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Hypouricemia and Mortality Risk in the US General Population
Author(s) -
D’Silva Kristin M.,
Yokose Chio,
Lu Na,
McCormick Natalie,
Lee Hwajeong,
Zhang Yuqing,
Choi Hyon K.
Publication year - 2021
Publication title -
arthritis care and research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.032
H-Index - 163
eISSN - 2151-4658
pISSN - 2151-464X
DOI - 10.1002/acr.24476
Subject(s) - medicine , hazard ratio , national health and nutrition examination survey , confidence interval , gout , population , cohort , cohort study , demography , mortality rate , environmental health , sociology
Objective The most recent European Alliance of Associations for Rheumatology (EULAR) recommendations for gout advise against maintaining a serum urate (SU) level of <3 mg/dl for prolonged periods of time. While several Asian cohort studies have shown higher rates of mortality in individuals with extremely low SU levels, data from non‐Asian cohort studies are scarce, and the relationship between hypouricemia, cardiovascular risk, and mortality remains unclear. Methods Using data collected from the 1988–1994 and 1999–2008 National Health and Nutrition Examination Survey (NHANES), we examined the relationship between SU level and overall and cause‐specific mortality in 41,807 adults in the US. We calculated multivariable hazard ratios (HRs) that were compared to a referent SU level of 5–6 mg/dl for SU categories <4, 4–5, 6–7, 7–8, and >8 mg/dl in men and SU categories <3, 3–4, 4–5, 6–7, and >7 mg/dl in women. Results A higher mortality risk was not observed in women who had an SU level of <3 mg/dl (HR 1.09 [95% confidence interval (95% CI) 0.92–1.28]). A 28% higher mortality risk was observed in men who had an SU level of <4 mg/dl (HR 1.28 [95% CI 1.13–1.45]), with a nearly three‐times higher mortality risk from diabetes mellitus also noted (HR 2.89 [95% CI 1.59–5.23]), but no increase in mortality from any other specific cause. Conclusion We found no long‐term excess mortality risk among American women with SU levels as low as <3 mg/dl, a finding which is incompatible with the notion of a causal relationship between hypouricemia and premature mortality in women. We found excess all‐cause mortality and diabetes mellitus–related mortality among hypouricemic American men, which may in part be attributable to the uricosuric effect of hyperglycemia in fatal uncontrolled diabetes mellitus (analogous to reverse causality).