S-17-1: URIC ACID AND CARDIOVASCULAR DISEASES

Abstract

Uric acid (UA) is the final product of purine metabolism and its increase in the circulating blood defines the presence of hyperuricaemia commonly considered as a concentration of uric acid in serum above the threshold level of 7 mg/dL (416 mol/L) in men and > 6 mg/dL in women. The typical consequence of elevated UA levels is the development of gout, a condition affecting 2–3% of the general population but beside the effects on gout, the elevated levels of UA have been associated with a significant increase in the risk of hypertension, metabolic syndrome, and cardiovascular disease (CVD) regardless of the presence of serum urate deposition. All this evidence clearly supports a primary cardiovascular role for elevated serum UA probably based on multiple and interactive mechanisms of action not necessarily involving the articular and tissue deposition. The interaction between elevated UA and cardiovascular diseases has been extensively investigated in the last 10 years providing interesting results in terms of patients identification, threshold of risk, pathophysiology, results of clinical trials and effects of drugs not primary involved in the management of uric acid levels. In particular, the evidence supports an increase of CV mortality and morbidity in patients with levels of SUA between 4.5 and 5.5 that are common in a large proportion of subjects and patients with overt cardiovascular diseases. This observation along with the differences in the mechanism leading to elevated UA (hyperproduction vs. underexcretion) will allow a more functional identification of patients suitable for pharmacological treatment with urate lowering drugs (ULT). Furthermore, the dynamic analysis of time-dependent trajectories of UA levels is a new approach to the interpretation and clinical management of cardiovascular disease. The overall representativity of a pattern of modification seems to better define the prognostic role of elevated UA and could be probably improved by an integrated interpretation of the different patterns beyond the role of risk cards and algorithms. Very recently, the management of elevated UA has also included the effects of non-ULT drugs as Losartan, SGLT-2 inhibitors, vericiguat whose administration in randomized clinical trials has improved uric acid levels with a linear proportion with the amount of UA reduction. The interaction between hyperuricemia and CVD is a very dynamic issue that has been recently enriched with several additional information that have allowed a more effective identification of those subsets of patients that can successfully treated in daily clinical practice