Urine 8-hydroxy-2'-deoxyguanosine as an Independent Predictor of Mortality in Patients With Chronic Heart Failure

Abstract

Background: Oxidative stress has been implicated in the pathogenesis of chronic heart failure (CHF). However, there is little information as to the relationship between oxidative stress and status of CHF patients. In our preliminary study, blood sampling from both coronary sinus and artery showed that cardiac tissue produced 8-OHdG in CHF patients. Based on these findings, we hypothesized that urine (U)-8-OHdG can be a clinically useful biomarker for the evaluation of severity and prognosis in CHF. Methods and results: We measured U-8-OHdG in 30 control subjects and 111 CHF patients. U-8-OHdG in CHF was higher than that of control subjects. The mean value of U-8-OHdG increased in parallel with an increase in NYHA class. These patients were prospectively followed during a median follow-up period of 650 days with end points of cardiac death or re-hospitalization due to progressive heart failure. From the ROC curve analysis, the cut-off value of U-8-OHdG was determined as 12.5 ng/mg. Kaplan-Meier analysis demonstrated that the high U-8-OHdG group had a significantly higher incidence of cardiac events than these in the low U-8-OHdG group. In the multivariate Cox analysis, U-8-OHdG level was an independent risk factor for cardiac events. Conclusion: An increase in the U-8-OHdG level was associated with higher mortality in CHF, suggesting that U-8-OHdG can be a clinically useful biomarker for CHF patients.