Abstract 3564: Urine 8-hydroxy-2′-deoxyguanosine is Well Correlated With Cardiac Dysfunction and Poor Prognosis in Chronic Heart Failure Patients
Background: Oxidative stress has been implicated in the pathogenesis of chronic heart failure (CHF). However, there is little information as to the relationship between biomarkers of oxidative stress and status of heart failure in patients with CHF. In our preliminary study, the level of serum 8-hydroxy-2′-deoxyguanosine (8-OHdG: ng/ml), a marker of oxidative DNA damage, was higher in coronary sinus (CS) than in artery (A) in CHF(n=30), while it was not in normal subjects (N:n=10) (CHF: 0.55±0.43 in CS; 0.28±0.15 in A; N: 0.17±0.07 in CS; 0.16±0.06 in A), indicating that reactive oxygen species is produced in failing cardiac tissue. On the basis of these findings, we hypothesized that urine (U)-8-OHdG can be a clinically useful biomarker for the evaluation of severity, cardiac dysfunction, and prognosis in CHF.
Methods and results: we measured U-8-OHdG in 30 control subjects (no prior clinical history of HF or LV dysfunction, age and gender-matched) and 111 patients with CHF (mean age: 57±16 years; male: 52%; LVEF: 34±13%). Then, we examined the relationship between U-8-OHdG and LVEF, PCWP, or plasma BNP. The U-8-OHdG level (ng/mg creatinine) indeed correlated with the NYHA class (r=0.62, p<0.001), LVEF (r=0.43, p<0.001) and PCWP (r=0.54, p<0.001), while other biomarkers of oxidative stress and inflammation such as the urine 8-isoprostane, serum IL-6, serum TNFα and high sensitive CRP did not. 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 receiver operating characteristic curve analysis, the cut-off value of U-8-OHdG was determined as 12.5 ng/mg. Kaplan-Meier analysis clearly 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 (P<0.0001). In the multivariate Cox analysis, U-8-OHdG level was an independent risk factor for cardiac events (hazard ratio 1.15, 95% confidence interval 1.05–1.13, P<0.005).
Conclusion: Level of U-8-OHdG is a clinically useful biomarker for the evaluation of severity, cardiac dysfunction and prognosis in CHF.