Elevated Plasma Aldosterone Levels Despite Complete Inhibition of the Vascular Angiotensin-Converting Enzyme in Chronic Heart Failure

Abstract

Background-Plasma aldosterone levels are elevated in patients with chronic heart failure (CHF) taking angiotensinconverting enzyme (ACE) inhibitors. Elevated aldosterone levels may reflect incomplete inhibition of the vascular converting enzyme during long-term ACE inhibition. We simultaneously measured plasma aldosterone levels and the degree of inhibition of the vascular converting enzyme in patients with CHF. Methods and Results-Thirty-four subjects with CHF receiving the maximum recommended doses of ACE inhibitors for a duration of 3 to 105 months were studied. The pressor response to exogenous angiotensin I (AI) was measured and normalized for the pressor response to angiotensin II (AII) to assess inhibition of the vascular converting enzyme (AII/AI ratio). Aldosterone levels were determined by solid-phase radioimmunoassay. Eleven of the 34 subjects had plasma aldosterone levels above the upper limit of normal, ie, Ͼ15.0 ng/dL. Seven of these 11 subjects (64%) had an AII/AI ratio Յ0.05, indicating complete inhibition of the vascular converting enzyme. In the entire cohort, the AII/AI ratio did not correlate with the duration of ACE inhibitor therapy. Conclusions-Plasma aldosterone levels are elevated in patients with CHF during long-term ACE inhibitor therapy despite complete inhibition of the vascular converting enzyme. Complete inhibition of the vascular converting enzyme does not obviate the need for aldosterone receptor blockade in patients with CHF.

Toward a broader understanding of aldosterone in congestive heart failure

“…10 the inability of angiotensin-converting enzyme (ACE) inhibition to provide for sustained suppression of plasma ALDO in patients with CHF, 11,12 which indicated that the regulation of its secretion by zona glomerulosa cells of the adrenal cortex is more complex than that governed by angiotensin II (Ang II) alone; and finally, the results of a controlled clinical trial (Randomised ALdactone Evaluation Study [RALES]), conducted in 19 countries on five continents in over 1,600 patients with CHF, wherein spironolactone (vis-à-vis placebo), in combination with an ACE inhibitor (ACE-I) and loop diuretic, reduced the risk of allcause and cardiac-related mortality and cardiovascular morbidity by 30%. 13 Herein, less well recognised properties of ALDO, mediated by receptor-ligand binding, are briefly reviewed.…”

Mineralocorticoid receptor activation in myocardial infarction and failure: recent advances

“…Prolonged elevation of angiotensin II and aldosterone could be an adaptive response to maintain blood pressure on the short term, but in chronic heart failure induces detrimental effects on cardiovascular structure. Moveover, despite complete vascular ACE inhibition, plasma aldosterone levels are elevated in patients with heart failure [55]. Even the combination of ACE inhibition and angiotensin II antagonism only transiently reduces aldosterone plasma levels in patients with heart failure [56] suggesting angiotensin II-independent aldosterone production.…”

A Janus‐headed electrolyte and ‘RALES' disease’

“…Aldosterone and eplerenone retain potassium and have direct effects on the myocardium. Because aldosterone levels are often increased despite RAAS blockade,7 simultaneous application of MRA has an additive effect over ACE inhibitors and angiotensin receptor blockers.…”