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Circulating multiple metals and mortality after myocardial infarction: incremental value beyond GRACE
Minmin Wu1,2,3, Junhan Chen1,2, Zhijie Lin1,2
1Department of Cardiology, Shengli Clinical Medical College of Fujian Medical University, Fujian Provincial Hospital, Fuzhou University Affiliated Provincial Hospital.
Insights
Elevated plasma copper, lead, and strontium levels are linked to increased mortality risk in myocardial infarction (MI) survivors. Incorporating an environmental metal risk score (ERS) improved prognostic accuracy in clinical risk models.
Area of Science:
- Cardiovascular Medicine
- Environmental Health
- Toxicology
Background:
- Emerging evidence links heavy metals (e.g., arsenic, cadmium, lead) to cardiovascular disease.
- Current clinical risk stratification for myocardial infarction (MI) patients does not account for metal exposure.
- This gap highlights the need to investigate the prognostic impact of metals in post-MI populations.
Purpose of the Study:
- To investigate the association between plasma metal concentrations and all-cause mortality in patients post-MI.
- To develop and validate an environmental metal risk score (ERS) for improved risk prediction.
- To assess the incremental prognostic value of ERS when added to the established GRACE risk score.
Main Methods:
- Prospective cohort study of 1,283 post-MI patients undergoing percutaneous coronary intervention (PCI).
- Plasma levels of 19 metals measured using inductively coupled plasma mass spectrometry.
- Multivariable Cox models and elastic net regularized Cox models used to assess associations and derive ERS.
Main Results:
- 122 all-cause mortality events occurred during a median follow-up of 4.28 years.
- Higher plasma copper, lead, and strontium levels were significantly associated with increased all-cause mortality.
- The environmental metal risk score (ERS) improved risk discrimination and reclassification when added to the GRACE score.
Conclusions:
- Plasma copper, lead, and strontium are associated with mortality risk in post-MI patients.
- The developed ERS demonstrates potential for enhancing cardiovascular risk prediction.
- Further validation in independent cohorts is recommended prior to clinical application.
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.
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