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

Circ J. 2012;76(1):117-26. doi: 10.1253/circj.cj-11-0537. Epub 2011 Oct 19.

Abstract

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.

Methods and 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 8-Hydroxy-2'-Deoxyguanosine
  • Adrenergic beta-Antagonists / therapeutic use*
  • Adult
  • Aged
  • Biomarkers / blood
  • Biomarkers / urine
  • Carbazoles / therapeutic use*
  • Carvedilol
  • Chronic Disease
  • Death, Sudden, Cardiac / epidemiology*
  • Deoxyguanosine / analogs & derivatives*
  • Deoxyguanosine / urine
  • Female
  • Follow-Up Studies
  • Heart Failure, Systolic / drug therapy*
  • Heart Failure, Systolic / mortality*
  • Heart Failure, Systolic / urine
  • Humans
  • Male
  • Middle Aged
  • Natriuretic Peptide, Brain / blood
  • Predictive Value of Tests
  • Propanolamines / therapeutic use*
  • Prospective Studies
  • Risk Factors
  • Treatment Outcome

Substances

  • Adrenergic beta-Antagonists
  • Biomarkers
  • Carbazoles
  • Propanolamines
  • Carvedilol
  • Natriuretic Peptide, Brain
  • 8-Hydroxy-2'-Deoxyguanosine
  • Deoxyguanosine