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


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.
Wollert
Kai C
KC
Department of Cardiology and Angiology, Hannover Medical School, Germany. wollert.kai@mh-hannover.de
Kempf
Tibor
T
Peter
Timo
T
Olofsson
Sylvia
S
James
Stefan
S
Johnston
Nina
N
Lindahl
Bertil
B
Horn-Wichmann
Rüdiger
R
Brabant
Georg
G
Simoons
Maarten L
ML
Armstrong
Paul W
PW
Califf
Robert M
RM
Drexler
Helmut
H
Wallentin
Lars
L
D000208:Acute Disease; D000368:Aged; D015415:Biomarkers; D002097:C-Reactive Protein / Q000032:analysis; D002637:Chest Pain / Q000097:blood / Q000175:diagnosis* / Q000401:mortality; D003327:Coronary Disease / Q000097:blood / Q000175:diagnosis* / Q000401:mortality; D016207:Cytokines / Q000097:blood*; D005260:Female; D055436:Growth Differentiation Factor 15; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000209:etiology; D011379:Prognosis; D012008:Recurrence
D015415:Biomarkers; D016207:Cytokines; C526140:GDF15 protein, human; D055436:Growth Differentiation Factor 15; D002097:C-Reactive Protein