Fetal programming and epigenetic mechanisms in arterial hypertension.

PURPOSE OF REVIEW To provide an overview of available evidence of the potential role of epigenetics in the pathogenesis of hypertension and vascular dysfunction. RECENT FINDINGS Arterial hypertension is a highly heritable condition. Surprisingly, however, genetic variants only explain a tiny fraction of the phenotypic variation and the term 'missing heritability' has been coined to describe this phenomenon. Recent evidence suggests that phenotypic alteration that is unrelated to changes in DNA sequence (thereby escaping detection by classic genetic methodology) offers a potential explanation. Here, we present some basic information on epigenetics and review recent work consistent with the hypothesis of epigenetically induced arterial hypertension. SUMMARY New technologies that enable the rigorous assessment of epigenetic changes and their phenotypic consequences may provide the basis for explaining the missing heritability of arterial hypertension and offer new possibilities for treatment and/or prevention.

Prevention of vascular dysfunction and arterial hypertension in mice generated by assisted reproductive technologies by addition of melatonin to culture media.

Assisted reproductive technologies (ART) induce vascular dysfunction in humans and mice. In mice, ART-induced vascular dysfunction is related to epigenetic alteration of the endothelial nitric oxide synthase (eNOS) gene, resulting in decreased vascular eNOS expression and nitrite/nitrate synthesis. Melatonin is involved in epigenetic regulation, and its administration to sterile women improves the success rate of ART. We hypothesized that addition of melatonin to culture media may prevent ART-induced epigenetic and cardiovascular alterations in mice. We, therefore, assessed mesenteric-artery responses to acetylcholine and arterial blood pressure, together with DNA methylation of the eNOS gene promoter in vascular tissue and nitric oxide plasma concentration in 12-wk-old ART mice generated with and without addition of melatonin to culture media and in control mice. As expected, acetylcholine-induced mesenteric-artery dilation was impaired (P = 0.008 vs. control) and mean arterial blood pressure increased (109.5 ± 3.8 vs. 104.0 ± 4.7 mmHg, P = 0.002, ART vs. control) in ART compared with control mice. These alterations were associated with altered DNA methylation of the eNOS gene promoter (P < 0.001 vs. control) and decreased plasma nitric oxide concentration (10.1 ± 11.1 vs. 29.5 ± 8.0 μM) (P < 0.001 ART vs. control). Addition of melatonin (10(-6) M) to culture media prevented eNOS dysmethylation (P = 0.005, vs. ART + vehicle), normalized nitric oxide plasma concentration (23.1 ± 14.6 μM, P = 0.002 vs. ART + vehicle) and mesentery-artery responsiveness to acetylcholine (P < 0.008 vs. ART + vehicle), and prevented arterial hypertension (104.6 ± 3.4 mmHg, P < 0.003 vs. ART + vehicle). These findings provide proof of principle that modification of culture media prevents ART-induced vascular dysfunction. We speculate that this approach will also allow preventing ART-induced premature atherosclerosis in humans.

Arterial hypertension in children

PURPOSE OF REVIEW Although arterial hypertension is less common in children than in adults, there is growing concern about elevated blood pressure (BP) in children and adolescents not only because of the association of elevated values with the overweight epidemic, but also as cardiovascular functions are determined in childhood and track into adulthood. The purpose of the review is to discuss new aspects of childhood hypertension. RECENT FINDINGS Guidelines advocate determining BP in children as part of routine health maintenance. This recommendation was recently subject to review by the US Preventive Services Task Force. It was concluded that evidence is insufficient to assess the benefits of this screening. In our opinion, however, assessing BP is part of any thorough physical examination.Sophisticated approaches demonstrate the role of sympathetic nervous system overdrive in the field of sympathetic cardiovascular modulation of childhood arterial hypertension. SUMMARY Elevated BP in children is increasing in frequency and is now recognized as having relevant short-term and long-term consequences. Although efforts to address the childhood overweight epidemic may eventually reduce the number of young patients with hypertension, improved therapies for childhood hypertension also offer the potential for preventing or ameliorating early cardiovascular disease.

Hepatocellular Carcinoma Screening With Computed Tomography Using the Arterial Enhancement Fraction With Radiologic-Pathologic Correlation.

OBJECTIVE The aim of this study was to investigate the performance of the arterial enhancement fraction (AEF) in multiphasic computed tomography (CT) acquisitions to detect hepatocellular carcinoma (HCC) in liver transplant recipients in correlation with the pathologic analysis of the corresponding liver explants. MATERIALS AND METHODS Fifty-five transplant recipients were analyzed: 35 patients with 108 histologically proven HCC lesions and 20 patients with end-stage liver disease without HCC. Six radiologists looked at the triphasic CT acquisitions with the AEF maps in a first readout. For the second readout without the AEF maps, 3 radiologists analyzed triphasic CT acquisitions (group 1), whereas the other 3 readers had 4 contrast acquisitions available (group 2). A jackknife free-response reader receiver operating characteristic analysis was used to compare the readout performance of the readers. Receiver operating characteristic analysis was used to determine the optimal cutoff value of the AEF. RESULTS The figure of merit (θ = 0.6935) for the conventional triphasic readout was significantly inferior compared with the triphasic readout with additional use of the AEF (θ = 0.7478, P < 0.0001) in group 1. There was no significant difference between the fourphasic conventional readout (θ = 0.7569) and the triphasic readout (θ = 0.7615, P = 0.7541) with the AEF in group 2. Without the AEF, HCC lesions were detected with a sensitivity of 30.7% (95% confidence interval [CI], 25.5%-36.4%) and a specificity of 97.1% (96.0%-98.0%) by group 1 looking at 3 CT acquisition phases and with a sensitivity of 42.1% (36.2%-48.1%) and a specificity of 97.5% (96.4%-98.3%) in group 2 looking at 4 CT acquisition phases. Using the AEF maps, both groups looking at the same 3 acquisition phases, the sensitivity was 47.7% (95% CI, 41.9%-53.5%) with a specificity of 97.4% (96.4%-98.3%) in group 1 and 49.8% (95% CI, 43.9%-55.8%)/97.6% (96.6%-98.4%) in group 2. The optimal cutoff for the AEF was 50%. CONCLUSION The AEF is a helpful tool to screen for HCC with CT. The use of the AEF maps may significantly improve HCC detection, which allows omitting the fourth CT acquisition phase and thus making a 25% reduction of radiation dose possible.

Incidence and outcomes of symptomatic neonatal arterial ischemic stroke.

BACKGROUND AND OBJECTIVES Neonatal arterial ischemic stroke (NAIS) is associated with considerable lifetime burdens such as cerebral palsy, epilepsy, and cognitive impairment. Prospective epidemiologic studies that include outcome assessments are scarce. This study aimed to provide information on the epidemiology, clinical manifestations, infarct characteristics, associated clinical variables, treatment strategies, and outcomes of NAIS in a prospective, population-based cohort of Swiss children. METHODS This prospective study evaluated the epidemiology, clinical manifestations, vascular territories, associated clinical variables, and treatment of all full-term neonates diagnosed with NAIS and born in Switzerland between 2000 and 2010. Follow-up was performed 2 years (mean 23.3 months, SD 4.3 months) after birth. RESULTS One hundred neonates (67 boys) had a diagnosis of NAIS. The NAIS incidence in Switzerland during this time was 13 (95% confidence interval [CI], 11-17) per 100,000 live births. Seizures were the most common symptom (95%). Eighty-one percent had unilateral (80% left-sided) and 19% had bilateral lesions. Risk factors included maternal risk conditions (32%), birth complications (68%), and neonatal comorbidities (54%). Antithrombotic and antiplatelet therapy use was low (17%). No serious side effects were reported. Two years after birth, 39% were diagnosed with cerebral palsy and 31% had delayed mental performance. CONCLUSIONS NAIS in Switzerland shows a similar incidence as other population-based studies. About one-third of patients developed cerebral palsy or showed delayed mental performance 2 years after birth, and children with normal mental performance may still develop deficits later in life.

Longitudinal Telomere Erosion in Lymphocyte Subsets of Patients with Atherosclerotic Peripheral Arterial Disease (PAD).

Telomere attrition has been linked to accelerate vascular ageing and seems to predispose for vascular disease. Our aim was to study the telomere length dynamics over time and in subsets of leukocytes from 15 patients with peripheral arterial disease (PAD). The mean telomere length in subsets of leukocytes of patients with PAD was in the normal range of age-related telomere length values from healthy individuals. However, we found significant higher telomere attrition for T-cells from patients with PAD over a time period of six months when compared to the controls. The higher telomere loss in T-cells of patients with PAD most likely reflects a higher cell turnover of this leukocyte subset, which is involved in the process of chronic inflammatory disease underlying vascular disease. Further studies are needed to confirm these data and to assess how far this T-cell telomere attrition will correlate to the extent of the disease.

Investigation of arterial spin labeling MRI for quantitative cerebral blood flow measurement

Arterial spin labeling (ASL) is a technique for noninvasively measuring cerebral perfusion using magnetic resonance imaging. Clinical applications of ASL include functional activation studies, evaluation of the effect of pharmaceuticals on perfusion, and assessment of cerebrovascular disease, stroke, and brain tumor. The use of ASL in the clinic has been limited by poor image quality when large anatomic coverage is required and the time required for data acquisition and processing. This research sought to address these difficulties by optimizing the ASL acquisition and processing schemes. To improve data acquisition, optimal acquisition parameters were determined through simulations, phantom studies and in vivo measurements. The scan time for ASL data acquisition was limited to fifteen minutes to reduce potential subject motion. A processing scheme was implemented that rapidly produced regional cerebral blood flow (rCBF) maps with minimal user input. To provide a measure of the precision of the rCBF values produced by ASL, bootstrap analysis was performed on a representative data set. The bootstrap analysis of single gray and white matter voxels yielded a coefficient of variation of 6.7% and 29% respectively, implying that the calculated rCBF value is far more precise for gray matter than white matter. Additionally, bootstrap analysis was performed to investigate the sensitivity of the rCBF data to the input parameters and provide a quantitative comparison of several existing perfusion models. This study guided the selection of the optimum perfusion quantification model for further experiments. The optimized ASL acquisition and processing schemes were evaluated with two ASL acquisitions on each of five normal subjects. The gray-to-white matter rCBF ratios for nine of the ten acquisitions were within ±10% of 2.6 and none were statistically different from 2.6, the typical ratio produced by a variety of quantitative perfusion techniques. Overall, this work produced an ASL data acquisition and processing technique for quantitative perfusion and functional activation studies, while revealing the limitations of the technique through bootstrap analysis. ^

Intensive care noise and mean arterial blood pressure in ELBW neonates

Objective. Loud noises in neonatal intensive care units (NICUs) may impede growth and development for extremely low birthweight (ELBW, < 1000 grams) newborns. The objective of this study was to measure the association between NICU sound levels and ELBW neonates' arterial blood pressure to determine whether these newborns experience noise-induced stress. ^ Methods. Noise and arterial blood pressure recordings were collected for 9 ELBW neonates during the first week of life. Sound levels were measured inside the incubator, and each subject's arterial blood pressures were simultaneously recorded for 15 minutes (at 1 sec intervals). Time series cross-correlation functions were calculated for NICU noise and mean arterial blood pressure (MABP) recordings for each subject. The grand mean noise-MABP cross-correlation was calculated for all subjects and for lower and higher birthweight groups for comparison. ^ Results. The grand mean noise-MABP cross-correlation for all subjects was mostly negative (through 300 sec lag time) and nearly reached significance at the 95% level at 111 sec lag (mean r = -0.062). Lower birthweight newborns (454-709 g) experienced significant decreases in blood pressure with increasing NICU noise after 145 sec lag (peak r = -0.074). Higher birthweight newborns had an immediate negative correlation with NICU sound levels (at 3 sec lag, r = -0.071), but arterial blood pressures increased to a positive correlation with noise levels at 197 sec lag (r = 0.075). ^ Conclusions. ELBW newborns' arterial blood pressure was influenced by NICU noise levels during the first week of life. Lower birthweight newborns may have experienced an orienting reflex to NICU sounds. Higher birthweight newborns experienced an immediate orienting reflex to increasing sound levels, but arterial blood pressure increased approximately 3 minutes after increases in noise levels. Increases in arterial blood pressure following increased NICU sound levels may result from a stress response to noise. ^

Incidencia del agua consumida en la zona de influencia del centro de salud nº 127 El Cortaderal, como determinante de prevalencia de hipertensión arterial en sus habitantes, Malargüe, 2011

La EPA (Environmental Protection Agency) ha establecido estándares de seguridad para más de 80 contaminantes que pueden encontrarse en el agua potable y presentan un riesgo a la salud humana. Los efectos agudos ocurren dentro de unas horas o días posteriores al momento en que la persona consume un contaminante. Casi todos los contaminantes pueden tener un efecto agudo si se consume en niveles extraordinariamente altos en el agua potable, en esos casos los contaminantes más probables que causen efectos agudos son las bacterias y virus. Los contaminantes en el agua potable que pueden causar efectos crónicos son los químicos (tales como solventes y plaguicidas), radionucléidos (tal como el radio) y minerales (tal como el arsénico y algunas sales). Entre los ejemplos de efectos crónicos de los contaminantes del agua potable, están el cáncer, problemas del hígado o riñones o dificultades en la reproducción. Este estudio persigue los siguientes objetivos: -Determinar si las características del agua de consumo de El Manzano son determinante de la alta prevalencia de HTA entre sus habitantes -Conocer las características físicas de la composición del agua de consumo del Paraje El Cortaderal. -Comparar la calidad del agua de consumo de las localidades de El Cortaderal y El Manzano. -Comparar si los hábitos alimenticios de los parajes estudiados presentan diferencias significativas que pudieran incidir en la aparición de las Patologías como la HTA y la Fluorosis

Determinar en qué medida influye el estilo de vida en los pacientes con hipertensión arterial en la comunidad de Los Campamentos, distrito de Bowen, General Alvear, Mendoza.

El presente estudio tiene como finalidad determinar en qué medida influye el estilo de vida en la hipertensión arterial, en la población atendida regularmente en el centro de salud Los Campamentos. Esta comunidad es rural, se encuentra a 16 km de la ciudad de General Alvear, en la provincia de Mendoza. Para determinar dicha influencia se utiliza un diseño metodológico cuantitativo, de tipo descriptivo con un corte transversal. La muestra se extrajo de toda la población adulta que se encuentra registrada con HTA. Los datos se obtuvieron por medio de una encuesta estructurada a través de la cual se pudo obtener resultados sobre la prevalencia de la patología según sexo y edad, el nivel educativo alcanzado, la realización de actividades físicas, la dieta hipo sódica que requiere la HTA y el apoyo y contención que el paciente recibe por parte de la familia. Por último se detalla un análisis de los resultados, la interpretación de los mismos y se realizan recomendaciones.

Anticuerpos anticardiolipina en pacientes con hipertensión arterial esencial

Los anticuerpos antifosfolípidos pueden activar el endotelio, modificar su función, alterar la regulación del tono vascular, producir daño renal, y así participar en la patogenia de la hipertensión arterial esencial.

La hipertensión arterial y sus factores modificables.

El presente estudio pretende identificar los factores modificables que influyen en la hipertensión arterial en los pacientes mayores de 30 años, masculinos y femeninos de la comunidad rural a cargo del Centro de Salud nº 141, para mejorar la calidad de atención. Los objetivos son: describir los factores modificables que influyen en los valores de la hipertensión arterial: alimentación, obesidad, sedentarismo y falta de actividad física; mostrar el reflejo de esos factores modificables en los valores de la presión arterial en la población mayor de 30 años de sexo femenino y masculino, de la población en estudio y proponer alternativas que mejoren la calidad de atención a los pacientes afectados por esta enfermedad.

Efeito de 16 semanas de treinamento físico, sem controle alimentar, sobre o perfil lipídico e pressão arterial

Este estudo investiga a importância do exercício físico na prevençao de Doenças Crônicas Nao Transmissíveis. Seu objetivo é verificar o efeito de 16 semanas de exercícios físicos no perfil lipídico e pressao arterial. O grupo de estudo foi composto por 12 voluntários, com faixa etária de 40 a 60 anos, com média de colesterol total e LDL insignificantemente acima dos valores limítrofe e pré-hipertensos. Os indivíduos foram submetidos á avaliaçao médica; análise laboratorial; teste físico e 16 semanas de treinamento físico com frequência de três vezes por semana. Todos os procedimentos foram repedidos ao final. Houve reduçao significativa do Indice de Massa Corporal, Colesterol LDL, Pressao Arterial Diastólica e aumento da glicemia e do desempenho físico. Nao se modificaram o Colesterol Total, Colesterol HDL e Triglicerídeos. O programa de exercícios, mesmo sem o controle de dieta, foi suficiente para provocar as alteraçoes descritas do perfil lipídico, comprovando sua importância na prevençao de doenças cardíacas

Efeito de 16 semanas de treinamento físico, sem controle alimentar, sobre o perfil lipídico e pressão arterial

Este estudo investiga a importância do exercício físico na prevençao de Doenças Crônicas Nao Transmissíveis. Seu objetivo é verificar o efeito de 16 semanas de exercícios físicos no perfil lipídico e pressao arterial. O grupo de estudo foi composto por 12 voluntários, com faixa etária de 40 a 60 anos, com média de colesterol total e LDL insignificantemente acima dos valores limítrofe e pré-hipertensos. Os indivíduos foram submetidos á avaliaçao médica; análise laboratorial; teste físico e 16 semanas de treinamento físico com frequência de três vezes por semana. Todos os procedimentos foram repedidos ao final. Houve reduçao significativa do Indice de Massa Corporal, Colesterol LDL, Pressao Arterial Diastólica e aumento da glicemia e do desempenho físico. Nao se modificaram o Colesterol Total, Colesterol HDL e Triglicerídeos. O programa de exercícios, mesmo sem o controle de dieta, foi suficiente para provocar as alteraçoes descritas do perfil lipídico, comprovando sua importância na prevençao de doenças cardíacas