Abstract 14568: Urinary 8-hydroxy-2'-deoxyguanosine, An Oxidative Stress Marker, Predicts The Inflammatory Activity within the Heart in Patients with Cardiac Sarcoidosis
Background: It is difficult to diagnose cardiac sarcoidosis (SAR) and to evaluate the inflammatory activity. Here, we investigated whether urinary (U) 8-hydroxy-2’-deoxyguanosine(8-OHdG), a marker of oxidative DNA damage, predicts the inflammatory activity in SAR.
Methods and Results: Immunohistochemical examination of 8-OHdG in the autopsy samples of left ventricle (LV) obtained from a patient with cardiac sarcoidosis, revealed positive staining for 8-OHdG on the LV sections corresponding to the focus with accumulation of 18F-FDG by PET/CT. Serum 8-OHdG level was significantly higher in coronary sinus (CS) than in aorta(A) in patients with active SAR, suggesting that 8-OHdG was produced from cardiac tissue. We also measured U-8-OHdG in 30 control subjects, 30 DCM patients (LVEF: 27±15%) and 32 SAR patients (LVEF: 33.8±15%). All patients with SAR underwent 18F-FDG PET/CT to evaluate the inflammation status for dividing active SAR (n=20) and non-active SAR (n=12). In all active SAR patients, U-8-OHdG levels were re-examined in comparison with 18F-FDG PET/CT to assess response to corticosteroids. U-8-OHdG (ng/mg creatinine) in all SAR patients was higher than that of control subjects (Control; 8.0±1.9 vs. all SAR; 17.6±5.3, p<0.01). Interestingly, U-8-OHdG level in active SAR was higher than that of non-active SAR or DCM (active SAR; 22.3±6.3 vs. non-active SAR; 12.4±4.3, DCM; 11.3±4.5), although there was no significant difference among these 3 groups in cardiac function (NYHA class, LVEF and serum BNP levels), as well as in other biomarkers (serum IL-6, TNFα, hs CRP, ACE). In ROC curve analysis, U-8OHdG powerfully predicted active SAR (AUC: 0.97; 95% CI 0.91-1.02) from all SAR patients. The optimal cutoff value for predicton of active SAR was 14.8 ng/mg creatinine. In a multivariate regression analysis, moreover, U-8-OHdG was the strongest independent predictor of active SAR (HR5.5; 95%CI 0.798-3.118, p<0.019). U-8-OHdG level in active SAR patients was significantly decreased 6 months after corticosteroid treatment, in proportion with a decrease in the focal pathological tracer uptake in heart.
Conclusion: U-8-OHdG presents a novel and powerful predictor of active SAR as well as a marker for evaluating the effectiveness to steroid therapy for SAR.
- © 2012 by American Heart Association, Inc.