Published ahead of print on February 8, 2008, doi:10.1164/rccm.200712-1786OC
© 2008 American Thoracic Society doi: 10.1164/rccm.200712-1786OC
Growth Differentiation Factor-15 for Prognostic Assessment of Patients with Acute Pulmonary Embolism1 Department of Cardiology and Pulmonology, University of Goettingen, Goettingen, Germany; 2 Department of Cardiology and Angiology, Hannover University Medical School, Hannover, Germany; and 3 Department of Medical Biometry and Statistics, University of Freiburg, Freiburg, Germany Correspondence and requests for reprints should be addressed to Stavros Konstantinides, M.D., Department of Cardiology and Pulmonology, University of Goettingen, D-37075 Goettingen, Germany. E-mail: skonstan{at}med.uni-goettingen.de Rationale: Growth differentiation factor (GDF)-15 is a cytokine induced in the heart after ischemia or pressure overload. Circulating levels of GDF-15 provide independent prognostic information in patients with acute coronary syndromes or heart failure. Objectives: We investigated the prognostic value of GDF-15 in acute pulmonary embolism. Methods: In a prospective cohort study, plasma levels of GDF-15 were determined by immunoradiometric assay in 123 consecutive patients with confirmed acute pulmonary embolism. Measurements and Main Results: GDF-15 concentrations on admission ranged from 553 to 47,274 ng/L; 101 patients (82%) had GDF-15 levels above the upper limit of normal (1,200 ng/L). Patients who experienced pulmonary embolism–related complications during the first 30 days had higher baseline levels of GDF-15 (median, 6,039 [25th to 75th percentiles, 2,778 to 19,772] ng/L) compared with those with an uncomplicated course (median, 2,036 [25th to 75th percentiles, 1,279 to 3,176] ng/L; P < 0.001). By multivariable logistic regression analysis, which included clinical characteristics, cardiac biomarkers (troponin T and NT-proBNP [N-terminal propeptide of B-type natriuretic peptide]), and echocardiographic findings, GDF-15 emerged as an independent predictor of a complicated 30-day outcome (P = 0.033). The c-statistic for GDF-15 was 0.84 (95% confidence interval, 0.76–0.90), as compared with 0.72 for cardiac troponin T, and 0.65 for NT-proBNP. The ability of troponin T, NT-proBNP, and echocardiographic findings of right ventricular dysfunction to predict the risk of a complicated 30-day outcome was enhanced by GDF-15. Furthermore, multivariable Cox regression identified baseline levels of GDF-15 as an independent predictor of long-term mortality (P < 0.001). Conclusions: GDF-15 is a promising new biomarker for risk stratification of pulmonary embolism.
Key Words: pulmonary embolism • prognosis • risk stratification • growth differentiation factor-15
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