Associations of Plasma Metal Exposure With the Risk and Severity of Acute Coronary Syndrome: Evidence From Epidemiological and Adverse Outcome Pathway Analyses.

BACKGROUND: Evidence links environmental metal exposure to cardiovascular disease, but its association with acute coronary syndrome (ACS) risk and severity remains insufficiently characterized. METHODS: This case-control study included 413 newly diagnosed patients with ACS and 413 controls matched 1:1 by sex and age (within 5 years). Conditional logistic regression assessed associations between individual plasma metals and ACS risk, and ordinal logistic regression evaluated ACS severity. RESULTS: Higher plasma zinc and selenium levels were inversely associated with ACS risk, whereas arsenic and lead showed positive associations. The odds ratios for extreme quantiles were 0.44 (95% CI, 0.22-0.89) for zinc, 0.23 (95% CI, 0.11-0.48) for selenium, 1.70 (95% CI, 0.85-3.41) for arsenic, and 2.46 (95% CI, 1.24-4.87) for lead. Monocyte counts partially mediated the selenium-ACS association, whereas lymphocyte counts mediated the lead-ACS association. Regarding disease severity, selenium was inversely associated with Gensini score (odds ratio, 0.57 [95% CI, 0.32-1.02]) and the number of lesioned vessels (odds ratio, 0.51 [95% CI, 0.28-0.91]), whereas copper was positively associated with the number of lesioned vessels (odds ratio, 1.48 [95% CI, 0.81-2.71]). Bayesian kernel machine regression suggested an inverse association between metal mixtures and ACS risk, with no significant association with severity. Adverse outcome pathway analysis implicated inflammation, oxidative stress, and actin cytoskeleton dysregulation as potential mechanisms. CONCLUSIONS: Plasma metal profiles were associated with ACS occurrence and severity, highlighting potential inflammatory, oxidative, and cytoskeletal mechanisms.