Hagström Emil, Held Claes, Stewart Ralph A H, Aylward Philip E, Budaj Andrzej, Cannon Christopher P, Koenig Wolfgang, Krug-Gourley Sue, Mohler Emile R, Steg Philippe Gabriel, Tarka Elizabeth, Östlund Ollie, White Harvey D, Siegbahn Agneta, Wallentin Lars
Department of Medical Sciences, Cardiology, Uppsala University, Uppsala, Sweden;
Uppsala Clinical Research Center (UCR), Uppsala University, Uppsala, Sweden.
Clin Chem. 2017 Jan;63(1):325-333. doi: 10.1373/clinchem.2016.260570. Epub 2016 Nov 3.
Higher growth differentiation factor 15 (GDF-15) concentrations are associated with cardiovascular (CV) and non-CV morbidity and mortality. However, information on associations between GDF-15 and the risk of specific CV and non-CV events in stable coronary heart disease (CHD) patients is limited.
In 14 577 patients with stable CHD participating in the Stabilization of Atherosclerotic Plaque by Initiation of Darapladib Therapy Trial (STABILITY), GDF-15 and other prognostic biomarkers (N-terminal pro-B-type natriuretic peptide, high-sensitivity troponin T, cystatin C, and high-sensitivity C-reactive protein) were measured. In adjusted Cox regression models, the associations between GDF-15 and the composite CV end point [CV death, myocardial infarction (MI), and stroke], as well as other CV and non-CV events, were assessed.
The median concentration (interquartile range) of GDF-15 at baseline was 1253 (915-1827) ng/L. The hazard ratio for the composite end point for the highest compared to the lowest quartile of GDF-15 was 1.8 (95% CI, 1.5-2.2); for CV death, 2.63 (1.9-3.6); for sudden death, 3.06 (1.9-4.8); for heart failure (HF) death, 4.3 (1.3-14); for cancer death, 2.5 (1.3-4.7); for hospitalization for HF, 5.8 (3.2-10); for MI 1.4 (95% CI, 1.1-1.9); and for stroke, 1.8 (95% CI, 1.1-2.8). After adjustment for other prognostic biomarkers, GDF-15 remained significantly associated with all outcomes except for MI.
In stable CHD, GDF-15 was independently associated with CV, non-CV, and cancer mortality, as well as with MI and stroke. When also adjusting for other prognostic biomarkers, the associations to all fatal and nonfatal events were maintained except for MI. Information on GDF-15, therefore, might be helpful when assessing the risk of adverse outcomes in patients with stable CHD. ClinicalTrials.gov Identifier: NCT00799903.
较高的生长分化因子15(GDF - 15)浓度与心血管(CV)及非心血管疾病的发病率和死亡率相关。然而,关于GDF - 15与稳定型冠心病(CHD)患者特定CV和非CV事件风险之间关联的信息有限。
在参与“通过启动达拉匹林治疗试验稳定动脉粥样硬化斑块”(STABILITY)的14577例稳定型CHD患者中,测量了GDF - 15和其他预后生物标志物(N末端前B型利钠肽、高敏肌钙蛋白T、胱抑素C和高敏C反应蛋白)。在调整后的Cox回归模型中,评估了GDF - 15与复合CV终点[CV死亡、心肌梗死(MI)和中风]以及其他CV和非CV事件之间的关联。
基线时GDF - 15的中位数浓度(四分位间距)为1253(915 - 1827)ng/L。与GDF - 15最低四分位数相比,最高四分位数的复合终点风险比为1.8(95%CI,1.5 - 2.2);CV死亡为2.63(1.9 - 3.6);猝死为3.06(1.9 - 4.8);心力衰竭(HF)死亡为4.3(1.3 - 14);癌症死亡为2.5(1.3 - 4.7);HF住院为5.8(3.2 - 10);MI为1.4(95%CI,1.1 - 1.9);中风为1.8(95%CI,1.1 - 2.8)。在对其他预后生物标志物进行调整后,GDF - 15除与MI外仍与所有结局显著相关。
在稳定型CHD中,GDF - 15与CV、非CV和癌症死亡率以及MI和中风独立相关。在对其他预后生物标志物进行调整时,除MI外,与所有致命和非致命事件的关联仍然存在。因此,在评估稳定型CHD患者不良结局风险时,GDF - 15的信息可能会有所帮助。临床试验.gov标识符:NCT00799903。