Association of single and joint urinary metal exposure with carotid atherosclerosis in non-dyslipidemic middle-aged and elderly adults: A retrospective case-control study

Ecotoxicol Environ Saf. 2025 Sep 2;303:118981. doi: 10.1016/j.ecoenv.2025.118981. Online ahead of print.

ABSTRACT

BACKGROUND: Carotid atherosclerosis (CAS) is a major contributor to cerebrovascular incidence and mortality, yet its etiology in non-dyslipidemic individuals remains poorly understood. Emerging evidence suggests that environmental metal exposure may play a critical role in CAS development.

METHODS: We conducted a retrospective matched case-control study involving 1290 non-dyslipidemic middle-aged and elderly individuals to examine the association between urinary metal exposure and CAS. Twenty-eight urinary metals were measured using inductively coupled plasma mass spectrometry (ICP-MS), and statistical analyses-including conditional logistic regression, weighted quantile sum (WQS) regression, and Bayesian kernel machine regression (BKMR)-were applied to assess single and mixed-metal effects. Mediation analysis was performed to evaluate the potential role of metabolic and inflammatory clinical indicator.

RESULTS: Conditional logistic regression found that six metals (OR_Q4vsQ1=1.63, 95 %CI: 1.14-2.34 for lithium (Li); OR_Q4vsQ1= 1.65, 95 %CI: 1.16-2.35 for titanium (Ti); OR_Q4vsQ1= 1.53, 95 %CI: 1.07-2.22 for cobalt (Co); OR_Q4vsQ1= 1.77, 95 %CI: 1.24-2.51 for nickel (Ni); OR_Q4vsQ1= 1.93, 95 %CI: 1.33-2.79 for copper (Cu), and OR_Q4vsQ1= 2.14, 95 %CI: 1.45-3.18 for cadmium (Cd)) were significantly associated with increased CAS risk, while selenium (Se) (OR _Q2vsQ1 = 0.65, 95 %CI: 0.46-0.93, OR_Q2vsQ1 = 0.59, 95 %CI: 0.41-0.84) was negatively associated with the risk of CAS. Mixed-metal exposure analyses, including WQS (OR=1.35, 95 %CI 1.12-1.63) and BKMR, consistently demonstrated a positive correlation with CAS, primarily driven by Ti. Mediation analysis further revealed that 11.54 % of association between Cu and CAS explained by remnant cholesterol (RC).

CONCLUSION: Our findings revealed a significant correlation between environmental metal exposure and CAS, independent of traditional lipid abnormalities. Future prospective studies are warranted to confirm these associations and elucidate the underlying biological mechanisms, potentially guiding targeted prevention strategies.

PMID:40902247 | DOI:10.1016/j.ecoenv.2025.118981