Significance of uric acid for the heart and vessels

The recent article describing a positive association between serum uric acid and several inflammatory markers in the InCHIANTI study addresses the issue of whether uric acid is an independent cardiovascular risk factor. Uric acid is an antioxidant and appears to contribute to salutary immune reactions, but the cardiovascular significance of rises in its serum level remains poorly understood. I would like to summarize the intricacies of this question. Increases in serum uric acid concentration could be primarily unrelated to the heart and vessels, they could originate in or form part of the processes that account for the development or progress of several cardiovascular conditions, including atherosclerosis, hypertension and heart failure, or they could constitute compensatory reactions to such processes. Mechanistically, elevations in serum uric acid may result from increases in its synthesis, from reductions in its renal excretion, in theory from decrements in its transformation rate (i.e. from diminutions in the rate at which it quenches reactive species), and from combinations thereof. In terms of their effects on cardiovascular structures and functions, rises in serum uric acid could theoretically be inconsequential, beneficial, or untoward, by and of themselves or as a resultant, depending upon the mechanisms involved in their genesis and the circumstances in which they occur. Reactive oxygen species are co-generated when the synthesis of uric acid or the formation of its precursor xanthine from hypoxanthine is catalyzed by the xanthine oxidase form of xanthine oxidoreductase. No study has disclosed that reducing serum uric in human beings attenuates the development or progress of any cardiovascular disorder independently of co-changes in other variables. Moreover, decrements in serum uric acid secondary to the inhibition of its synthesis with allopurinol or oxypurinol have failed to benefit patients with heart failure. For all the preceding reasons, speculation on the significance of increases in serum uric acid for cardiovascular prognosis must be particularly thorough and circumspect. I was glad to note that Ruggiero et al. have impressed these qualities upon the discussion of the results of their timely analysis.