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Original Articles

Osteopontin, a New Prognostic Biomarker in Patients With Chronic Heart Failure

Mark Rosenberg, MD; Christian Zugck, MD; Manfred Nelles, MD; Claus Juenger, MD, MPH; Derk Frank, MD; Andrew Remppis, MD; Evangelos Giannitsis, MD; Hugo A. Katus, MD and Norbert Frey, MD

From the Department of Internal Medicine III (M.R., C.Z., M.N., D.F., A.R., E.G., H.A.K., N.F.), University of Heidelberg, Heidelberg, Germany, and Institut für Herzinfarktforschung an der Universität Heidelberg (C.J.), Ludwigshafen, Germany.

Correspondence to Norbert Frey, MD, Department of Internal Medicine III, University of Heidelberg, Im Neuenheimer Feld 410, 69120 Heidelberg, Germany. E-mail norbert.frey{at}med.uni-heidelberg.de

Received October 18, 2007; accepted February 11, 2008.

Background— Osteopontin, a glycoprotein that can be detected in plasma, was found to be upregulated in several animal models of cardiac failure and may thus represent a new biomarker that facilitates risk stratification in patients with heart failure. We therefore tested whether osteopontin plasma levels are elevated in patients with chronic heart failure and whether they provide independent prognostic information.

Methods and Results— We analyzed osteopontin plasma levels in 420 patients with chronic heart failure due to significantly impaired left ventricular systolic function and correlated the results with disease stage and prognostic information (median follow-up of 43 months). We found that osteopontin plasma levels were significantly elevated in patients with heart failure as compared with healthy control subjects (532 versus 382 ng/mL, P=0.008), irrespective of heart failure origin (ischemic versus dilated cardiomyopathy). Furthermore, osteopontin levels were higher in patients with moderate to severe heart failure than in patients with no or mild symptoms (672 ng/mL for New York Heart Association class III/IV versus 479 ng/mL for class I/II, P<0.0001). Estimated 4-year death rates in patients with osteopontin levels above or below a cutoff value derived from receiver operating characteristic analyses were 56.5% and 28.4%, respectively (hazard ratio 3.4, 95% confidence interval 2.2 to 5.3, P<0.0001). In a multivariable model that included demographic, clinical, and biochemical parameters such as N-terminal prohormone brain natriuretic peptide, osteopontin emerged as an independent predictor of death (hazard ratio 2.3, 95% confidence interval 1.4 to 3.5, P<0.001).

Conclusion— Our findings suggest that osteopontin might be useful as a novel prognostic biomarker in patients with chronic heart failure.

Key Words: heart failure • prognosis • biomarker

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