Aldosterone and the Heart: From Basic Research to Clinical Evidence

Abstract

Recent views suggest that long-term exposure to elevated aldosterone concentrations might result in cardiac, vascular, renal, and metabolic sequelae that occur independent of the blood pressure level. Indirect evidence of the untoward effects of aldosterone on the heart has been clearly established in clinical studies that have tested the effects of mineralocorticoid receptor antagonists in the treatment of systolic heart failure. As it has become clear in recent years, the interaction between aldosterone and the heart has to deal with additional actions of the hormone on specific cell types, cellular mechanisms, and molecules that are involved in regulation of tissue responses, leading to hypertrophy, remodeling, and fibrosis. The majority of these effects are mediated by activation of the mineralocorticoid receptors that are expressed in cardiomyocytes and cardiac fibroblasts, and mediate the genomic effects of the hormone. Evidence of interactions between aldosterone and the heart that occur independent of the renal effects of aldosterone, however, is not limited to the context of systolic heart failure and observations obtained in other disease states have led, together with findings of animal studies, to a better understanding of the potential benefits of aldosterone antagonists. In this narrative overview, we highlight the most recent findings that have been obtained in experimental animal models and in clinical conditions that include, in addition to systolic heart failure, primary aldosteronism, essential hypertension, diastolic heart failure, and arrhythmia.

Dietary Salt Intake Is a Determinant of Cardiac Changes After Treatment of Primary Aldosteronism

“…Elevated aldosterone is associated with fibrotic and inflammatory changes in the heart and both animal and clinical studies have documented that these changes are associated with LV hypertrophy. 20 Evidence of a relationship between circulating aldosterone levels and LV mass has been obtained in population studies, 21,22 in cross-sectional 23,24 and longitudinal studies of patients with primary hypertension, 25 and in normotensive patients with familial hyperaldosteronism type I. 26 However, most of the clinical evidence in support of an independent contribution of aldosterone to the development and progression of LV hypertrophy comes from studies conducted in patients with primary aldosteronism.…”

Comparison of Cardiovascular Complications in Patients with and without <i>KCNJ5</i> Gene Mutations Harboring Aldosterone-producing Adenomas

“…Excess aldosterone secretion induces both pressure overload and hypervolemia via sodium retention and vasoconstriction and directly triggers the onset of cardiac fibrosis, possibly induced by various inflammatory reactions 7,49,50) . In the present study, the patients in the wild type group did not display any changes in the LVMI values at one year postoperatively.…”

Cardiovascular Complications Associated With Primary Aldosteronism

“…3,[35][36][37] The mechanisms by which aldosterone exerts its deleterious effect are outside the scope of this clinical study but include chronic intravascular fluid retention, oxidative stress, endothelial dysfunction, inflammation, remodeling, hypertrophy, and fibrosis. 3,35,38,39 These mechanisms lead to structural abnormalities, including an increase in arterial wall stiffness 40 and carotid intima-media thickness, 41 the formation of carotid plaques, 42 and myocardial fibrosis. 43 Many hypotheses have been proposed to explain the higher frequency of AF in PA patients: low potassium concentration per se, the increase in left atrial volume, the excess LVM secondary to both excess aldosterone and hypertension, myocardial fibrosis or ischemia, magnesium losses, and catecholamine potentiation.…”

“…In addition to these well-known effects, there is compelling evidence to suggest that prolonged exposure to high aldosterone concentrations has a deleterious effect on cardiovascular tissues and is associated with target organ damage, independently of blood pressure (BP). [2][3][4] Previous studies have been limited by small sample sizes and potential confounders not accounted for in the study design or analysis.…”