on February 5, 2007
Published online before print February 5, 2007, doi: 10.1161/CIRCULATIONAHA.106.650846
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Submitted on July 10, 2006
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. * To whom correspondence should be addressed. E-mail: wollert.kai{at}mh-hannover.de.
Background--Growth-differentiation factor-15 (GDF-15) is a member of the transforming growth factor- 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.
Accepted on December 11, 2006
Prognostic Value of Growth-Differentiation Factor-15 in Patients With Non-ST-Elevation Acute Coronary Syndrome
Kai C. Wollert MD*,
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.
Key words: acute coronary syndrome • biomarkers • growth-differentiation factor-15 • prognosis
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