Overview
This single-center, cross-sectional case-control study compared serum pentraxin-3 (PTX-3) and whole-blood concentrations of lead, arsenic, nickel, cadmium, mercury, tin, aluminum, and cobalt between 50 patients with angiographically confirmed acute coronary syndrome (ACS) and 50 age- and sex-matched controls without cardiovascular disease. PTX-3, a local vascular inflammatory marker produced by endothelial cells and macrophages, was markedly elevated in ACS cases. Lead, arsenic, and nickel were concurrently elevated and showed substantial between-group discrimination by ROC analysis, suggesting a shared environmental-cardiovascular inflammatory pathway.
Key numbers
Whole-blood metal concentrations in ACS cases vs controls (median [IQR], ng/mL; Table 2):
- Lead (Pb): 17.43 [15.86-20.39] vs 10.08 [9.23-11.16]; AUC 0.962 (95% CI: 0.923-1.000); sensitivity 100%, specificity 92%; q <0.001.
- Arsenic (As): 3.65 [3.00-4.51] vs 1.21 [0.48-2.86]; AUC 0.859 (95% CI: 0.784-0.933); sensitivity 96%, specificity 72%; q <0.001.
- Nickel (Ni): 3.85 [2.69-6.90] vs 0.87 [0.54-1.44]; approximately 4.4-fold higher in ACS; AUC 0.838 (95% CI: 0.758-0.917); sensitivity 80%, specificity 86%; q <0.001.
- PTX-3: 1.89 [1.64-3.51] vs 0.40 [0.37-0.42] ng/mL; AUC 0.951 (95% CI: 0.907-0.995); sensitivity 94%, specificity 100%; q <0.001.
- Tin (Sn): modestly elevated; q = 0.016.
- Aluminum (Al): modestly elevated; q = 0.040.
- Cadmium (Cd): did not differ between groups (q = 0.828).
- Mercury (Hg): marginally lower in ACS cases (q = 0.040).
- Independent multivariable association with ACS (Firth penalized logistic regression): PTX-3 (adjusted OR 38.0, 95% CI 6.6-1261.4; p <0.001) and Pb (aOR 1.66 per 1 ng/mL, 95% CI 1.25-2.67; p <0.001) retained after adjustment.
- PTX-3 not significantly correlated with angiographic disease severity (Gensini score; rho = 0.12, p = 0.41).
- Within-ACS group: nickel weakly inversely correlated with PTX-3 (rho = -0.29, p = 0.038).
Methods (brief)
Cross-sectional case-control. Metal quantification: whole-blood ICP-MS (iCAP Qc, Thermo Scientific); acid-digestion sample preparation; calibration with Seronorm WBL-2 reference material; RSD <5%. PTX-3: serum ELISA. All blood samples obtained at emergency department presentation before any cardiac medications. Statistical analysis: Mann-Whitney U test; Benjamini-Hochberg FDR correction; ROC analysis with 1000-bootstrap internal validation; Firth penalized logistic regression for near-separation problems with lead and PTX-3. Cadmium measured in whole blood, which primarily reflects acute circulating cadmium rather than cumulative body burden (the authors note this limitation).
Limitations
Single-center, single country; n=50 per group limits statistical power. Cross-sectional design precludes causal inference; metal concentrations at presentation may reflect acute physiological responses to myocardial injury rather than prior cumulative exposure. Dietary metal intake, water source, and occupational exposure not systematically collected. Cadmium’s lack of between-group difference may reflect biomarker choice (blood vs. urine). Cut-off values derived and validated in the same cohort; prospective validation required.
Implications
Certification: Documents concurrent elevation of Pb, As, and Ni in ACS patients alongside the vascular inflammatory marker PTX-3. Provides biological plausibility for Pb and Ni cardiovascular risk pathways. Relevant to HMT&C’s Ni coverage rationale.
Courses: Useful for the cardiovascular effects and vascular inflammation module. Illustrates that heavy metal exposure can be framed as an atherogenic dimension beyond traditional cardiovascular risk factors.
App: Blood metal concentrations not translatable to food concentrations; labeled context-only.
Microbiome: Does not address gut microbiota.
Related evidence
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