Growth differentiation factor-15 in patients presenting with acute chest pain: Diagnostic and prognostic utility

BACKGROUND: Growth differentiation factor 15 (GDF-15) is a stress-induced circulating cytokine known to predict mortality in patients with established myocardial infarction (MI) and has been implicated in the development of cachexia. METHODS: This international multicenter study aimed to investigate the diagnostic and prognostic performance of GDF-15 among unselected patients presenting with acute chest pain to the emergency department (ED). GDF-15, high-sensitivity cardiac troponin T (hs-cTnT), and N-terminal pro-B-type natriuretic peptide (NT-proBNP) concentrations were measured at ED presentation. The primary diagnostic endpoint was Non-ST-elevation MI at presentation, and the primary prognostic endpoints were all-cause death at 90 days and 5-year follow-up. RESULTS: Among 4779 patients, median age 61 years, 33.2% female, 856 (17.9 %) were adjudicated to have MI, 994 (20.8%) to have other cardiac conditions, and 2929 (61.3%) to have non-cardiac disorders. GDF-15 exhibited only modest diagnostic accuracy for MI (AUC 0.69). During 5 years of follow-up, 557 (12.1%) deaths occurred. GDF-15 demonstrated a very high discriminative ability for all-cause death, both at 90 days (C-index 0.86, 95% CI 0.82-0.90) and at 5 years (C-index 0.84, 95% CI 0.82-0.85). This was comparable to hs-cTnT and NT-proBNP at 90 days, and higher at 5 years. When added to a rich-for-prior-information base model incorporating age, sex, cardiovascular risk factors, creatinine, hs-cTnT and NT-proBNP, GDF-15 provided meaningful incremental prognostic discrimination for 90 days and 5-year all-cause mortality. CONCLUSIONS: In chest pain patients presenting to the ED, GDF-15 had very high prognostic accuracy for all-cause mortality over 5 years, outperforming both hs-cTnT and NT-proBNP.