Uric acid in chronic heart failure: a marker of chronic inflammation

BACKGROUND: Chronic heart failure is associated with hyperuricaemia and elevations in circulating markers of inflammation. Activation of xanthine oxidase, through free radical release, causes leukocyte and endothelial cell activation. Associations could therefore be expected between serum uric acid level, as a marker of increased xanthine oxidase activity, and markers of inflammation. We have explored these associations in patients with chronic heart failure, taking into account the hyperuricaemic effects of diuretic therapy and insulin resistance. METHODS AND RESULTS: Circulating uric acid and markers of inflammation were measured in 39 male patients with chronic heart failure and 16 healthy controls. All patients underwent a metabolic assessment, which provided a measure of insulin sensitivity (intravenous glucose tolerance tests and minimal modelling analysis). Compared to controls, patients with chronic heart failure had significantly higher levels of circulating uric acid, interleukin-6, soluble tumour necrosis factor receptor (sTNFR)-1, soluble intercellular adhesion molecule-1 (ICAM-1, all P<0.001), E-selectin and sTNFR2 (both P<0.05). In patients with chronic heart failure, serum uric acid concentrations correlated with circulating levels of sTNFR1 (r=0.74), interleukin-6 (r=0.66), sTNFR2 (r=0.63), TNFa (r=0.60) (all P<0.001), and ICAM-1 (r=0.41, P<0.01). In stepwise regression analyses, serum uric acid emerged as the strongest predictor of ICAM-1, interleukin-6, TNF, sTNFR1 and sTNFR2, independent of diuretic dose, age, body mass index, alcohol intake, serum creatinine, plasma insulin and glucose, and insulin sensitivity. CONCLUSIONS: Serum uric acid is strongly related to circulating markers of inflammation in patients with chronic heart failure. This is consistent with a role for increased xanthine oxidase activity in the inflammatory response in patients with chronic heart failure.