Growth differentiation factor 15 for risk stratification and selection of an invasive treatment strategy in non ST-elevation acute coronary syndrome.

Abstract

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 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.

• Authors: Kai C Wollert, Tibor Kempf, Bo Lagerqvist, Bertil Lindahl, Sylvia Olofsson, Tim Allhoff, Timo Peter, Agneta Siegbahn, Per Venge, Helmut Drexler, Lars Wallentin
• Journal: Circulation (Circulation) Vol. 116 Issue 14 Pg. 1540-8 (Oct 02 2007) ISSN: 1524-4539 [Electronic] United States
• PMID: 17848615 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Biomarkers
• Cytokines
• GDF15 protein, human
• Growth Differentiation Factor 15
• Troponin T

Topics

• Acute Disease
• Aged
• Biomarkers (blood)
• Coronary Artery Disease (blood, diagnosis, epidemiology, therapy)
• Cytokines (blood)
• Electrocardiography
• Female
• Growth Differentiation Factor 15
• Humans
• Male
• Middle Aged
• Myocardial Revascularization
• Risk Factors
• Treatment Outcome
• Troponin T (blood)