title: How often are angiotensin II and aldosterone concentrations raised during chronic ACE inhibitor treatment in cardiac failure?
abstract: OBJECTIVE
  Angiotensin 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.
  
  
  METHODS
  91 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.
  
  
  RESULTS
  Supine 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.
  
  
  CONCLUSIONS
  AII "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.
authors.affiliation: Departments of Clinical Pharmacology and Cardiology, Cardiovascular Research Group, Ninewells Hospital and Medical School, University of Dundee, Dundee DD1 9SY, UK. rjmacf@aol.com
authors.forename: R J
authors.initials: RJ
authors.lastname: MacFadyen
authors.forename: A F
authors.initials: AF
authors.lastname: Lee
authors.forename: J J
authors.initials: JJ
authors.lastname: Morton
authors.forename: S D
authors.initials: SD
authors.lastname: Pringle
authors.forename: A D
authors.initials: AD
authors.lastname: Struthers
mesh_terms: D000368:Aged; D000450:Aldosterone / Q000097:blood*; D000804:Angiotensin II / Q000097:blood*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood; D002216:Captopril / Q000627:therapeutic use; D004656:Enalapril / Q000627:therapeutic use; D005260:Female; D017328:Fosinopril / Q000627:therapeutic use; D006333:Heart Failure / Q000097:blood* / Q000188:drug therapy*; D006801:Humans; D007211:Indoles / Q000627:therapeutic use; D017706:Lisinopril / Q000627:therapeutic use; D008297:Male; D007703:Peptidyl-Dipeptidase A / Q000097:blood; D020913:Perindopril; D017211:Treatment Failure
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D015415:Biomarkers; D007211:Indoles; D000804:Angiotensin II; D000450:Aldosterone; D004656:Enalapril; D002216:Captopril; D017706:Lisinopril; D007703:Peptidyl-Dipeptidase A; D017328:Fosinopril; D020913:Perindopril