Prognostic value of growth-differentiation factor-15 in patients with non-ST-elevation acute coronary syndrome.

Abstract

BACKGROUND:

Growth-differentiation factor-15 (GDF-15) is a member of the transforming growth factor-beta 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.

• Authors: Kai C Wollert, Tibor Kempf, Timo Peter, Sylvia Olofsson, Stefan James, Nina Johnston, Bertil Lindahl, Rüdiger Horn-Wichmann, Georg Brabant, Maarten L Simoons, Paul W Armstrong, Robert M Califf, Helmut Drexler, Lars Wallentin
• Journal: Circulation (Circulation) Vol. 115 Issue 8 Pg. 962-71 (Feb 27 2007) ISSN: 1524-4539 [Electronic] United States
• PMID: 17283261 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Biomarkers
• Cytokines
• GDF15 protein, human
• Growth Differentiation Factor 15
• C-Reactive Protein

Topics

• Acute Disease
• Aged
• Biomarkers
• C-Reactive Protein (analysis)
• Chest Pain (blood, diagnosis, mortality)
• Coronary Disease (blood, diagnosis, mortality)
• Cytokines (blood)
• Female
• Growth Differentiation Factor 15
• Humans
• Male
• Middle Aged
• Myocardial Infarction (etiology)
• Prognosis
• Recurrence