Published online before print February 5, 2007, doi: 10.1161/CIRCULATIONAHA.106.650846
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(Circulation. 2007;115:962-971.)
© 2007 American Heart Association, Inc.
Coronary Heart Disease |
Prognostic Value of Growth-Differentiation Factor-15 in Patients With Non–ST-Elevation Acute Coronary Syndrome
From the Department of Cardiology and Angiology (K.C.W., T.K., T.P., H.D.) and Department of Gastroenterology, Hepatology, and Endocrinology (R.H.-W., G.B.), Hannover Medical School, Germany; the Department of Cardiology, Thoraxcenter (M.L.S.), Rotterdam, the Netherlands; the Division of Cardiology (P.W.A.), University of Alberta, Edmonton, Canada; Duke Clinical Research Institute (R.M.C.), Duke University, Durham, NC; and the Department of Cardiology and Uppsala Clinical Research Center (S.O., S.J., N.J., B.L., L.W.), University of Uppsala, Sweden.
Correspondence to Prof Dr Kai C. Wollert, Abteilung Kardiologie und Angiologie, Medizinische Hochschule Hannover, Carl-Neuberg Str. 1, 30625 Hannover, Germany. E-mail wollert.kai{at}mh-hannover.de
Received July 10, 2006; accepted December 11, 2006.
Background— Growth-differentiation factor-15 (GDF-15) is a member of the transforming growth factor-ß 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.
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