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Urinary 8-oxo-7,8-dihydroguanosine as a potential biomarker of frailty for elderly patients with cardiovascular disease.
Free Radical Biology and Medicine ( IF 7.4 ) Pub Date : 2020-03-23 , DOI: 10.1016/j.freeradbiomed.2020.03.011
Yao-Dan Liang 1 , Qian Liu 2 , Ming-Hui Du 3 , Zhen Liu 4 , Si-Min Yao 3 , Pei-Pei Zheng 3 , Yu-Hao Wan 3 , Ning Sun 3 , Ying-Ying Li 3 , Jun-Peng Liu 3 , Yao Luo 3 , Jian-Ping Cai 4 , Jie-Fu Yang 3 , Hua Wang 3
Affiliation  

The diagnosis of frailty is usually subjective, which calls for objective biomarkers in clinical medicine. 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodGsn) and 8-oxo-7, 8-dihydroguanosine (8-oxoGsn) in urine are two aging biomarkers that have not been explored deeply in cases of frailty. A total of 508 elderly patients with cardiovascular disease (mean age 75.0 ± 6.5 years, 50.8% males) were enrolled consecutively. Frailty was assessed by the Fried phenotype (robust: 0 score; pre-frail: 1-2 scores; frail: 3-5 scores). The concentrations of 8-oxoGsn and 8-oxodGsn in urine were measured by improved ultra-high-performance liquid chromatography-mass spectrometry (UPLC-MS/MS). Urinary creatinine (Cre) was tested to correct the 8-oxoGsn and 8-oxodGsn levels. According to the Fried phenotype score, the proportions of robust, pre-frail, and frail subjects were 20.5% (104/508), 53.9% (274/508), and 25.6% (130/508), respectively. The urinary 8-oxoGsn/Cre (P < 0.001) differed significantly among these 3 groups, but the urinary 8-oxodGsn/Cre (P = 0.600) showed no marked difference. Univariate and multivariate logistic regression showed that the age (odds ratio [OR] = 1.090, P < 0.001), systolic blood pressure (OR = 0.981, P = 0.008), 8-oxoGsn/Cre (OR = 1.203, P = 0.007), hemoglobin (OR = 0.980, P = 0.007), and sodium (OR = 0.915, P = 0.044) were independently associated with frailty. The sensitivity and specificity to identify frailty were 53.08% and 71.96%, respectively, for 8-oxoGsn/Cre at the optimal cut-off value of 3.879 μmol/mol according to the maximal Youden index. Urinary 8-oxoGsn, as a recognized biomarker of RNA oxidation, is independently associated with frailty in elderly patients with cardiovascular disease. However, the urinary 8-oxodGsn shows no obvious correlation with frailty. To obtain a better diagnostic performance for frailty, more biomarkers from different pathophysiological pathways should be explored in the future.

中文翻译:

尿液中的8-oxo-7,8-dihydroguanosine作为老年心血管疾病患者虚弱的潜在生物标志物。

身体虚弱的诊断通常是主观的,这需要在临床医学中使用客观的生物标志物。尿液中的8-oxo-7,8-dihydro-2'-deoxyguanosine(8-oxodGsn)和8-oxo-7,8-dihydroguanosine(8-oxoGsn)是两个衰老生物标志物,在衰弱的情况下尚未深入研究。连续登记了508名老年心血管疾病患者(平均年龄75.0±6.5岁,男性为50.8%)。通过Fried表型评估脆弱性(健壮:0分;脆弱前:1-2分;脆弱:3-5分)。通过改进的超高效液相色谱-质谱法(UPLC-MS / MS)测量尿液中的8-oxoGsn和8-oxodGsn浓度。测试了尿肌酐(Cre)以纠正8-oxoGsn和8-oxodGsn水平。根据弗里德表型评分,健壮,虚弱,体弱的受试者分别为20.5%(104/508),53.9%(274/508)和25.6%(130/508)。这三组尿中的8-oxoGsn / Cre(P <0.001)有显着差异,但尿中的8-oxodGsn / Cre(P = 0.600)没有显着差异。单因素和多因素logistic回归显示年龄(比值比[OR] = 1.090,P <0.001),收缩压(OR = 0.981,P = 0.008),8-oxoGsn / Cre(OR = 1.203,P = 0.007) ,血红蛋白(OR = 0.980,P = 0.007)和钠(OR = 0.915,P = 0.044)分别与体弱相关。根据最佳Youden指数,在3.879μmol/ mol的最佳临界值下,对8-oxoGsn / Cre识别脆弱的敏感性和特异性分别为53.08%和71.96%。尿液中的8-oxoGsn作为公认的RNA氧化生物标记,与老年心血管疾病患者的虚弱独立相关。然而,尿中的8-oxodGsn与衰弱无明显相关性。为了获得更好的体弱诊断性能,将来应探索更多来自不同病理生理途径的生物标志物。
更新日期:2020-03-26
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