Urinary 8-oxo-7,8-dihydroguanosine as a potential biomarker of frailty for elderly patients with cardiovascular disease
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.
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