Neurohormonal activation in heart failure after acute myocardial infarction treated with beta-receptor antagonists.
BACKGROUND
Few studies have described how neurohormonal activation is influenced by treatment with beta-receptor antagonists in patients with heart failure after acute myocardial infarction. The aims were to describe neurohormonal activity in relation to other variables and to investigate treatment effects of a beta(1) receptor-antagonist compared to a partial beta(1) receptor-agonist.


METHODS
Double-blind, randomized comparison of metoprolol 50-100 mg b.i.d. (n=74), and xamoterol 100-200 mg b.i.d (n=67). Catecholamines, neuropeptide Y-like immunoreactivity (NPY-LI), renin activity, and N-terminal pro-atrial natriuretic factor (N-ANF) were measured in venous plasma before discharge and after 3 months. Clinical and echocardiographic variables were assessed.


RESULTS
N-ANF showed the closest correlations to clinical and echocardiographic measures of heart failure severity, e.g. NYHA functional class, furosemide dose, exercise tolerance, systolic and diastolic function. Plasma norepinephrine, dopamine and renin activity decreased after 3 months on both treatments, in contrast to a small increase in NPY-LI which was greater (by 3.9 pmol/l, 95% CI 1.2-6.6) in the metoprolol group. N-ANF increased on metoprolol, and decreased on xamoterol (difference: 408 pmol/l, 95% CI 209-607). Increase above median of NPY-LI (>25.2 pmol/l, odds ratio 2.8, P=0.0050) and N-ANF (>1043 pmol/l, odds ratio 2.8, P=0.0055) were related to long term (mean follow-up 6.8 years) cardiovascular mortality.


CONCLUSIONS
Decreased neurohormonal activity, reflecting both the sympathetic nervous system and the renin-angiotensin system, was found 3 months after an acute myocardial infarction with heart failure treated with beta-receptor antagonists. The small increase in NPY-LI may suggest increased sympathetic activity or reduced clearance from plasma. The observed changes of N-ANF may be explained by changes in cardiac preload, renal function, and differences in beta-receptor mediated inhibition of atrial release of N-ANF. NPY-LI, and N-ANF at discharge were related to long term cardiovascular mortality.
Persson
Hans
H
Section of Cardiology, Division of Internal Medicine, Karolinska Institutet Danderyd Hospital, S-182 88, Stockholm, Sweden. hans.persson@med.ds.sll.se
Andréasson
Karin
K
Kahan
Thomas
T
Eriksson
Sven V
SV
Tidgren
Bo
B
Hjemdahl
Paul
P
Hall
Christian
C
Erhardt
Leif
L
D000208:Acute Disease; D000319:Adrenergic beta-Antagonists / Q000008:administration & dosage*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D009320:Atrial Natriuretic Factor / Q000378:metabolism; D016009:Chi-Square Distribution; D004298:Dopamine / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D015150:Echocardiography, Doppler; D004837:Epinephrine / Q000378:metabolism; D005260:Female; D005500:Follow-Up Studies; D006333:Heart Failure / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000209:etiology* / Q000378:metabolism; D006801:Humans; D008297:Male; D008790:Metoprolol / Q000008:administration & dosage*; D008875:Middle Aged; D009203:Myocardial Infarction / Q000150:complications* / Q000000981:diagnostic imaging / Q000401:mortality; D009478:Neuropeptide Y / Q000378:metabolism; D009638:Norepinephrine / Q000378:metabolism; D011336:Probability; D016016:Proportional Hazards Models; D011446:Prospective Studies; D015996:Survival Rate; D016896:Treatment Outcome; D017307:Xamoterol / Q000008:administration & dosage*
D000319:Adrenergic beta-Antagonists; D009478:Neuropeptide Y; D017307:Xamoterol; D009320:Atrial Natriuretic Factor; D008790:Metoprolol; D004298:Dopamine; D009638:Norepinephrine; D004837:Epinephrine