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Original Articles

Prognostic Value of Biomarkers in Heart Failure

Application of Novel Methods in the Community

Shannon M. Dunlay, MD; Yariv Gerber, PhD; Susan A. Weston, MS; Jill M. Killian, BS; Margaret M. Redfield, MD and Véronique L. Roger, MD, MPH

From the Division of Cardiovascular Diseases (S.M.D., M.M.R., V.L.R.) and Department of Health Sciences Research (Y.G., S.A.W., J.M.K., V.L.R.), Mayo Clinic, Rochester, Minn; and Department of Epidemiology and Preventive Medicine (Y.G.), School of Public Health, Sackler Medical School, Tel Aviv University, Tel Aviv, Israel.

Correspondence to Véronique L. Roger, MD, MPH, Department of Health Sciences Research, Mayo Clinic, 200 First Street SW, Rochester, MN 55905. E-mail roger.veronique{at}mayo.edu

Received January 6, 2009; accepted June 30, 2009.

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 (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.

Key Words: epidemiology • heart failure • prognosis • inflammation • community

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