title: Prognostic impact of plasma N-terminal pro-brain natriuretic peptide in severe chronic congestive heart failure: a substudy of the Carvedilol Prospective Randomized Cumulative Survival (COPERNICUS) trial.
abstract: BACKGROUND
  The utility of N-terminal proBNP (NT-proBNP) to predict the occurrence of death and hospitalization was prospectively evaluated in the COPERNICUS study, which enrolled patients with an ejection fraction <25% and symptoms of chronic congestive heart failure at rest or on minimal exertion.
  
  
  RESULTS
  Baseline plasma concentrations of NT-proBNP were measured in a subgroup of 814 men and 197 women with symptoms at rest or on minimal exertion who were enrolled in the COPERNICUS study and were randomized to placebo (n=506) or carvedilol (n=505). Values of NT-proBNP were markedly increased despite the requirement that patients be euvolemic before the start of treatment (mean+/-SD, 3235+/-4392 pg/mL; median, 1767 pg/mL). By univariate Cox regression analysis, NT-proBNP was found to be a powerful predictor of subsequent all-cause mortality (relative risk [RR], 2.7; 95% CI, 1.7 to 4.3; P=0.0001 for above versus below median) and all-cause mortality or hospitalization for heart failure (RR, 2.4; 95% CI, 1.8 to 3.4; P=0.0001 for above versus below median). The predictive value of NT-proBNP was similar when both placebo and carvedilol patients were analyzed separately. No significant interaction was found between NT-proBNP and treatment group (P=0.93 for above- versus below-median NT-proBNP).
  
  
  CONCLUSIONS
  NT-proBNP was consistently associated with increased risk for all-cause mortality and for all-cause mortality or hospitalization for heart failure in patients with severe congestive heart failure, even in those who were clinically euvolemic. This marker therefore may be a useful tool in risk stratification of patients with severe congestive heart failure.
authors.affiliation: Medizinische Klinik II, Universitaetsklinikum Schleswig-Holstein, Campus Luebeck, Ratzeburger Allee 160, D-23538 Luebeck, Germany. hartmann@medinf.mu-luebeck.de
authors.forename: Franz
authors.initials: F
authors.lastname: Hartmann
authors.forename: Milton
authors.initials: M
authors.lastname: Packer
authors.forename: Andrew J S
authors.initials: AJ
authors.lastname: Coats
authors.forename: Michael B
authors.initials: MB
authors.lastname: Fowler
authors.forename: Henry
authors.initials: H
authors.lastname: Krum
authors.forename: Paul
authors.initials: P
authors.lastname: Mohacsi
authors.forename: Jean L
authors.initials: JL
authors.lastname: Rouleau
authors.forename: Michal
authors.initials: M
authors.lastname: Tendera
authors.forename: Alain
authors.initials: A
authors.lastname: Castaigne
authors.forename: Stefan D
authors.initials: SD
authors.lastname: Anker
authors.forename: Ildiko
authors.initials: I
authors.lastname: Amann-Zalan
authors.forename: Silke
authors.initials: S
authors.lastname: Hoersch
authors.forename: Hugo A
authors.initials: HA
authors.lastname: Katus
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use; D000368:Aged; D015415:Biomarkers; D001794:Blood Pressure; D002227:Carbazoles / Q000627:therapeutic use; D002317:Cardiovascular Agents / Q000627:therapeutic use; D000077261:Carvedilol; D003404:Creatinine / Q000097:blood; D004359:Drug Therapy, Combination; D005060:Europe / Q000453:epidemiology; D005260:Female; D006333:Heart Failure / Q000097:blood* / Q000209:etiology / Q000401:mortality; D006760:Hospitalization / Q000706:statistics & numerical data; D006801:Humans; D015993:Life Tables; D008297:Male; D008875:Middle Aged; D017202:Myocardial Ischemia / Q000150:complications; D020097:Natriuretic Peptide, Brain; D009419:Nerve Tissue Proteins / Q000097:blood*; D010446:Peptide Fragments / Q000097:blood*; D011237:Predictive Value of Tests; D011379:Prognosis; D011412:Propanolamines / Q000627:therapeutic use; D016016:Proportional Hazards Models; D011446:Prospective Studies; D013318:Stroke Volume; D016019:Survival Analysis
chemical_list: D000319:Adrenergic beta-Antagonists; D015415:Biomarkers; D002227:Carbazoles; D002317:Cardiovascular Agents; D009419:Nerve Tissue Proteins; D010446:Peptide Fragments; D011412:Propanolamines; C109794:pro-brain natriuretic peptide (1-76); D000077261:Carvedilol; D020097:Natriuretic Peptide, Brain; D003404:Creatinine