Associations of circulating multiple metals with the risk of incident hyperuricemia and the average annual change in uric acid levels.

ABSTRACT

BACKGROUND: Hyperuricemia has been linked to exposure to certain metals in cross-sectional studies. However, prospective studies evaluating the associations of multiple metal exposures with incident hyperuricemia are scarce. OBJECTIVES: To prospectively investigate the associations of multiple metal/metalloid concentrations with incident hyperuricemia as well as average annual change in uric acid levels in a longitudinal cohort. METHODS: A longitudinal cohort study included 3957 subjects who were free of cardiovascular disease with certain risk factors for cardiovascular disease at baseline. Incident hyperuricemia was ascertained if serum uric acid level was ≥ 420 µmol/L for men and ≥ 360 µmol/L for women during the follow-up visit in 2013. The relationships between 17 single plasma metals/metalloids and incident hyperuricemia were assessed using unconditional logistic regression models. For metals/metalloids significantly related to incident hyperuricemia, we further utilized generalized linear regression models to evaluate their associations with the average annual change in uric acid levels. Finally, we applied the weighted quantile sum (WQS) regression to investigate the joint effects of metals/metalloids on hyperuricemia risk and uric acid changes, and to identify the most significant metals. RESULTS: After adjusting for potential confounders, plasma aluminum, arsenic, barium, lead, strontium, vanadium, and zinc concentrations were positively associated with incident hyperuricemia in both main analyses and sensitivity analyzes. Compared to the lowest quartiles, participants in the highest quartiles had 63 %-125 % higher risks of incident hyperuricemia (all FDR < 0.05). Furthermore, the positive associations of these seven metals with an average annual uric acid increase reinforced the findings. Finally, the WQS analyses showed that plasma metals mixtures were positively associated with the risk of incident hyperuricemia (OR 1.47; 95 % CI 1.23, 1.76) and the average annual change in uric acid levels (ß 3.17; 95 % CI 2.42, 3.93), and strontium and vanadium were the most heavily weighted metals, respectively. CONCLUSION: Our findings identify aluminum, arsenic, barium, lead, strontium, vanadium, and zinc exposures as independent risk factors for hyperuricemia and provide new insights into the prevention of hyperuricemia.