión y la obesidad son importantes problemas de salud en todo el mundo con notables consecuencias sobre la morbilidad y la mortalidad. De hecho, tanto la hipertensión como la obesidad son importantes factores de riesgo para el desarrollo de enfermedades cardiovasculares. La disfunción endotelial, el remodelado vascular y las alteraciones en la mecánica vascular son aspectos comunes del daño vascular en la hipertensión, la obesidad y los aneurismas. Durante las últimas décadas, se ha demostrado la importancia de la inflamación de bajo grado en el daño vascular asociado a las enfermedades cardiovasculares. Dicha inflamación se caracteriza por la acumulación de células inflamatorias en la vasculatura, así como por el aumento de citoquinas proinflamatorias locales y circulantes. Por tanto, la identificación de nuevos mediadores inflamatorios implicados en dicho daño se ha convertido en un área de investigación muy importante. El interferón-γ (IFNγ) o el factor de necrosis tumoral-α (TNFα) son importantes citoquinas implicadas en el daño vascular asociado a la hipertensión. Además, se acepta que el TNFα es un mediador clave implicado en la resistencia a la insulina y el daño vascular observado en la obesidad. Ambas citoquinas inducen la expresión del gen 15 estimulado por interferón (ISG15), una proteína similar a la ubiquitina que induce una modificación postraducional reversible (ISGilación) y que también puede secretarse como forma libre. Las funciones de ISG15 están principalmente relacionadas con la respuesta inmune frente a infecciones, sin embargo, podría ser también una interesante nueva diana del daño cardiovascular.(AU)

Hypertension and obesity are major health problems worldwide with significant consequences on morbidity and mortality. In fact, both hypertension and obesity are important risk factors for the development of cardiovascular diseases. Endothelial dysfunction, vascular remodeling, and alterations in vascular mechanics are common aspects of vascular damage in hypertension, obesity, and aneurysms. During the last decades, the importance of low-grade inflammation in vascular damage associated with cardiovascular diseases has been demonstrated. This inflammation is characterized by the accumulation of inflammatory cells in the vasculature, as well as by the increase of local and circulating pro-inflammatory cytokines. Therefore, the identification of new inflammatory mediators involved in this damage has become a very important area of research. Interferón-γ (IFNγ) or tumor necrosis tumoral-α (TNFα) are important cytokines involved in the vascular damage associated with hypertension. Furthermore, it is accepted that TNFα is a key mediator involved in insulin resistance and vascular damage observed in obesity. Both cytokines induce the expression of interferon-stimulated gene 15 (ISG15), a protein similar to ubiquitin that induces a reversible post-translational modification (ISGylation) and that can also be secreted as a free form. The functions of ISG15 are mainly related to the immune response against infections, however, it could also be an interesting new target for cardiovascular damage.(AU)

Disfunción endotelial en niños con enfermedad renal crónica / Endothelial dysfunction in children with chronic kidney disease

Antecedentes y objetivo: La enfermedad cardiovascular es la principal causa de muerte en niños con enfermedad renal crónica. La inflamación y la disfunción endotelial se presenta en la mayoría de estos pacientes y son factores asociados a enfermedad cardiovascular. La dilatación mediada por flujo (DMF)<7% es un marcador subrogado validado en la evaluación de la disfunción endotelial. Nuestro objetivo fue identificar los factores de riesgo asociados a disfunción endotelial en niños con enfermedad renal crónica. Materiales y métodos: Se estudió a niños de 2-16 años de edad. Se recopiló su información clínica y variables bioquímicas, incluidos hormona paratiroidea intacta (iPTH), interleucinas 6 y 1β, proteína C reactiva de alta sensibilidad (hsCRP), glutatión reducido, óxido nítrico, malondialdehído y homocisteína. Se consideró DMF alterada<7%. Resultados: Se incluyó a 129 pacientes con edad de 13,1±2,6 años. Tuvieron DMF<7% 69 (52,7%). Los pacientes con DMF<7% tuvieron niveles más altos de triglicéridos y de hsCRP que aquellos con DMF≥7% (145,5 vs. 120,0mg/dl, p=0,042, y 1,24 vs. 0,55U/l, p=0,007, respectivamente), así como una mayor frecuencia de iPTH baja (19,1 vs. 4,9%, p=0,036). Los niveles de hsCRP se correlacionaron significativamente con la DMF (Rho=−0,28, p=0,003). Los pacientes con iPTH baja (OR 4,41, IC 95% 1,13-17,27, p=0,033) y con hsCRP incrementada (OR 2,89, IC 95% 1,16-7,17, p=0,022) tuvieron un riesgo ajustado mayor de DMF<7%. Conclusiones: La hipertrigliceridemia, la inflamación y una iPTH baja se asociaron significativamente a una DMF alterada. Son factores de riesgo de enfermedad cardiovascular frecuentes y tratables. (AU)

Background and objective: Cardiovascular disease is the main cause of death in children with chronic kidney disease. Inflammation and endothelial dysfunction are found in the majority of these patients and are factors associated to cardiovascular disease. Flow mediated dilatation (FMD) is a surrogate marker validated for evaluating endothelial dysfunction. Our objective was to identify risk factors associated to endothelial dysfunction in children with chronic kidney disease. Materials and methods: Children 2-16 years of age were studied. Clinical information and biochemical variables were gathered, including intact parathyroid hormone (iPTH), interleukins 6 and 1β, high sensitivity C reactive protein (hsCRP), reduced glutathione, nitric oxide, malondialdehyde and homocysteine. FMD was measured, and considered altered if<7%. Results: Included were 129 patients aged 13.1±2.6 years. FMD<7% was found in 69 (52.7%). Patients with altered FMD had higher levels of triglycerides and hsCRP than those with normal FMD (145.5 vs. 120.0mg/dL, P=.042, and 1.24 vs. 0.55U/L, P=.007, respectively), as well as higher frequency of low iPTH (19.1 vs. 4.9%, P=.036). Levels of hsCRP correlated significantly with FMD (Rho=−0.28, P=.003). Patients with low iPTH (OR 4.41, 95% CI 1.13-17.27, P=.033) and increased hsCRP (OR 2.89, 95% CI 1.16-7.17, P=.022) had higher adjusted risk of having FMD<7%. Conclusions: Hypertriglyceridemia, inflammation and low iPTH associated significantly with altered FMD. They are frequent, treatable risk factors for cardiovascular disease. (AU)

The role of triglycerides in the origin and progression of atherosclerosis.

Hypertriglyceridaemia has been associated with cardiovascular disease risk in humans for several decades. However, only recently, data from basic research, as well as from genetic and observational studies, have suggested triglyceride-rich lipoproteins (TRLs) as causal factors for atherosclerotic cardiovascular disease. Novel findings highlighting the relevance of TRL-derived lipolytic products (remnant lipoprotein particles "RLPs"), rather than plasma triglycerides or TRL themselves, as the true mediators in atherosclerosis, have contributed to explain a causal relationship through a number of direct and indirect mechanisms. Thus, experimental studies in animal models and in vitro cell culture methods reveal that RLPs, having sizes below 70-80nm, enter the arterial wall and accumulate within the sub-endothelial space. They then become involved in the cholesterol deposition of cholesterol in the intima in addition to several pro-inflammatory and pro-apoptotic pathways. In this review, a summary is presented of current understanding of the pathophysiological mechanisms by which TRLs and their lipolytic derived RLP induce the formation and progression of atherosclerotic lesions, and actively contribute to cardiovascular disease.

Intensidad del síndrome vasomotor y su relación con la función endotelial en mujeres de edad mediana / Intensity of the vasomotor syndrome and its relation with endothelial function in middle age women

Introducción: El síndrome vasomotor constituye la manifestación clínica más frecuente de la transición menopaúsica y a menudo se asocia con cambios en la función endotelial. Objetivo: Determinar la relación entre la intensidad del síndrome vasomotor y la función endotelial en mujeres de edad mediana aparentemente sanas. Método: Estudio descriptivo transversal, en 133 mujeres de 40-59 años sin factores de riesgo cardiovascular. Se excluyeron aquellas mujeres con menopausia quirúrgica, uso previo de terapia hormonal de reemplazo seis meses antes. Se evaluó la función endotelial mediante la prueba de dilatación mediada por el flujo de la arteria braquial, y la intensidad del síndrome vasomotor mediante la escala de Pérez Piñeiro. Las mujeres fueron distribuidas en dos subgrupos: uno con disfunción endotelial y el otro con función endotelial normal. Para identificar la asociación entre variables se utilizó la prueba Kruskal-Wallis y la prueba Chi Cuadrado para evaluar la significación estadística, considerándose significativos los valores de p < 0,05. Resultados: El 63 por ciento de las mujeres presentaron síndrome vasomotor, 29 de intensidad leve, 31 moderado y muy molesto 33 mujeres. Del total de mujeres, 51 tuvieron disfunción endotelial, para un 38,3 por ciento, mostrando un promedio de dilatación dependiente del endotelio de 1,81±1,57 cm. No se encontró asociación significativa entre la intensidad del síndrome vasomotor y la función endotelial p = 0,139. Conclusiones: La intensidad del síndrome vasomotor no se relacionó con la disfunción endotelial en mujeres de edad mediana. Se necesita ampliar la muestra y realizar estudios prospectivos para identificar el daño vascular en ese grupo de mujeres(AU)

Introduction: The vasomotor syndrome is the most frequent clinical manifestation of the menopausal transition and it is often associated with changes in the endothelial function. Objective: Determine the relation among the intensity of the vasomotor syndrome and the endothelial function in apparently healthy middle age women. Methods: Descriptive cross-sectional study in 113 women of 40-59 years without cardiovascular risk factors. There were excluded women with surgical menopause, and use of replacement hormonal therapy six months before. It was assessed the endothelial function through the dilation test and the flow of the brachial artery, and the intensity of the vasomotor syndrome through the scale of Pérez. The women were organized in two groups: one group of women with endothelial dysfunction and the other of women with normal endothelial function. It was used the Kruskal-Wallis test to identify the association among variables and the chi-Square test to assess the statistical significance considering important the values of p < 0.05. Results: 63 percent of the women presented vasomotor syndrome, 29 of them of slight intensity, 31 moderate and 33 women had a very uncomfortable one. Of the total, 51 women presented endothelial dysfunction representing a 38.3 percent and showing an average of dilation dependant of endothelium of 1.81±1.57 cm. There was not found significant association among the intensity of the vasomotor syndrome and the endothelial function p = 0.139. Conclusions: The intensity of the vasomotor syndrome was not related with the endothelial dysfunction in middle age women. It is needed to expand the sample and to implement prospective studies in order to identify the vascular damage in that group of women(AU)

Manifestaciones pulmonares y sistémicas de la hipertensión arterial pulmonar: Un enfoque panvascular

La hipertensión arterial pulmonar (HAP) es una grave enfermedad cuyo resultado final de la interacción entre el tono vascular y la alteración progresiva de la remodelación de las arterias pulmonares provoca insuficiencia cardíaca derecha y muerte. El remodelado vascular pulmonar es la alteración estructural clave en la hipertensión pulmonar. Este proceso implica cambios en la íntima, media, adventicia y espacio perivascular, a menudo con la interacción de células inflamatorias. Los mecanismos fisiopatológicos de la HAP abarcan una serie de modificaciones vasculares que producen un aumento de la resistencia vascular pulmonar. Las modificaciones vasculares que se producen en la HAP incluyen: la vasoconstricción, la proliferación del músculo liso, la inflamación, la apoptosis endotelial, la proliferación endotelial resistente a la apoptosis, la fibrosis, la trombosis in-situ, y finalmente, las lesiones plexiformes. Hasta hace poco, la HAP se consideraba una enfermedad restringida a la circulación pulmonar. Sin embargo, existe una creciente evidencia de que los pacientes con HAP también exhiben disfunción vascular sistémica, como lo demuestra la alteración de la dilatación mediada por el flujo de la arteria braquial, el flujo sanguíneo cerebral anormal, la miopatía esquelética y la enfermedad renal intrínseca. Los datos recientes apoyan un vínculo con los eventos genéticos y moleculares detrás de la patogénesis de la HAP. Esta revisión sirve de introducción a los principales hallazgos sistémicos en la HAP y la evidencia que apoya un vínculo común con la fisiopatología de la HAP. Sobre la base de la evidencia disponible, proponemos un paradigma en el que las anomalías metabólicas, la lesión genética y la disfunción vascular sistémica contribuyen a las manifestaciones sistémicas de la HAP. Este concepto no sólo abre interesantes posibilidades de investigación, sino que también anima a considerar las manifestaciones extrapulmonares en el tratamiento de los pacientes con HAP, pues la disfunción vascular sistémica contribuiría a las manifestaciones sistémicas de la HAP.

Pulmonary arterial hypertension (PAH) is a serious disease whose end result of the interaction between vascular tone and the progressive alteration of the remodeling of the pulmonary arteries causes right heart failure and death. Pulmonary vascular remodeling is the key structural alteration in pulmonary hypertension. This process involves changes in the intima, media, adventitia, and perivascular space, often with the interaction of inflammatory cells. The pathophysiological mechanisms of PAH include a series of vascular modifications that produce an increase in pulmonary vascular resistance. Vascular modifications that occur in PAH include: vasoconstriction, proliferation of smooth muscle, inflammation, Endothelial apoptosis, apoptosis-resistant endothelial proliferation, fibrosis, in-situ thrombosis, and finally, plexiform lesions. Until recently, PAH was considered a disease restricted to the pulmonary circulation. However, there is growing evidence that patients with PAH also exhibit systemic vascular dysfunction, as evidenced by impaired brachial artery flow-mediated dilation, abnormal cerebral blood flow, skeletal myopathy, and intrinsic kidney disease. Recent data support a link to the genetic and molecular events behind the pathogenesis of PAH. This review serves as an introduction to the main systemic findings in PAH and the evidence supporting a common link with the pathophysiology of PAH. Based on the available evidence, we propose a paradigm in which metabolic abnormalities, genetic injury, and systemic vascular dysfunction contribute to the systemic manifestations of PAH. This concept not only opens up interesting research possibilities, but also encourages consideration of extrapulmonary manifestations in the treatment of patients with PAH, since systemic vascular dysfunction would contribute to the systemic manifestations of PAH.

A hipertensão arterial pulmonar (HAP) é uma doença grave cujo resultado final da interação entre o tônus vascular e a alteração progressiva da remodelação das artérias pulmonares causa insuficiência cardíaca direita e morte. A remodelação vascular pulmonar é a principal alteração estrutural na hipertensão pulmonar. Esse processo envolve mudanças na íntima, média, adventícia e espaço perivascular, muitas vezes com a interação de células inflamatórias. Os mecanismos fisiopatológicos da HAP incluem uma série de modificações vasculares que produzem um aumento na resistência vascular pulmonar. As modificações vasculares que ocorrem na HAP incluem: vasoconstrição, proliferação do músculo liso, inflamação, apoptose endotelial, proliferação endotelial resistente à apoptose, fibrose, trombose in situ e, finalmente, lesões plexiformes. Até recentemente, a HAP era considerada uma doença restrita à circulação pulmonar. No entanto, há evidências crescentes de que os pacientes com HAP também apresentam disfunção vascular sistêmica, conforme evidenciado pela dilatação prejudicada mediada pelo fluxo da artéria braquial, fluxo sanguíneo cerebral anormal, miopatia esquelética e doença renal intrínseca. Dados recentes suportam uma ligação com os eventos genéticos e moleculares por trás da patogênese da HAP. Esta revisão serve como uma introdução aos principais achados sistêmicos em HAP e as evidências que apoiam uma ligação comum com a fisiopatologia da HAP. Com base nas evidências disponíveis, propomos um paradigma em que anormalidades metabólicas, lesão genética e disfunção vascular sistêmica contribuem para as manifestações sistêmicas da HAP. Esse conceito não apenas abre possibilidades interessantes de pesquisa, mas também incentiva a consideração das manifestações extrapulmonares no tratamento de pacientes com HAP, uma vez que a disfunção vascular sistêmica contribuiria para as manifestações sistêmicas da HAP.

Coronary endothelial and microvascular function distal to polymer-free and endothelial cell-capturing drug-eluting stents. The randomized FUNCOMBO trial.

INTRODUCTION AND OBJECTIVES: The vasomotor function of new-generation drug-eluting stents designed to enhance stent healing and reendothelialization is unknown. This study aimed to compare the endothelial function of the infarct-related artery (IRA) treated with bioactive circulating endothelial progenitor cell-capturing sirolimus-eluting stents (COMBO) vs polymer-free biolimus-eluting stents (BioFreedom) in ST-segment elevation myocardial infarction patients at 6 months. Secondary objectives were to compare the microcirculatory function of the IRA and stent healing at 6 months. METHODS: Sixty patients were randomized to bioactive sirolimus-eluting stent vs polymer-free biolimus-eluting stents implantation. At 6 months, patients underwent coronary angiography with vasomotor, microcirculatory and optical coherence tomography examinations. Endothelial dysfunction of the distal coronary segment was defined as ≥ 4% vasoconstriction to intracoronary acetylcholine infusion. RESULTS: Endothelial dysfunction was similarly observed between groups (64.0% vs 62.5%, respectively; P=.913). Mean lumen diameter decreased by 16.0 ±20.2% vs 16.1 ±21.6% during acetylcholine infusion (P=.983). Microcirculatory function was similar in the 2 groups: coronary flow reserve was 3.23 ±1.77 vs 3.23±1.62 (P=.992) and the index of microcirculatory resistance was 24.8±16.8 vs 21.3±12.0 (P=.440). Optical coherence tomography findings were similar: uncovered struts (2.3% vs 3.2%; P=.466), malapposed struts (0.1% vs 0.3%; P=.519) and major evaginations (7.1% vs 5.6%; P=.708) were observed in few cases. CONCLUSIONS: Endothelial dysfunction of the IRA was frequent and was similarly observed with new-generation drug-eluting stents designed to enhance stent reendothelialization at 6 months. Endothelial dysfunction was observed despite almost preserved microcirculatory function and complete stent coverage. Larger and clinically powered studies are needed to assess the role of residual endothelial dysfunction in ST-segment elevation myocardial infarction patients. Registered in ClinicalTrials.gov: NCT04202172.

Endothelial dysfunction in children with chronic kidney disease.

BACKGROUND AND OBJECTIVE: Cardiovascular disease (CVD) is the main cause of death in children with chronic kidney disease (CKD). Inflammation and endothelial dysfunction (ED) are found in the majority of these patients and are factors associated to CVD. Flow mediated dilatation (FMD) is a surrogate marker validated for evaluating ED. Our objective was to identify risk factors associated to ED in children with CKD. MATERIALS AND METHODS: Children 2-16 years of age were studied. Clinical information and biochemical variables were gathered, including intact parathyroid hormone (iPTH), interleukins 6 and 1b, high sensitivity C reactive protein (hsCRP), reduced glutathione, nitric oxide, malondialdehyde and homocysteine. FMD was measured, and considered altered if <7%. RESULTS: Included were 129 patients aged 13.1 ±â€¯2.6 years. FMD < 7% was found in 69 (52.7%). Patients with altered FMD had higher levels of triglycerides and hsCRP than those with normal FMD (145.5 mg/dl vs. 120.0 mg/dl, P = .042, y 1.24 U/L vs. 0.55 U/L, P = .007, respectively), as well as higher frequency of low iPTH (19.1% vs. 4.9%, P = .036). Levels of hsCRP correlated significantly with FMD (Rho = -0.28, P = .003). Patients with low iPTH (OR = 4.41, 95%CI 1.13-17.27, P = .033) and increased hsCRP (OR = 2.89, 95%CI 1.16-7.17, P = .022) had higher adjusted risk of having FMD < 7%. CONCLUSIONS: Hypertriglyceridemia, inflammation and low iPTH associated significantly with altered FMD. They are frequent, treatable risk factors for CVD.

Parámetros de laboratorio de importancia en el manejo de pacientes con COVID-19 / Laboratory parameters of importance in the management of COVID-19 patients

Resumen El coronavirus 2 del síndrome respiratorio agudo grave (SARS-CoV-2) detona el padecimiento la enfermedad por coronavirus 2019 (COVID-19), poniendo en riesgo de muerte a la población vulnerable. El laboratorio clínico enfrenta un reto para el diagnóstico, seguimiento, pronóstico y evaluación de los tratamientos, que se ofrecen a los enfermos de COVID-19. Nuestro objetivo es mostrar al lector un resumen de los principales cambios en los parámetros que se estudian en los laboratorios clínicos. Material y métodos: Se hizo una búsqueda bibliográfica cruzando los términos COVID-19 y laboratorio clínico. Se analizaron las publicaciones relevantes por los miembros del Comité de Trombosis y Hemostasia-AMEH A.C. y se plasmaron las pruebas que a criterio de los participantes destacan por la relación entre la información que proporcionan respecto al seguimiento, pronóstico y evaluación al tratamiento. Resultados: Se recomienda solicitar una citometría hemática (recuento de células blancas, relación neutrófilo:linfocito), química sanguínea (transaminasas, bilirrubinas, albúmina, urea, creatinina, glucosa, lactato deshidrogenasa), pruebas de coagulación (tiempo de protrombina, tiempo de tromboplastina parcial activado, fibrinógeno y dímeros D) y pruebas especiales (proteína C reactiva, ferritina, procalcitonina, troponina).

Abstract The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) triggers the coronavirus disease 2019 (COVID-19), putting the vulnerable population at risk of death. The clinical laboratory faces a challenge for the diagnosis, monitoring, prognosis and evaluation of therapy with low molecular weight heparin. Our objective in this article is to offer a brief discuss of the main changes in the clinical parameters, studied on behalf of COVID-19 patients by a clinical laboratory. Material and methods: A bibliographic search was made crossing the terms COVID-19 and clinical laboratory. Relevant publications were analyzed by the members of the Committee for Thrombosis and Hemostasis-AMEH A.C. The relevant articles were discussed, and the clinical tests discussed in the article are those, that meet the criteria of providing information referring to the follow-up, prognosis and evaluation of treatment against the lower cost. Results: It is recommended to request a blood count (white cell count, neutrophyl/ lymphocytes ratio), clinical chemistry (transaminases, bilirubin, albumin, urea, creatinine, glucose, lactate dehydrogenase), coagulation tests (prothrombin time, activated partial thromboplastin time, fibrinogen, DD dimers) and special tests (C-reactive protein, ferritin, procalcitonin, troponins).