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Increased serum uric acid has been identified as an independent risk factor for cardiovascular disease. However, because of its antioxidant capacity, uric acid may play a beneficial role in endothelial function. This paradoxical relationship between uric acid and endothelial function in chronic heart failure patients remains poorly understood. Thirty-eight chronic heart failure patients (New York Heart Association functional class II-III, mean age 58 ± 10 years and mean left ventricular ejection fraction 25 ± 8%) and twelve age-and-sex-matched healthy controls were studied. Chronic heart failure patients showed higher uric acid levels (7.3 ± 2.3 mg/dL vs. 6.1 ± 0.2 mg/dL, p b 0.05) and lower extracellular superoxide dismutase activity (136 ± 36 U ml − 1 min − 1 vs. 203 ± 61 U ml − 1 min − 1 , p b 0.01) and endothelium-dependent vasodilatation (4.0 ± 1.6% v. 9.1 ± 3.0%, p b 0.01) when compared with control subjects. In chronic heart failure patients, correlations between both uric acid levels and extracellular superoxide dismutase activity (r = 0.45; p b 0.01), and uric acid and endothelium-dependent vasodilatation (r = 0.35; p = 0.03) were detected. These correlations were not observed in healthy individuals, suggesting a positive effect of uric acid on endothelial function partially mediated by modulation of extracellular superoxide dismutase activity in chronic heart failure.

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Background: Our previous studies suggest that the increase in heart rate from rest to peak exercise is reduced in patients with chronic heart failure (CHF) and this is associated with increased oxidative stress, as determined by malondialdehyde (MDA) plasma levels. Aim: To investigate the effects of carvedilol on the heart rate response to exercise and oxidative stress in patients with CHF. Methods and results: Thirty stable NYHA classes II-III CHF patients received carvedilol therapy for 6 months, at a mean maintenance dose of 25 mg (range 6.25-50 mg/day). After treatment, the patients showed a significant improvement in their functional NYHA class ( p=0.013), increased left ventricular ejection fraction (LVEF) (24F1.4% to 31F2.3%, p=0.003) and 6-min walk distance (499F18 to 534F18 m, p=0.03), without changes in the peak VO 2 . At baseline, norepinephrine (NE) plasma levels increased with exercise (510F51 to 2513F230 pg/mL, pb0.001), and these levels were not affected by carvedilol. Chronotropic responsiveness index (increase in heart rate divided by the increase in NE from rest to peak exercise) was not changed by carvedilol (0.049F0.001 to 0.042F0.001, p=0.6). MDA levels of CHF patients decreased after treatment with carvedilol (2.4F0.2 to 1.1F0.2 AM, pb0.001), without changes in antioxidant enzyme activities. Conclusions: Carvedilol treatment in patients with CHF results in reduced oxidative stress without restoration of the chronotropic responsiveness index.

Abstract:We investigated the clinical response of chronic heart failure patients with β 2 -adrenergic receptor Gln 27 → Glu polymorphism treated for 6 months with carvedilol, a α / β -antagonist with antioxidant properties. The 6-min. walk test, the left ventricular ejection fraction, heart rate, plasma norepinephrine and malondialdehyde, a stress oxidative marker, concentrations were evaluated at baseline and after treatment for 6 months with carvedilol in 33 stable chronic heart failure patients with the Gln 27 → Glu β 2 -adrenergic receptor polymorphism. Carvedilol significantly increased the left ventricular ejection fraction, while decreasing the heart rate and malondialdehyde plasma concentrations in chronic heart failure patients with the Glu 27 β 2 -adrenergic receptor allele. There were however, no significant changes in patients with the Gln 27 β 2 -adrenergic receptor variant.