Growth differentiation factor 15 for risk stratification and selection of an invasive treatment strategy in non ST-elevation acute coronary syndrome.
BACKGROUND
An invasive treatment strategy improves outcome in patients with non-ST-elevation acute coronary syndrome at moderate to high risk. We hypothesized that the circulating level of growth differentiation factor 15 (GDF-15) may improve risk stratification.


RESULTS
The Fast Revascularization during InStability in Coronary artery disease II (FRISC-II) trial randomized patients with non-ST-elevation acute coronary syndrome to an invasive or conservative strategy with a follow-up for 2 years. GDF-15 and other biomarkers were determined on admission in 2079 patients. GDF-15 was moderately elevated (between 1200 and 1800 ng/L) in 770 patients (37.0%), and highly elevated (>1800 ng/L) in 493 patients (23.7%). Elevated levels of GDF-15 independently predicted the risk of the composite end point of death or recurrent myocardial infarction in the conservative group (P=0.016) but not in the invasive group. A significant interaction existed between the GDF-15 level on admission and the effect of treatment strategy on the composite end point. The occurrence of the composite end point was reduced by the invasive strategy at GDF-15 levels >1800 ng/L (hazard ratio, 0.49; 95% confidence interval, 0.33 to 0.73; P=0.001), between 1200 and 1800 ng/L (hazard ratio, 0.68; 95% confidence interval, 0.46 to 1.00; P=0.048), but not <1200 ng/L (hazard ratio, 1.06; 95% confidence interval, 0.68 to 1.65; P=0.81). Patients with ST-segment depression or a troponin T level >0.01 microg/L with a GDF-15 level <1200 ng/L did not benefit from the invasive strategy.


CONCLUSIONS
GDF-15 is a potential tool for risk stratification and therapeutic decision making in patients with non-ST-elevation acute coronary syndrome as initially diagnosed by ECG and troponin levels. A prospective randomized trial is needed to validate these findings.
Wollert
Kai C
KC
Department of Cardiology and Angiology, Hannover University Medical School, Hannover, Germany.
Kempf
Tibor
T
Lagerqvist
Bo
B
Lindahl
Bertil
B
Olofsson
Sylvia
S
Allhoff
Tim
T
Peter
Timo
T
Siegbahn
Agneta
A
Venge
Per
P
Drexler
Helmut
H
Wallentin
Lars
L
D000208:Acute Disease; D000368:Aged; D015415:Biomarkers / Q000097:blood*; D003324:Coronary Artery Disease / Q000097:blood* / Q000175:diagnosis / Q000453:epidemiology / Q000628:therapy*; D016207:Cytokines / Q000097:blood*; D004562:Electrocardiography; D005260:Female; D055436:Growth Differentiation Factor 15; D006801:Humans; D008297:Male; D008875:Middle Aged; D009204:Myocardial Revascularization; D012307:Risk Factors; D016896:Treatment Outcome; D020107:Troponin T / Q000097:blood
D015415:Biomarkers; D016207:Cytokines; C526140:GDF15 protein, human; D055436:Growth Differentiation Factor 15; D020107:Troponin T