Abstract 2068: Growth-Differentiation Factor-15 is a New Biomarker that Provides Prognostic Information Beyond Established Biomarkers in Patients with Non-ST-Elevation Acute Coronary Syndrome
Growth-differentiation factor-15 (GDF-15) is a member of the TGF-β cytokine superfamily that is induced in the heart after experimental ischemia/reperfusion injury. We hypothesized that circulating levels of GDF-15 increase and provide prognostic information in patients with non-ST-elevation acute coronary syndrome (NSTE-ACS). To determine the concentration of GDF-15 in serum and plasma samples, we developed and extensively validated an immuno-radiometric assay (IRMA) using a polyclonal, GDF-15 affinity chromatography-purified, goat anti-human GDF-15 IgG antibody. Blood samples were obtained on admission from 2081 patients with acute chest pain and either ST-segment depression or troponin elevation that were included in the GUSTO-IV NSTE-ACS trial and from a matching cohort of 429 healthy individuals. Levels of the established biomarkers, troponin T, N-terminal pro-B-type natriuretic peptide (NT-proBNP), C-reactive protein (CRP), and creatinine clearance, were also determined. Patients with NSTE-ACS had elevated GDF-15 levels on admission as compared to healthy controls [median (rounded tertiles): 1445 (1200 to 1800) ng/L vs. median (rounded 10th and 90th percentile): 762 (450 to 1200) ng/L; P<0.001]. Increasing tertiles of GDF-15 were associated with an enhanced risk of death at 30 days (0.6, 2.0, and 4.3%; P<0.001) and at one year (1.5, 5.0, and 14.1%; P<0.001). In a univariate logistic regression analysis, several demographic and clinical baseline characteristics, as well as the levels of troponin T, NT-proBNP, CRP, creatinine clearance, and GDF-15 were related to 1-year mortality (all biomarkers: P<0.001). In a multivariable analysis, only the levels of GDF-15 (P<0.001) and NT-proBNP (P=0.01), together with age (P=0.006) and history of previous myocardial infarction (P=0.004) contributed independently to 1-year mortality. In a receiver operating characteristic (ROC) curve analysis, GDF-15 also emerged as the biomarker with the strongest relation to mortality. In conclusion, GDF-15 is a new biomarker of the short-term and long-term risk for death in patients with NSTE-ACS that provides prognostic information beyond and above established clinical and biochemical markers.