P rimary aldosteronism (PA) is a common curable cause of high blood pressure (BP).1 PA is of peculiar interest because the excess aldosterone secretion is held to be autonomous from angiotensin II, which allows elucidating the cardiovascular effects of excess aldosterone without the confounding effects of excess angiotensin II. Moreover, as the excess of aldosterone is cured with adrenalectomy in practically all patients, 2 causation between aldosterone excess and the cardiovascular changes could be inferred. However, whether surgery or pharmacological blockade of the mineralocorticoid receptor (MR) warrant cure of high BP and regression of cardiovascular damage, and of cardiac remodeling, at long term remains unclear because limited data exist. 3,4 The adaption of the left ventricle (LV) to the increased afterload of patients with high BP involves development of hypertrophy (LVH), which predicts cardiovascular events and death, 5 and when regressed improved prognosis. 6 In the complex interplay of hemodynamic, genetic, and endocrine-paracrine factors that underlie development of LVH aldosterone plays a pivotal role. [7][8][9] In the setting of a high sodium intake, this major effector of the system causes LVH, transcription of collagen type I and III genes, 10 and promotes fibroblasts proliferation, oxidative stress, and inflammation, 11 in part, by potentiating the effects of angiotensin II on AT-1 receptors.12-15 These actions, alongside the effects of the steroid on pre-and after-load, are held to cause inflammation and fibrosis, which contribute to worsening prognosis of patients with hyperaldosteronism, 8,16 and can explain the survival benefit conferred by MR antagonists to optimally treated patients with LV systolic dysfunction. 17,18 Compared with BP-matched primary (essential) hypertensive patients, those with PA have an excess LVH and a LV mass inappropriately high for the degree of LV workload and BP elevation. [2][3][4]9,[19][20][21][22][23][24][25][26][27][28] Cardiac fibrosis with ensuing altered LV diastolic dysfunction can lead to left atrium dilatation and increased risk of atrial fibrillation (AF) 7,8,29 ; whether these changes regress with specific treatment for PA remains uncertain. 3,4,19,20,26 We, therefore, set out to prospectively investigate the long-term effects of correction of hyperaldosteronism on BP, LV mass, and cardiovascular events in a large cohort of patients with PA.Abstract-Primary aldosteronism (PA), a common cause of high blood pressure (BP), induces left ventricular (LV) hypertrophy and an excess rate of cardiovascular events. Whether its treatment provides long-term cure of hypertension and regression of cardiovascular damage remains uncertain. To the aim of assessing the effect of treatment of PA on BP and LV changes, we prospectively recruited 323 patients in a long-term follow-up study entailing serial echocardiography evaluations. Of them, 180 had PA and were assigned to either adrenalectomy (n=110) or medical therapy (n=70)

Abstract-Hyperaldosteronism has been causally linked to myocardial interstitial fibrosis experimentally, but it remains unclear if this link also applies to humans. Thus, we investigated the effects of excess aldosterone due to primary aldosteronism (PA) on collagen deposition in the heart. We used echocardiography to estimate left ventricular (LV) wall thickness and dimensions and for videodensitometric analysis of myocardial texture in 17 consecutive patients with PA and 10 patients with primary (essential) hypertension who were matched for demographics, casual blood pressure, and known duration of hypertension. The groups differed in serum K ϩ , ECG PQ interval duration, plasma renin activity, and aldosterone levels (all PՅ0.002) but not for casual blood pressure values, demographics, and duration of hypertension. Compared with hypertensive patients, PA patients showed a higher LV mass index (53.7Ϯ1.8 versus 45.5Ϯ2.0 g/m 2.7 ; Pϭ0.008) and lower values of the cyclic variation index of the myocardial mean gray level of septum (CVI s ; Ϫ12.02Ϯ5.84% versus 6.06Ϯ3.08%; Pϭ0.012) and posterior wall (Ϫ11.13Ϯ6.42% versus 8.63Ϯ9.62%; Pϭ0.012). A regression analysis showed that CVI s was predicted by the PQ duration, supine plasma renin activity, plasma aldosterone, and age, which collectively accounted for Ϸ36% of CVI s variance. PA is associated with alterations of myocardial textures that suggest increased collagen deposition and that can explain both the dependence of LV diastolic filling from presystole and the prolongation of the PQ interval. Key Words: hypertension, endocrine Ⅲ aldosterone Ⅲ myocardial Ⅲ hypertrophy Ⅲ fibrosis Ⅲ echocardiography L eft ventricular hypertrophy (LVH) is commonly associated with arterial hypertension and represents an important independent predictor of cardiovascular events, 1 including congestive heart failure. Extracellular matrix and collagen deposition are invariable findings of LVH and lead to cardiac fibrosis (CF), which occurs particularly in the perivascular areas and correlates directly with the severity of LVH. 2 CF is a major cause of cardiac dysfunction because an excessive deposition of collagen may be responsible for abnormal tissue stiffness and diastolic dysfunction. The latter is an early marker of heart involvement in hypertension (for review, see Agabiti-Rosei and Muiesan 3 ) and is associated with CF more closely than with LVH. 4,5 Fibroblasts constitute the vast majority (Ͼ90%) of nonmyocyte cells in the heart; they can increase the production of extracellular matrix on exposure to a variety of injuries, including pressure overload. The latter seems to be only one of the determinants of CF, because it was experimentally shown, both in vitro and in vivo, that CF in both ventricles was linked to activation of the renin-angiotensin-aldosterone system 6 and that it could be prevented by nonantihypertensive dosages of spironolactone. 7 Thus, angiotensin II and aldosterone play important roles in the heart (for review, see Swynghedauw 8 ). Angiotensin II induces cardi...

The Allergic Rhinitis and its Impact on Asthma (ARIA) initiative commenced during a World Health Organization workshop in 1999. The initial goals were (1) to propose a new allergic rhinitis classification, (2) to promote the concept of multi-morbidity in asthma and rhinitis and (3) to develop guidelines with all stakeholders that could be used globally for all countries and populations. ARIA—disseminated and implemented in over 70 countries globally—is now focusing on the implementation of emerging technologies for individualized and predictive medicine. MASK [MACVIA (Contre les Maladies Chroniques pour un Vieillissement Actif)-ARIA Sentinel NetworK] uses mobile technology to develop care pathways for the management of rhinitis and asthma by a multi-disciplinary group and by patients themselves. An app (Android and iOS) is available in 20 countries and 15 languages. It uses a visual analogue scale to assess symptom control and work productivity as well as a clinical decision support system. It is associated with an inter-operable tablet for physicians and other health care professionals. The scaling up strategy uses the recommendations of the European Innovation Partnership on Active and Healthy Ageing. The aim of the novel ARIA approach is to provide an active and healthy life to rhinitis sufferers, whatever their age, sex or socio-economic status, in order to reduce health and social inequalities incurred by the disease.

The renin-angiotensin-aldosterone (RAA) system and the endothelin (ET) system entail the most potent vasopressor mechanisms identified to date. Although they were studied in depth in relation to arterial hypertension and cardiovascular diseases, limited information on their interrelationships in causing hypertension and related target organ damage exists. The identification of consensus sequences for jun in the regulatory region of the preproendothelin-1 (ppET-1) gene raised the possibility of its transcriptional regulation by angiotensin II (Ang II). This was confirmed by the finding that stimulation with Ang II of cultured vascular smooth muscle cells (VSMCs) and endothelial cells (ECs) induced expression of the ppET-1 gene and synthesis of ET-1. Endogenously produced ET-1 was found to contribute to the hypertrophic response of cardiomyocytes to Ang II and thereby to cardiac hypertrophy. Furthermore, ET-1 exerts multifaceted effects on the RAA system, such as dose-dependent inhibition of renin synthesis, and stimulation of aldosterone secretion. The finding of abundant specific ET-1 receptors in the adrenocortical zona glomerulosa (ZG) suggested a direct secretagogue effect of ET-1. In rats, ETB receptors mediate such an effect, whilst in humans, both ETA and ETB receptor subtypes intervene in regulating the transcription of the aldosterone synthase gene. In addition, ET-1 stimulates DNA synthesis and proliferation of ZG cells via ETA receptors and, therefore, might play a role in cell turnover of the normal adrenal cortex and in the onset of adrenal tumours. Studies on the in vivo interactions between ETs and the RAA system have given conflicting results, insofar as some suggested a participation of ET-1 in the pressor and cellular effects of exogenously administered Ang II, whereas others did not in the transgenic TGR(Ren 2m)27 rats and in the two-kidney, one clip.

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Objective— Galectin-3 (Gal-3) can affect atherogenesis by multiple mechanisms, but it remains scarcely known whether plasma Gal-3 levels predict cardiovascular events in patients with coronary artery disease. Therefore, we investigated if Gal-3 predicts cardiovascular death in patients with coronary artery disease of the Genetic and ENvironmental factors In Coronary Artery disease study. Approach and Results— In a prospective cohort study, we measured the plasma levels of Gal-3 in 1013 randomly selected patients who underwent coronary angiography and long-term follow-up to assess incident cardiovascular events. The primary end points were (1) cardiovascular death and (2) a composite of cardiovascular death, acute coronary syndrome, and stroke. Secondary end points entailed (1) acute myocardial infarction, (2) stroke, and (3) a composite fatal ischemic event including fatal myocardial infarction and stroke. The effect of Gal-3 on prognosis was assessed using Kaplan–Meier analysis and multivariate Cox’s regression. During long-term follow-up (median, 7.2 years), 115 cardiovascular deaths occurred (15.2%), more commonly in the high Gal-3 tertile (25.2%) than in the intermediate and the low tertiles (13.6% versus 7.5%, respectively; P <0.001). The adverse prognostic effect of high Gal-3 was confirmed in subgroup analysis of the patients with angiographically documented coronary artery disease and also of those with a normal left ventricular ejection fraction. At multivariate analysis, Gal-3 was a predictor of cardiovascular mortality (hazard ratio, 1.79; 95% confidence interval, 1.10–2.93; P =0.020) along with age, left ventricular ejection fraction, and coronary atherosclerotic burden. Conclusions— In high cardiovascular risk patients referred for coronary angiography Gal-3 is a strong independent predictor of cardiovascular death.

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Several peptides of the RAS other than angiotensin (1-8) have been identified. They are generally referred as 'angiotensin fragments': Ang (2-8), Ang (3-8) and Ang (1-7) and have been detected in human tissues. There is evidence that they may play a functional role in humans by acting in concert with angiotensin (1-8) and aldosterone. Available knowledge on the pathways leading to synthesis and degradation of angiotensin fragments, as well as on their interactions with receptors and on their possible role in cardiovascular homeostasis and disease are reviewed.