Association of hyperuricemia with cardiovascular diseases: current evidence

The aim of the present study is to present a historical and unified perspective on the association of serum uric acid (SUA) in the cause of cardiovascular diseases (CVDs). The association of hyperuricemia (HUC) with CVD begun to be appreciated in the middle 1950s and early 1990s when clinical evidence was shown on the association of HUC with CVD. However, this association was disputed by several investigators including the Framingham group and by professional societies, like the American Heart Association and the American Society of Hypertension. This dispute was weakened or reversed by later studies, which showed a positive association of HUC with CVD, CHD, HF, CKD, and stroke, mediated by several risk factors, both molecular such as, oxidative stress, inflammatory stress, insulin resistance, and endothelial dysfunction, as well as clinical factors such as, atherosclerosis, hypertension, metabolic syndrome, and type 2 diabetes mellitus. The great majority of recent studies show a positive association of HUC with CVDs, and CKD. However, the cutoff of the damaging levels of SUA have not been established as yet. The European Society of Hypertension (ESH) Treatment Guidelines have proposed a cutoff level of SUA for CVD > 7 mg/dl for men and > 6 mg/dl for women. In contrast, the URRAH study has shown a SUA level of 4.7 mg/dl for all-cause mortality and 5.6 mg/dl for CV mortality. These levels are lower than the SUA levels proposed by the ESH, which are consistent with HUC. For a better understanding of this association, a Medline search of the English literature was conducted between 2015 and 2022 and 44 pertinent papers were selected. These papers together with collateral literature will be discussed in this review.