Hyperuricemia and cardiovascular diseases: from phylogenesys to patogenetic mechanisms

During human evolution, the accumulation of loss of function mutations of the uricase gene led progressively to the lack of the ability to metabolize uric acid into further end-products. Consequently, serum uric acid levels progressively increased over time along with the dietary availability of purine-rich foods. At first, the increase in uricemia contributed positively to primate development by increasing the antioxidant power of the organism, favouring an increase in blood pressure and lipid metabolism. However, later, these positive effects have been overcome by more dangerous consequences. In fact, in the recent period of human being history, the impact of dietary changes on uricemia was so significant that pathological consequences such as gout or renal stones appeared. Furthermore, it has been proved that abnormal uric acid level induces endothelial dysfunction and renal fibrosis. The shift between positive and negative consequences secondary to uric acid is clearly in accordance with the J curve shaped relation that describes the correlation between mortality and serum uric acid level.