Wollert Kai C, Kempf Tibor, Lagerqvist Bo, Lindahl Bertil, Olofsson Sylvia, Allhoff Tim, Peter Timo, Siegbahn Agneta, Venge Per, Drexler Helmut, Wallentin Lars
Department of Cardiology and Angiology, Hannover University Medical School, Hannover, Germany.
Circulation. 2007 Oct 2;116(14):1540-8. doi: 10.1161/CIRCULATIONAHA.107.697714. Epub 2007 Sep 11.
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.
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.
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.
侵入性治疗策略可改善中度至高度风险的非ST段抬高型急性冠状动脉综合征患者的预后。我们假设生长分化因子15（GDF-15）的循环水平可能会改善风险分层。
冠状动脉疾病不稳定期快速血运重建II（FRISC-II）试验将非ST段抬高型急性冠状动脉综合征患者随机分为侵入性或保守性策略组，并随访2年。对2079例患者入院时测定了GDF-15和其他生物标志物。770例患者（37.0%）的GDF-15中度升高（1200至1800 ng/L之间），493例患者（23.7%）的GDF-15高度升高（>1800 ng/L）。GDF-15水平升高独立预测保守治疗组死亡或复发性心肌梗死复合终点的风险（P=0.016），但在侵入性治疗组中无此作用。入院时GDF-15水平与治疗策略对复合终点的影响之间存在显著交互作用。在GDF-15水平>1800 ng/L时，侵入性策略可降低复合终点的发生率（风险比，0.49；95%置信区间，0.33至0.73；P=0.001），在1200至1800 ng/L之间时也可降低（风险比，0.68；95%置信区间，0.46至1.00；P=0.048），但在<1200 ng/L时则不能降低（风险比，1.06；95%置信区间，0.68至1.65；P=0.81）。ST段压低或肌钙蛋白T水平>0.01μg/L且GDF-15水平<1200 ng/L的患者未从侵入性策略中获益。
GDF-15是用于非ST段抬高型急性冠状动脉综合征患者风险分层和治疗决策的潜在工具，这些患者最初通过心电图和肌钙蛋白水平诊断。需要进行前瞻性随机试验来验证这些发现。
