The present review of the available literature shows that there is an association between serum urate levels and hypertension, CKD, heart failure, the metabolic syndrome, obesity and cardiovascular events. However, as is often the case in the published literature, support is not unanimous. Understanding in the field is hampered by the difference in urate metabolism between laboratory animals and man, which makes animal studies difficult to interpret. Thus, there is limited evidence for a causal relationship. The interventional studies in man can be considered more as hypothesis-generating, since design quality, duration, and sample size are often insufficient to clarify the role of urate in cardiovascular disease. In addition, most interventional studies are with allopurinol, which is lowering urate via inhibition of XO, leading to decreased production of ROS, which may have contributed to any apparent beneficial effect. A definitive answer to the question of whether urate-lowering therapy can reduce cardiovascular morbidity and mortality will, in the end, require large interventional trials, but it is doubtful that the safety profile of allopurinol is sufficient for such large-scale studies. The recently approved and emerging novel urate-lowering agents may have a better safety profile for these much needed larger and longer-term studies. Ideally, these studies would compare cardiovascular endpoints in patients treated with placebo versus XO and/or URAT1 inhibition, to establish both the benefits and mechanisms of treating hyperuricaemia.
A very recent online publication has used mendelian randomization to investigate the association of plasma uric acid (SLC2A9) with ischaemic heart disease and hypertension (Palmer et al, BMJ 2013;347:f4262 doi: 10.1136/bmj.f4262) and concluded that there is no strong evidence for a causal association, and that the apparent link is confounded by body weight.