Selective targeting of the mineralocorticoid receptor in cardiovascular disease

2015 ◽  
Author(s):  
Morag Young
Hypertension ◽  
2021 ◽  
Vol 77 (5) ◽  
pp. 1442-1455
Author(s):  
Pantelis Sarafidis ◽  
Christodoulos E. Papadopoulos ◽  
Vasilios Kamperidis ◽  
George Giannakoulas ◽  
Michael Doumas

Chronic kidney disease (CKD) and cardiovascular disease are intimately linked. They share major risk factors, including age, hypertension, and diabetes, and common pathogenetic mechanisms. Furthermore, reduced renal function and kidney injury documented with albuminuria are independent risk factors for cardiovascular events and mortality. In major renal outcome trials and subsequent meta-analyses in patients with CKD, ACE (angiotensin-converting enzyme) inhibitors and ARBs (angiotensin II receptor blockers) were shown to effectively retard CKD progression but not to significantly reduce cardiovascular events or mortality. Thus, a high residual risk for cardiovascular disease progression under standard-of-care treatment is still present for patients with CKD. In contrast to the above, several outcome trials with SGLT-2 (sodium-glucose cotransporter-2) inhibitors and MRAs (mineralocorticoid receptor antagonists) clearly suggest that these agents, apart from nephroprotection, offer important cardioprotection in this population. This article discusses existing evidence on the effects of SGLT-2 inhibitors and MRAs on cardiovascular outcomes in patients with CKD that open new roads in cardiovascular protection of this heavily burdened population.


2018 ◽  
Vol 31 (11) ◽  
pp. 1165-1174 ◽  
Author(s):  
Mathieu Buonafine ◽  
Benjamin Bonnard ◽  
Frédéric Jaisser

Hypertension ◽  
2020 ◽  
Vol 76 (5) ◽  
pp. 1600-1607
Author(s):  
Aisha T. Langford ◽  
Oluwasegun P. Akinyelure ◽  
Tony L. Moore ◽  
George Howard ◽  
Yuan-I Min ◽  
...  

Resistant hypertension, defined as blood pressure levels above goal while taking ≥3 classes of antihypertensive medication or ≥4 classes regardless of blood pressure level, is associated with increased cardiovascular disease risk. The 2018 American Heart Association Scientific Statement on Resistant Hypertension recommends healthy lifestyle habits and thiazide-like diuretics and mineralocorticoid receptor antagonists for adults with resistant hypertension. The term apparent treatment-resistant hypertension (aTRH) is used when pseudoresistance cannot be excluded. We estimated the use of healthy lifestyle factors and recommended antihypertensive medication classes among US Black adults with aTRH. Data were pooled for Black participants in the JHS (Jackson Heart Study) in 2009 to 2013 (n=2496) and the REGARDS study (Reasons for Geographic and Racial Differences in Stroke) in 2013 to 2016 (n=3786). Outcomes included lifestyle factors (not smoking, not consuming alcohol, ≥75 minutes of vigorous-intensity or ≥150 minutes of moderate or vigorous physical activity per week, and body mass index <25 kg/m 2 ) and recommended antihypertensive medications (thiazide-like diuretics and mineralocorticoid receptor antagonists). Overall, 28.3% of participants who reported taking antihypertensive medication had aTRH. Among participants with aTRH, 14.5% and 1.2% had ideal levels of 3 and 4 of the lifestyle factors, respectively. Also, 5.9% of participants with aTRH reported taking a thiazide-like diuretic, and 9.8% reported taking a mineralocorticoid receptor antagonist. In conclusion, evidence-based lifestyle factors and recommended pharmacological treatment are underutilized in Black adults with aTRH. Increased use of lifestyle recommendations and antihypertensive medication classes specifically recommended for aTRH may improve blood pressure control and reduce cardiovascular disease–related morbidity and mortality among US Black adults. Graphic Abstract A graphic abstract is available for this article.


2009 ◽  
Vol 42 (6) ◽  
pp. 449-459 ◽  
Author(s):  
Amanda J Rickard ◽  
Morag J Young

The mineralocorticoid receptor (MR) and glucocorticoid receptor are ligand-activated transcription factors that have important physiological and pathophysiological actions in a broad range of cell types including monocytes and macrophages. While the glucocorticoids cortisol and corticosterone have well-described anti-inflammatory actions on both recruited and tissue resident macrophages, a role for the mineralocorticoid aldosterone in these cells is largely undefined. Emerging evidence, however, suggests that MR signalling may promote pro-inflammatory effects. This review will discuss the current understanding of the role of corticosteroid receptors in macrophages and their effect on diseases involving inflammation, with a particular focus on cardiovascular disease.


2019 ◽  
Vol 181 (6) ◽  
pp. C23-C28 ◽  
Author(s):  
Onno C Meijer ◽  
Alberto M Pereira

A comprehensive study from Denmark established that the systemic use of glucocorticoids hormones has an annual prevalence of 3% and has been stable from 1999 to 2014. We comment on the risk of potentially long-lasting adverse effects, dependent on glucocorticoid receptor overactivation, but also mineralocorticoid receptor under-activation. We discuss the potential effects of glucocorticoid use on efficacy and toxicity of other drugs that are frequently taken concomitantly. We discuss the potential alternatives such as more selective targeting, and novel types of glucocorticoid receptor ligands. We conclude that pending improved therapies more conservative prescription of glucocorticoids may be warranted in clinical practice.


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