Uric acid as a risk factor for cardiovascular disease

Abstract

Over recent years there has been renewed debate about the nature of the association between raised serum uric acid concentration and cardiovascular disease.1 Several large studies have identified the value, in populations, of serum uric acid concentration in predicting the risk of cardiovascular events, such as myocardial infarction. This has directed research towards the potential mechanisms by which uric acid might have direct or indirect effects on the cardiovascular system. It has been difficult to identify the specific role of elevated serum uric acid because of its association with established cardiovascular risk factors such as hypertension, diabetes mellitus, hyperlipidaemia and obesity.2,,3 Indeed, it is not even clear at this stage whether uric acid has a damaging or protective effect in these circumstances. Increased understanding of the mechanisms underlying these associations may allow a clearer interpretation of the importance of elevated serum uric acid concentrations, and the potential value of specific urate‐lowering treatment on cardiovascular disease. Purines arise from metabolism of dietary and endogenous nucleic acids, and are degraded ultimately to uric acid in man, through the action of the enzyme xanthine oxidase (Figure 1). Uric acid is a weak acid (pKa 5.8), distributed throughout the extracellular fluid compartment as sodium urate, and cleared from the plasma by glomerular filtration.4 Around 90% of filtered uric acid is reabsorbed from the proximal renal tubule, while active secretion into the distal tubule by an ATPase‐dependent mechanism contributes to overall clearance.5 Serum uric acid concentration within the population has a Gaussian distribution, with a typical reference range (95% CI) of 120–420 μmol/l. For an individual, urate concentration is determined by a combination of the rate of purine metabolism (both endogenous and exogenous) and the efficiency of renal clearance. Purine metabolism is influenced by dietary, as well as genetic factors regulating …