Cardiovascular Division, Department of Internal Medicine, Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Taoyuan 33305, Taiwan.
Department of Life Science, Chinese Culture University, Taipei 11114, Taiwan.
Mediators Inflamm. 2017;2017:9398401. doi: 10.1155/2017/9398401. Epub 2017 Jul 17.
Plasma GDF15 concentrations were measured in 612 Taiwanese individuals without overt systemic disease. Clinical parameters, genetic variants, and 22 biomarker levels were analyzed. We further enrolled 86 patients with PAD and 481 patients with CAD, who received endovascular intervention and coronary angiography, respectively, to examine the role of GDF15 level in predicting all-cause mortality. Significant associations were found between genotypes/haplotypes and GDF15 levels. The circulating GDF15 level was positively associated with age, smoking, hypertension, and diabetes mellitus as well as circulating levels of lipocalin 2 and various biomarkers of inflammation and oxidative stress. Kaplan-Meier survival analysis showed that baseline GDF15 levels of above 3096 pg/mL and 1123 pg/mL were strong predictors of death for patients with PAD and CAD, respectively ( = 0.011 and < 0.001). GDF15 more accurately reclassified 17.3% and 29.2% of patients with PAD and CAD, respectively ( = 0.0046 and = 0.0197), compared to C-reactive protein. Both genetic and nongenetic factors, including cardiometabolic and inflammatory markers and adipokines, were significantly associated with GDF15 level. A high level of GDF15 was significantly associated with an increase of all-cause mortality in patients with high-risk PAD and in patients with angiographically documented CAD.
在 612 名没有明显系统性疾病的台湾个体中测量了血浆 GDF15 浓度。分析了临床参数、遗传变异和 22 种生物标志物水平。我们进一步招募了 86 名 PAD 患者和 481 名 CAD 患者,他们分别接受了血管内介入治疗和冠状动脉造影,以检查 GDF15 水平在预测全因死亡率中的作用。基因型/单倍型与 GDF15 水平之间存在显著关联。循环 GDF15 水平与年龄、吸烟、高血压和糖尿病以及循环脂联素 2 和各种炎症和氧化应激生物标志物呈正相关。生存分析表明,基线 GDF15 水平高于 3096pg/ml 和 1123pg/ml 分别是 PAD 和 CAD 患者死亡的强烈预测因子(=0.011 和 < 0.001)。与 C 反应蛋白相比,GDF15 更准确地重新分类了分别为 17.3%和 29.2%的 PAD 和 CAD 患者(=0.0046 和 = 0.0197)。遗传和非遗传因素,包括心脏代谢和炎症标志物和脂肪因子,与 GDF15 水平显著相关。高水平的 GDF15 与高危 PAD 患者和经血管造影证实的 CAD 患者全因死亡率增加显著相关。