Background: In addition to the controversy regarding the association of hyperuricemia with mortality, uncertainty also remains regarding the association between low serum uric acid (SUA) and mortality. We aimed to assess the relationship between SUA and all-cause and cause-specific mortality. Methods: This cohort study included 9118 US adults from the National Health and Nutrition Examination Survey (1999-2002). Multivariable Cox proportional hazards models were used to evaluate the relationship between SUA and mortality. Our analysis included the use of a generalized additive model and smooth curve fitting (penalized spline method), and 2-piecewise Cox proportional hazards models, to address the nonlinearity between SUA and mortality. Results: During a median follow-up of 5.83 years, 448 all-cause deaths occurred, with 100 cardiovascular disease (CVD) deaths, 118 cancer deaths, and 37 respiratory disease deaths. Compared with the reference group, there was an increased risk of all-cause, CVD, cancer, and respiratory disease mortality for participants in the first and third tertiles of SUA. We further found a nonlinear and U-shaped association between SUA and mortality. The inflection point for the curve was found at a SUA level of 5.7 mg/dL. The hazard ratios (95% confidence intervals) for all-cause mortality were 0.80 (0.65-0.97) and 1.24 (1.10-1.40) to the left and right of the inflection point, respectively. This U-shaped association was observed in both sexes; the inflection point for SUA was 6 mg/dL in males and 4 mg/dL in females. Conclusion: Both low and high SUA levels were associated with increased all-cause and cause-specific mortality, supporting a U-shaped association between SUA and mortality.

Background: Uncertainty remains regarding the association between blood lead levels (BLL) and serum uric acid (SUA) with relatively low BLL exposure because of limited data in the adolescent population. We examined the association between BLL and SUA in U.S. adolescents. Methods: In this cross-sectional study, 8303 adolescents aged 12–19 years from NHANES 1999–2006 were analyzed. BLL was Ln-transformed for analysis for the skewed distribution. Elevated SUA was defined as ≥5.5 mg/dL. Multivariate linear and multiple logistic regression analyses were performed to evaluate the association of BLL with SUA and elevated SUA. Moreover, a generalized additive model (GAM) and a fitted smoothing curve (penalized spline method) were conducted. Results: The overall mean BLL was 1.3 μg/dL. Multivariate linear regression analyses showed that LnBLL was independently and positively correlated with SUA level (β = 0.13, 95%CI: 0.09–0.17). Multiple logistic analyses showed that LnBLL was associated with a 24% increased prevalence of elevated SUA (OR = 1.24; 95% CI, 1.11–1.38). Analyses using restricted cubic spline confirmed that the associations of LnBLL with SUA and elevated SUA were linear. Subgroup analyses showed that stronger associations between LnBLL and SUA were detected in adolescents with lower levels of education and estimated glomerular filtration rate (eGFR) (all P for interaction < 0.05). Conclusions: BLL was independently and positively correlated with SUA level and elevated SUA among U.S. adolescents, particularly with lower levels of education and eGFR. The data suggest that there is no “safe” threshold level of exposure to lead. Graphical