Circulating multiple metals and mortality after myocardial infarction: incremental value beyond GRACE

Background Metals such as arsenic, cadmium, and lead have been increasingly recognized as emerging cardiovascular risk factors, yet it is not considered in current clinical risk stratification for patients after myocardial infarction (MI). Methods This prospective study consecutively enrolled 1,283 post-MI patients undergoing percutaneous coronary intervention between 2017 and 2021, with follow-up through April 2024. Baseline plasma levels of 19 metals were measured by inductively coupled plasma mass spectrometry. Associations between metals and all-cause mortality were evaluated using multivariable Cox proportional hazards models. Models were adjusted for age, sex, body mass index, smoking status, diabetes, hypertension, hyperlipidemia, estimated glomerular filtration rate, peak troponin I, prior PCI, and stent implantation. To assess joint associations of multiple metals, we fitted elastic net regularized Cox models and derived environmental metal risk scores (ERSs), which were added to the GRACE risk score to assess incremental prognostic value via C-statistics, time-dependent receiver operating characteristic curves, and reclassification metrics. Results Among 1,283 patients, 122 all-cause mortality occurred during a median follow-up of 4.28 years. Higher plasma concentrations of copper, lead, and strontium were significantly associated with increased risks of all-cause mortality. Fully adjusted hazard ratios with 95% confidence intervals (per 1–standard deviation increase in log-transformed concentrations) were 1.67 (1.34–2.07) for copper, 1.26 (1.06–1.50) for lead, and 1.43 (1.20–1.71) for strontium. Higher ERS was also positively associated with all-cause mortality. Incorporation of ERS into the GRACE score improved discrimination at 5 years, increasing the area under the curve from 0.77 to 0.81 ( P = 0.013), and significantly enhanced risk reclassification. Conclusions Plasma copper, lead, and strontium levels were associated with all-cause mortality after MI, and further validation in independent cohorts is warranted before clinical implementation.