The role of serum uric acid (sUA) as a risk factor for cardiovascular (CV) disease has been extensively debated for many years. In particular, most of the evidence about the pathogenetic role of UA in CV disease has been achieved in the population of patients with severe hyperuricemia or gout while the relevance in patients with mildly elevated serum levels of UA is only poorly established. Serum UA had been described as an important, independent risk factor for CV and renal disease in the general population as well as in patients with gout, hypertension, heart failure, or diabetesCitation1.
Elevated serum sUA is highly predictive of mortality in patients with heart failure or coronary artery disease and increased the risk of CV events in patients with diabetes. Although the mechanisms responsible for the deleterious effect of sUA in CV disease is still unclear, several data have been provided supporting a negative effect of hyperuricemia on endothelial function, oxidative metabolism and platelet aggregation. From the therapeutic point of view, recent findings suggest the possibility that a treatment-induced decrease in serum UA may attenuate CV risk and the development of CV diseasesCitation2.
The recent approval of a new drug for the treatment of gout, febuxostat, with a mechanism of action as a selective non-purine inhibitor of xanthine oxidase, has given a renewed interest in this fieldCitation3,Citation4. Febuxostat has shown to be more effective than allopurinol in reducing SUA levels in patients with gout; moreover, it effectively inhibits both forms of XO enzyme. These promising features could represent important points in the treatment choice for these patients.
The main purpose of this special supplement to Current Medical Research and Opinion is two-fold: first of all to emphasize the role of UA in the pathogenesis of gout and provide updated summaries of diagnosis and management of gout patientsCitation5; secondly, to provide an updated review of the evidence supporting a possible and relevant role of (elevated) UA as a risk factor for renal and CV diseasesCitation6.
A board of eminent experts, whom I have the honor to represent, has prepared this publication.
The first article by Punzi and So, ‘Serum uric acid and gout: from the past to molecular biology’, is an overview of the epidemiology and risk factors of gout, with a focus on recent advances. The authors also list the most updated recommendations for diagnosis of gout.
The paper of Richette and Perez-Ruiz presents the information available on the role of UA on metabolic risk and on the link between hyperuricemia and metabolic syndrome. Increasing evidence suggests that UA may play a critical role in metabolic syndrome and lowering UA may represent a novel treatment target for preventing diabetes.
In their review, Bardin and Desideri discuss how to properly manage gout and to provide the right education to gout patients for understanding of the disease and adherence to long-term therapy, particularly in the elderly.
The problem of the interactions between serum UA, gout, hypertension and kidney disease are discussed by Ruilope and Pontremoli who emphasized the results of clinical and experimental studies carried out in this very interesting field. Some of these clinical trials using urate lowering therapy provide some promising evidence that lowering UA levels may retard the progression of chronic kidney disease.
Lastly, in ‘Beyond gout: uric acid and cardiovascular diseases’, Agabiti-Rosei and Grassi clearly show how strong is the association of hyperuricemia and gout with CV disease. XO inhibitors appear to be the most promising agents for prevention and treatment of CV outcomes associated with hyperuricemia. More studies are needed, however, to determine the potential of these drugs for reducing the risk of developing CV disease.
In conclusion, this series of comprehensive reviews wants to provide the most recent progress and future directions in the association of hyperuricemia and gout with CV and renal diseases.
Transparency
Declaration of funding
Editorial assistance for this supplement was funded by Menarini International.
Declaration of financial/other relationships
C.B. has received no remuneration for his role as an author on this editorial. He has disclosed that he has received grants from Menarini, Eli Lilly, and Sevier, is a consultant to Menarini and Sevier, and holds stock in Abbott and BMS.
References
- Feig DI, Kang DH, Johnson RJ. Uric acid and cardiovascular risk. N Engl J Med 2008;359:1811-21
- Higgins P, Dawson J, Lees KR, et al. Xanthine oxidase inhibition for the treatment of cardiovascular disease: a systematic review and metanalysis. Cardiovasc Ther 2012;30:217-26
- Schumacher HR Jr, Becker MA, Wortmann RL, et al. Effects of febuxostat versus allopurinol and placebo in reducing serum urate in subjects with hyperuricemia and gout: A 28-week, phase III, randomized, double-blind, parallel-group trial. Arthritis Rheum 2008;59:1540-8
- Garcia-Valladares I, Khan T, Espinoza LR. Efficacy and safety of febuxostat in patients with hyperuricemia and gout. Ther Adv Musculoskel Dis 2011;3:245-53
- Perez-Ruiz F. Treating to target: a strategy to cure gout. Rheumatology 2009;48:ii9-14
- Johnson RJ, Kang DH, Feig D, et al. Is there a pathogenetic role for uric acid in hypertension and cardiovascular and renal disease? Hypertension 2003;41:1183-90