The relationship between serum manganese concentration with all-cause and cause-specific mortality: a retrospective and population-based cross-sectional study.

BACKGROUND: The study aimed to explore the association between manganese concentration and all-cause, cardiovascular disease (CVD)-related, and cancer-related mortality in the general population of the United States.

METHODS: We integrated the data from the National Health and Nutrition Examination Survey from 2011 to 2018. A total of 9,207 subjects were selected based on the inclusion and exclusion criteria. The relationship between manganese concentration and all-cause, CVD-related, and cancer-related mortality was analyzed by constructing a Cox proportional hazard regression model and a restricted cubic spline (RCS) plot. Additionally, subgroup analyses stratified by age, sex, race/ethnicity, hypertension, diabetes mellitus (DM), chronic heart disease, chronic heart failure, angina pectoris, heart attack, stroke, and BMI were further performed.

RESULTS: In the full adjusted model, compared with the lowest quartile, the adjusted hazard ratios with 95% confidence intervals (CIs) for all-cause, CVD-related, and cancer-related mortality across manganese quartiles were (1.11 (0.87,1.41), 0.96 (0.74, 1.23), and 1.23 (0.96, 1.59); P-value for trend =0.041), (0.86 (0.54, 1.37), 0.87 (0.55, 1.40), and 1.07 (0.67, 1.72); P-value for trend =0.906), and (1.45 (0.92, 2.29), 1.14 (0.70, 1.88), and 1.26 (0.75, 2.11); P-value for trend =0.526), respectively. The RCS curve shown a U-shaped association between manganese concentration and all-cause mortality and CVD-related mortality (P-value for nonlinear <0.05). However, there was an increase and then a decrease in the link between manganese concentration and cancer-related mortality (P-value for nonlinear <0.05). Manganese exposure was positively correlated with sex (correlation coefficient, r =0.19, P-value <0.001) and negatively correlated with age (correlation coefficient, r =-0.11, P-value <0.001) and serum creatinine (correlation coefficient, r =-0.12, P-value <0.001), respectively.

CONCLUSIONS: Our findings suggest that elevated serum manganese concentrations are associated with all-cause and CVD-related mortality in the U.S. population and that maintenance of serum manganese between 8.67-9.23 µg/L may promote public health.