A new HOPE for aldosterone blockade?

Abstract

Aldosterone is increasingly recognized to play an important role in the pathophysiology of heart failure due to systolic left ventricular dysfunction (SLVD) and aldosterone blockade (AB) to be effective in reducing mortality and morbidity in patients with severe chronic heart failure and heart failure due to SLVD after myocardial infarction.1,2 AB has also been shown to reduce blood pressure and target-organ damage in patients with essential hypertension.3 The effect of AB on mortality and morbidity will soon be investigated in patients with mild to moderate heart failure due to SLVD and in patients with heart failure with preserved left ventricular systolic function. Although AB has been shown to be effective in patients with SLVD and in those with essential hypertension without SLVD, increasing evidence suggests that it may have an even greater role in patients with atherosclerosis of the coronary and other vascular beds. See p 1819 It is reasonable to assume that aldosterone influences vascular function because mineralocorticoid receptors are expressed in vascular endothelial and smooth muscle cells as well as in cardiac fibroblasts and cardiomyocytes.4 Many of the pathophysiological effects of angiotensin II on the myocardium and vascular wall may, in a large part, be due to aldosterone and can be blocked by AB as well as by an angiotensin-converting enzyme inhibitor (ACE-I) or angiotensin receptor blocker (ARB); however, it appears that the combination of an AB with an ACE-I or ARB may be more effective than either alone in preventing myocardial and vascular inflammation and remodeling. Although angiotensin II is a major stimulus for the production of aldosterone, other stimuli such as potassium are also important (“aldosterone escape”), as illustrated by the ability to stimulate aldosterone production in the angiotensinogen-knockout mouse.5 These data suggest that AB could add to the benefits of ACE-I …