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Association of Mixed Metal Exposures with Cardiovascular Disease: Insights from a Population-Based Study.

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Τίτλος: Association of Mixed Metal Exposures with Cardiovascular Disease: Insights from a Population-Based Study.
Συγγραφείς: Jin X; School of Medicine, Nankai University, Tianjin, China.; Department of Molecular Pharmacology, School of Medicine, Nankai University, Tianjin, China.; Department of Cardiology, Tianjin Union Medical Center, The First Affiliated Hospital of Nankai University, Tianjin, P.R. China., Wu H; School of Medicine, Nankai University, Tianjin, China.; Department of Cardiology, Tianjin Union Medical Center, The First Affiliated Hospital of Nankai University, Tianjin, P.R. China., Zhang H; School of Medicine, Nankai University, Tianjin, China.; Department of Molecular Pharmacology, School of Medicine, Nankai University, Tianjin, China.; Department of Cardiology, Tianjin Union Medical Center, The First Affiliated Hospital of Nankai University, Tianjin, P.R. China., Jin Y; School of Medicine, Nankai University, Tianjin, China.; Department of Molecular Pharmacology, School of Medicine, Nankai University, Tianjin, China., Feng Y; School of Medicine, Nankai University, Tianjin, China.; Department of Molecular Pharmacology, School of Medicine, Nankai University, Tianjin, China., Liu Y; Department of Cardiology, Tianjin Union Medical Center, The First Affiliated Hospital of Nankai University, Tianjin, P.R. China., Li J; Department of Cardiology, Tianjin Union Medical Center, The First Affiliated Hospital of Nankai University, Tianjin, P.R. China., Wei L; School of Medicine, Nankai University, Tianjin, China. weilipingme@163.com.; Department of Molecular Pharmacology, School of Medicine, Nankai University, Tianjin, China. weilipingme@163.com.; Department of Cardiology, Tianjin Union Medical Center, The First Affiliated Hospital of Nankai University, Tianjin, P.R. China. weilipingme@163.com., Qi Z; School of Medicine, Nankai University, Tianjin, China. qizhi@nankai.edu.cn.; Department of Molecular Pharmacology, School of Medicine, Nankai University, Tianjin, China. qizhi@nankai.edu.cn.; Department of Cardiology, Tianjin Union Medical Center, The First Affiliated Hospital of Nankai University, Tianjin, P.R. China. qizhi@nankai.edu.cn., Qi X; School of Medicine, Nankai University, Tianjin, China. qixinx2011@126.com.; Department of Molecular Pharmacology, School of Medicine, Nankai University, Tianjin, China. qixinx2011@126.com.; Department of Cardiology, Tianjin Union Medical Center, The First Affiliated Hospital of Nankai University, Tianjin, P.R. China. qixinx2011@126.com.
Πηγή: Cardiovascular toxicology [Cardiovasc Toxicol] 2026 Oct 03; Vol. 26 (10). Date of Electronic Publication: 2026 Oct 03.
Τύπος έκδοσης: Journal Article
Γλώσσα: English
Στοιχεία περιοδικού: Publisher: Humana Press Country of Publication: United States NLM ID: 101135818 Publication Model: Electronic Cited Medium: Internet ISSN: 1559-0259 (Electronic) Linking ISSN: 15307905 NLM ISO Abbreviation: Cardiovasc Toxicol Subsets: MEDLINE
Imprint Name(s): Original Publication: Totowa, NJ : Humana Press, c2001-
Ιατρικοί όροι (MeSH): Cardiovascular Diseases*/epidemiology , Cardiovascular Diseases*/diagnosis , Cardiovascular Diseases*/blood , Cardiovascular Diseases*/chemically induced , Environmental Exposure*/adverse effects , Metals, Heavy*/blood , Metals, Heavy*/adverse effects , Environmental Pollutants*/blood , Environmental Pollutants*/adverse effects, Biomarkers/blood ; United States/epidemiology ; Humans ; Male ; Female ; Risk Assessment ; Middle Aged ; Nutrition Surveys ; Risk Factors ; Aged ; Adult ; Heart Disease Risk Factors ; Cross-Sectional Studies
Περίληψη: Environmental metal exposure has been increasingly recognized as a contributor to cardiovascular toxicity, yet the effects of single and mixed metal burdens, as well as susceptible population subgroups, remain insufficiently characterized. This study aimed to investigate the associations of blood copper (Cu), zinc (Zn), Cu/Zn ratio, selenium (Se), lead (Pb), cadmium (Cd), total mercury (HgT), and manganese (Mn) with cardiovascular disease (CVD), and to evaluate the joint association of multiple metal exposures and potential heterogeneity across population subgroups. Data from 1,967 participants (211 CVD cases) in the 2011-2016 NHANES were analyzed. Spearman correlation, logistic regression, restricted cubic spline (RCS), weighted quantile sum (WQS) regression, and quantile-based g-computation (QGcomp) were applied to assess associations of single metals and mixtures with CVD. Subgroup analyses were conducted by demographics and health conditions. Network pharmacology was applied to identify candidate pathways and toxicological targets. CVD patients had higher levels of Cu, Cu/Zn ratio, Pb, and Cd, but lower levels of Zn, HgT, and Mn. Spearman analyses showed Cd (rho = 0.114) and Pb (rho = 0.111) have positive associations with CVD, whereas Mn has a negative connection (rho=-0.069) (all P < 0.05). In quartile-based logistic regression, Cd showed the most consistent positive association with CVD, with participants in the highest quartile having higher odds of CVD in the fully adjusted model (OR = 2.29, 95% CI: 1.37-3.87, P = 0.002). The Cu/Zn ratio was positively associated with CVD in partially adjusted models, but the association was attenuated and no longer statistically significant after full adjustment (OR = 1.55, 95% CI: 0.94-2.57, P = 0.089). RCS revealed linear correlations between Pb, Cd and Mn with prevalent CVD. The WQS index was positively associated with higher odds of CVD (OR = 1.70, 95% CI: 1.16-2.52, P = 0.008), with Cd, the Cu/Zn ratio, and Pb showing the largest positive weights. QGcomp similarly indicated a positive overall mixture association (OR = 1.64, 95% CI: 1.10-2.45, P = 0.014), while Mn contributed in the negative direction. Subgroup analyses indicated that specific metals exerted positive contributions in vulnerable populations, including younger males, smokers, drinkers, elderly, hypertensive, and low-BMI groups. GAPDH, AKT1, CTNNB1, MYC, TNF, and TP53 were predicted to be key targets. Elevated blood Cd showed the most consistent positive association with CVD across individual and mixture-based analyses. The Cu/Zn ratio and Pb also contributed substantially to the positive association of the metal mixture with CVD, although the independent association of the Cu/Zn ratio was attenuated after full multivariable adjustment. Mn showed a potential inverse association. These findings highlight the toxicological relevance of metal mixtures in cardiovascular disease and underscore the need for mechanistic studies to establish causality.
(© 2026. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)
Competing Interests: Declarations. Conflict of interest: The authors report no conflicts of interest; Ethical Approval and Informed Consent: The NHANES study protocol was approved by the Institutional Review Board (IRB) of the National Centre for Health Statistics (NCHS), and all participants provided informed consent. All research procedures were conducted in accordance with the ethical principles established by the Declaration of Helsinki. Clinical Trial Number: Not applicable.
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Grant Information: No.23JCYBJC01470 Tianjin Science and Technology Project; No.16ZXMJSY00060 Tianjin Science and Technology Planning Project
Contributed Indexing: Keywords: Cardiovascular disease; Environmental toxicology; Metal exposure; Mixed metals; Network pharmacology
Substance Nomenclature: 0 (Biomarkers)
0 (Metals, Heavy)
0 (Environmental Pollutants)
Entry Date(s): Date Created: 20261003 Date Completed: 20261003 Latest Revision: 20261003
Update Code: 20261004
DOI: 10.1007/s12012-026-10195-8
PMID: 42828596
Βάση Δεδομένων: MEDLINE
Περιγραφή
ISSN:1559-0259
DOI:10.1007/s12012-026-10195-8