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

被引:303
作者
Wollert, Kai C.
Kempf, Tibor
Peter, Timo
Olofsson, Sylvia
James, Stefan
Johnston, Nina
Lindahl, Bertil
Horn-Wichmann, Ruediger
Brabant, Georg
Simoons, Maarten L.
Armstrong, Paul W.
Califf, Robert M.
Drexler, Helmut
Wallentin, Lars
机构
[1] Hannover Med Sch, Dept Cardiol & Angiol, D-3000 Hannover, Germany
[2] Hannover Med Sch, Dept Gastroenterol Hepatol & Endocrinol, D-3000 Hannover, Germany
[3] Thorax Ctr Rotterdam, Dept Cardiol, Rotterdam, Netherlands
[4] Univ Alberta, Div Cardiol, Edmonton, AB, Canada
[5] Duke Univ, Duke Clin Res Inst, Durham, NC USA
[6] Uppsala Univ, Dept Cardiol, S-75105 Uppsala, Sweden
[7] Uppsala Univ, Uppsala Clin Res Ctr, S-75105 Uppsala, Sweden
关键词
acute coronary syndrome; biomarkers; growth-differentiation factor-15; prognosis;
D O I
10.1161/CIRCULATIONAHA.106.650846
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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.
引用
收藏
页码:962 / 971
页数:10
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