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

## TL;DR

Adding Growth Differentiation Factor-15 improves long-term mortality prediction for patients with acute coronary syndrome beyond existing risk scores.

## Contribution

GDF-15 significantly enhances mortality risk prediction beyond the GRACE 2.0 score in ACS patients.

## Key findings

- GDF-15 outperformed GRACE 2.0 for 3-year mortality prediction (AUC 0.82 vs. 0.76).
- Adding GDF-15 to GRACE 2.0 improved long-term prognostic accuracy (C-index increased from 0.74 to 0.76).
- LVEF and GLS provided minor improvements in mortality prediction compared to GDF-15.

## 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.

The online version contains supplementary material available at 10.1038/s41598-026-38905-w.