Arnold Natalie, Rehm Martin, Büchele Gisela, Peter Raphael Simon, Brenner Rolf Erwin, Günther Klaus-Peter, Brenner Hermann, Koenig Wolfgang, Rothenbacher Dietrich
Department of General and Interventional Cardiology, University Heart Centre Hamburg, 20251 Hamburg, Germany.
German Center for Cardiovascular Research (DZHK), partner site Hamburg/Kiel/Luebeck, 20251 Hamburg, Germany.
J Clin Med. 2020 Sep 26;9(10):3107. doi: 10.3390/jcm9103107.
Subjects with osteoarthritis (OA) are at increased risk for cardiovascular (CV) and all-cause mortality. Whether biomarkers improve outcome prediction in these patients remains to be elucidated. We investigated the association between growth differentiation factor 15 (GDF-15), a novel stress-responsive cytokine, and long-term all-cause mortality among OA patients.
Within the Ulm Osteoarthritis Study, GDF-15 has been measured in the serum of 636 subjects, who underwent hip or knee arthroplasty between 1995 and 1996 (median age 65 years).
During a median follow-up of 19.7 years, a total of 402 deaths occurred. GDF-15 was inversely associated with walking distance. Compared to the bottom quartile (Q), subjects within the top quartile of GDF-15 demonstrated a 2.69-fold increased risk of dying (hazard ratio (HR) (95% confidence interval (CI)) 2.69 (1.82-3.96) adjusted for age, sex, BMI, smoking status, localization of OA, diabetes, maximum walking distance, total cholesterol, and cystatin C. Further adjustment for NT-proBNP, troponin I, and hs-C-reactive protein did not change the results appreciably (HR (95%CI) 1.56 (1.07-2.28); 1.75 (1.21-2.55); 2.32 (1.55-3.47) for Q2, Q3, and Q4 respectively, for trend < 0.001).
In subjects with OA, GDF-15 represents a potent predictor of decreased survival over >20 years, independently of conventional CV risk factors, renal, cardiac, and inflammatory biomarkers as well as walking disability, previously associated with increased mortality and lower extremity OA.
骨关节炎（OA）患者发生心血管（CV）疾病和全因死亡的风险增加。生物标志物能否改善这些患者的预后预测仍有待阐明。我们研究了一种新型应激反应细胞因子生长分化因子15（GDF-15）与OA患者长期全因死亡率之间的关联。
在乌尔姆骨关节炎研究中，对1995年至1996年间接受髋关节或膝关节置换术的636名受试者（中位年龄65岁）的血清进行了GDF-15检测。
在中位随访19.7年期间，共发生402例死亡。GDF-15与步行距离呈负相关。与最低四分位数（Q）相比，GDF-15最高四分位数的受试者死亡风险增加2.69倍（风险比（HR）（95%置信区间（CI））2.69（1.82-3.96），校正了年龄、性别、体重指数、吸烟状况、OA部位、糖尿病、最大步行距离、总胆固醇和胱抑素C。进一步校正N末端脑钠肽前体（NT-proBNP）、肌钙蛋白I和高敏C反应蛋白后，结果无明显变化（Q2、Q3和Q4的HR（95%CI）分别为1.56（1.07-2.28）；1.75（1.21-2.55）；2.32（1.55-3.47），趋势<0.001）。
在OA患者中，GDF-15是20多年生存率降低的有力预测指标，独立于传统的CV危险因素、肾脏、心脏和炎症生物标志物以及与死亡率增加和下肢OA相关的步行障碍。
