title: Prognostic value of neurohumoral activation in patients with an acute myocardial infarction: effect of captopril.
abstract: OBJECTIVE
  This study attempted to evaluate whether neurohumoral activation at the time of hospital discharge in postinfarction patients helps to predict long-term prognosis and whether long-term therapy with the angiotensin-converting enzyme inhibitor captopril modifies this relation.
  
  
  BACKGROUND
  Neurohumoral activation persists at the time of hospital discharge in a large number of postinfarction patients. The Survival and Ventricular Enlargement (SAVE) study demonstrated that the angiotensin-converting enzyme inhibitor captopril improves survival and decreases the development of severe heart failure in patients with left ventricular dysfunction (left ventricular ejection fraction < or = 40%) but no overt postinfarction heart failure.
  
  
  METHODS
  In 534 patients in the SAVE study, plasma neurohormone levels were measured a mean of 12 days after infarction. Patients were then randomized to receive captopril or placebo and were followed up for a mean (+/- SD) of 38 +/- 6 months (range 24 to 55). The association between activation of plasma neurohormones at baseline and subsequent cardiovascular mortality or the development of heart failure was assessed with and without adjustment for other important prognostic factors.
  
  
  RESULTS
  By univariate analysis, activation of plasma renin activity and aldosterone, norepinephrine, atrial natriuretic peptide and arginine vasopressin levels were related to subsequent cardiovascular events, whereas epinephrine and dopamine levels were not. By multivariate analysis, only plasma renin activity (relative risk 1.6, 95% confidence interval [CI] 1.0 to 2.5) and atrial natriuretic peptide (relative risk 2.2, 95% CI 1.3 to 3.8) were independently predictive of cardiovascular mortality, whereas the other neurohormones were not. Only plasma renin activity and aldosterone, atrial natriuretic peptide and arginine vasopressin were independent predictors of the combined end points of cardiovascular mortality, development of severe heart failure or recurrent myocardial infarction. Except for 1-year cardiovascular mortality, the use of captopril did not significantly modify these relations.
  
  
  CONCLUSIONS
  Neurohumoral activation at the time of hospital discharge in postinfarction patients is an independent sign of poor prognosis. This is particularly true for plasma renin activity and atrial natriuretic peptide. Except for 1-year cardiovascular mortality, captopril does not significantly modify these relations.
authors.affiliation: Montreal Heart Institute, Quebec, Canada.
authors.forename: J L
authors.initials: JL
authors.lastname: Rouleau
authors.forename: M
authors.initials: M
authors.lastname: Packer
authors.forename: L
authors.initials: L
authors.lastname: Moyé
authors.forename: J
authors.initials: J
authors.lastname: de Champlain
authors.forename: D
authors.initials: D
authors.lastname: Bichet
authors.forename: M
authors.initials: M
authors.lastname: Klein
authors.forename: J R
authors.initials: JR
authors.lastname: Rouleau
authors.forename: B
authors.initials: B
authors.lastname: Sussex
authors.forename: J M
authors.initials: JM
authors.lastname: Arnold
authors.forename: F
authors.initials: F
authors.lastname: Sestier
mesh_terms: D000368:Aged; D000450:Aldosterone / Q000097:blood; D000704:Analysis of Variance; D001127:Arginine Vasopressin / Q000097:blood; D009320:Atrial Natriuretic Factor / Q000097:blood; D002170:Canada; D002216:Captopril / Q000627:therapeutic use*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009203:Myocardial Infarction / Q000097:blood* / Q000188:drug therapy / Q000401:mortality; D018377:Neurotransmitter Agents / Q000097:blood*; D009638:Norepinephrine / Q000097:blood; D011379:Prognosis; D016016:Proportional Hazards Models; D012083:Renin / Q000097:blood
chemical_list: D018377:Neurotransmitter Agents; D001127:Arginine Vasopressin; D000450:Aldosterone; D009320:Atrial Natriuretic Factor; D002216:Captopril; D012083:Renin; D009638:Norepinephrine