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

Background Chronic heart failure is associated with hyperuricaemia and elev ations in circulating markers of inflammation. Activation of xanthine oxida se, through free radical release, causes leukocyte and endothelial cell act ivation. Associations could therefore be expected between serum uric acid l evel, as a marker of increased xanthine oxidase activity, and markers of in flammation. We have explored these associations in patients with chronic he art failure, taking into account the hyperuricaemic effects of diuretic the rapy 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 cont rols. All patients underwent a metabolic assessment, which provided a measu re of insulin sensitivity (intravenous glucose tolerance tests and minimal modelling analysis). Compared to controls, patients with chronic heart fail ure 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 concentrat ions correlated with circulating levels of sTNFR1 (r = 0.74), interleukin-6 (r = 0.66), sTNFR2 (r = 0.63), TNF alpha (r = 0.60) (all P < 0.001), and I CAM-1 (r = 0.41, P < 0.01). In stepwise regression analyses, serum uric aci d emerged as the strongest predictor of ICAM-1, interleultin-6, TNF, sTNFR1 and sTNFR2, independent of diuretic dose, age, body mass index, alcohol in take, serum creatinine,plasma insulin and glucose, and insulin sensitivity. Conclusions Serum uric acid is strongly related to circulating markers of i nflammation in patients with chronic heart failure. This is consistent with a role for increased xanthine oxidase activity in the inflammatory respons e in patients with chronic heart failure.