Association between exposure to urinary metal and all-cause and cardiovascular mortality in US adults

Abstract

Background: Further evidence is required regarding the influence of metal mixture exposure on mortality. Therefore, we employed diverse statistical models to evaluate the associations between eight urinary metals and the risks of all-cause and cardiovascular mortality.

Methods: We measured the levels of 8 metals in the urine of adults who participated in the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2018. Based on follow-up data, we determined whether they died and the reasons for their deaths. We estimated the association between urine metal exposure and all-cause mortality using Cox regression, weighted quantile sum (WQS) regression, and Bayesian kernel machine regression (BKMR) models. Additionally, we used a competing risk model to estimate the relationship between metal exposure and cardiovascular mortality.

Results: Among the 14,305 individuals included in our final analysis, there were 2,066 deaths, with 1,429 being cardiovascular-related. Cox regression analysis showed that cobalt (Co) (HR: 1.21; 95% CI: 1.13, 1.30) and antimony (Sb) (HR: 1.26; 95% CI: 1.12, 1.40) were positively associated with all-cause mortality (all P for trend <0.001). In the competing risk model, Co (HR: 1.29; 95% CI: 1.12, 1.48), lead (Pb) (HR: 1.18; 95% CI: 1.03, 1.37), and Sb (HR: 1.44; 95% CI: 1.18, 1.75) were significantly associated with an increased risk of cardiovascular mortality (all P for trend <0.001). Sb, Pb, cadmium (Cd), and molybdenum (Mo) had the highest weight rankings in the final WQS model. All metals showed a complex non-linear relationship with all-cause mortality, with high posterior inclusion probabilities (PIPs) in the final BKMR models.

Conclusions: Combining all models, it is possible that Sb may have a more stable impact on all-cause and cardiovascular mortality. Meaningful metal effects in individual statistical models still require careful attention.

Fig 1. Selection criteria for participants in this study.

Fig 2. Weighted quantile sum (WQS) model regression index weights for all-cause mortality.

(Ba: Barium; Cd: Cadmium; Co: Cobalt; Cs: Cesium; Mo: Molybdenum; Pb: Lead; Sb: Antimony; TI: Thallium; A: Adjusted for none; B: Adjusted for age, sex, race; C: Adjusted for age, sex, race, BMI, marital status, PIR, education, smoking, drinking, and health insurance; D: Adjusted for age, sex, race, BMI, marital status, PIR, education, smoking, drinking, health insurance, diabetes, stroke, cancer, CVD, and hypertension).

Fig 3. Univariate exposure-response function (95% CI) between urinary metals and all-cause mortality when fixing the concentrations of other metals at the median.

(Ba: Barium; Cd: Cadmium; Co: Cobalt; Cs: Cesium; Mo: Molybdenum; Pb: Lead; Sb: Antimony; TI: Thallium; A: Adjusted for none; B: Adjusted for age, sex, race; C: Adjusted for age, sex, race, BMI, marital status, PIR, education, smoking, drinking, and health insurance; D: Adjusted for age, sex, race, BMI, marital status, PIR, education, smoking, drinking, health insurance, diabetes, stroke, cancer, CVD, and hypertension).

Fig 4. Joint effect of the mixture on all-cause mortality when all metals at particular percentiles were compared to all the metals at their 50th percentile by Bayesian kernel machine regression (BKMR) model.

(A: Adjusted for none; B: Adjusted for age, sex, race; C: Adjusted for age, sex, race, BMI, marital status, PIR, education, smoking, drinking, and health insurance; D: Adjusted for age, sex, race, BMI, marital status, PIR, education, smoking, drinking, health insurance, diabetes, stroke, cancer, CVD, and hypertension).