Uric acid levels, kidney function, and cardiovascular mortality in US adults: National Health and Nutrition Examination Survey (NHANES) 1988-1994 and 1999-2002

Background: Chronic kidney disease (CKD) and hyperuricemia often coexist, and both conditions are increasing in prevalence in the United States. However, their shared role in cardiovascular risk remains highly debated.

Study design: Cross-sectional and longitudinal.

Setting & participants: Participants in the National Health and Nutrition Examination Survey (NHANES) from 1988 to 2002 (n = 10,956); data were linked to mortality data from the National Death Index through December 31, 2006.

Predictors: Serum uric acid concentration, categorized as the sex-specific lowest (< 25th), middle (25th- < 75th), and highest (≥ 75th) percentiles; and kidney function assessed by estimated glomerular filtration rate (eGFR) based on the CKD-EPI (CKD Epidemiology Collaboration) creatinine-cystatin C equation and urinary albumin-creatinine ratio (ACR).

Outcomes: Cardiovascular death and all-cause mortality.

Results: Uric acid levels were correlated with eGFR(cr-cys) (r = -0.29; P < 0.001) and were correlated only slightly with ACR (r = 0.04; P < 0.001). There were 2,203 deaths up until December 31, 2006, of which 981 were due to cardiovascular causes. Overall, there was a U-shaped association between uric acid levels and cardiovascular mortality in both women and men, although the lowest risk of cardiovascular mortality occurred at a lower level of uric acid for women compared with men. There was an association between the highest quartile of uric acid level and cardiovascular mortality even after adjustment for potential confounders (HR, 1.48; 95% CI, 1.13-1.96), although this association was attenuated after adjustment for ACR and eGFR(cr-cys) (HR, 1.25; 95% CI, 0.89-1.75). The pattern of association between uric acid levels and all-cause mortality was similar.

Limitations: GFR not measured; mediating events were not observed.

Conclusions: High uric acid level is associated with cardiovascular and all-cause mortality, although this relationship was no longer statistically significant after accounting for kidney function.