What is the clinical evidence from this study?

Study design: Observational. Population: Dilated Cardiomyopathy (n=76). Intervention: Carvedilol vs. Baseline (before treatment). Primary outcome: Serum 8-OHdG levels (19% decrease, p=<0.05).

January 1, 2006Circulation Journal106 citationsOpen Access

Elevated Levels of Oxidative DNA Damage in Serum and Myocardium of Patients With Heart Failure

Q: What are the key findings of this study?

Carvedilol treatment significantly decreased serum levels of 8-OHdG, a marker of oxidative DNA damage, by 19% in patients with dilated cardiomyopathy.

YKYasuyuki KonoOkayama University KNKazufumi NakamuraHeart Failure & Transplant HKHideo KimuraSanyo-Onoda City University

Key Result

Carvedilol treatment significantly decreased serum levels of 8-OHdG, a marker of oxidative DNA damage, by 19% in patients with dilated cardiomyopathy.

Study Design

Type

Observational (n=76)

Multicenter

Structured PICO

Does carvedilol reduce oxidative DNA damage (8-OHdG levels) in patients with dilated cardiomyopathy?

Population

56 patients with dilated cardiomyopathy and 20 healthy controls, with a subset of 11 patients evaluated before and after a mean of 12 months of carvedilol treatment.

Intervention

Carvedilol started at 1 mg/day and gradually increased to a maximum of 5-30 mg/day (mean dosage 20±8 mg/day) for a mean period of 12±9 months (administered to a subset of 11 patients).

Comparator

Healthy controls for the cross-sectional biomarker comparison. Baseline (pre-treatment) values served as the comparator for the carvedilol intervention subset (no placebo group).

Outcome

Serum levels of 8-hydroxy-2-deoxyguanosine (8-OHdG) measured by enzyme immunoassay, and myocardial expression of 8-OHdG evaluated immunohistochemically.surrogate

Oxidative DNA damage is elevated in patients with dilated cardiomyopathy, and treatment with the antioxidant beta-blocker carvedilol may reduce this damage while improving cardiac function.

Main Result

Effect estimate: 19% decrease

Absolute Event Rate: 5.1% vs 6.3%

p-value: p=<0.05

Limitations

Absence of a placebo group, making it unclear if changes in 8-OHdG were solely attributable to carvedilol.

Abstract

BACKGROUND: Oxidative stress has been implicated in the pathogenesis of chronic heart failure. The present study investigated whether the levels of 8-hydroxy-2-deoxyguanosine (8-OHdG), a marker of oxidative DNA damage, were elevated in the serum and myocardium of patients with dilated cardiomyopathy (DCM), and furthermore whether carvedilol, a vasodilating beta-blocker with antioxidant activity, could reduce the levels. METHODS AND RESULTS: Serum levels of 8-OHdG were measured by enzyme immunoassay in 56 patients with DCM and in 20 control subjects. DCM patients had significantly elevated serum levels of 8-OHdG compared with control subjects. Endomyocardial biopsy samples obtained from 12 DCM patients and 5 control subjects with normal cardiac function were studied immunohistochemically for the expression of 8-OHdG. Positive 8-OHdG staining was found in the nuclei of cardiomyocytes from DCM patients but not in those from control subjects. After treatment with carvedilol, the serum levels of 8-OHdG in DCM patients significantly decreased by 19%, together with amelioration of heart failure. CONCLUSIONS: Levels of 8-OHdG are elevated in the serum and myocardium of patients with heart failure. Treatment with carvedilol might be effective for decreasing the oxidative DNA damage.

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