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

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.

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.

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.

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.