U-Shaped Association Between Serum Uric Acid Level and Risk of Mortality: A Cohort Study

Arthritis Rheumatol. 2018 Jul;70(7):1122-1132. doi: 10.1002/art.40472. Epub 2018 May 9.

Abstract

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 (HRs) and 95% confidence intervals (95% CIs) 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 HRs 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 HRs 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Cardiovascular Diseases / blood
  • Cardiovascular Diseases / mortality*
  • Cause of Death
  • Female
  • Humans
  • Hyperuricemia / blood
  • Hyperuricemia / mortality*
  • Male
  • Middle Aged
  • Proportional Hazards Models
  • Republic of Korea / epidemiology
  • Retrospective Studies
  • Risk Factors
  • Uric Acid / blood*

Substances

  • Uric Acid