Insulin-like Growth Factor Binding Protein 2 Predicts Mortality Risk in Heart Failure.

Background: Insulin-like Growth Factor Binding Protein 2 (IGFBP2) showed greater heart failure (HF) diagnostic accuracy than the "grey zone" B-type natriuretic peptides, and may have prognostic utility as well. Objectives: To determine if IGFBP2 provides independent information on cardiovascular mortality in HF. Methods: A retrospective study of 870 HF patients from 3 independent international cohorts. Presentation IGFBP2 plasma levels were measured by EUSA, and patients were followed from 1 year (Maastricht. Netherlands) to 6 years (Atlanta, GA, USA and Toulouse, France). Multivariate analysis, Net Reclassification Improvement (NRI) and Integrated Discrimination Improvement (IDI) were performed in the 3 cohorts. The primary outcome was cardiovascular mortality. Results: In multivariate Cox proportional hazards analysis, the highest quartile of IGFBP2 was associated with mortality in the Maastricht cohort (adjusted hazard ratio 1.69 (95% CI 1.18-2.41), p = 0.004) and in the combined Atlanta and Toulouse cohorts (adjusted hazard ratio 2.04 (95%CI, 13-3.3), p = 0.003). Adding IGFBP2 to a clinical model allowed a reclassification of adverse outcome risk in the Maastricht cohort (NRI - 18.7% p = 0.03; IDI - 3.9% p = 0.02) and with the Atlanta/Toulouse patients (NRI of 40.4% p = 0.01, 31,2% p = 0.04, 315% p = 0,02 and IDI of 2,9% p = 0,0005, 3.1% p = 0,0005 and 4,2%, p = 0.0005, fora follow-up of 1, 2 and 3 years, respectively). Conclusion: In 3 international cohorts, IGFBP2 level is a strong prognostic factor for cardiovascular mortality in HF, adding information to natriuretic monitoring and usual clinical markers, that should be further prospectively evaluated for patients optimized care. (C) 2019 Elsevier B.V. All rights reserved.