Growth differentiation factor-15 in patients with or at risk of heart failure but before first hospitalisation
Joshua Bradley, Erik B. Schelbert, Laura Bonnett, Gavin A. Lewis, Jakub Lagan, Christopher Orsborne, Pamela Frances Brown, Nicholas Black, Josephine H. Naish, Simon G. Williams, Theresa A. McDonagh, Matthias Schmitt, Chris Miller
Abstract
OBJECTIVE: Identification of patients at risk of adverse outcome from heart failure (HF) at an early stage is a priority. Growth differentiation factor (GDF)-15 has emerged as a potentially useful biomarker. This study sought to identify determinants of circulating GDF-15 and evaluate its prognostic value, in patients at risk of HF or with HF but before first hospitalisation. METHODS: Prospective, longitudinal cohort study of 2166 consecutive patients in stage A-C HF undergoing cardiovascular magnetic resonance and measurement of GDF-15. Multivariable linear regression investigated determinants of GDF-15. Cox proportional hazards modelling, Net Reclassification Improvement and decision curve analysis examined its incremental prognostic value. Primary outcome was a composite of first hospitalisation for HF or all-cause mortality. Median follow-up was 1093 (939-1231) days. RESULTS: 0.51). Log-transformed GDF-15 was the strongest predictor of outcome (HR 2.12, 95% CI 1.71 to 2.63) and resulted in a risk prediction model with higher predictive accuracy (continuous Net Reclassification Improvement 0.26; 95% CI 0.13 to 0.39) and with greater clinical net benefit across the entire range of threshold probabilities. CONCLUSION: In patients at risk of HF, or with HF but before first hospitalisation, GDF-15 provides unique information and is highly predictive of hospitalisation for HF or all-cause mortality, leading to more accurate risk stratification that can improve clinical decision making. TRIAL REGISTRATION NUMBER: NCT02326324.