title: Uric acid and oxidative stress: relative impact on cardiovascular risk?
abstract: Post-hoc analyses of the GREACE and the LIFE trials have renewed the interest in elevated serum uric acid (SUA) as a factor contributing to atherosclerotic cardiovascular disease (CVD) and in the possible benefit derived from its pharmacological reduction. The results of these trials are consistent with reports indicating favourable effects of SUA lowering treatment with allopurinol on the rate of cardiovascular complications in patients with coronary heart disease, congestive heart failure and dilated cardiomyopathy. Two recent overviews have concluded that, while in population samples at relatively low risk of CVD, SUA is at best a very weak predictor of CVD, by contrast it is a significant independent predictor among subjects at high or very high risk. This raises the question of a different meaning of excess SUA levels under different circumstances. Whereas in uncomplicated obese, insulin-resistant and hypertensive patients SUA levels increase mainly as a consequence of impaired renal excretion, in conditions of local ischemia an increased production of uric acid occurs in parallel with that of reactive oxygen species (ROS). Thus, although clinical and experimental evidence suggest that uric acid has actually antioxidant properties, it is conceivable that under these conditions its antioxidant activity is overcome by the pro-oxidant and pro-inflammatory effects of ROS accumulation. At present, there is no solid evidence to recommend treatment of the mild asymptomatic hyperuricemia associated with obesity, diabetes and/or hypertension (up to 10mg/dL). By contrast, similar SUA elevations in patients at higher cardiovascular risk should be taken more seriously. A controlled trial to investigate the effects of SUA reduction in these patients, while monitoring concomitant changes in parameters of oxidative stress and inflammation, is warranted.
authors.affiliation: Department of Clinical and Experimental Medicine, Federico II University Medical School, Via S. Pansini 5, 80131 Naples, Italy. strazzul@unina.it <strazzul@unina.it>
authors.forename: Pasquale
authors.initials: P
authors.lastname: Strazzullo
authors.forename: Juan Garcia
authors.initials: JG
authors.lastname: Puig
mesh_terms: D050197:Atherosclerosis / Q000097:blood / Q000150:complications / Q000209:etiology* / Q000378:metabolism; D015415:Biomarkers / Q000097:blood; D002318:Cardiovascular Diseases / Q000097:blood / Q000209:etiology* / Q000378:metabolism; D006801:Humans; D033461:Hyperuricemia / Q000097:blood / Q000150:complications / Q000378:metabolism*; D018384:Oxidative Stress; D017382:Reactive Oxygen Species / Q000378:metabolism; D018570:Risk Assessment; D012307:Risk Factors; D014527:Uric Acid / Q000097:blood*
chemical_list: D015415:Biomarkers; D017382:Reactive Oxygen Species; D014527:Uric Acid