Association between Mixed Heavy Metal Exposure and Arterial Stiffness, with Alkaline Phosphatase Identified as a Mediator.

Abstract

Elevated arterial stiffness has been associated with exposure to heavy metals such as lead (Pb) and cadmium (Cd). However, the collective impact of multiple metals and the underlying mechanisms are not fully elucidated. The purpose of this study was to assess the combined effects of exposure to nine heavy metals on arterial stiffness and explore whether serum alkaline phosphatase (ALP) acts as a mediator in this relationship. In the retrospective analysis, data from 8,700 participants were retrieved from the National Health and Nutrition Examination Survey (NHANES) spanning from 1999 to 2018. Arterial stiffness was measured by estimated pulse wave velocity (ePWV). The cumulative impact of exposure to multiple metals was examined using adaptive elastic-net, environmental risk score, weighted quantile sum regression, and quantile g-computation. Additionally, mediation analysis was conducted to explore the potential mediating role of serum ALP. We found that combined exposure to multiple metals was consistently associated with elevated ePWV, with Ba, Pb, and Sb exhibiting the greatest contributions. Notably, serum ALP partially mediated the associations between individual (Pb, Sb) and mixed metal exposure with ePWV, with mediation proportions at 10.76% for Pb, 18.22% for Sb, and 11.07% for mixed metal exposure. In conclusion, this study demonstrates a clear association between exposure to heavy metals, either individually or in combination, and heightened arterial stiffness. Furthermore, the findings suggest that serum ALP activity may act as a mediator in these relationships.