Serum
uric acid was first noted to be associated with increased BP by Frederick Mohamed in the 1870s. Although the link was rediscovered periodically over the years, it generally was dismissed as a
surrogate marker for decreased renal function that led to increased
uric acid and increased risk for
hypertension and cardiovascular (CV) disease. Recently, however, several lines of evidence suggest that increased serum
uric acid may be a significant modifiable risk factor. Increased serum
uric acid is associated with increased risk for future
hypertension in several large longitudinal clinical trials as well as an independent risk factor for poor CV prognosis. Animal model experiments demonstrate that increased serum
uric acid causes increased BP that initially is reversible but becomes irreversible,
salt sensitive, and
uric acid independent over time. The mechanisms include the direct action of
uric acid on smooth muscle and vascular endothelial cells. Finally, in adolescents with new-onset
essential hypertension, the prevalence of elevated serum
uric acid is >90%, and preliminary clinical trial evidence suggests that agents that lower serum
uric acid may lower BP in this select population. Although the investigations are still preliminary, serum
uric acid represents a possible new and intriguing target for the reduction of morbidity and mortality associated with
hypertension and CV disease.