Plasma endothelin in congestive heart failure: effect of the ACE inhibitor, fosinopril.
OBJECTIVE
The study evaluates the influence of treatment with the angiotensin-converting enzyme inhibitor, fosinopril, on the plasma endothelin level in patients with congestive heart failure, and the relationship between plasma endothelin and clinical study parameters (bicycle exercise test, echocardiography, heart failure score and blood pressure).


METHODS
Plasma endothelin was measured in 34 patients with moderately severe congestive heart failure at randomisation in the fosinopril/placebo-controlled study 'Fosinopril Efficacy and Safety Trial' and at the end of the 12-week study period.


RESULTS
The patients had elevated pre-treatment plasma endothelin concentrations (3.5 +/- 1.2 pg/ml, mean +/- s.d., n = 34) compared with healthy volunteers (2.0 +/- 0.4 pg/ml, n = 21, P < 0.0001). Treatment with fosinopril for 12 weeks lowered plasma endothelin from 3.5 +/- 1.2 to 2.5 +/- 0.7 pg/ml (m = 18, P < 0.005), in contrast to the non-significant increase in the placebo-treated group 3.5 +/- 1.3 to 4.3 +/- 2.4 pg/ml, n = 16). A multiple regression analysis for baseline study parameters, demonstrated a significant relationship between plasma endothelin and exercise test duration and a composite heart failure score classification (r = 0.53, P < 0.001).


CONCLUSIONS
Treatment of patients with congestive heart failure with the angiotensin-converting enzyme inhibitor, fosinopril, reduce the elevated plasma endothelin level to normal values. The relation between plasma endothelin and clinical parameters indicates that endothelin may play a pathophysiological role in the progression of congestive heart failure.
Galatius-Jensen
S
S
Department of Medicine B, University Hospital, Rigshospitalet, Copenhagen, Denmark.
Wroblewski
H
H
Emmeluth
C
C
Bie
P
P
Haunsø
S
S
Kastrup
J
J
D000368:Aged; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D004311:Double-Blind Method; D004452:Echocardiography; D016232:Endothelins / Q000097:blood*; D005080:Exercise Test; D005260:Female; D017328:Fosinopril / Q000627:therapeutic use*; D006333:Heart Failure / Q000097:blood* / Q000188:drug therapy / Q000503:physiopathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D012044:Regression Analysis
D000806:Angiotensin-Converting Enzyme Inhibitors; D016232:Endothelins; D017328:Fosinopril