Urate-lowering drugs and prevention of cardiovascular disease. the emerging role of xanthine oxidase inhibition

The relevance of elevated plasma levels of serum uric acid (SUA) in patients with cardiovascular disease was historically described 2 centuries century ago when Alexander Heig published a paper dealing with the causative role of hyperuricermia in patients with hypertension and several other diseases. More recently, a remarkable number of epidemiological and experimental studies have demonstrated that hyperuricemia and gout are strongly related with hypertension, metabolic syndrome, chronic kidney disease, and cardiovascular disease. The relationship between hyperuricemia and hypertension and metabolic syndrome has been confirmed in both pediatric and adolescent populations and is maintained after an extensive adjustment for almost all of the possible confounding conditions (eg, hypertension, diabetes mellitus, lipid disorders, renal function, etc), thereby supporting the role of elevated SUA as an emerging independent cardiovascular risk factor in patients with and without gout. The mechanisms that link elevated SUA levels and gout with cardiovascular comorbidities seem to be multifactorial, implicating low-grade systemic inflammation and xanthine oxidase (XO) activity, as well as the deleterious effects of hyperuricemia itself.