Uric acid and cardiovascular disease

Uric acid (UA) is an end product of purine metabolism in humans and great apes. UA acts as an antioxidant and it accounts for 50% of the total antioxidant capacity of biological fluids in humans. When present in cytoplasm of the cells or in acidic/hydrophobic milieu in atherosclerotic plaques, UA converts into a pro-oxidant agent and promotes oxidative stress and through this mechanism participates in the pathophysiology of human disease including cardiovascular disease (CVD). Most epidemiological studies but not all of them suggested the existence of an association between elevated serum UA level and CVD, including coronary heart disease (CHD), stroke, congestive heart failure, arterial hypertension and atrial fibrillation as well as an increased risk for mortality due to CVD in general population and subjects with confirmed CHD. Evidence available also suggests an association between elevated UA and traditional cardiovascular risk factors, metabolic syndrome, insulin resistance, obesity, non-alcoholic fatty liver disease and chronic kidney disease. Experimental and clinical studies have evidenced several mechanisms through which elevated UA level exerts deleterious effects on cardiovascular health including increased oxidative stress, reduced availability of nitric oxide and endothelial dysfunction, promotion of local and systemic inflammation, vasoconstriction and proliferation of vascular smooth muscle cells, insulin resistance and metabolic dysregulation. Although the causality in the relationship between UA and CVD remains unproven, UA may be pathogenic and participate in the pathophysiology of CVD by serving as a bridging mechanism mediating (enabling) or potentiating the deleterious effects of cardiovascular risk factors on vascular tissue and myocardium.