Abstract 3389: Growth-Differentiation Factor-15 is a New Powerful Biomarker in Patients with Chronic Heart Failure
Growth-differentiation factor-15 (GDF-15) is a member of the TGF-β cytokine superfamily that is induced in the heart in experimental models of myocardial ischemia, hypertrophy, and cardiac failure. To determine if circulating levels of GDF-15 provide prognostic information in patients with chronic heart failure (CHF), we developed and extensively validated an immunoradiometric assay (IRMA) using a polyclonal, GDF-15 affinity chromatography-purified, goat anti-human GDF-15 IgG antibody. Blood samples were obtained from a cohort of 235 patients with CHF enrolled at four European centers: 91.5% male, 71.5% ischemic etiology, median age (interquartile range): 66 (56 to 72) years, median left ventricular ejection fraction (LVEF): 30 (24 to 40) %. Patients were stable on medication for at least four weeks prior to study entry. Levels of the established biomarkers, N-terminal pro-B-type natriuretic peptide (NT-proBNP), creatinine, uric acid, and hemoglobin were also determined. The median level of GDF-15 in patients with CHF was 2240 (1232 to 4010) ng/L, which was significantly (P<0.001) higher as compared to the upper limit of normal (1200 ng/L) that we previously established in a cohort of 429 healthy elderly individuals. GDF-15 levels in patients with CHF were closely related to CHF severity as assessed by NYHA class (P<0.001) or NT-proBNP levels (P<0.001). The risk of death during follow-up markedly increased with increasing quartiles of GDF-15, with 12-month mortality rates of 2.0%, 8.7%, 10.5%, and 37.5% (P<0.001). By univariable Cox regression analysis, age (P=0.007), LVEF, NYHA class, NT-proBNP, creatinine, and uric acid (all: P<0.001), and hemoglobin concentration (P=0.011, inverse relation) predicted 12-month mortality. Using a multivariable approach, only LVEF (P<0.001) and GDF-15 (P=0.003) emerged as independent predictors. The results were unchanged with GDF-15 as a continuous variable or when using stratification in quartiles. In conclusion, GDF-15 is a new, powerful biomarker of poor survival in patients with CHF that appears to provide prognostic information beyond established clinical and biochemical markers.