title: An oxidative stress biomarker, urinary 8-hydroxy-2'-deoxyguanosine, predicts cardiovascular-related death after steroid therapy for patients with active cardiac sarcoidosis.
abstract: BACKGROUND
  We investigated whether urinary 8-hydroxy-2'-deoxyguanosine (U-8-OHdG), a marker of oxidative DNA damage, is a prognosticator of cardiovascular-related death in patients with cardiac sarcoidosis (CS).
  
  
  RESULTS
  In this prospective study, 30 consecutive patients were divided into the active CS (n=20) and non-active CS (n=10) groups, based on abnormal isotope accumulation in the heart on (18)F-fluorodeoxyglucose positron-emission tomography/computed tomography ((18)F-FDG PET/CT) imaging. Nineteen patients in the active CS group underwent corticosteroid therapy. Before corticosteroid therapy initiation, U-8-OHdG, brain natriuretic peptide (BNP), other biomarkers, and indices of cardiac function were measured. Patients were followed-up for a median of 48months. The primary endpoint was the incidence of cardiovascular-related death. During the follow-up period, in the corticosteroid-treated active CS group, 7 of 19 patients experienced cardiovascular-related death. By contrast, in the non-active CS group, 1 of 10 patients died from cardiovascular-related causes. Univariate and multivariate analyses showed that U-8-OHdG and BNP were independent predictors for cardiovascular-related death. The cut-off values for predicting cardiovascular death in corticosteroid-treated patients with active CS were 19.1ng/mg·Cr and 209pg/mL for U-8-OHdG and BNP, respectively. Patients with a U-8-OHdG concentration ≥19.1ng/mg·Cr or a BNP concentration ≥209pg/mL had a significantly higher cardiovascular-related death risk, but U-8-OHdG had better predictive value compared with BNP.
  
  
  CONCLUSIONS
  These findings suggested that U-8-OHdG was a powerful predictor of cardiovascular-related death in patients with CS, suggesting that active CS patients with elevated U-8-OHdG levels might be resistant to corticosteroid therapy.
authors.affiliation: Division of Cardiology, Department of Medicine and Clinical Science, Yamaguchi University Graduate School of Medicine, Ube, Japan.
authors.forename: Takeki
authors.initials: T
authors.lastname: Myoren
authors.affiliation: Division of Cardiology, Department of Medicine and Clinical Science, Yamaguchi University Graduate School of Medicine, Ube, Japan. Electronic address: skoba@yamaguchi-u.ac.jp.
authors.forename: Shigeki
authors.initials: S
authors.lastname: Kobayashi
authors.affiliation: Division of Cardiology, Department of Medicine and Clinical Science, Yamaguchi University Graduate School of Medicine, Ube, Japan.
authors.forename: Seiko
authors.initials: S
authors.lastname: Oda
authors.affiliation: Division of Cardiology, Department of Medicine and Clinical Science, Yamaguchi University Graduate School of Medicine, Ube, Japan.
authors.forename: Takuma
authors.initials: T
authors.lastname: Nanno
authors.affiliation: Division of Cardiology, Department of Medicine and Clinical Science, Yamaguchi University Graduate School of Medicine, Ube, Japan.
authors.forename: Hironori
authors.initials: H
authors.lastname: Ishiguchi
authors.affiliation: Division of Cardiology, Department of Medicine and Clinical Science, Yamaguchi University Graduate School of Medicine, Ube, Japan.
authors.forename: Wakako
authors.initials: W
authors.lastname: Murakami
authors.affiliation: Division of Cardiology, Department of Medicine and Clinical Science, Yamaguchi University Graduate School of Medicine, Ube, Japan.
authors.forename: Shinichi
authors.initials: S
authors.lastname: Okuda
authors.affiliation: Department of Radiology, Yamaguchi University Graduate School of Medicine, Ube, Japan.
authors.forename: Munemasa
authors.initials: M
authors.lastname: Okada
authors.affiliation: Department of Internal Medicine, Asahi University School of Dentistry, Mizuho, Japan.
authors.forename: Genzou
authors.initials: G
authors.lastname: Takemura
authors.affiliation: Department of Radiology, St Hill Hospital, Ube, Japan.
authors.forename: Kazuyoshi
authors.initials: K
authors.lastname: Suga
authors.affiliation: Division of Cardiology, Department of Medicine and Clinical Science, Yamaguchi University Graduate School of Medicine, Ube, Japan.
authors.forename: Masunori
authors.initials: M
authors.lastname: Matsuzaki
authors.affiliation: Division of Cardiology, Department of Medicine and Clinical Science, Yamaguchi University Graduate School of Medicine, Ube, Japan.
authors.forename: Masafumi
authors.initials: M
authors.lastname: Yano
mesh_terms: D000080242:8-Hydroxy-2'-Deoxyguanosine; D000305:Adrenal Cortex Hormones / Q000627:therapeutic use*; D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000652:urine; D009202:Cardiomyopathies / Q000188:drug therapy* / Q000401:mortality / Q000652:urine*; D003849:Deoxyguanosine / Q000031:analogs & derivatives* / Q000652:urine; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D020097:Natriuretic Peptide, Brain / Q000652:urine; D011237:Predictive Value of Tests; D011446:Prospective Studies; D012507:Sarcoidosis / Q000188:drug therapy* / Q000401:mortality / Q000652:urine*; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D000305:Adrenal Cortex Hormones; D015415:Biomarkers; D020097:Natriuretic Peptide, Brain; D000080242:8-Hydroxy-2'-Deoxyguanosine; D003849:Deoxyguanosine
keywords: Biomarker; Cardiac sarcoidosis; Oxidative stress