Uric acid and xanthine oxidase: future therapeutic targets in the prevention of cardiovascular disease?

摘要

The role of serum uric acid in the development of cardiovascular disease has been the subject of controversy for many years. Epidemiological evidence clearly suggests an association between increasing uric acid concentrations and event rates and mortality in a variety of cardiovascular disease states. However, the presence of a causal relationship is less clear. Elevated concentrations of uric acid may reflect a separate underlying disease process, atherosclerosis itself or increased xanthine oxidase activity, all of which may influence vascular risk. Conversely, a causal role has been suggested by posthoc analyses of the losartan intervention for endpoint reduction (LIFE) study , clinical trials of fenofibrate and atorvastatin and preclinical data suggestive of direct deleterious effects on platelet and endothelial function. Interventional studies of xanthine oxidase inhibition, which will reduce both uric acid and oxidative stress, have been conducted in patients with or at high risk of vascular disease [4-13]. Although these are small and few in number, their results suggest a potential benefit of intervention to modify uric acid metabolism in the prevention of cardiovascular disease