Heart 1999;82:57-61 ( July )

How often are angiotensin II and aldosterone concentrations raised during chronic ACE inhibitor treatment in cardiac failure?

R J MacFadyen^a, A F C Lee^a, J J Morton^b, S D Pringle^a, A D Struthers^a

^a Departments of Clinical Pharmacology and Cardiology, Cardiovascular Research Group, Ninewells Hospital and Medical School, University of Dundee, Dundee DD1 9SY, UK, ^b Medical Research Council Clinical Research Initiative in Heart Failure, Wolfson Building, University of Glasgow, Glasgow G11 6NT, UK

Correspondence to: Dr MacFadyen, Cardiac Unit (Floor 7), Raigmore Hospital, Inverness IV2 3UJ, UK. email: rjmacf{at}aol.com

Accepted for publication 4 February 1999

OBJECTIVEAngiotensin II (AII) and aldosterone are not always fully suppressed during chronic angiotensin converting enzyme (ACE) inhibitor treatment. In congestive heart failure (CHF) such failure of hormonal suppression is associated with increased mortality. This study examined how common AII and aldosterone increases are observed during routine clinical practice.
PATIENTS AND METHODS91 patients with symptomatic (mean New York Heart Association class 2.7) CHF (mean (SD) left ventricular ejection fraction 29.9 (8)%, range 9-46%) were studied 4-6 hours after ACE inhibitor dosing. A representative range of ACE inhibitors (enalapril, lisinopril, captopril, perindopril, and fosinopril) was examined.
RESULTSSupine measurements showed a wide range of AII (10.5 (25.5) pg/ml), aldosterone (130.8 (136) pg/ml), and serum ACE (12.1 (13.3) EU/l; excludes captopril data) concentrations on diuretics. AII concentrations > 10 pg/ml were seen in 15% of patients, and aldosterone concentrations > 144 pg/ml were seen in 38% of patients. AII concentrations were significantly correlated (p < 0.001) with ACE but not with aldosterone concentrations. Aldosterone concentrations were not significantly correlated with ACE concentrations.
CONCLUSIONSAII "reactivation" occurred in 15% and failure of aldosterone suppression in 38% of routine CHF patients taking ACE inhibitor treatment. AII "reactivation" was associated with both low and high levels of ACE activity, which suggests that multiple different mechanisms are at play. In patients with high plasma ACE concentrations, non-compliance should be considered along with inadequate dose titration. In patients with low plasma ACE and high AII concentrations, non-ACE mediated production of AII may be operative. Raised aldosterone concentrations appear to be more common than AII "reactivation". It is important to establish the cause of detectable or increased AII concentrations in a heart failure patient treated with an ACE inhibitor. The measurement of serum ACE may help to identify the likely cause as poor compliance or inadequate dose.


Keywords: heart failure; hormone suppression; angiotensin II; aldosterone; angiotensin converting enzyme inhibitors; compliance

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© 1999 by Heart
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