Growth differentiation factor-15 improves long-term mortality risk prediction beyond the GRACE 2.0 score after acute coronary syndrome

Abstract

Abstract This study examined whether Growth Differentiation Factor-15 (GDF-15) and echocardiographic measures of systolic left ventricular function improve intermediate- and long-term mortality risk prediction beyond the guideline-endorsed GRACE 2.0 score after Acute Coronary Syndrome (ACS). 751 ACS patients were included. GDF-15, left ventricular ejection fraction (LVEF), and global longitudinal strain (GLS) were added stepwise to GRACE 2.0 in Cox regression models. Discriminative performance was assessed using the C-index for all-cause mortality at 3 years and long-term up to a median follow-up of 6.4 years. Mean age was 64.4 years, and 77% were men. There were 40 deaths at 3 years and 104 deaths by end-of-study. GDF-15 outperformed GRACE 2.0 for 3-year mortality prediction (time-dependent AUC 0.82 [95% CI 0.75–0.89] vs. 0.76 [95% CI 0.67–0.84]; P  = 0.001). Adding GDF-15 to GRACE 2.0 improved long-term prognostic accuracy, increasing the C-index from 0.74 (95% CI 0.69–0.79) to 0.76 (95% CI 0.70–0.81). LVEF and GLS improved the C-index in the order of 0.01 when added to GRACE 2.0. GDF-15 meaningfully improved discrimination of all-cause death, both at intermediate- and long-term follow-up, when added on top of GRACE 2.0 whereas LVEF and GLS both provided minor improvements.