Fiftieth anniversary of aldosterone: from discovery to cardiovascular therapy.
Half a century after the elucidation of its molecular structure, aldosterone is generating the greatest interest, not in the fields of endocrinology or renal medicine but in cardiology-where aldosterone over-activation is now perceived as detrimental in heart failure (HF) and ischaemic heart disease. Clinically, excess aldosterone is associated with higher morbidity and mortality after myocardial infarction (MI) and HF. The Randomised Aldactone Evaluation Study (RALES) study in severe chronic heart failure and the Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival (EPHESUS) study in post-MI heart failure have shown that use of non-selective and selective aldosterone receptor antagonists, respectively, improves prognosis. The pathophysiological mechanisms underpinning these damaging aldosterone-mediated cardiovascular effects are still being elucidated, but prime candidates include cardiomyocyte necrosis and apoptosis, and myocardial fibrosis resulting in adverse cardiac remodelling, coronary vasculopathy, tachyarrhythmia and positive feedback activation of the renin-angiotensin-aldosterone system. Practical points for consideration when instigating therapy include preferential use of aldosterone receptor antagonists to maintain electrolyte balance whenever loop or thiazide diuretics are used (vulnerable HF patients require higher ranges of potassium and magnesium to minimise propensity for tachyarrthythmia), for renoprotection and for counteracting aldosterone breakthrough despite adequate ACE inhibition; use of the minimum doses of loop diuretics required to lessen activation of the renin-angiotensin-aldosterone system in HF; use of selective aldosterone receptor antagonists to avoid gynaecomastia/mastalgia and impotence; and prophylactic use of aldosterone receptor antagonists to improve prognosis.
Academic Unit of Molecular Cardiovascular Medicine, University of Leeds, G Floor, Martin Wing, Leeds General Infirmary, Leeds, LS1 3EX, UK.
Lip-Bun
LB
Tan
Dominik
D
Schlosshan
Diane
D
Barker
D000450:Aldosterone / Q000502:physiology*; D006333:Heart Failure / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology*; D006801:Humans; D000451:Mineralocorticoid Receptor Antagonists / Q000627:therapeutic use; D009203:Myocardial Infarction / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology*; D012084:Renin-Angiotensin System / Q000502:physiology; D020257:Ventricular Remodeling / Q000502:physiology
D000451:Mineralocorticoid Receptor Antagonists; D000450:Aldosterone