Platelet count partially mediates the association between mixed metal exposure and atherosclerotic cardiovascular disease risk: A case-control study

The relationship between platelets and atherosclerotic cardiovascular disease (ASCVD) risk has been extensively investigated. However, few studies have explored the interplay among platelets, mixed metal exposure, and ASCVD. This case-control study investigated the association between mixed metal exposure and ASCVD risk, as well as the partial mediating role of platelet count (PLT). Weighted quantile sum (WQS) regression and Bayesian kernel machine regression (BKMR) were used to analyze plasma metal mixtures and ASCVD risk. A nine-metal mixture was positively associated with ASCVD risk (WQS index: OR = 1.89, 95% CI: 1.69–2.12, P < 0.001), with cadmium (Cd), strontium (Sr), and thallium (Tl) as the major contributors, which was further confirmed by LASSO regression. Adjusted linear regression showed that Cd, Sr, and Tl were positively associated with PLT (all P < 0.05). Mediation analysis revealed that PLT partially mediated the association between Cd, Sr, Tl, and ASCVD risk, with mediation proportions of 3.7%, 8.4%, and 4.9%, respectively (all P < 0.05). In conclusion, mixed metal exposure significantly increases ASCVD risk, driven mainly by Cd, Sr, and Tl, with a modest partial mediating effect of PLT. • Mixed metal (Cd/Sr/Tl) exposure raises ASCVD risk; first to link Sr/Tl to ASCVD. • Platelet count partially mediates Cd/Sr/Tl-ASCVD associations, revealing a novel ASCVD pathway. • New light on ASCVD: mixed metal exposure and platelet-mediated mechanisms matter.