Diagnostic and Prognostic Utilities of Insulin-Like Growth Factor Binding Protein-7 in Patients With Dyspnea

Nasrien E. Ibrahim, Marc Afilalo, Annabel Chen-Tournoux, Robert H. Christenson, Hanna K. Gaggin, Judd E. Hollander, Peter Kastner, Phillip D. Levy, Anika Mang, Serge Masson, John T. Nagurney, Richard M. Nowak, Peter S. Pang, W. Frank Peacock, Vinzent Rolny Dipl-Stat, E. Lea Walters, James L. Januzzi

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Objectives: This study examined whether insulin-like growth factor binding protein-7 (IGFBP7) would aid in the diagnosis and prognosis of acute heart failure (HF) beyond N-terminal pro–B-type natriuretic peptide (NT-proBNP) concentration. Background: IGFBP7 is associated with impaired ventricular relaxation and worse prognosis. Methods: The ICON-RELOADED (International Collaborative of NT-proBNP-Re-evaluation of Acute Diagnostic Cut-Offs in the Emergency Department) study was a prospective, multicenter clinical trial that enrolled subjects presenting with dyspnea. Six-month prognosis for death or repeat hospitalization was obtained. Results: Among 1,449 patients, 274 (18.9%) were diagnosed with acute HF. Those with IGFBP7 concentrations in the highest quartile were older, male, had hypertension and HF, had lower estimated glomerular filtration rate (eGFR) and lowest ejection fraction (41 ± 20%; all p < 0.001). Independent predictors of IGFBP7 were age, male sex, history of diabetes, history of HF, and eGFR. Median concentrations of NT-proBNP (2,844 ng/ml vs. 99 ng/ml) and IGFBP7 (146.1 ng/ml vs. 86.1 ng/ml) were higher in those with acute HF (both; p < 0.001). Addition of IGFBP7 to NT-proBNP concentrations improved discrimination, therefore increasing the area under the receiver operating curve for diagnosis of acute HF (from 0.91 to 0.94; p < 0.001 for differences). Addition of IGFBP7 to a complete model of independent predictors of acute HF improved model calibration. IGFBP7 significantly reclassified acute HF diagnosis beyond NT-proBNP (net reclassification index: +0.25). Higher log2-IGFBP7 concentrations in patients with acute HF predicted death or rehospitalization at 6 months (hazard ratio: 1.84 per log2-SD; 95% confidence interval: 1.30 to 2.61; p = 0.001). In Kaplan-Meier analyses, supramedian concentrations of IGFBP7 were associated with shorter event-free survival (log-rank: p < 0.001). Conclusions: Among patients with acute dyspnea, concentrations of IGFBP7 add to NT-proBNP for diagnosis of acute HF and provide added prognostic utility for short-term risk.

Original languageEnglish (US)
Pages (from-to)415-422
Number of pages8
JournalJACC: Heart Failure
Issue number5
StatePublished - May 2020


  • biomarker
  • diagnosis
  • heart failure
  • prognosis

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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    Ibrahim, N. E., Afilalo, M., Chen-Tournoux, A., Christenson, R. H., Gaggin, H. K., Hollander, J. E., Kastner, P., Levy, P. D., Mang, A., Masson, S., Nagurney, J. T., Nowak, R. M., Pang, P. S., Peacock, W. F., Dipl-Stat, V. R., Walters, E. L., & Januzzi, J. L. (2020). Diagnostic and Prognostic Utilities of Insulin-Like Growth Factor Binding Protein-7 in Patients With Dyspnea. JACC: Heart Failure, 8(5), 415-422. https://doi.org/10.1016/j.jchf.2020.02.009