The clinical implications of aldosterone escape in congestive heart failure.
Angiotensin converting enzyme (ACE) inhibitor therapy does not reliably suppress aldosterone production, and 'aldosterone escape' occurs in up to 40% of patients with congestive heart failure (CHF). Aldosterone levels correlate with the risk of cardiovascular events. Aldosterone adversely affects the risk of cardiovascular events via mineralocorticoid receptors in the heart, blood vessels and other sites. Notably, aldosterone contributes to endothelial dysfunction and attenuates endothelium-dependent vasodilatation, at least partly by reducing nitric oxide bioavailability. Aldosterone also promotes myocardial fibrosis and cardiac remodelling by enhancing collagen synthesis, resulting in increased myocardial stiffness and increased left ventricular mass. These mechanisms mediated by aldosterone contribute to increased risk of ventricular arrhythmias and sudden cardiac death. Two major prospective trials, including one in which patients routinely received ACE inhibitor and beta blocker therapy, have shown that the use of an aldosterone blocker significantly reduces all-cause mortality, sudden cardiovascular death and hospitalisation in patients with acute or chronic left ventricular dysfunction or CHF. Inhibition of aldosterone's effect on mineralocorticoid receptors should now be considered standard therapy in these patient populations.
Division of Medicine and Therapeutics, Ninewells Hospital and Medical School, Dundee DD1 9SY, UK. a.d.struthers@dundee.ac.uk
Allan D
AD
Struthers
D000450:Aldosterone / Q000097:blood* / Q000502:physiology; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D016757:Death, Sudden, Cardiac; D004730:Endothelium, Vascular / Q000503:physiopathology; D000077545:Eplerenone; D005355:Fibrosis; D006333:Heart Failure / Q000097:blood* / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D009206:Myocardium / Q000473:pathology; D013148:Spironolactone / Q000031:analogs & derivatives* / Q000627:therapeutic use; D020257:Ventricular Remodeling / Q000502:physiology
D000806:Angiotensin-Converting Enzyme Inhibitors; D013148:Spironolactone; D000450:Aldosterone; D000077545:Eplerenone