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(Circulation. 2007;116:1540-1548.)
© 2007 American Heart Association, Inc.

Coronary Heart Disease

Growth Differentiation Factor 15 for Risk Stratification and Selection of an Invasive Treatment Strategy in Non–ST-Elevation Acute Coronary Syndrome

Kai C. Wollert, MD; Tibor Kempf, MD; Bo Lagerqvist, MD, PhD; Bertil Lindahl, MD, PhD; Sylvia Olofsson, BSc; Tim Allhoff, BSc; Timo Peter, BSc; Agneta Siegbahn, MD, PhD; Per Venge, MD, PhD; Helmut Drexler, MD; Lars Wallentin, MD, PhD

From the Department of Cardiology and Angiology (K.C.W., T.K., T.A., T.P., H.D.), Hannover University Medical School, Hannover, Germany, and the Department of Internal Medicine (Cardiology and Clinical Chemistry) and Uppsala Clinical Research Center (B. Lagerqvist, B. Lindahl, S.O., A.S., P.V., L.W.), University of Uppsala, Uppsala, Sweden.

Correspondence to Dr Lars Wallentin, Uppsala Clinical Research Center, 75185 Uppsala, Sweden. E-mail lars.wallentin{at}ucr.uu.se

Received February 19, 2007; accepted July 10, 2007.

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.

Methods and 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 µg/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.

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