Diagnostic and Prognostic Value of Osteopontin in Patients With Acute Congestive Heart Failure

Michael Behnes; Martina Brueckmann; Siegfried Lang; Florian Espeter; Christel Weiss; Michael Neumaier; Parviz Ahmad-Nejad; Martin Borggrefe; Ursula Hoffmann


Eur J Heart Fail. 2013;15(12):1390-1400. 

In This Article

Abstract and Introduction


Aims To evaluate the diagnostic and prognostic value of osteopontin in patients with acute dyspnoea and/or peripheral oedema suspected of having acute congestive heart failure (aCHF).

Methods and results A total of 401 patients presenting with acute dyspnoea and/or peripheral oedema to the emergency department were prospectively enrolled and followed up for up to 5 years. Blood samples for biomarker measurements were collected on admission to the emergency department. Osteopontin combined with NT-proBNP vs. NT-proBNP alone for diagnosis of aCHF was tested. Additionally, osteopontin vs. NT-proBNP for prognostic outcomes (i.e. all-cause mortality, aCHF-related rehospitalization, and both in combination) was tested. The diagnostic and prognostic capacity of osteopontin was tested by C-statistics, reclassification indices, and multivariable Cox prediction models. Osteopontin plus NT-proBNP improved the diagnostic capacity for aCHF diagnosis [accuracy 76%, 95% confidence interval (CI) 72–80%; specificity 74%, 95% CI 69–79%, net reclassification improvement (NRI) +0.10] compared with NT-proBNP alone in the emergency department (P = 0.0001). Osteopontin independently predicted all-cause mortality and aCHF-related rehospitalization after 1 and 5 years. Compared with NT-proBNP, osteopontin was of superior prognostic value, specifically in aCHF patients and for the prognostic outcome of aCHF-related rehospitalization.

Conclusion Osteopontin improves aCHF diagnosis when combined with NT-proBNP. Osteopontin identifies aCHF patients with high 1- and 5-year mortality and rehospitalization risk, and adds prognostic value to NT-proBNP.

Trial registration NCT00143793


The extracellular matrix (ECM) is a key regulator of remodelling processes in the heart. The ECM consists of structural (e.g. collagen or elastin) and non-structural ECM proteins interacting via specific cell surface receptors or soluble growth factors and cytokines.[1] Osteopontin represents a central member of the matricellular protein family, being initially found in bone matrix. However, osteopontin is synthesized in various tissues and cell types, thereby affecting cellular immunity by regulation of cell infiltration, restoration of tissues, angiogenesis, inhibition of cell death, and reconstitution of ECM.[2] Regarding the cardiovascular system, osteopontin is thought to be an inhibitor of vascular calcification; it is synthesized in reversible differentiable 'calcifying vascular cells', it is present in activated resident pericytes during angiogenetic processes, and has been found in fibrocalcific plaques.[3]

In healthy cardiac tissue, osteopontin has been found to be expressed only at low levels. However, in experimental mice models, mechanical stress (i.e. pressure and volume loading) as well as hypoxia strongly induced osteopontin synthesis in the heart.[4] Additionally, increased osteopontin levels have been associated with left ventricular (LV) hypertrophy and dilation.[5,6] Thus, osteopontin has been shown to be increasingly expressed coincident with the development of chronic cardiac failure after chronic pressure overload in animal models.[7]

Pathologically, heart failure (HF) is caused, among others, by an adverse structural remodelling,[8] characterized by ultrastructural changes of cardiac tissue including enhanced collagen deposition and fibrosis, finally promoting acute congestive heart failure (aCHF).[9] Acute CHF is defined as the rapid onset or change of symptoms and signs of HF—such as acute dyspnoea or peripheral oedema—underlying either a new onset or worsening of pre-existing chronic heart failure.[10] The emergency department represents the principal port of entry to evaluate aCHF patients. Patients suffering from aCHF are endangered by a more severe outcome specifically in the setting of a de novo aCHF presentation compared with those patients with a worsening of pre-existing chronic HF.[10]

Therefore, the present study aimed to investigate the diagnostic and prognostic value of measurements of osteopontin plasma levels in comparison with NT-proBNP within a prospective controlled trial enrolling patients initially presenting with symptoms of acute dyspnoea or peripheral oedema suspected of aCHF in the emergency department.