Primary aldosteronism (PA) is one of the common forms of curable hypertension. Recent views have suggested that PA is far from being relatively benign, as it was previously thought, but it is associated with a variety of cardiovascular and renal sequelae that reflect the capability of inappropriately elevated aldosterone to induce tissue damage over that induced by hypertension itself. The evidence supporting these views has been obtained from experiments conducted in hypertensive animal models and studies involving patients with PA. Preclinical studies have also indicated that aldosterone causes cardiovascular and renal tissue damage only in the context of inappropriate salt status. It has been suggested that untoward effects of high-salt intake are dependent on activation of mineralocorticoid receptors (MRs) that might result from increased oxidative stress and changes in the intracellular redox potential. Unilateral adrenalectomy or treatment with MR antagonists are the current options for treating an aldosterone-producing adenoma (APA) or idiopathic adrenal hyperplasia (IHA). Treatments are effective in correcting hypertension and hypokalemia, and currently available information on their capability to prevent cardiovascular events and deterioration of renal function indicates that surgery and medical treatment are equally beneficial in the long term.

(Fuente: American Journal of Hypertension 2010)

Por: Paul W. Armstrong, M.D.

The transformation of cardiac care over the past half century has been breathtaking to witness. In large part, this transformation is due to the advent of new drugs and devices, improved health care systems, and behavioral modifications such as smoking cessation. Four cardiac medicines developed before 1960 that survived the turn of the millennium are aspirin, digoxin, warfarin, and spironolactone. New competitors threaten the continued longevity of aspirin, the survival of digoxin depends on evidence of its ability to improve exercise tolerance and quality of life in patients with heart failure, and new pretenders for warfarin are here. Remarkably, after over 50 years, the aldosterone antagonism achieved by spironolactone (and more recently eplerenone) has earned an enduring role in the treatment of heart failure.1

When spironolactone was developed, it was a minor player complementing more powerful diuretics in achieving volume homeostasis. Our understanding of heart failure was then predominantly focused on hemodynamic perturbations. As long ago as 1960, the drug was found to protect rats against myocardial necrosis,2 yet this observation languished for decades. Subsequently, two parallel tracks of knowledge emerged, which are germane to a resurgence of interest in antagonizing aldosterone. The first track involves the complex adaptations affecting the failing and remodeled heart. Cardiac enlargement and increased sphericity are often accompanied by scarring and fibrosis. Neurohormonal activation and altered vascular compliance of coronary and peripheral blood vessels compound this unfavorable milieu.3 The second track concerns the pleiotropic effects of aldosterone antagonists. These include conservation of potassium and magnesium, the depletion of which potentiates ventricular arrhythmias and sudden death; inhibition of fibroblast proliferation and perivascular fibrosis, which are promoted by chronic hyperaldosteronism; and reversal of unfavorable coronary and renal vascular remodeling, which is modulated by endothelial-cell and baroreceptor dysfunction.3

These physiological observations now appear to have important clinical consequences. In the Randomized Aldactone Evaluation Study (RALES), Pitt and colleagues4 demonstrated that spironolactone therapy could significantly reduce rates of death and hospital readmission for worsening heart failure among patients with functional class III or IV heart failure. Four years after this seminal study, the same investigators conducted the Eplerenone Post–Acute Myocardial Infarction Heart Failure Efficacy and Survival Study (EPHESUS),5 which showed that eplerenone, a selective aldosterone-receptor blocker, reduced morbidity and mortality among patients recovering from acute myocardial infarction with complicating left ventricular dysfunction. As a result of these convincing findings, aldosterone-receptor blockade has become part of recommended therapy in such patients.6

In this issue of the Journal, Zannad and colleagues7 complete an aldosterone-trial trilogy with their report on the Eplerenone in Mild Patients Hospitalization and Survival Study in Heart Failure (EMPHASIS-HF; ClinicalTrials.gov number, NCT00232180), which shows that eplerenone reduces the rate of death from cardiovascular causes or hospitalization for heart failure by approximately 37%, as compared with placebo, in patients with functional class II heart failure. Although this effect seems surprisingly large for a trial of mildly symptomatic patients, careful review of the baseline characteristics is instructive.

The majority of the study patients were heart disease veterans: one half had previously been hospitalized for heart failure and had a history of myocardial infarction; hypertension, atrial fibrillation, and diabetes were also common. The mean ejection fraction of 26% (nearly identical to that in the more severely symptomatic patients in RALES) is a cogent reminder of the discordance between functional class and left ventricular function. An additional feature marking the EMPHASIS-HF patients as high risk is that approximately one quarter had left bundle-branch block, and the overall mean QRS duration was 122 msec (with one quarter having a QRS duration >130 msec). Although the concomitant use of beta-blockers and angiotensin-converting–enzyme inhibitors was common, the infrequent use of implantable defibrillators or cardiac resynchronization therapy raises the question of whether eplerenone would have fared as impressively had a larger proportion of the study population received implantable electrical devices, in alignment with current guidelines.6 This points to the need for further investigation, given that even the trial participants receiving active therapy had a 1-year mortality rate of approximately 5.0%.

The effect on death from cardiovascular causes or hospitalization for heart failure translates into an impressively low number needed to treat: 19 patients. The number needed to treat to prevent one death is 51 patients, positioning this therapy in the front rank of therapeutic choices. The survival curves invite speculation about whether the effect of eplerenone on volume homeostasis came into play early, thereby affecting hospitalization for heart failure sooner, whereas structural changes such as favorable cardiac remodeling might have accounted for the more delayed reduction in mortality.

The EMPHASIS-HF investigators have added real value to the management of heart failure. Since spironolactone is available for pennies a day, one might reasonably ask whether the greater cost of eplerenone is warranted or whether it is reasonable to simply assume that the current findings also apply to spironolactone and reserve the newer, more expensive therapy for those few patients in whom the side effects of spironolactone are disabling. I believe this would be a reasonable tactic. It is now time to overcome undertreatment by ensuring that this form of therapy is incorporated into all heart-failure regimens.8 It is incumbent on the prescriber to perform appropriate monitoring of renal and electrolyte status, which can enhance the safety of such treatment.9

As one reflects on the EMPHASIS-HF results, the question arises: Do they open doors for investigating aldosterone antagonism in other cardiovascular diseases? The answer is, most emphatically, yes. In fact, studies of this therapy in patients with diastolic dysfunction and acute myocardial infarction are ongoing, and the results are eagerly awaited. A preventive approach in patients at high cardiovascular risk might even be on the horizon.10 Of the quartet of therapies that have served us well over the past half century, aldosterone antagonism seems most likely to be the last man standing.

[Fuente: This article was published on November 14, 2010, at NEJM.org].

Los países más pobres no solo se mueren de hambre o de enfermedades infecciosas. El corazón de sus habitantes también sufre las consecuencias de vivir con pocos recursos sanitarios. El infradiagnóstico de la hipertensión arterial es una de las principales causas de muerte cardiovascular y, por ello, la Organización Mundial de la Salud (OMS) ha cofinanciado un tensiómetro que, por 25 euros, puede detectar este trastorno.

Fabricado por Omron, el llamado ‘HEM-SOLAR’ logró hacerse con el visto bueno de la OMS gracias a su bajo coste pero también a su facilidad de uso -no requiere de un especialista-, su eficacia y a que aprovecha la energía solar para ponerse en marcha (también puede funcionar con pilas).

El citado dispositivo ya ha probado su potencial eficacia en tres ensayos con 700 pacientes, realizados durante seis meses en Uganda y Zambia. Esta innovación se comparó con el tensiómetro común de mercurio que, como ya les pasara a los termómetros con ese componente, está en proceso de ser retirado del mercado.

“El manejo de la presión sanguínea alta es particularmente inadecuado en los países con menos recursos. En ellos, el no disponer de un dispositivo fiable, duradero y asequible es un gran obstáculo para realizar un diagnóstico”, explican los responsables de estos estudios, cuyos resultados aparecen ahora reflejados en la revista ‘Hypertension’.

Como indican estos expertos, capitaneados por Eoin O’Brien, del University College de Dublín (Irlanda), el dispositivo solar mostró unos valores generales muy similares a los del manómetro de mercurio. El primero detectó hipertensión en un 19% de los participantes, frente al 20% indicado por el otro método.

Además de esta información más ‘objetiva’, los autores del documento recalcan la buena acogida entre los usuarios, que recomendaron el nuevo tensiómetro en un 97% de los casos. Su sencillo manejo y la posibilidad de obtener mediciones automatizadas fueron algunas de sus características más valoradas.

Su talón de Aquiles

A pesar de sus beneficios, sus propios creadores aclaran que no se trata de una herramienta perfecta. Como limitación principal, es menos precisa al medir la presión diastólica (cuando el corazón se relaja) que la sistólica (cuando el órgano se contrae).

Mientras intentan mejorar esta función, los miembros de este proyecto -que proceden de distintas partes del mundo, además de Irlanda- aclaran que “la presión sistólica es la que más contribuye a los episodios cardiovasculares, especialmente en las zonas más necesitadas”.

Éstas y otras iniciativas, como los electrocardiogramas de bajo coste, están destinadas a reducir la importante carga que suponen las enfermedades cardiovasculares en países con menos recursos, y que a menudo pasa desapercibida.

“La hipertensión es el factor de riesgo de infarto cerebral más importante en las naciones en vías de desarrollo, y está detrás del 35% de estos episodios”, recalca la mencionada investigación.

Y añade: “en un esfuerzo por reducir la alta incidencia de mortalidad infantil en los países africanos, nos hemos embarcado en un programa que utiliza este dispositivo para diagnosticar la hipertensión durante el embarazo”.

(Fuente: El Mundo.es)

Científicos crearon un nuevo aparato de energía solar y de bajo costo para medir la presión arterial de pacientes en los países más pobres del mundo.

Lectura de presión arterial

Unas mil millones de personas podrían padecer hipertensión en el mundo.

El dispositivo, afirman los investigadores, podría ayudar a reducir la creciente epidemia de enfermedades cardiovasculares en el mundo que ya causan más muertes que el cáncer y el sida.

Según los científicos del la Universidad de Dublín, Irlanda, que están probando el aparato en Uganda y Zambia, éste ya demostró ser igualmente efectivo para el control de la presión arterial sistólica que los aparatos de medición tradicionales, pero con un costo más bajo.

Los detalles del estudio, financiado por la Organización Mundial de la Salud (OMS), aparecen publicadon en Hypertension (Hipertensión), la revista de la Asociación Estadounidense del Corazón.

“La incidencia de hipertensión está aumentando de forma drástica en muchos países” afirma el profesor Eoin O´Brien, quien dirigió el estudio.

“La hipertensión conduce a derrame cerebral e infarto que son unas de las principales causas de muerte en todo el mundo. Es mayor que la malnutrición, el cáncer y el sida” señala el experto.
Difícil de detectar

La hipertensión es un trastorno crónico que se caracteriza por un aumento sostenido de las cifras de presión sanguínea en las arterias. Según el consenso internacional, una presión sistólica sostenida de 140 mmHg o mayor o una presión diastólica sostenida de 90 mmHg o mayor son consideradas como hipertensión clínica.

Logramos crear un dispositivo preciso, robusto y de bajo costo para diagnosticar hipertensión arterial. Es un comienzo. Porque si no logramos medir la presión arterial, ciertamente no lograremos combatir y tratar la hipertensión

El Prof. Eoin O’Brien cree que el trastorno afecta a unos mil millones de personas en el mundo, tanto en países desarrollados como en desarrollo y como por lo general el paciente no presenta síntomas es muy difícil de detectar.

Por eso hoy en día se le considera como uno de los problemas más graves de salud pública mundial.

La única forma de detectar la enfermedad es monitoreando la presión arterial de la persona de forma regular pero muchos países de bajos ingresos carecen de personal médico entrenado o equipo para llevar a cabo el diagnóstico.

Por eso la OMS pidió a varias compañías en todo el mundo que diseñaran un aparato para medir la presión arterial que fuera preciso, fácil de usar y de energía solar.

El dispositivo que está siendo probado ahora cumplió esos criterios y según los expertos, 88% de los profesionales que lo han utilizado lo consideran tan bueno o mejor que el aparato tradicional.

Y además, la mayoría de los profesionales de salud que lo probaron consideran que el hecho de poder ser utilizado con energía solar es una ventaja muy importante.

Bajo costo

La hipertensión causa más muertes que el cáncer y el sida.

“La energía solar elimina la necesidad de adquirir costosas baterías recargables en zonas remotas donde la electricidad y la disponibilidad de baterías pueden ser escasas pero donde hay mucha luz solar”, expresa el profesor O’Brien.

“El aparato puede funcionar también con baterías pero se le deja bajo el sol para cargarlo, lo cual lo hace ideal para usarlo en áreas rurales” agrega.

Tal como explica el investigador el dispositivo -que está siendo utilizado en dos clínicas en Uganda y una en Zambia- es totalmente automatizado y el personal que llevó a cabo las lecturas recibió un entrenamiento previo de 15 minutos.

En la prueba participaron 716 pacientes a quienes se tomaron lecturas tanto con el nuevo aparato como con el aparato tradicional.

Y tanto los profesionales de salud como los pacientes dijeron que preferían el nuevo dispositivo.

Los expertos notan, sin embargo, que aunque el dispositivo demostró ser preciso para la medición de la presión sistólica, es menos preciso para la medición diastólica (la presión cuando el corazón se relaja).

Aunque esto, afirma el profesor O’Brien, está siendo actualmente corregido por los fabricantes.

“Logramos crear un dispositivo preciso, robusto y de bajo costo para diagnosticar hipertensión arterial” expresa el científico.

“Es un comienzo. Porque si no logramos medir la presión arterial, ciertamente no lograremos combatir y tratar la hipertensión”.

El aparato, fabricado por la compañía Omron, costará unos US$32.

(Fuente. BBC Ciencia)

Por. Masahiro Akishita. Department of Geriatric Medicine, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, Japan.

Elderly hypertensive patients, particularly those aged 75 years or above, should be carefully treated because they are at higher risk for both cardiovascular and adverse drug events than younger patients. A number of trials showed the efficacy of lowering systolic blood pressure (SBP) to some extent in the elderly with SBP >160 mm Hg irrespective of drug classes. Recently, the  Hypertension in the Very Elderly Trial1 demonstrated the benefits of antihypertensive treatment even in patients over the age of 80 years with SBP greater than or equal to160 mm Hg. In this study, the target SBP was <150 mm Hg with the achieved SBP of 144 mm Hg after the mean follow-up period of 2 years. These results rationalize to consider that SBP should be maintained below 150 mm Hg in elderly patients including those over 75 years old.

It is still controversial whether SBP should be lowered below 140 mm Hg in elderly patients, although epidemiological studies and the meta-analysis of 147 randomized trials2 suggest a proportional reduction in cardiovascular events according to BP level.

In fact, no previous trials have achieved SBP <140 mm Hg. Conversely, excessive BP lowering in the elderly may cause adverse reactions, such as light-headedness and falls, and has been associated with the J-curve phenomenon.

The Japanese trial to assess optimal systolic blood pressure in elderly hypertensive patients (JATOS) was the first study that was specially designed to compare the strict (<140 mm Hg) with the mild (140–159 mm Hg) target of SBP for 2 years in the elderly aged 65–85 years. Principal results of JATOS by intention-to-treat analysis revealed that the outcomes were similar between the strict and mild treatment groups.4 However, a large amount of subjects failed to achieve the target SBP, resulting in a weak statistical power of JATOS.

In this issue of Hypertension Research, Rakugi et al.5 reported a per-protocol analysis of JATOS to evaluate the outcomes among the target SBP-achieved subjects. In JATOS, 54% (1192 of 2212 subjects) in the strict treatment group and 69% (1531 of 2206 subjects) in the mild treatment group achieved their target SBPs by use of efonidipine, a long-acting calcium antagonist, as the first-line drug. Although average SBP and DBP were different by 14.3 and 4.3 mm Hg, respectively, the incidence of the primary end points, a composite of cardiovascular disease and renal failure, was similar between the two groups. There was no difference in each of end point components or the incidence of adverse events between the strict target-achieved group and the mild target-achieved group.

These results are consistent with the principal intention-to-treat analysis of JATOS and with the recently published Valsartan in Elderly Isolated Systolic Hypertension (VALISH) Study6 as well. VALISH study compared the strict (<140 mm Hg) with the moderate (140–149 mm Hg) target of SBP for greater than or equal to2 years in 3260 hypertensive patients aged 70–84 years on valsartan-based treatment. Both intention-to-treat and per-protocol analyses showed that a composite of end points and adverse events were similar between the two groups. By contrast, an Italian study7 demonstrated that the aggressive target of SBP
<130 mm Hg (achieved SBP of 131.9 mm Hg) was superior to the less aggressive target of SBP <140 mm Hg (achieved SBP of 135.6 mm Hg) in non-diabetic hypertensive patients. Reduced end points of this study, however, were left ventricular hypertrophy, coronary revascularization and new-onset atrial fibrillation, most of which were not included in JATOS and VALISH study. In addition, the subjects were younger (greater than or equal to55 years of age, mean age of 67 years) than those of JATOS and VALISH, and the event rate was remarkably higher than those of the two Japanese studies.

Finally, what should we do in clinical practice? Although JATOS targeted SBP <140 vs. 140–159 mm Hg, it may be commonly accepted that SBP should be kept <150 mm Hg in the elderly as HYVET showed.  This view can be strengthened by the finding of JATOS that target-unachieved patients had worse prognosis than target-achieved patients, despite the study groups. Then, should we reduce SBP below 140 mm Hg or maintain SBP between 140 and 150 mm Hg in elderly patients? At present, no clinical trial has confirmed the benefits of lowering SBP below 140 mm Hg in the elderly. Obviously, however, cardiovascular disease risk is higher in elderly patients than younger ones. Accordingly, one might expect the benefits of reducing SBP <140 mm Hg or lower, which have been shown in younger populations such as Cardio-Sis.7  Statistical power might have been insufficient in JATOS and VALISH to detect a small difference between the groups, if present. Furthermore, targeting SBP <140 mm Hg was not associated with the increase in adverse events in JATOS and VALISH. Taken together, strict control of SBP <140 mm Hg may be of little clinical importance for the prevention of cardiovascular and renal events in the elderly. This may not be applicable to patients with cardiovascular disease or non-Asian populations. Conversely, it may not be necessary to withdraw antihypertensive therapy once SBP is safely maintained below 140 mm Hg. Pending future trials and meta-analyses determining the optimal SBP level for elderly patients, we should follow the JSH 2009 guidelines8 that are compatible with the above-mentioned points.

(Fuente: www.nature.com/hr/journal)