U‐Shaped Association Between Serum Uric Acid Level and Risk of Mortality

Objective In addition to the controversy regarding the association of hyperuricemia with cardiovascular disease ( CVD ) mortality, few studies have examined the impact of a low uric acid level on mortality. We undertook the present study to evaluate the relationship between both low and high uric acid levels and the risk of all‐cause and cause‐specific mortality in a large sample of Korean adults over a full range of uric acid levels. Methods A cohort study was performed in 375,163 South Korean men and women who underwent health check‐ups from 2002 to 2012. Vital status and cause of death were ascertained from the national death records. Hazard ratios ( HR s) and 95% confidence intervals (95% CI s) for mortality outcomes were estimated using Cox proportional hazards regression analysis. Results During a total of 2,060,721.9 person‐years of follow‐up, 2,020 participants died, with 287 CVD deaths and 963 cancer deaths. Low and high uric acid levels were associated with increased all‐cause, CVD , and cancer mortality. The multivariable‐adjusted HR s for all‐cause mortality in the lowest uric acid categories (<3.5 mg/dl for men and <2.5 mg/dl for women) compared with the sex‐specific reference category were 1.58 (95% CI 1.18–2.10) and 1.80 (95% CI 1.10–2.93), respectively. Corresponding HR s in the highest uric acid categories (≥9.5 mg/dl for men and ≥8.5 mg/dl for women) were 2.39 (95% CI 1.57–3.66) and 3.77 (95% CI 1.17–12.17), respectively. Conclusion In this large cohort study of men and women, both low and high uric acid levels were predictive of increased mortality, supporting a U‐shaped association between serum uric acid levels and adverse health outcomes.