A U-shaped association between serum uric acid with all-cause mortality in normal-weight population

ABSTRACT

Background

It is uncertain how serum uric acid (SUA) associated with all-cause mortality among people with normal weight, hence was explored in this study.

Methods

We enrolled participants from 1999 to 2006 National Health and Nutrition Examination Survey (NHANES) that had mortality status through 31 December 2015. We estimated adjusted hazard ratios (HRs) and 95% confidence intervals (CI) for all-cause mortality using Cox proportional hazard models, and propensity score analyses were performed. We also performed restricted cubic splines to demonstrate the nonlinear relationship, and used subgroup analysis to examine the effect modification.

Results

We enrolled 6169 participants (2905 men and 3264 women, mean age 42.3 ± 21.4 years) and 1060 (17.2%) cases of all-cause mortality occurred during the mean follow-up of 11.9 years. When using the lowest quartile of SUA as referent, the multivariable HRs for all-cause mortality increased in not parallel with the quartiles of SUA (HRs were 0.92 (95%CI: 0.68, 1.23), 1.10 (95%CI: 0.82, 1.47), and 1.08 (95%CI: 0.80, 1.45) from the second to the fourth quartiles, respectively. When treating SUA as continuous variable, the HRs for all-cause mortality were 1.07 (95%CI: 1.00, 1.15; P = 0.046), 1.03 (95%CI: 0.94, 1.12; P = 0.518) and 1.15 (95%CI: 1.01, 1.31; P = 0.032) in all population, male and female subjects, respectively. Elevated SUA was associated with all-cause mortality and the propensity scores analysis showed the similar results. Subgroup analysis showed SUA was an independent risk of all-cause mortality in female (HR1.17, 95%CI: 1.05, 1.31, P = 0.005), people aged <60 years (HR1.18, 95%CI: 1.03, 1.35, P = 0.018), non-diabetic population (HR1.10, 95%CI: 1.02, 1.18, P = 0.017) and people with eGFR<90 (HR1.10, 95%CI: 1.02, 1.19, P = 0.016). Smoothing spline plots suggested the optimal SUA for the lowest risk of all-cause mortality was approximately 4.7 mg/dl.

Conclusion

In normal-weight population, SUA was seemed to be a U-shaped relationship with all-cause mortality.

KEYWORDS:

• Serum uric acid
• all-cause mortality
• normal weight
• body mass index

Disclosure Statement

No potential conflict of interest was reported by the authors.

Declarations of interest

The authors declared no conflict of interest.

Additional information

Funding

This work was supported by the Science and Technology Program of Guangzhou [No.201803040012, No.201604020143, No.201604020018, No.201604020186], the National Key Research and Development Program of China [No.2017YFC1307603, No.2016YFC1301305] and the Key Area R&D Program of Guangdong Province [No.2019B020227005]. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.