Abstract
BackgroundElevation of serum uric acid (SUA) is associated with increased mortality; however, controversy exists regarding the nature of the relationship and differences between men and women. We explored relationships of SUA levels with all-cause mortality in a large cohort of patients within the Irish health system. MethodsA retrospective cohort study of 26,525 participants was conducted using data from the National Kidney Disease Surveillance System. SUA was modelled in increments of 59.48 µmol/L (1 mg/dL), Cox's proportional hazards model estimated hazard ratios (HRs) and 95% Confidence Intervals (CI), median lifetimes were also computed separately for men and women. Mortality patterns were further explored using penalised splines. ResultsThere were 1,288 (4.9%) deaths over a median follow-up of 5.1 years. In men, the risk of mortality was greatest for the lowest (<238 µmol/L) and highest (>535 µmol/L) categories [HR 2.35 (1.65–3.14) and HR 2.52 (1.87–3.29) respectively]; the corresponding median lifetimes for men were reduced by 9.5 and 11.7 years respectively compared to the referent. In women, mortality risks were elevated for SUA >416 mol/L [HR 1.69 (1.13–2.47) and beyond; the corresponding median lifetime for women were reduced by 5.9 years compared to the referent. Spline analysis revealed a U-shaped association between SUA and mortality in men, while for women, the pattern of association was J-shaped. ConclusionMortality patterns attributed to SUA differ between men and women. Optimal survival was associated with SUA concentrations of 304–454 µmol/L for men and < 409 µmol/L for women.
Highlights
It is widely considered that serum uric acid (SUA), the final break down product of purine metabolism in humans, may represent a major cardiovascular risk factor and contribute to adverse health outcomes and mortality [1,2,3,4,5,6]
We investigated whether the presence of CKD as defined by an estimated glomerular filtration rate (eGFR) threshold of less than 60 ml/min/1.73 m2 modified the relationship between SUA and mortality as SUA has been reported to play a causal role in kidney injury and the presence of hyperuricemia may reflect poor renal function [27,28]
Serum uric acid levels were higher in men than in women and most of patients were seen in general practice or primary care setting
Summary
It is widely considered that serum uric acid (SUA), the final break down product of purine metabolism in humans, may represent a major cardiovascular risk factor and contribute to adverse health outcomes and mortality [1,2,3,4,5,6]. Elevation of serum uric acid (SUA) is associated with increased mortality; controversy exists regarding the nature of the relationship and differences between men and women. We explored re lationships of SUA levels with all-cause mortality in a large cohort of patients within the Irish health system. The risk of mortality was greatest for the lowest (535 μmol/L) categories [HR 2.35 (1.65–3.14) and HR 2.52 (1.87–3.29) respectively]; the corresponding median lifetimes for men were reduced by 9.5 and 11.7 years respectively compared to the referent. Mortality risks were elevated for SUA >416 mol/L [HR 1.69 (1.13–2.47) and beyond; the corresponding median lifetime for women were reduced by 5.9 years compared to the referent. Optimal survival was associated with SUA concentrations of 304–454 μmol/L for men and < 409 μmol/L for women
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