Urinary 8-hydroxy-2'-deoxyguanosine as a novel biomarker for predicting cardiac events and evaluating the effectiveness of carvedilol treatment in patients with chronic systolic heart failure.
BACKGROUND
The authors recently reported that urinary 8-hydroxy-2'-deoxyguanosine (U8-OHdG) derived from cardiac tissue reflects clinical status and cardiac dysfunction severity in patients with chronic heart failure (CHF). The aim of the present study was to investigate whether U8-OHdG levels can accurately predict cardiac events in CHF patients and their response to β-blocker treatment.


RESULTS
Plasma brain natriuretic peptide (BNP) and U8-OHdG levels were measured in 186 consecutive CHF patients before discharge. Patients were then prospectively followed (median follow-up, 649 days) with endpoints of cardiac death or hospitalization due to progressive heart failure. From receiver operating characteristic curve analysis, cut-offs were 12.4ng/mg creatinine (Cr) for U8-OHdG and 207pg/ml for BNP. On multivariate Cox analysis, U8-OHdG and BNP were independent predictors of cardiac events. Patients were classified into 4 groups according to U8-OHdG and BNP cut-offs. The hazard ratio for cardiac events in patients with BNP ≥207pg/ml and U8-OHdG ≥12.4ng/mg Cr was 16.2 compared with approximately 4 for patients with only 1 indicator above its respective cut-off. Furthermore, carvedilol therapy was initiated in 30 CHF patients. In responders (≥10% increase in left ventricular ejection fraction [LVEF] or ≥1 class decrease in New York Heart Association [NYHA] class), U8-OHdG levels decreased significantly along with improved NYHA class, LVEF, and BNP levels after treatment.


CONCLUSIONS
U8-OHdG may be a useful biomarker for predicting cardiac events and evaluating β-blocker therapy effectiveness in CHF patients.
Division of Cardiology, Department of Medicine and Clinical Science, Yamaguchi University Graduate School of Medicine, Ube, Japan.
Takehisa
T
Susa
Shigeki
S
Kobayashi
Takeo
T
Tanaka
Wakako
W
Murakami
Shintaro
S
Akashi
Ichiro
I
Kunitsugu
Shinichi
S
Okuda
Masahiro
M
Doi
Yasuaki
Y
Wada
Tomoko
T
Nao
Jutaro
J
Yamada
Takeshi
T
Ueyama
Takayuki
T
Okamura
Masafumi
M
Yano
Masunori
M
Matsuzaki
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use*; D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood / Q000652:urine; D002227:Carbazoles / Q000627:therapeutic use*; D000077261:Carvedilol; D002908:Chronic Disease; D016757:Death, Sudden, Cardiac / Q000453:epidemiology*; D003849:Deoxyguanosine / Q000031:analogs & derivatives* / Q000652:urine; D005260:Female; D005500:Follow-Up Studies; D054143:Heart Failure, Systolic / Q000188:drug therapy* / Q000401:mortality* / Q000652:urine; D006801:Humans; D008297:Male; D008875:Middle Aged; D020097:Natriuretic Peptide, Brain / Q000097:blood; D011237:Predictive Value of Tests; D011412:Propanolamines / Q000627:therapeutic use*; D011446:Prospective Studies; D012307:Risk Factors; D016896:Treatment Outcome
D000319:Adrenergic beta-Antagonists; D015415:Biomarkers; D002227:Carbazoles; D011412:Propanolamines; D000077261:Carvedilol; D020097:Natriuretic Peptide, Brain; D000080242:8-Hydroxy-2'-Deoxyguanosine; D003849:Deoxyguanosine