Abstract 15395: Urinary 8-Hydroxy-2'-Deoxyguanosine is a Biomarker for Evaluating the Inflammatory Activity and the Effectiveness to Corticosteroids in Patients with Cardiac Sarcoidosis
Background: In a preliminary study, serum 8-hydroxy-2'-deoxyguanosine (8-OHdG :ng/ml) was found to be significantly higher in coronary sinus(CS) than in aorta(A) only in patients with active cardiac sarcoidosis (SAR), suggesting that oxidative stress plays a critical role in the pathogenesis and activity of SAR (active SAR, n=10: 0.70 ±0.11 in CS; 0.35 ± 0.10 in A; non-active SAR, n=8: 0.40±0.13 in CS; 0.35± 0.11 in A). Here, we investigated whether inflammatory activity or the effectiveness to corticosteroid treatment correlates with the level of urinary(u) 8-OHdG, a marker of oxidative stress, in patients with SAR.
Methods: We measured u-8-OHdG in 30 control subjects, 25 patients with DCM (NYHA I/II: 90%, LVEF: 27±15%) and 32 patients with SAR (NYHA I/II: 90%, LVEF: 27±15%). All patients with SAR underwent 18F-FDG PET/CT or 67Ga scintigraphy to evaluate the inflammation status for dividing active SAR (n=18) and non-active SAR (n=14). In all patients with active SAR, u-8-OHdG were re-examined in comparison with 18F-FDG PET/CT or 67Ga scintigraphy to assess response to corticosteroid treatment.
Results: U-8-OHdG (ng/ml•creatinine) in SAR was higher than that of control subjects (Control vs. all SAR: 8.5±1.9 vs. 16.8±8.2, p<0.01). U-8-OHdG in active SAR was higher than that of non-active SAR or DCM (active SAR; 22.8±8.2 vs. non-active SAR; 13.5±4.2, DCM; 12.6±4.5, p<0.01), 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 (urine 8-isoprostane, serum IL-6, TNFα, hs CRP, and ACE). Moreover, U-8-OHdG in 12 patients with active SAR, significantly decreased, 1–6 months after corticosteroid treatment, in proportion with a decrease in the focal pathological tracer uptake in heart. In contrast, u-8-OHdG in 6 patients with active SAR, whose clinical status (i.e. venricular tachycardia, heart failure) was worsening, increased in parallel with the accumulation of 18F-FDG by PET/CT.
Conclusion: U-8-OHdG seems to reflect well inflammatory activity in patients with SAR, thereby being a clinically useful biomarker for evaluating clinical status and effectiveness to corticosteroid therapy.
- © 2010 by American Heart Association, Inc.