Demonstration of Blood Pressure-Independent Noninfarct Myocardial Fibrosis in Primary Aldosteronism

Abstract

Background-Primary aldosteronism (PA) is common and associates with excess cardiovascular morbidity independent of blood pressure. Exposure to aldosterone and sodium leads to cardiac fibrosis and hypertrophy in humans and animals possibly mediated by inflammation and oxidative stress. We aimed to clarify the effects of aldosterone excess on myocardial structure and composition in human subjects with PA and essential hypertension using contrast-enhanced cardiac magnetic resonance imaging as well as explore the mechanistic basis for any observed differences. Methods and Results-Twenty-seven subjects with recently diagnosed PA and 54 essential hypertension controls were recruited. Subjects underwent gadolinium-enhanced cardiac magnetic resonance; noninfarct related myocardial fibrosis was identified by a diffuse pattern of late gadolinium enhancement. Patients also underwent assessment of pulse wave velocity, measurement of circulating superoxide anion and C-reactive protein, as well as blood pressure and biochemical assessment. Subjects were well matched with no difference in severity or duration of hypertension. There was a significant increase in the frequency of noninfarct late gadolinium enhancement in PA (70%) when compared with essential hypertension subjects (13%; P<0.0001) with no difference in left ventricular mass. Pulse wave velocity, superoxide, and C-reactive protein were significantly higher in subjects with PA. Conclusions-These data illustrate that patients with PA exhibit frequent myocardial fibrosis as demonstrated by late gadolinium enhancement using cardiac magnetic resonance imaging; this finding is independent of blood pressure. This may be mediated partly through inflammation and oxidative stress. This study highlights the importance of specific targeting of aldosterone excess as well as blood pressure reduction to minimize cardiac morbidity in PA. (Circ Cardiovasc Imaging. 2012;5:740-747.)

Reactive Oxygen Species, Vascular Noxs, and Hypertension: Focus on Translational and Clinical Research

“…Patients with primary hyperaldosteronism exhibit increased levels of plasma ROS and markers of subclinical inflammation compared with essential hypertensive patients (60,196). These findings were associated with increased cardiac fibrosis, phenomena that were independent of blood pressure elevation but related to proinflammatory and oxidative stress effects of aldosterone.…”

An update on novel mechanisms of primary aldosteronism

“…Comparison of cardiovascular events in a large controlled cross-sectional study, involving 459 patients with PA and 1290 controls with essential hypertension, individually matched for sex, age, and office systolic blood pressure, showed an increased prevalence of left ventricular hypertrophy, coronary artery disease, nonfatal myocardial infarction, heart failure, and atrial fibrillation (Savard et al 2013). The excess cardiovascular morbidity is related to blood pressure-independent cardiac remodeling (Rossi et al 1997) and myocardial fibrosis (Freel et al 2012), with left ventricular changes being reversible in the long-term with surgical or medical treatment of PA (Rossi et al 2013). Vascular remodeling associated with aldosterone excess and duration of hypertension predict the outcome of adrenalectomy in patients with PA, emphasizing the importance of early diagnosis of unilateral forms of the disease (Rossi et al 2008).…”

Progrès récents dans la génétique de l’hyperaldostéronisme primaire

“…Dans une autre étude multicentrique, les mutations ATP1A1 et ATP2B3 étaient plus fréquentes chez les hommes, et associées à une aldostéronémie plus élevée et une kaliémie plus basse [11]. 4 [27]. Récemment, l'origine génétique du FH-III dans cette famille a été attribuée à la mutation p.Thr158Ala du gène KCNJ5 [8].…”

“…Ainsi, une large étude transversale comparant ces deux types de patients appariés individuellement selon le sexe, l'âge et la pression artérielle systolique, a montré, chez les patients avec HAP, une augmentation de la survenue d'événements cardiovasculaires tels que hypertrophie ventriculaire gauche, maladies coronariennes, infarctus du myocarde ou encore fibrillation auriculaire [2]. Cette augmentation de la morbidité cardiovasculaire pourrait être liée à un remodelage cardiaque [3] et une fibrose myocardique [4], se déve-loppant de façon indépendante du niveau de pression artérielle. À long terme, le traitement de l'hyperaldostéronisme primaire permet une réversibilité de l'hypertrophie ventriculaire gauche [5].…”