The mediating role of vascular age in the association between blood metals and atherosclerosis from Manganese-exposed workers healthy cohort

Abstract Background The occurrence and development of atherosclerosis are fundamentally linked to the aging of blood vessels. Previous researches have found that exposure to metals in the environment is linked to atherosclerosis, yet the underlying biological mechanism remains unclear. Methods Twelve blood metals, vascular age and brachial-ankle pulse wave velocity (baPWV) were quantified among the 431 individuals involved in Manganese-exposed workers healthy cohort in 2023. Results The generalized linear model (GLM) indicated that chromium (Cr) was negatively associated with baPWV (β = -0.041). The GLM, least absolute shrinkage and selection operator and weighted quantile sum (WQS) analysis indicated that lead (Pb) was positively associated with baPWV. Pb contributed the most to the positive association between metal mixtures (Pb, selenium, manganese, Cr, calcium) and baPWV, showing that for every unit increase in the WQS index of metal mixtures, baPWV increased by 0.014 m/s. Subsequently, positive associations were found between Pb and vascular age as well as between vascular age and baPWV. Mediation analysis revealed that vascular age partially mediated (42%, P < 0.001) the association between Pb and baPWV. Additionally, joint effect analyses revealed that smoking, drinking, older age and higher BMI might enhance the association between Pb exposure and baPWV. Conclusions Vascular age can partly mediate the association between Pb exposure and baPWV, showing higher Pb level related to higher atherosclerosis risk. And healthy habits and BMI may help mitigate the harmful effects of Pb. Further prospective and mechanistic studies are recommended to corroborate the findings and clarify the elusive mechanism.