Serum Uric Acid As an Index of Impaired Oxidative Metabolism in Chronic Heart Failure

Background: Elevated serum uric acid concentrations have been observed in clinical conditions associated with hypoxia. Since chronic heart failure is a state of impaired oxidative metabolism, we sought to determine whether serum uric acid concentrations correlate with measures of functional capacity and disease severity.

Methods: Fifty nine patients with a diagnosis of chronic heart failure due to coronary heart disease (n = 34) or idiopathic dilated cardiomyopathy (n = 25) and 20 healthy controls underwent assessment of functional capacity. Maximal oxygen uptake (MVO2) and regression slope relating to minute ventilation to carbon dioxide output (VE-VCO2) were measured during a maximal treadmill exercise test. Metabolic assessment consisted of measuring serum uric acid and fasting lipids, and insulin sensitivity, obtained by minimal modelling analysis of glucose and insulin responses during an intravenous glucose tolerance test. Clustering of indices of functional disease capacity and metabolic factors was explored using factor analysis and multivariate regression analysis.

Results: Compared to 20 healthy controls, patients with chronic heart failure had a 52% lower MVO2 (P < 0.001), 56.8% higher serum uric acid concentrations (P < 0.001) as well as a 60.5% lower insulin sensitivity (P < 0.001). Salient univariate correlations in the chronic heart failure group included serum uric acid concentrations with exercise time during the exercise test (r = -0.53), MVO2 (r = -0.50) (both P < 0.001), VE-VCO2 slope (r = 0.45), and NYHA functional class (r = 0.36) (both P < 0.01). In factor analysis of the chronic heart failure group, serum uric acid formed part of a principal cluster of metabolic variables which included MVO2 and VE-VCO2 slope. In multivariate regression analysis, serum uric acid concentrations emerged as a significant predictor of MVO2, exercise time (both P < 0.001,) VE-VCO2 slope and NYHA functional class (both P < 0.02), independent of diuretic dose, age, body mass index, serum creatinine, alcohol intake, plasma insulin levels, and insulin sensitivity index.

Conclusions: There is an inverse relationship between serum uric acid concentrations and measures of functional capacity in patients with cardiac failure. The strong correlation between serum uric acid and MVO2 suggests that in chronic heart failure, serum uric acid concentrations reflect an impairment of oxidative metabolism.