Eficacia de una estrategia estandarizada y simplificada para tratamiento de la hipertensión arterial en Chile: la Iniciativa HEARTS en las Américas / Efficacy of a standardized and simplified strategy for the treatment of high blood pressure in Chile: the HEARTS Initiative in the Americas / Eficácia de uma estratégia padronizada e simplificada para o tratamento da hipertensão arterial no Chile: a iniciativa HEARTS nas Américas

RESUMEN Objetivo. Evaluar la eficacia de un protocolo estandarizado y simplificado basado en los pilares técnicos de la Iniciativa HEARTS para el control de pacientes hipertensos del Programa de Salud Cardiovascular en el primer nivel de atención de salud en Chile. Métodos. Estudio observacional longitudinal (cohorte histórica), en 2 centros de salud familiar del primer nivel de atención en Santiago, que comparó el control de presión arterial en adultos hipertensos logrado con el protocolo estandarizado y simplificado, frente al protocolo habitual, según las guías nacionales. Las innovaciones del protocolo estandarizado incluyeron cambios en la coordinación del equipo de salud, inicio de tratamiento farmacológico inmediatamente después de confirmación diagnóstica, tratamiento farmacológico estandarizado con combinación de al menos 2 o 3 fármacos antihipertensivos en un sólo comprimido, en una toma diaria. Se realizó seguimiento por 1 año para evaluar el porcentaje de adherencia al tratamiento y cumplimiento de metas de control de presión arterial (menor a 140/90 mmHg). Resultados. Se evaluaron 1 490 pacientes: 562 que utilizaron el protocolo estandarizado y simplificado y 928 tratados con el protocolo habitual (centros de salud familiar-1: 650, centros de salud familiar -2: 278). A 1 año de seguimiento, los pacientes del grupo del protocolo estandarizado y simplificado tuvieron mayor proporción de cumplimiento de metas de control de presión arterial (65% versus 37% y 41%, p<0,001) y mayor porcentaje de adherencia al tratamiento en comparación con aquellos con el protocolo habitual (71% versus 18% y 23%, p<0,001). Conclusiones. Los resultados muestran que el protocolo estandarizado y simplificado es más efectivo que el protocolo habitual en el control de hipertensión arterial en pacientes en tratamiento en el primer nivel de atención en Chile. Su implementación a nivel nacional podría contribuir a la disminución de eventos cardiovasculares mayores.

ABSTRACT Objective. To evaluate the effectiveness of a standardized and simplified protocol based on the technical pillars of the HEARTS Initiative for the control of hypertensive patients in the Cardiovascular Health Program at the first level of care in Chile. Methods. Longitudinal observational study (historical cohort) in two family health centers at the first level of care in Santiago. The control of blood pressure in hypertensive adults using a standardized and simplified protocol was compared to the usual protocol based on national guidelines. Innovations in the standardized protocol included changes in how the health team is coordinated, initiation of pharmacological treatment immediately after confirmed diagnosis, standardized pharmacological treatment with a combination of at least two or three antihypertensive drugs taken daily in a single tablet. Follow-up was conducted after one year to assess the percentage of adherence to treatment and achievement of blood pressure control targets (< 140/90 mmHg). Results. A total of 1490 patients were evaluated: 562 who followed the standardized and simplified protocol, and 928 who were treated with the usual protocol (family health centers: 650; family health centers: 278). After one year, patients in the standardized and simplified protocol group had a higher proportion of adherence to blood pressure control targets (65% versus 37% and 41%, p<0.001) and higher adherence to treatment compared to those following the usual protocol (71% versus 18% and 23%, p<0.001). Conclusions. The results show that the standardized and simplified protocol is more effective than the usual protocol in controlling arterial hypertension in patients undergoing treatment at the first level of care in Chile. Its implementation at the national level could contribute to a decrease in major cardiovascular events.

RESUMO Objetivo. Avaliar a eficácia de um protocolo padronizado e simplificado, com base nos pilares técnicos da iniciativa HEARTS, para o controle de pacientes com hipertensão arterial do Programa de Saúde Cardiovascular na atenção primária à saúde do Chile. Métodos. Estudo observacional longitudinal (coorte histórica) em 2 centros de atenção primária de saúde da família em Santiago, que comparou o controle da pressão arterial em adultos com hipertensão, atingido com o protocolo padronizado e simplificado, versus o protocolo habitual, de acordo com as diretrizes nacionais. As inovações do protocolo padronizado incluíram mudanças na coordenação da equipe de saúde, início do tratamento farmacológico imediatamente após a confirmação do diagnóstico e tratamento farmacológico padronizado com associação de pelo menos 2 ou 3 anti-hipertensivos em um único comprimido, tomados uma vez ao dia. O acompanhamento foi realizado por 1 ano para avaliar o percentual de adesão ao tratamento e o cumprimento das metas de controle da pressão arterial (menor que 140/90 mmHg). Resultados. Foram avaliados 1.490 pacientes: 562 que utilizaram o protocolo padronizado e simplificado e 928 que foram tratados com o protocolo habitual (unidade de saúde da família 1: 650, unidade de saúde da família 2: 278). Em 1 ano de seguimento, os pacientes do grupo do protocolo padronizado e simplificado apresentaram maior proporção de cumprimento das metas de controle da pressão arterial (65% versus 37% e 41%, p<0,001) e maior percentual de adesão ao tratamento, em comparação com aqueles que utilizaram o protocolo habitual (71% versus 18% e 23%, p<0,001). Conclusões. Os resultados mostram que o protocolo padronizado e simplificado é mais eficaz que o protocolo habitual no controle da hipertensão arterial em pacientes que estão em tratamento na atenção primária do Chile. Sua implementação no nível nacional poderia contribuir para a redução de eventos cardiovasculares maiores.

La inflamación en la hipertensión arterial, mecanismos de producción e implicancias terapéuticas / Role of inflammation in hypertension

Even though the mechanisms that mediate essential hypertension (HT) are not fully understood, an immunological-inflammatory mechanism could be the common pathway for diverse pathophysiological mechanisms. We analyze in a simplified way the participation of the immune system in HT. T lymphocytes (TL) and antigen presenting cells (APCs) are components of the immune system capable of generating proinflammatory cytokines. They cause endothelial damage, vasoconstriction, and decreased urinary sodium excretion. CD4+ and CD8+ TL are effector cells, causally implicated in the development of HT, whereas type γδ TL play their pathogenic role in HT enhancing endothelial dysfunction. Additionally, a immunomodulation decrease by regulatory TL, worsens endothelial dysfunction and reduces vasodilation in experimental HT. Results of recent studies indicate that lymphocyte activation would be mediated by antigens captured by antigen APCs for subsequent presentation to "naive" TL. On the other hand, proinflammatory states such as obesity, the change of the intestinal microbiota and the increase in salt intake favors TL and APC activation, contributing to HT development.

Sensibilidad aumentada a lidocaína: estudio genético de un caso / Increased sensitivity to lidocaine: Genetic study of a case

Systemic toxicity by local anesthetics (LAs) is a severe and feared complication in anesthetic practice that generally results from the administration of an inappropriately high dose of LAs or an injection at an inappropriate place, either intravascular or a site with high absorption[1]. However, it is known that the susceptibility to these drugs may vary within the population, which may occur due to genetic changes in the LA binding site, located in the potential-dependent Na+ channels (Nav), thus increasing or decreasing its affinity and, therefore, its clinical consequences. We present a case of a 61 years-old female patient with a medical history of increased sensitivity to LAs. In this scenario, a genetic study was performed to exclude a Nav channel dysfunction.

La toxicidad sistémica por anestésicos locales (ALs) es una grave y temida complicación en la práctica anestésica que generalmente resulta de la administración de una dosis inapropiadamente alta de ALs o a una inyección en un lugar inadecuado, llámese intravascular o un sitio al alta absorción[1]. A pesar de lo anterior, es conocido que la susceptibilidad al efecto de estos fármacos puede variar dentro de la población, lo cual puede ocurrir debido a cambios genéticos en el sitio de unión de los AL, localizado en los canales de Na+ dependientes de potencial (Nav), incrementando o disminuyendo así su afinidad y, por ende, sus consecuencias clínicas. Presentamos el caso de una paciente de 61 años con historia de sensibilidad aumentada a Als. En este escenario, se le ofreció un estudio genético para excluir una disfunción específica a nivel de canal Nav

El efecto anti-hipertensivo de angiotensina-(1-9) es mediado por aumento temprano de la diuresis y natriuresis / Cardiac arrest associated to intramural hematoma of the anterior descending coronary artery

Introducción: Angiotensina (Ang)-(1-9) posee propiedades anti-hipertensivas y efecto protector a nivel cardiovascular en ratas hipertensas. Sin embargo, se desconoce si estos efectos están asociados a un mecanismo de desbalance de sodio a nivel renal. Objetivo: Determinar si el efecto anti-hipertensivo de Ang-(1-9) está asociado a un mecanismo diurético-na-triurético. Método: Ratas macho Sprague Dawley (200 ± 10g) fueron aleatorizadas para recibir Ang II (400 ng/kgmin) vía bomba osmótica. Como control se utilizaron ratas con operación sham (n=18). Después de 2 semanas desde la instalación de bomba, las ratas Sham e hipertensas fueron randomizadas para recibir vehículo (n=10), Ang-(1-9) (602 ng/kg/min, n=17) o una co-administración de Ang-(1-9) y A779 (100 ng kg-1min-1, n=7 bloqueador del receptor MAS) por 2 semanas. Resultados: Se determinó la presión arterial sistólica (PAS), masa ventricular relativa (MVR), área y perímetro de los cardiomiocitos (AC y PC) y la fracción volumétrica de colágeno total (FVCT). Para evaluar la diuresis y natriuresis se utilizaron ratas normotensas que fueron randomizadas para recibir vehículo (n=8) o Ang-(1-9) (600 ngKg-1min-1, n=8) por 6 días. Se observó un incremento significativo(p<0.05) de PAS (33%), MVR (17%), AC (64%), PC (20%), FVCT (46%). La administración crónica de Ang-(1-9) disminuyó PAS (20%), MVR (13 %), AC (35%), PC (20%) y FVCT (20%). Estos efectos no fueron mediados por el receptor MAS. Al comparar las ratas normotensas tratadas con vehículo o Ang-(1-9), se observó un aumento significativo de la diuresis y natriuresis en los días 2 y 3 en los animales con infusión de Ang-(1-9). Conclusión: Ang-(1-9) reduce la hipertensión y el remodelamiento cardíaco en ratas hipertensas. En animales normotensos se demostró que el tratamiento con Ang-(1-9)-induce diuresis y natriuresis. Este es el primer reporte que señala que el efecto de Ang-(1-9) está asociado a una regulación del sodio a nivel renal.

Background: Angiotensin-(1-9) has anti-hypertensive properties and protective cardiovascular effect in hypertensive rats. However, it is unknown whether its effects are related to a kidney mechanism to balance sodium. Aim: To determine if the anti-hypertensive effect of Ang-(1-9) is associated to a diuretic-natriuretic mechanism. Method: Sprague Dawley male rats (200±10 grs) were randomized to receive Angiotensin II by osmotic pump (400 ng/kg/min). Sham operated rats were utilized as control (n=18). Two weeks after pump setting, Sham rats with hypertension were randomized to receive placebo (n=10), Ang-(1-9)(602 ng/kg/min, n=17) or Ang-(1-9) plus A779 (Ang-(1-7) Receptor Mas blocker, 100ng/kg-1min-1, n=7) co-administration for two weeks. Arterial systolic pressure (PAS), ventricular relative mass (MVR), cardiomyocytes area and perimeter (AC and PC) and total collagen volume fraction (FVCT) were measured. Normotensive rats were utilized to evaluate diuresis and natriuresis which were randomized to receive placebo (n=8) or Ang-(1-9) (600ng/kg-1/min-1, n=8) for six days. Results: It was observed a significant rise (p<0.05) of PAS (33%), MVR (17%), AC (64%), PC (26%), FVCT (46%) was observed. Chronic administration of Ang-(1-9) reduced PAS (20%), MVR (13%), AC (35%), PC (20%) and FCVT (20%). All those effects were not mediated by Mas receptor. A significant raise was observed of diuresis and natriuresis at the second and third day of treatment in rats receiving Ang-(1-9) in comparison with normotensive rats treated with placebo. Conclusion: Ang-(1-9) reduces hypertension and cardiac remodeling in hypertensive rats. Ang-(1-9) induces natriuresis and diuresis in normotensive rats. This is the first report showing that Ang-(1-9) is associated to sodium balance in the kidney.

Daño arterial asociado a la enfermedad renal crónica: evaluación mediante técnicas de laboratorio no invasivo en pacientes hemodializados / Assesment of arterial damage by noninvasive peripheral arterial tonometry in non-diabetic hemodialysis patients

Background: Hemodialysis patients (HD) display high rates of cardiac disease and mortality. The cardiovascular morbidity and mortality of HD patients is attributable in a significant proportion to endothelial dysfunction, arterial stiffness, and vascular calcifications. Aim: To measure vascular reactivity in HD subjects and compare them with healthy volunteers. Material and Methods: Forty eight non diabetic patients aged 58 ± 4.6 years (29 males) on hemodialysis for a mean lapse of 4.8 years were studied. Arterial stiffness was measured in the radial artery. Pulse wave velocity was measured by noninvasive peripheral arterial tonometry in carotid and femoral arteries. Endothelial function was assessed, measuring reactive hyperemia response after a 5 min period of ischemia. As a control, all values were also measured in age and gender-matched healthy volunteers. Results: Arterial stiffness was significantly higher in HD patients than controls (23.9 ± 3.3 and 18.4 ± 3.4% respectively, p < 0.05). HD subjects had an increased pulse wave velocity (10.0 ± 0.8 and 7.6 ± 0.9 m/s respectively, p < 0.05). A reduction in the change in pulse amplitude pressure, as a measure of arterial dysfunction, was only observed in male patients (1.7± 0.4 and2.7 ± 0.4 respectively p < 0.01). Conclusions: Noninvasive assessment of peripheral vascular function may be useful for the identification of patients at risk for late cardiac events.

IL-17A levels increase in the infarcted region of the left ventricle in a rat model of myocardial infarction

Th17 cells, a recently described subtype of CD4+ effector lymphocytes, have been linked to cell-mediated autoimmune and inflammatory diseases as well as to cardiovascular diseases. However, the participation of IL-17A in myocardial ischemic injury has not been clearly defined. We therefore conducted the present study to evaluate IL-17A and Th17-related cytokine levels in a rat model of myocardial infarction (MI). MI was induced in male Sprague Dawley rats by coronary artery ligation. Controls were sham-operated (Sh) or non-operated (C). Blood and samples from the left ventricle (LV) were collected at weeks 1 and 4 post-MI. At week 1, MI animals exhibited increased IL-6, IL-23 and TGF-β mRNA levels with no apparent change in IL-17 mRNA or protein levels in whole LV. Only TGF-β mRNA remained elevated at week 4 post-MI. However, further analysis revealed that IL-17A mRNA and protein levels as well as IL-6 and IL-23 mRNA were indeed increased in the infarcted region, though not in the remote non infarcted region of the LV, except for IL-23 mRNA. The increased expression of IL-17A and Th17-related cytokines in the infarcted region of LV, suggests that this proinflammatory pathway might play a role in early stages of post MI cardiac remodelling.

Evolución del compromiso cardiovascular de pacientes insuficientes renales, en hemodiálisis, sin bloqueo del eje renina-angiotensina / Cardiovascular assessment of non diabetic patients on hemodialysis

Background: Diabetes mellitus is an important risk factor for cardiovascular complications among patients on hemodialysis. However, the incidence of these complications among non diabetic patients on hemodialysis is not well known. Aim: To assess the incidence of cardiovascular complications in non diabetic patients on hemodialysis. Patients and methods: Seventy five non diabetic patients aged 55.6 ± 17 years (48 males), receiving hemodialysis three times a week were evaluated with laboratory tests, echocardiogram anda carotid ultrasound. In 26 patients, interleukin 6, tumor necrosis factor alpha, and intercellular adhesión molecule (ICAM-1) were also measured. Patients were followed during two years. Results: The mean lapse of dialysis therapy was 6.5 ±5 years. The main cause of renal failure was hypertension. Sixty two percent had systolic hypertension, 86 percent had concentric left ventricular hypertrophy, 43 percent had atrial dilatation and 60 percent had calcifications in the thoracic aorta. Compared with normal controls, patients had higher levels of interleukin 6, tumor necrosis factor alpha and ICAM-1. Carotid media thickness was also higher and increased in the two years of follow up. No correlations were found between ventricular hypertrophy and dialysis lapse, packed red cell volume, calcium phosphorus product, parathormone levels or median arterial pressure. No cardiovascular events were recorded during the follow up period. Conclusions: Non diabetic patients on chronic hemodialysis have a high frequency of ventricular hypertrophy, carotid media thickening, aortic calcifications and an increase in proinflammatory cytokines.