OP0015 SEX-SPECIFIC U-SHAPED RELATIONSHIP BETWEEN SERUM URATE AND MORTALITY IN THE UNITED STATES GENERAL POPULATION

Abstract

Background:A U-shaped relationship may exist between serum urate (SU) and cardiovascular events, although the relationship between SU and mortality is unclear. The most recent EULAR recommendations for gout advise against maintaining SU <3 mg/dl for prolonged periods.Objectives:To examine the relationship between SU and all-cause and cause-specific mortality in large cohorts in the United States (US).Methods:We examined National Health and Nutrition Examination Survey (NHANES) data from 1988-1994 (NHANES III) and 1999-2007 including subjects aged ≥18 with an enrollment SU measurement. We used Cox proportional hazards regression models to estimate sex-specific mortality risk relative to a referent SU 5-6 mg/dL, adjusting for NHANES cycle, age, race, body mass index (BMI), education, alcohol use, smoking, hypertension, total cholesterol, estimated glomerular filtration rate (GFR), and competing risks, using age as a time scale for survival analysis.Results:Among 19,954 men and 21,853 women, there were 5,714 male deaths and 4,901 female deaths (median follow-up 14.2 ± 6.9 years). Among men, there was a 33% increased all-cause mortality risk at SU <4 mg/dL (HR 1.33, 95% CI 1.17-1.51) and 52% increased all-cause mortality risk at SU >8 mg/dL (HR 1.52, 95% CI 1.37-1.69) compared to subjects with SU 5-6 mg/dL, driven by cause-specific mortality from diabetes at low SU and chronic lower respiratory diseases and cardiovascular disease at high SU (Table). In women, there was no increased mortality risk at low SU and a 45% increased all-cause mortality risk at SU >7 mg/dL (HR 1.45, CI 1.31-1.61) compared to subjects with SU 5-6 mg/dL, driven by cause-specific mortality from diabetes. Mortality from Alzheimer’s disease was lower at high SU among men (HR 0.23, 95% CI 0.05-0.99) and women (HR 0.54, 95% CI 0.25-1.15).Table.Multivariable hazard ratios for all-cause and cause-specific mortality in NHANES III and 1999-2007.Conclusion:In large cohorts representative of the US population, there was a U-shaped relationship between SU and all-cause mortality in men but not women. In men with low SU, mortality was driven primarily by diabetes, which may be explained by the uricosuric effect of uncontrolled hyperglycemia in diabetes patients. The lower mortality from Alzheimer’s disease at high SU agrees with previously shown inverse associations between gout and Alzheimer’s disease. Further studies are needed to determine the presence of causality underlying these associations.Disclosure of Interests:Kristin D’Silva: None declared, Chio Yokose: None declared, Leo Lu: None declared, Yuqing Zhang: None declared, Hyon Choi Grant/research support from: Ironwood, Horizon, Consultant of: Takeda, Selecta, Horizon, Kowa, Vaxart, Ironwood