Long-term prognostic value of growth differentiation factor-15 in acute coronary syndromes

Background: Growth Differentiation Factor-15 (GDF-15) predicts death and cardiovascular events in acute coronary syndromes (ACS). We aimed to assess the long-term prognostic value of GDF-15 in ACS. Methods: We included 358 patients with ACS who underwent coronary angiography. Plasma GDF-15 was measured and clinical data and long-term events were registered. Incremental value of GDF-15 for prognosing all-cause death above a clinical model including GRACE score, left ventricular ejection fraction < 40%, prior myocardial infarction and age was assessed. Results: GDF-15 concentrations > 1800 ng/L were associated with an increased prevalence of cardiovascular risk factors. During 6.5 years of follow-up 56 patients died, 7 had values of GDF-15 < 1200 ng/L, 7 between 1200 and 1800 ng/L and 42 > 1800 ng/L. After adjustment for potential confounders, GDF-15 > 1800 ng/L were independently associated with all-cause death (HR 4.09; 95% CI 1.57-10.71; p = .004) and the composite of major adverse cardiovascular events (MACE) (HR 2.48; 95% CI 1.41-4.34; p = .001). For long-term all-cause death a significant increase of ROC curve was seen after addition of GDF-15 to a clinical model 0.876 (95% CI 0.823-0.928; p = .014). Same improvements were found for net reclassification improvement (0.776; 95% CI 0.494-1.037; p < .001) and integrated discrimination improvement (0.112; 95% CI 0.055-0.169; p < .001). Multivariate competing risk model showed a significant association between GDF-15 > 1800 ng/L and the incidence of heart failure but not of myocardial infarction. Conclusions: In the setting of ACS, GDF-15 is associated with long-term all-cause death, MACE and heart failure and provides incremental prognostic value beyond traditional risks factor.