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Uric acid in chronic heart failure—current pathophysiological concepts *
Author(s) -
Doehner Wolfram,
Springer Jochen,
Anker Stefan D.,
Landmesser Ulf,
Struthers Allan D.
Publication year - 2008
Publication title -
european journal of heart failure
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.149
H-Index - 133
eISSN - 1879-0844
pISSN - 1388-9842
DOI - 10.1016/j.ejheart.2008.10.005
Subject(s) - xanthine oxidase , uric acid , heart failure , medicine , oxidative stress , endogeny , endothelial dysfunction , pathophysiology , gout , antioxidant , xanthine , oxidative phosphorylation , cardiology , biochemistry , enzyme , chemistry
In their recent article [1] Alcaino and colleagues report a beneficial effect of hyperuricaemia in preventing oxidative stress and improving endothelial function in chronic heart failure (CHF). The conclusions from this observational correlation study in 38 patients with CHF are opposite to a substantial body of evidence. We would like to discuss these surprising results and put the findings in perspective with other data and current thinking. Based on the background presented by the authors to support their study hypothesis, we believe that the authors have a misconception of the character of hyperuricaemia in CHF and its pathophysiologic meaning. Several studies are cited to support the role of uric acid (UA) as antioxidant preventing oxidative damage and endothelial dysfunction. All of these studies tested the impact of administration of exogenous uric acid, but not endogenous physiologically derived UA. There are two major differences between exogenous and endogenous UA. Firstly, UA levels after exogenous UA infusion are generally higher than endogenous UA levels. Secondly, and even more importantly, endogenous UA is produced by xanthine oxidase (XO), which in parallel is a predominant source of oxygen free radicals in human physiology. It has been shown by direct assessment of XO that elevated XO activity is the major cause of hyperuricaemia in CHF [2]. For each oxidative step two electrons are transferred to XO and the fully reduced XO yields the production of two H2O2 and two O2 − [3]. Hyperuricaemia in CHF hence implies increased oxygen radical accumulation rather than an improved antioxidative state. The suggestion by the authors that elevated (endogenous) UA levels may exert a beneficial effect on endothelial function and prognosis opposes a large number of studies on vascular function [2,4,5] and mortality [6] in CHF, in other cardiovascular patient populations as in general populations [7].