Serum uric acid and CV risk: a look into epidemiology.

Cardiovascular diseases are the major cause of death in the Western world as a consequence of the elevated prevalence and poor control of cardiovascular risk factors in the general population. During the last 25 year many possible risk factors have been identified in addition to those include in the main CV risk algorhytms as elevated blood pressure, diabetes and lipid disorders. Elevated levels of serum uric acid are the mechanism responsible for the development of gout but have been also frequently associated with an increase in individual risk of CV diseases in addition with the more consolidated CV risk factors. A recognition of an association among hyperuricemia, kidney diseases and cardiovascular diseases dates to the late 19th century, but has been recently resurged to investigation in reason of the increase in the amount of information about the possible pathogenetic mechanism(s) and the demonstration of a remarkable degree of residual cardiovascular risk in patients undergoing an appropriate control of many independent CV risk factors. The hypothesis linking uric acid with cardiovascular disease is well grounded in animal models where the development in hyperuricemia is associated with an increase in blood pressure that can be prevented by the use of xantine-oxidase inhibitors leading to a decrease in serum uric acid. Data from observational studies and physiological experiments suggest that there may be a causal relationship between plasma levels of uric acid and the incidence of cardiovascular and renal disease. However, definitely convincing evidence remains elusive for many different reasons that complicate the relationship between the study of uric acid, its determinants and its confounders. In particular among the confounder a prominent role is played by statistical and methodological issues as well as by the confounding role of co-variants that might be also mediators of biological pathways (e.g. kidney) or might variably interact with additional cardiovascular risk factors. In particular the assessment of the role of uric acid as a risk factor for CV diseases should be conducted in patients free from gout and kidney disease, with a balanced age-range and gender distribution and across an appropriate period of follow-up. Cross-sectional investigations that have been often claimed to confirm or interpret because of the elevated number of co-morbidities that affect approach, the possible association between serum uric acid and cardiovascular disease is well supported by several epidemiological observation, can be reasonably explain by mechanicistic approach and might be favorably modified by appropriate treatment strategies involving both a biochemical and a structural approach addressing the protection of target organ. Understanding the complex relationship between uric acid and cardiovascular diseases is necessary to quantify of uric acid as a risk factor and should force the researcher and clinicians to balance evidence supporting causality vs. associations. From the epidemiological point of view the association between uric acid and subsequent cardiovascular disease remains uncertain. While some recent epidemiological studies have independently related uric acid to hypertension, diabetes, metabolic syndrome, renal disease and cardiovascular complications, other studies have found that, following adjustments for cardiovascular risk factors and estimated GFR the independent role of uric acid in cardiovascular disease cannot be confirmed. All these evidence support a possible role of serum uric acid as an independent risk factor for cardiovascular disease and suggest the importance of a more extensive investigation with the aim to increase the possibility of effectively reduce the impressive burden of cardiovascular diseases.