8-Hydroxy-2′-deoxyguanosine is a prognostic mediator for cardiac event

Abstract

DNA in the nucleus is one of the major targets of reactive oxygen species (ROS), and oxidative DNA damage has been implicated in the pathogenesis of chronic heart failure. 8-Hydroxy-2'-deoxyguanosine (8-OHdG) is produced from deoxyguanosine in DNA by ROS. The purpose of this present study was to examine the clinical significance of serum 8-OHdG levels in patients with heart failure. We measured serum 8-OHdG levels in 230 patients with chronic heart failure and 42 control subjects without heart failure by sandwich enzyme-linked immunosorbent assay. Patients were prospectively followed during a median follow-up period of 472 days with the end points of cardiac death or progressive heart failure requiring re-hospitalization. Serum 8-OHdG concentrations were higher in patients with heart failure than in control subjects (P < 0·001) and increased with advancing New York Heart Association (NYHA) functional class (P < 0·001). Normal upper limit of 8-OHdG level was determined as mean ± 2SD value from 42 control subjects (0·40 ng mL(-1)). Abnormally high serum 8-OHdG levels (> 0·40 ng mL(-1)) were observed in 21·2%, 43·1%, 42·6% and 69·4% through NYHA I to IV (P < 0·001). A total of 66 cardiac events occurred during a follow-up period, and Kaplan-Meier survival curves demonstrated that cardiac event rate was markedly higher in patients with high 8-OHdG levels than in those with normal 8-OHdG levels (62·4% vs. 29·6%, P = 0·0007). Serum 8-OHdG levels provide important prognostic information for the risk stratification of patients with heart failure.