Serum 25-hydroxyvitamin D mediates the association between heavy metal exposure and cardiovascular disease.

Background: Mediation analysis aims to determine how intermediate variables affect exposure to disease. In this study, 25-hydroxyvitamin D (25(OH)D) was evaluated to assess its role in mediating heavy metal exposure and cardiovascular disease (CVD).

Methods: A total of 9,377 participants from the National Health and Nutrition Examination Survey (NHANES) for the years 2011-2018 were included. Firstly, restricted cubic spline (RCS), and multivariable logistic regression model were performed to estimate the association between heavy metal exposure (Cadmium, Lead, Mercury, Manganese, and Selenium), as well as serum 25(OH)D and CVD. Secondly, using generalized linear regression model and generalized additive models with smooth functions, we investigated the correlation between heavy metal exposure and serum 25(OH)D. Finally, the mediation effect of serum 25(OH)D in the associations between heavy metal exposure and CVD was explored.

Results: The RCS plots revealed that Cadmium, and Lead were positively and linearly associated with CVD, while Mercury, and Manganese were inversely and linearly associated with CVD. Additionally, a roughly L- and U-shaped relationship existed between Selenium, as well as 25(OH)D and CVD. When potential confounding factors were adjusted for, serum 25(OH)D had negative associations with Cadmium, Lead, and Manganese, while serum 25(OH)D had positive relationship with Selenium. There was a mediation effect between Manganese exposure and CVD, which was mediated by 25(OH)D.

Conclusion: According to the mediation analysis, the negative association between Manganese exposure and incident CVD was increased by 25(OH)D. The increasing dietary intake of Vitamin D could increase the protective effect of manganese intake on CVD.