Background— Growth-differentiation factor-15 (GDF-15) is a member of the transforming growth factor-β cytokine superfamily that is induced in the heart after ischemia-and-reperfusion injury. Circulating levels of GDF-15 may provide prognostic information in patients with non–ST-elevation acute coronary syndrome. Methods and Results— Blood samples were obtained on admission from 2081 patients with acute chest pain and either ST-segment depression or troponin elevation who were included in the Global Utilization of Strategies to Open Occluded Arteries (GUSTO)-IV Non–ST-Elevation Acute Coronary Syndrome trial and from a matching cohort of 429 apparently healthy individuals. GDF-15 levels were determined by immunoradiometric assay. Approximately two thirds of patients presented with GDF-15 levels above the upper limit of normal in healthy controls (1200 ng/L); one third presented with levels >1800 ng/L. Increasing tertiles of GDF-15 were associated with an enhanced risk of death at 1 year (1.5%, 5.0%, and 14.1%; P <0.001). By multiple Cox regression analysis, only the levels of GDF-15 and N-terminal pro–B-type natriuretic peptide, together with age and a history of previous myocardial infarction, contributed independently to 1-year mortality risk. Receiver operating characteristic curve analyses further illustrated that GDF-15 is a strong marker of 1-year mortality risk (area under the curve, 0.757; best cutoff, 1808 ng/L). At this cutoff value, GDF-15 added significant prognostic information in patient subgroups defined by age; gender; time from symptom onset to admission; cardiovascular risk factors; previous cardiovascular disease; and the risk markers ST-segment depression, troponin T, N-terminal pro–B-type natriuretic peptide, C-reactive protein, and creatinine clearance. Conclusions— GDF-15 is a new biomarker of the risk for death in patients with non–ST-elevation acute coronary syndrome that provides prognostic information beyond that provided by established clinical and biochemical markers.

Background: Growth-differentiation factor 15 (GDF15) is a member of the transforming growth factor ␤ (TGF-␤) cytokine superfamily. There has been increasing interest in using circulating GDF15 as a biomarker in patients, for example those with cardiovascular disease. Methods: We developed an IRMA that uses a polyclonal, affinity chromatography-purified goat antihuman GDF15 IgG antibody, assessed the preanalytic characteristics of GDF15, and determined circulating GDF15 concentrations in 429 apparently healthy elderly individuals and 153 patients with chronic heart failure (CHF). Results: The assay had a detection limit of 20 ng/L, an intraassay imprecision of <10.6%, and an interassay imprecision of <12.2%. Specificity was demonstrated with size-exclusion chromatography, parallel measurements with polyclonal and monoclonal anti-GDF15 antibody, and lack of cross-reactivity with TGF-␤. The assay was not appreciably influenced by the anticoagulant matrix or unrelated biological substances. GDF15 was stable at room temperature for 48 h and resistant to 4 freeze-thaw cycles. Apparently healthy, elderly indi-