Eplerenone Survival Benefits in Heart Failure Patients Post-Myocardial Infarction Are Independent From its Diuretic and Potassium-Sparing Effects

Rossignol, Patrick; Ménard, Joël; Fay, Renaud; Gustafsson, Finn; Pitt, Bertram; Zannad, Faı̈ez

doi:10.1016/j.jacc.2011.04.049

Cited by 118 publications

(41 citation statements)

References 35 publications

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“…27 The lack of available data to help clinicians in decongestion strategies is worrisome and requires further investigation. 28,29 More recently, hemoconcentration has emerged as a possible target to assess decongestion in HF, 12–18 particularly when assessed both at admission and discharge, since early improvements in congestion that are not sustained through hospital stay are not likely to be associated with improved outcomes. 30 The difference between admission and discharge Hb is likely to be a good candidate to assess hemoconcentration.…”

Section: Discussionmentioning

confidence: 99%

Enlarging Red Blood Cell Distribution Width During Hospitalization Identifies a Very High-Risk Subset of Acutely Decompensated Heart Failure Patients and Adds Valuable Prognostic Information on Top of Hemoconcentration

et al. 2016

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Section: Discussionmentioning

confidence: 99%

Enlarging Red Blood Cell Distribution Width During Hospitalization Identifies a Very High-Risk Subset of Acutely Decompensated Heart Failure Patients and Adds Valuable Prognostic Information on Top of Hemoconcentration

et al. 2016

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“…The addition of MR antagonists to standard treatment of heart and renal failure not only decreases morbidity and mortality, it has been shown in many studies to increase quality of life measures (386, 431, 502, 509). In addition, treatment of hypertensive subjects was reported to increase their score on a cognitive test (488).…”

Section: Pathophysiological Implications Of Inappropriate Mr Activationmentioning

confidence: 99%

“…Inappropriate activation of MR in the heart, vessels, kidneys, and brain hemodynamic control centers results in increased reactive oxygen species, inflammation and cardiovascular and renal disease (175). Use of MR antagonists has increased considerably in the last decade since clinical studies demonstrated their significant benefit as additions to standard therapy for chronic heart failure despite normal to low plasma aldosterone (aldo) levels in these patients (175, 386, 499). Addition of MR antagonists to hypertension treatment reduces diuretic-induced sympathetic nervous system activation resulting in insulin resistance (366), as well as the insulin resistance of the metabolic syndrome (440, 478).…”

Section: Introductionmentioning

confidence: 99%

The Multifaceted Mineralocorticoid Receptor

Gómez-Sánchez

2014

Comprehensive Physiology

277

224

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The primary adrenal cortical steroid hormones, aldosterone, and the glucocorticoids cortisol and corticosterone, act through the structurally similar mineralocorticoid (MR) and glucocorticoid receptors (GRs). Aldosterone is crucial for fluid, electrolyte, and hemodynamic homeostasis and tissue repair; the significantly more abundant glucocorticoids are indispensable for energy homeostasis, appropriate responses to stress, and limiting inflammation. Steroid receptors initiate gene transcription for proteins that effect their actions as well as rapid non-genomic effects through classical cell signaling pathways. GR and MR are expressed in many tissues types, often in the same cells, where they interact at molecular and functional levels, at times in synergy, others in opposition. Thus the appropriate balance of MR and GR activation is crucial for homeostasis. MR has the same binding affinity for aldosterone, cortisol, and corticosterone. Glucocorticoids activate MR in most tissues at basal levels and GR at stress levels. Inactivation of cortisol and corticosterone by 11β-HSD2 allows aldosterone to activate MR within aldosterone target cells and limits activation of the GR. Under most conditions, 11β-HSD1 acts as a reductase and activates cortisol/corticosterone, amplifying circulating levels. 11β-HSD1 and MR antagonists mitigate inappropriate activation of MR under conditions of oxidative stress that contributes to the pathophysiology of the cardiometabolic syndrome; however, MR antagonists decrease normal MR/GR functional interactions, a particular concern for neurons mediating cognition, memory, and affect.

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“…Obesity is associated with increased risk for cardiovascular disease [3], but the underlying mechanisms are not completely understood. Substantial evidence supports an independent role of aldosterone in the development and progression of cardiovascular disease [4–6]. According to the classic view of physiology, aldosterone is secreted by the adrenal gland and is involved in blood pressure regulation by acting on the kidney via activation of epithelial mineralocorticoid receptors (MR) [7].…”

Section: Introductionmentioning

confidence: 99%

Mineralocorticoid receptors modulate vascular endothelial function in human obesity

et al. 2013

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Obesity increases linearly with age and is associated with impaired vascular endothelial function and increased risk for cardiovascular disease. Mineralocorticoid receptors (MR) contribute to impaired vascular endothelial function in cardiovascular disease; however, their role in uncomplicated human obesity is unknown. Because plasma aldosterone levels are elevated in obesity and adipocytes may be a source of aldosterone, we hypothesized that MR modulate vascular endothelial function in older adults in an adiposity-dependent manner. To test this hypothesis, we administered MR blockade (Eplerenone; 100 mg/day) for 1 month in a balanced, randomized, double-blind, placebo-controlled, crossover study to 22 older adults (10 men, 55–79 years) varying widely in adiposity (body mass index: 20–45 kg/m2) but who were free from overt cardiovascular disease. We evaluated vascular endothelial function (brachial artery flow-mediated dilation [FMD] via ultrasonography) and oxidative stress (plasma F2-isoprostanes and vascular endothelial cell protein expression of nitrotyrosine and NADPH oxidase p47phox) during placebo and MR blockade. In the whole group, oxidative stress (P>0.05) and FMD did not change with MR blockade (6.39±0.67 vs. 6.23±0.73 %, P=0.7, placebo vs. Eplerenone). However, individual improvements in FMD in response to Eplerenone were associated with higher total body fat (body mass index: r=0.45, P=0.02 and DXA-derived % body fat: r=0.50, P=0.009) and abdominal fat (total: r=0.61, P=0.005, visceral: r=0.67, P=0.002 and subcutaneous: r=0.48, P=0.03). In addition, greater improvements in FMD with Eplerenone were related with higher baseline fasting glucose (r=0.53, P=0.01). MR influence vascular endothelial function in an adiposity-dependent manner in healthy older adults.

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Eplerenone Survival Benefits in Heart Failure Patients Post-Myocardial Infarction Are Independent From its Diuretic and Potassium-Sparing Effects

Abstract: Eplerenone's beneficial effects on long-term survival and cardiovascular outcomes are independent from early potassium-sparing or diuretic effects, suggesting that mineralocorticoid receptor antagonism provides cardiovascular protection beyond its diuretic and potassium-sparing properties.

Cited by 118 publications

References 35 publications

Enlarging Red Blood Cell Distribution Width During Hospitalization Identifies a Very High-Risk Subset of Acutely Decompensated Heart Failure Patients and Adds Valuable Prognostic Information on Top of Hemoconcentration

Enlarging Red Blood Cell Distribution Width During Hospitalization Identifies a Very High-Risk Subset of Acutely Decompensated Heart Failure Patients and Adds Valuable Prognostic Information on Top of Hemoconcentration

The Multifaceted Mineralocorticoid Receptor

Mineralocorticoid receptors modulate vascular endothelial function in human obesity

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