Prognostic value of growth-differentiation factor-15 in patients with non-ST-elevation acute coronary syndrome
Prognostic value of growth-differentiation factor-15 in patients with non-ST-elevation acute coronary syndrome
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DOI：
10.1161/circulationaha.106.650846
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发表时间：
2007-02-27
期刊：
影响因子：
37.8
通讯作者：
Wallentin, Lars
中科院分区：
文献类型：
--
作者：
Wollert, Kai C.;Kempf, Tibor;Wallentin, Lars
背景生长分化因子-15(GDF-15)是心肌缺血再灌注损伤后诱导的转化生长因子-β细胞因子超家族成员。循环GDF-15水平可提供非ST段抬高的急性冠脉综合征患者的预后信息。方法和结果-入院时采集了2081例急性胸痛和ST段压低或肌钙蛋白抬高的患者的血样，这些患者包括在全球利用策略开放闭塞动脉(GUSTO)-IV非ST段抬高的急性冠脉综合征试验和429名明显健康的匹配队列中。免疫放射分析法检测GDF-15水平。在健康对照组中，大约三分之二的患者GDF15水平高于正常上限(1 200 ng/L)；三分之一的患者GDF15水平高于正常上限1800 ng/L；GDF15水平升高与1年后死亡风险增加(1.5%、5.0%和14.1%；P<；0.001)相关。经多因素COX回归分析，只有GDF-15和N-末端前-B型利钠肽水平、年龄和既往心肌梗死病史对1年死亡风险有独立影响。受试者工作特征曲线分析进一步表明，GDF15是1年死亡风险的有力标记物(曲线下面积，0.757；最佳界值，1808 ng/L)。在这个临界值下，GDF-15增加了年龄、性别、从症状开始到入院的时间、心血管危险因素、既往心血管疾病以及ST段压低、肌钙蛋白T、N末端前B型利钠肽、C反应蛋白和肌酐清除的风险标记物的显著预后信息。结论：GDF-15是一个新的非ST段抬高急性冠脉综合征患者死亡风险的生物标记物，它提供了现有临床和生化标记物之外的预后信息。
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.Methods and 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.