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Abstract: FR-PO303

Relationship of Uric Acid with Cardiovascular Mortality: A Systematic Review and Meta-Analysis

Session Information

Category: CKD (Non-Dialysis)

  • 2101 CKD (Non-Dialysis): Epidemiology, Risk Factors, and Prevention

Authors

  • Browne, Leonard, University Of Limerick, Limerick, Ireland
  • Quinn, Eoghain, University Of Limerick, Limerick, Ireland
  • O'Ceallaigh, Oisin, University Of Limerick, Limerick, Ireland
  • Johnson, Richard J., University of Colorado Denver, Aurora, Colorado, United States
  • Stack, Austin G., University Of Limerick, Limerick, Ireland
Background

Uric acid (UA) levels predict cardiovascular (CV) and all-cause mortality, but uncertainty remains regarding optimal threshold values for intervention. The aim of this systematic review and meta-analysis was to investigate risk thresholds for UA on CV mortality in four distinct populations: general population, cardiovascular disease (CVD), chronic kidney disease (CKD) and end stage kidney disease (ESKD).

Methods

We searched electronic databases up to 1 July 2018 for observational studies reporting associations for three or more groups of UA with all-cause and CV mortality in the four distinct populations:general, CVD, CKD and ESKD. Study-specific associations between UA and adjusted relative risks (RR) were estimated using restricted cubic splines with three knots at 10th, 75th and 90th percentile of the UA distribution and a generalised least squares method before pooling study estimates with a multivariate random-effects meta-analysis.

Results

We included 1,665,013 participants from 37 cohorts with 25,334 CV deaths. The overall pattern of association between serum UA and CV-mortality was non-linear (p-value, non-linearity < 0.001). Mortality risks increased beyond UA of 6.0 mg/dL [RR: 1.03 (1.01-1.05)], with an almost linear increase in risk for higher concentrations (7.0 mg/dL, [RR: 1.13 (1.08- 1.18)]) compared to a referent of 5.5 mg/dL. There was evidence of heterogeneity across studies (I2=63.5). The shape of the UA-mortality association was similar for participants in the general, CKD, and CVD populations but differed significantly from ESKD (p<0.001). In ESKD, the pattern was completely reversed, with a reduced mortality for UA values above 5.5 mg/dL.

Conclusion

Uric acid exhibits a J-shaped association with CV mortality with increasing risk above 5.5 mg/dL in the general and CVD populations. This relationship was attenuated in CKD and completely reversed in ESKD. Large randomised clinical trials of urate-lowering therapy should test whether targeting this threshold will confer cardioprotection.

Nonlinear dose-response analyses of UA and risk of CV mortality by population type

Funding

  • Government Support - Non-U.S.