Hyperuricemia, Gout, and Related Comorbidities: Cause and Effect on a Two-Way Street

The prevalence of gout and hyperuricemia has increased dramatically during the last several decades, to the point that gout is the most common inflammatory arthritis in the United States, affecting approximately 8 million Americans. Patients with gout frequently have multiple comorbidities, including hypertension, chronic kidney disease, cardiovascular disease, obesity, diabetes, and hyperlipidemia, all of which have significant adverse impact on public health. In some cases (eg, chronic kidney disease) it is clear that the presence of the comorbidity contributes to the progression of hyperuricemia and/or gout. Conversely, the question of whether gout/hyperuricemia themselves contribute to the pathogenesis of gout comorbidities is an area of intensifying investigation. In vitro and animal models, large epidemiologic studies, and small clinical trials suggest that gout and/or hyperuricemia may contribute to hypertension, chronic kidney disease, and cardiovascular disease. More limited hypothesis-generating studies suggest a potential role for diabetes and obesity. Given that available drugs can lower serum urate levels and manage gout, it would be important to know whether not only gout and/or hyperuricemia can contribute to comorbidities but also better gout/hyperuricemic control can ameliorate some or all of these related conditions. We review the clinical associations between gout and its common comorbid conditions and the evidence supporting a causal relation between them. The evidence that gout and hyperuricemia contribute to the pathogenesis of their comorbidities creates greater urgency for appropriate gout management.