Abstract 19132: Urinary 8-hydroxy-2’-deoxyguanosine, a Biomarker of Oxidative Stress, Predicts Cardiac Events in Patients With Cardiac Sarcoidosis
Background: Enhanced production of reactive oxygen species plays a crucial role in the pathogenesis of cardiac sarcoidosis (CS). Here, we investigated whether urinary (U) 8-hydroxy-2’-deoxyguanosine (8-OHdG), a marker of oxidative DNA damage, predicts cardiac events in CS patients.
Methods: Thirty consecutive patients were diagnosed as CS according to 2006 Japanese guideline, and they were divided into active CS group (n=20) and non-active CS group (n=10) based on the abnormal accumulation of isotope on heart by 18FDG-PET/CT. U-OHdG, cardiac function and other biomarkers were measured in 30 CS patients before discharge (mean age: 64.8 ± 11.1 years; male: 52%; LVEF: 35 ±13%; NYHA: 1.8 ± 0.6, BNP: 315.0 ± 352.7 pg/ml; U8-OHdG: 16.7 ± 7.0 ng/mg·creatinine). Then, we prospectively followed these patients for a median follow-up period of 48 month, with primary endpoints of cardiac events (death).
Results: U-8OHdG (ng/mg·creatinine) in all CS patients was significantly increased as compared with control subjects (all CS; n=30: 16.7±7.0 vs. normal subjects; n=30: 8.0±2.0, p<0.01). U-8-OHdG in active CS group was higher than that of non-active CS (active CS; 22.3±6.3 vs. non-active CS; 12.4±4.3, p<0.01), although there was no significant difference among these 2 groups in cardiac function (NYHA class, LVEF and serum BNP levels), as well as in other biomarkers (serum IL-6, TNFα, hs CRP, ACE, Troponine T). Seven out of 20 active CS patients had cardiac events during the follow-up, while only 1 out of 10 non-active CS patients had cardiac event. From ROC analysis, the cut-off values of 19.1 for U8-OHdG (sensitivity=1.00, specificity=0.846, AUC=0.879) for predicting cardiac events in active CS patients. Kaplan-Meier event-free curves for patients with active CS revealed that patients with U-8-OHdG>19.1 had a significantly higher cardiac event rate than those with U-8-OHdG<19.1. In the multivariate Cox analysis, U-8-OHdG was an independent predictor of cardiac events (death). The hazard ratio of patients with U-8-OHdG>19.1 was 1.157 (95% confidence interval, 1.044-1.282) as compared with those with U-8-OHdG<19.1 for cardiac events.
Conclusion: These findings suggested that U8-OHdG is a novel and powerful predictor for cardiac death in CS patients.
Author Disclosures: T. Myoren: None.
- © 2014 by American Heart Association, Inc.