title: Prognostic value of biomarkers in heart failure: application of novel methods in the community.
abstract: BACKGROUND
  Mortality among patients with heart failure is high. Though individual biomarkers have been investigated to determine their value in mortality risk prediction, the role of a multimarker strategy requires further evaluation.
  
  
  RESULTS
  Olmsted County residents presenting with heart failure from July 2004 to September 2007 were recruited to undergo biomarker measurement. We investigated whether addition of C-reactive protein, B-type natriuretic peptide, and troponin T to a model including established risk indicators improved 1-year mortality risk prediction using the c statistic, integrated discrimination improvement, and net reclassification improvement. Among 593 participants, the mean age was 76.4 years, and 48% were men. After 1 year of follow-up, 122 (20.6%) participants had died. Patients with C-reactive protein (<11.8 mg/L), B-type natriuretic peptide (<350 pg/mL), and troponin T (< or = 0.01 ng/mL) less than the median had low 1-year mortality (3.3%), whereas those with 2 or 3 biomarkers greater than the median had markedly increased mortality (30.8% and 35.5%, respectively). The addition of 2 or more biomarkers to the model offered greater improvement in 1-year mortality risk prediction than use of a single biomarker. The combination of C-reactive protein and B-type natriuretic peptide resulted in an increase in the c statistic from 0.757 to 0.810 (P<0.001), an integrated discrimination improvement gain of 7.1% (P<0.001), and a net reclassification improvement of 22.1% (P<0.001). Use of all 3 biomarkers offered no incremental gain (integrated discrimination improvement gain 0.7% versus C-reactive protein+B-type natriuretic peptide, P=0.065).
  
  
  CONCLUSIONS
  Biomarkers improved 1-year mortality risk prediction beyond established indicators. The use of a 2-biomarker combination was superior to a single biomarker in risk prediction, though addition of a third biomarker conferred no added benefit.
authors.affiliation: Division of Cardiovascular Diseases, Mayo Clinic, Rochester, Minn, USA.
authors.forename: Shannon M
authors.initials: SM
authors.lastname: Dunlay
authors.forename: Yariv
authors.initials: Y
authors.lastname: Gerber
authors.forename: Susan A
authors.initials: SA
authors.lastname: Weston
authors.forename: Jill M
authors.initials: JM
authors.lastname: Killian
authors.forename: Margaret M
authors.initials: MM
authors.lastname: Redfield
authors.forename: Véronique L
authors.initials: VL
authors.lastname: Roger
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000378:metabolism*; D003153:Community Health Services; D005260:Female; D006333:Heart Failure / Q000097:blood / Q000175:diagnosis* / Q000401:mortality / Q000628:therapy; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D008910:Minnesota / Q000453:epidemiology; D020097:Natriuretic Peptide, Brain / Q000097:blood*; D011237:Predictive Value of Tests; D011379:Prognosis; D011446:Prospective Studies; D012372:ROC Curve; D018570:Risk Assessment; D013997:Time Factors; D020107:Troponin T / Q000097:blood*; D015854:Up-Regulation
chemical_list: D015415:Biomarkers; D020107:Troponin T; D020097:Natriuretic Peptide, Brain; D002097:C-Reactive Protein