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.

Methods and 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.

Figure 1. Observed 1-year Mortality by Median Biomarker Level

1-year mortality rates according to the number of biomarkers above the median level (0, 1, 2, 3) are shown overall, by ejection fraction, and by inpatient (In)/ outpatient (Out) status at enrollment.