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

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Title: Association of Mixed Metal Exposures with Cardiovascular Disease: Insights from a Population-Based Study.
Authors: 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.
Source: Cardiovascular toxicology [Cardiovasc Toxicol] 2026 Oct 03; Vol. 26 (10). Date of Electronic Publication: 2026 Oct 03.
Publication Type: Journal Article
Language: English
Journal Info: 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-
MeSH Terms: 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
Abstract: 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.
References: Cardiovascular diseases (CVDs). https://www.who.int/news-room/fact-sheets/detail/cardiovascular-diseases-(cvds ).
Mokdad, A. H., Bisignano, C., Hsu, J. M., Ababneh, H. S., Abbasgholizadeh, R., Abdelkader, A., & Doan, K. D. (2024). The burden of diseases, injuries, and risk factors by state in the USA, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021. The Lancet, 404(10469), 2314–2340. (PMID: 10.1016/S0140-6736(24)01446-6)
Jin, X., Liu, Y., Jia, W., Xu, R., Guan, X., Cui, M., Zhang, H., Wu, H., Wei, L., & Qi, X. (2025). Association between systemic immune-inflammatory indices and severity of coronary artery lesions in patients with coronary artery disease in different glucose metabolic states. Journal of Inflammation Research, 18, 3295–3309. (PMID: 400659071189250710.2147/JIR.S507696)
Wang, X., Ma, H., Li, X., Heianza, Y., Fonseca, V., & Qi, L. (2023). Joint association of loneliness and traditional risk factor control and incident cardiovascular disease in diabetes patients. European Heart Journal, 44(28), 2583–2591. (PMID: 373856291036100910.1093/eurheartj/ehad306)
Münzel, T., Hahad, O., Sørensen, M., Lelieveld, J., Duerr, G. D., Nieuwenhuijsen, M., & Daiber, A. (2022). Environmental risk factors and cardiovascular diseases: A comprehensive expert review. Cardiovascular Research, 118(14), 2880–2902. (PMID: 34609502964883510.1093/cvr/cvab316)
Jin, X., Jia, W., Liu, Y., Cui, M., Zhang, H., Wu, H., Li, J., Wei, L., & Qi, X. (2025). Association of platelet to high density lipoprotein cholesterol ratio with coronary lesion severity in middle aged and elderly adults. Scientific Reports, 15(1), 27336. (PMID: 407171691230147110.1038/s41598-025-12981-w)
Hong, X., Tian, G., Zhu, Y., & Ren T. (2023). Exogeneous metal ions as therapeutic agents in cardiovascular disease and their delivery strategies. Regenerative Biomaterials, 11, Article rbad103. (PMID: 3817377610.1093/rb/rbad103)
Wang, Y., Sun, Y., Jie, T., Wang, M., Zhang, S., Yang, H., Jian, W., Dai, D., Xu, R., Yue, B., & Qu, X. (2025). Association between serum copper-zinc-selenium mixture and multiple health outcomes. Bioactive Materials, 50, 432–442. (PMID: 403092561204176310.1016/j.bioactmat.2025.04.004)
Pires, J. G. P., Schereider, I. R. G., Cibin, F. W. S., Scorza, F. A., Wiggers, G. A., & Vassallo, D. V. (2025). Metals, cardiovascular risk, and the interplay with oxidative stress: A mini-review. Brazilian Journal of Medical and Biological Research = Revista Brasileira De Pesquisas Medicas E Biologica, 58, e14466.
Lin, B., Alexander, R., Fritzen, R., Mills, S., Stewart, A. J., & McCowan, C. (2025). Abnormal plasma/serum magnesium, copper, and zinc concentrations associate with the future development of cardiovascular diseases. Nutrients, 17(9), Article 1447. (PMID: 403627561207360710.3390/nu17091447)
Sun, Z., Xu, Y., Liu, Y., Tao, X., Zhou, P., Feng, H., Weng, Y., Lu, X., Wu, J., Wei, Y., Qu, C., & Liu, Z. (2025). Associations of exposure to 56 serum trace elements with the prevalence and severity of acute myocardial infarction: Omics, mixture, and mediation analysis. Biological Trace Element Research, 203(9), 4466–4478. (PMID: 398044531231672110.1007/s12011-024-04509-6)
Zhou, R., Zhai, W., Meng, L., Wei, C., & Sun. L. (2025). Serum multi-trace elements and post-stroke cognitive impairment: A prospective observational cohort study. Translational Psychiatry, 15, Article 222. (PMID: 405934721221688210.1038/s41398-025-03420-5)
Guan, D. X., Yang, C., & Nriagu, J. O. (2024). Editorial: The role of essential trace elements in health and disease. Frontiers in Public Health, 11, Article 1285603. (PMID: 382397931079516110.3389/fpubh.2023.1285603)
Eroglu. B., Eichelmann, F., Kuxhausf, O., Kipp, A. P., Schwerdtle, T., Haase, H., Schomburg, L., & Schulze, M. B. (2025). Trace elements and risk of diabetes-related vascular complications: Results from the EPIC-Potsdam cohort study. Cardiovascular Diabetology, 24, 302. (PMID: 407078971229152010.1186/s12933-025-02861-y)
Tsvetkov, P., Coy, S., Petrova, B., Dreishpoon, M., Verma, A., Abdusamad, M., Rossen, J., Joesch-Cohen, L., Humeidi, R., Spangler, R. D., Eaton, J. K., Frenkel, E., Kocak, M., Corsello, S. M., Lutsenko, S., Kanarek, N., Santagata, S., & Golub, T. R. (2022). Copper induces cell death by targeting lipoylated TCA cycle proteins. Science (New York, N.Y.), 375(6586), 1254–1261. (PMID: 35298263927333310.1126/science.abf0529)
Zhang, W., Li, Y., Zheng, K., Li, Y., & Yang, H. (2024). Nonlinear associations between dietary zinc intake and cardiovascular disease risk, a National cross-sectional study based on the NHANES 2005–2018. Preventive Medicine Reports, 45, Article 102830. (PMID: 10.1016/j.pmedr.2024.102830)
Yang, S., Li, Y., Zhou, L., Wang, X., Liu, L., & Wu, M. (2024). Copper homeostasis and cuproptosis in atherosclerosis: Metabolism, mechanisms and potential therapeutic strategies. Cell Death Discovery, 10(1), 25. (PMID: 382189411078775010.1038/s41420-023-01796-1)
Escobedo-Monge, M. F., Barrado, E., Parodi-Román, J., Escobedo-Monge, M. A., Torres-Hinojal, M. C., & Marugán-Miguelsanz, J. M. (2021). Copper and copper/Zn ratio in a series of children with chronic diseases: A cross-sectional study. Nutrients, 13(10), Article 3578. (PMID: 34684579853799410.3390/nu13103578)
Bizerea-Moga, T. O., Pitulice, L., Bizerea-Spiridon, O., & Moga, T. V. (2024). Exploring the link between oxidative stress, selenium levels, and obesity in youth. International Journal of Molecular Sciences, 25(13), Article 7276. (PMID: 390003831124290910.3390/ijms25137276)
Wen, L., Zhou, L., Zhu, X., & Mei, Y. (2025). Epidemiological profile and determinants of whole blood heavy metal levels in occupationally exposed populations: A cross-sectional study in Hunan Province, China. Frontiers in Public Health, 13, Article 1635236. (PMID: 407861671233173810.3389/fpubh.2025.1635236)
Chen, L. H., Zhong, J. F., Niu, Y. Y., Li, C. P., Li, J., Diao, Z. Q., Yan, H. Y., Xu, M., Huang, W. Q., Xu, Z. T., Su, C., & Liu, D. (2025). Association of dietary choline intake with incidence of frailty: A nationwide prospective cohort study from China. Journal of Cachexia, Sarcopenia and Muscle, 16(2), Article e13796. (PMID: 401892181197269010.1002/jcsm.13796)
Zhang, Y., Song, K., Bi, S., Li, M., & Yao, Z. (2024). Higher remnant cholesterol increases the risk of coronary heart disease and diabetes in postmenopausal women. Frontiers in Endocrinology, 15, Article 1475933. (PMID: 397171021166365810.3389/fendo.2024.1475933)
Zhang, Y., Qiu, X., Wu, Z., Li, Y., Shen, X., Wu, J., Cao, P., Sun, Z., & Wang, W. (2025). Comprehensive analysis of the association between volatile organic compound pollutants and chronic kidney disease in hypertensive populations: Insights from multi-omics approaches and identification of potential therapeutic targets. Environmental Research, 282, Article 121966. (PMID: 4044151010.1016/j.envres.2025.121966)
Keil, A. P., Buckley, J. P., O'Brien, K. M., Ferguson, K. K., Zhao, S., & White, A. J. (2020). A quantile-based g-computation approach to addressing the effects of exposure mixtures. Environmental Health Perspectives, 128(4), 047004. (PMID: 32255670722810010.1289/EHP5838)
Vo, T. T. T., Peng, T. Y., Nguyen, T. H., Bui, T. N. H., Wang, C. S., Lee, W. J., Chen, Y. L., Wu, Y. C., & Lee, I. T. (2024). The crosstalk between copper-induced oxidative stress and cuproptosis: A novel potential anticancer paradigm. Cell Communication and Signaling, 22(1), 353. (PMID: 389700721122528510.1186/s12964-024-01726-3)
Wu, X., Shi, M., Zhang, H., & Fang, S. (2025). Dietary zinc intake associated with stroke in American adults. Scientific Reports, 15(1), 18301. (PMID: 404196321210662010.1038/s41598-025-03122-4)
Perek, B., Rzymski, P., Proch, A., Puślecki, M., Poniedziałek, B., Fal, A., Komosa, A., Jemielity, M., & Niedzielski, P. (2025). Exploring the interplay between valvular and serum zinc and copper levels and disease markers in aortic stenosis. Vascular Pharmacology, 159, Article 107497. (PMID: 4027396410.1016/j.vph.2025.107497)
Zhao, H., Mei, K., Hu, Q., Wu, Y., Xu, Y., Qinling, Yu, P., Deng, Y., Zhu, W., Yan, Z., & Liu, X. (2024). Circulating copper levels and the risk of cardio-cerebrovascular diseases and cardiovascular and all-cause mortality: A systematic review and meta-analysis of longitudinal studies. Environmental Pollution, 340(Pt 2), 122711. (PMID: 3785231210.1016/j.envpol.2023.122711)
Guo, Q., Cai, J., Qu, Q., Cheang, I., Shi, J., Pang, H., & Li, X. (2024). Association of Blood Trace Elements Levels with Cardiovascular Disease in US Adults: A Cross-Sectional Study from the National Health and Nutrition Examination Survey 2011–2016. Biological Trace Element Research, 202(7), 3037–3050. (PMID: 3789136410.1007/s12011-023-03913-8)
Kwon, Y. J., Lee, H. S., Park, G., Yang, J., Kim, H. M., & Lee, J. W. (2023). Dietary zinc intake and all-cause and cardiovascular mortality in Korean middle-aged and older adults. Nutrients, 15(2), Article 358. (PMID: 36678229986293610.3390/nu15020358)
Zhang, N., Li, Z., Wu, Q., Huang, H., Wang, S., Liu, Y., Chen, J., & Ma, J. (2023). Associations of dietary zinc-vitamin B6 ratio with all-cause mortality and cardiovascular disease mortality based on National Health and Nutrition Examination Survey 1999–2016. Nutrients, 15(2), Article 420. (PMID: 10.3390/nu15020420)
Barragán, R., Sánchez-González, C., Aranda, P., Sorlí, J. V., Asensio, E. M., Portolés, O., Ortega-Azorín, C., Villamil, L. V., Coltell, O., Llopis, J., Rivas-García, L., & Corella, D. (2022). Single and combined associations of plasma and urine essential trace elements (Zn, Cu, Se, and Mn) with cardiovascular risk factors in a Mediterranean population. Antioxidants (Basel), 11(10), Article 1991. (PMID: 36290714959812710.3390/antiox11101991)
Ferreira, R. L. U., Sena-Evangelista, K. C. M., de Azevedo, E. P., Pinheiro, F. I., Cobucci, R. N., & Pedrosa, L. F. C. (2021). Selenium in human health and gut microflora: Bioavailability of selenocompounds and relationship with diseases. Frontiers in Nutrition, 8, Article 685317. (PMID: 34150830821173210.3389/fnut.2021.685317)
Karunakaran, V., Harding, K., Sarnowski, A., & Walter, E. (2025). Trace elements: Clinical perspectives in the critically ill. Journal of the Intensive Care Society, 26(2), 223–236. (PMID: 399263871180023010.1177/17511437241305269)
Zhu, D., Zhong, Q., Lin, T., & Song, T. (2023). Higher serum selenium concentration is associated with lower risk of all-cause and cardiovascular mortality among individuals with chronic kidney disease: A population-based cohort study of NHANES. Frontiers in Nutrition, 10, Article 1127188. (PMID: 370633401010251010.3389/fnut.2023.1127188)
Gupta, B. G., & Mukhopadhyay, R. (2025). Heavy metal contamination from textile wastewater and its health impacts: A case study from West Bengal with sustainable remediation approaches. Scientific Reports, 15(1), 29578. (PMID: 407966021234393410.1038/s41598-025-13357-w)
Verma, J., Rao, N., Kulshrestha, M. R., Singh, S., Singh, S., Tiwari, V., & Sharma, M. T. (2026). Exploring the association between potentially toxic elements and chronic kidney disease of unknown etiology in Eastern Uttar Pradesh, India. Biological Trace Element Research, 204(2), 1084–1098. (PMID: 4060380810.1007/s12011-025-04731-w)
Zhu, K., Zhang, Y., Lu, Q., Geng, T., Li, R., Wan, Z., Zhang, X., Liu, Y., Li, L., Qiu, Z., He, M., Liu, L., Pan, A., & Liu, G. (2022). Associations of exposure to lead and cadmium with risk of all-cause and cardiovascular disease mortality among patients with type 2 diabetes. Environmental Science and Pollution Research International, 29(51), 76805–76815. (PMID: 3567094510.1007/s11356-022-21273-z)
Verzelloni, P., Urbano, T., Wise, L. A., Vinceti, M., & Filippini, T. (2024). Cadmium exposure and cardiovascular disease risk: A systematic review and dose-response meta-analysis. Environmental Pollution, 345, Article 123462. (PMID: 3829593310.1016/j.envpol.2024.123462)
Cook, M. K., Zhang, J., & Wei, Y. (2022). Blood lead levels and risk of deaths from cardiovascular disease. The American Journal of Cardiology, 173, 132–138. (PMID: 3535128310.1016/j.amjcard.2022.03.002)
Yüksel, D., Yuksel, B., Kalafat, E., Yüce, T., Katlan, D. C., & Koç, A. (2022). Assessment of lead and mercury levels in maternal blood, fetal cord blood and placenta in pregnancy with intrauterine growth restriction. Journal of Basic and Clinical Health Sciences, 6(1), 199–205. (PMID: 10.30621/jbachs.1008609)
Hua, X., Zhu, L., & Chen, H. (2025). Association between blood heavy metal levels and COPD risk: A cross-sectional study based on NHANES data. Frontiers in Public Health, 13, Article 1494336. (PMID: 407563961231366710.3389/fpubh.2025.1494336)
Guo, X., Li, N., Wang, H., Su, W., Song, Q., Liang, Q., Liang, M., Sun, C., Li, Y., Lowe, S., Bentley, R., Song, E. J., Zhou, Q., Ding, X., & Sun, Y. (2022). Combined exposure to multiple metals on cardiovascular disease in NHANES under five statistical models. Environmental Research, 215(Pt 3), Article 114435. (PMID: 3617476110.1016/j.envres.2022.114435)
Duan, W., Xu, C., Liu, Q., Xu, J., Weng, Z., Zhang, X., Basnet, T. B., Dahal, M., & Gu, A. (2020). Levels of a mixture of heavy metals in blood and urine and all-cause, cardiovascular disease and cancer mortality: A population-based cohort study. Environmental Pollution, 263(Pt A), Article 114630. (PMID: 3361848110.1016/j.envpol.2020.114630)
Yim, G., Wang, Y., Howe, C. G., & Romano, M. E. (2022). Exposure to metal mixtures in association with cardiovascular risk factors and outcomes: A scoping review. Toxics, 10(3), Article 116. (PMID: 35324741895563710.3390/toxics10030116)
Udom, G. J., Iyaye, D., Oritsemuelebi, B., Nwanaforo, E., Bede-Ojimadu, O., Abdulai, P. M., Frazzoli, C, & Orisakwe, O. E. (2025). Public health concerns of multifaceted exposures to metal and metalloid mixtures: A systematic review. Environmental Monitoring and Assessment, 197(5), 502. (PMID: 4017270610.1007/s10661-025-13963-1)
He, Y., Zhou, X., Huang, W., Wu, Y., Zhang, Z., Jin, Y., Li, F., Chen, G., Tao, K., Zhan, Y., Zou, X., Wei, Q., Wei, X., & Qiu, S. (2025). Cadmium exposure and advanced cardiovascular-kidney-metabolic syndrome: An integrated multi-organ perspective based on epidemiology and adverse outcome pathways. Ecotoxicology and Environmental Safety, 303, Article 118885. (PMID: 4081940210.1016/j.ecoenv.2025.118885)
Ozarde, Y., Purandare, D., Deshmukh, S., & Gadhave, R. (2025). Heavy metals and cardiovascular health: Uncovering links and health challenges. Journal of Trace Elements in Medicine and Biology, 89, Article 127648. (PMID: 4022839910.1016/j.jtemb.2025.127648)
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
Database: MEDLINE
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  Data: &lt;searchLink fieldCode=&quot;JN&quot; term=&quot;%22101135818%22&quot;&gt;Cardiovascular toxicology&lt;/searchLink&gt; [Cardiovasc Toxicol] 2026 Oct 03; Vol. 26 (10). &lt;i&gt;Date of Electronic Publication: &lt;/i&gt;2026 Oct 03.
– Name: TypePub
  Label: Publication Type
  Group: TypPub
  Data: Journal Article
– Name: Language
  Label: Language
  Group: Lang
  Data: English
– Name: TitleSource
  Label: Journal Info
  Group: Src
  Data: &lt;i&gt;Publisher: &lt;/i&gt;&lt;searchLink fieldCode=&quot;PB&quot; term=&quot;%22Humana+Press%22&quot;&gt;Humana Press &lt;/searchLink&gt;&lt;i&gt;Country of Publication: &lt;/i&gt;United States &lt;i&gt;NLM ID: &lt;/i&gt;101135818 &lt;i&gt;Publication Model: &lt;/i&gt;Electronic &lt;i&gt;Cited Medium: &lt;/i&gt;Internet &lt;i&gt;ISSN: &lt;/i&gt;1559-0259 (Electronic) &lt;i&gt;Linking ISSN: &lt;/i&gt;&lt;searchLink fieldCode=&quot;IS&quot; term=&quot;%2215307905%22&quot;&gt;15307905 &lt;/searchLink&gt;&lt;i&gt;NLM ISO Abbreviation: &lt;/i&gt;Cardiovasc Toxicol &lt;i&gt;Subsets: &lt;/i&gt;MEDLINE
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  Data: &lt;i&gt;Original Publication&lt;/i&gt;: Totowa, NJ : Humana Press, c2001-
– Name: SubjectMESH
  Label: MeSH Terms
  Group: Su
  Data: &lt;searchLink fieldCode=&quot;MM&quot; term=&quot;%22Cardiovascular+Diseases%22&quot;&gt;Cardiovascular Diseases*&lt;/searchLink&gt;/&lt;searchLink fieldCode=&quot;MM&quot; term=&quot;%22Cardiovascular+Diseases+epidemiology%22&quot;&gt;epidemiology&lt;/searchLink&gt; &lt;br /&gt;&lt;searchLink fieldCode=&quot;MM&quot; term=&quot;%22Cardiovascular+Diseases%22&quot;&gt;Cardiovascular Diseases*&lt;/searchLink&gt;/&lt;searchLink fieldCode=&quot;MM&quot; term=&quot;%22Cardiovascular+Diseases+diagnosis%22&quot;&gt;diagnosis&lt;/searchLink&gt; &lt;br /&gt;&lt;searchLink fieldCode=&quot;MM&quot; term=&quot;%22Cardiovascular+Diseases%22&quot;&gt;Cardiovascular Diseases*&lt;/searchLink&gt;/&lt;searchLink fieldCode=&quot;MM&quot; term=&quot;%22Cardiovascular+Diseases+blood%22&quot;&gt;blood&lt;/searchLink&gt; &lt;br /&gt;&lt;searchLink fieldCode=&quot;MM&quot; term=&quot;%22Cardiovascular+Diseases%22&quot;&gt;Cardiovascular Diseases*&lt;/searchLink&gt;/&lt;searchLink fieldCode=&quot;MM&quot; term=&quot;%22Cardiovascular+Diseases+chemically+induced%22&quot;&gt;chemically induced&lt;/searchLink&gt; &lt;br /&gt;&lt;searchLink fieldCode=&quot;MM&quot; term=&quot;%22Environmental+Exposure%22&quot;&gt;Environmental Exposure*&lt;/searchLink&gt;/&lt;searchLink fieldCode=&quot;MM&quot; term=&quot;%22Environmental+Exposure+adverse+effects%22&quot;&gt;adverse effects&lt;/searchLink&gt; &lt;br /&gt;&lt;searchLink fieldCode=&quot;MM&quot; term=&quot;%22Metals%2C+Heavy%22&quot;&gt;Metals, Heavy*&lt;/searchLink&gt;/&lt;searchLink fieldCode=&quot;MM&quot; term=&quot;%22Metals%2C+Heavy+blood%22&quot;&gt;blood&lt;/searchLink&gt; &lt;br /&gt;&lt;searchLink fieldCode=&quot;MM&quot; term=&quot;%22Metals%2C+Heavy%22&quot;&gt;Metals, Heavy*&lt;/searchLink&gt;/&lt;searchLink fieldCode=&quot;MM&quot; term=&quot;%22Metals%2C+Heavy+adverse+effects%22&quot;&gt;adverse effects&lt;/searchLink&gt; &lt;br /&gt;&lt;searchLink fieldCode=&quot;MM&quot; term=&quot;%22Environmental+Pollutants%22&quot;&gt;Environmental Pollutants*&lt;/searchLink&gt;/&lt;searchLink fieldCode=&quot;MM&quot; term=&quot;%22Environmental+Pollutants+blood%22&quot;&gt;blood&lt;/searchLink&gt; &lt;br /&gt;&lt;searchLink fieldCode=&quot;MM&quot; term=&quot;%22Environmental+Pollutants%22&quot;&gt;Environmental Pollutants*&lt;/searchLink&gt;/&lt;searchLink fieldCode=&quot;MM&quot; term=&quot;%22Environmental+Pollutants+adverse+effects%22&quot;&gt;adverse effects&lt;/searchLink&gt;&lt;br /&gt;&lt;searchLink fieldCode=&quot;MH&quot; term=&quot;%22Biomarkers%22&quot;&gt;Biomarkers&lt;/searchLink&gt;/&lt;searchLink fieldCode=&quot;MH&quot; term=&quot;%22Biomarkers+blood%22&quot;&gt;blood&lt;/searchLink&gt; ; &lt;searchLink fieldCode=&quot;MH&quot; term=&quot;%22United+States%22&quot;&gt;United States&lt;/searchLink&gt;/&lt;searchLink fieldCode=&quot;MH&quot; term=&quot;%22United+States+epidemiology%22&quot;&gt;epidemiology&lt;/searchLink&gt; ; &lt;searchLink fieldCode=&quot;MH&quot; term=&quot;%22Humans%22&quot;&gt;Humans&lt;/searchLink&gt; ; &lt;searchLink fieldCode=&quot;MH&quot; term=&quot;%22Male%22&quot;&gt;Male&lt;/searchLink&gt; ; &lt;searchLink fieldCode=&quot;MH&quot; term=&quot;%22Female%22&quot;&gt;Female&lt;/searchLink&gt; ; &lt;searchLink fieldCode=&quot;MH&quot; term=&quot;%22Risk+Assessment%22&quot;&gt;Risk Assessment&lt;/searchLink&gt; ; &lt;searchLink fieldCode=&quot;MH&quot; term=&quot;%22Middle+Aged%22&quot;&gt;Middle Aged&lt;/searchLink&gt; ; &lt;searchLink fieldCode=&quot;MH&quot; term=&quot;%22Nutrition+Surveys%22&quot;&gt;Nutrition Surveys&lt;/searchLink&gt; ; &lt;searchLink fieldCode=&quot;MH&quot; term=&quot;%22Risk+Factors%22&quot;&gt;Risk Factors&lt;/searchLink&gt; ; &lt;searchLink fieldCode=&quot;MH&quot; term=&quot;%22Aged%22&quot;&gt;Aged&lt;/searchLink&gt; ; &lt;searchLink fieldCode=&quot;MH&quot; term=&quot;%22Adult%22&quot;&gt;Adult&lt;/searchLink&gt; ; &lt;searchLink fieldCode=&quot;MH&quot; term=&quot;%22Heart+Disease+Risk+Factors%22&quot;&gt;Heart Disease Risk Factors&lt;/searchLink&gt; ; &lt;searchLink fieldCode=&quot;MH&quot; term=&quot;%22Cross-Sectional+Studies%22&quot;&gt;Cross-Sectional Studies&lt;/searchLink&gt;
– Name: Abstract
  Label: Abstract
  Group: Ab
  Data: 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.&#160;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.&#160;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 &amp;lt; 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.&#160;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.&lt;br /&gt; (&#169; 2026. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)
– Name: Abstract
  Label: Competing Interests
  Group: Ab
  Data: 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.
– Name: Ref
  Label: References
  Group: RefInfo
  Data: Cardiovascular diseases (CVDs). https://www.who.int/news-room/fact-sheets/detail/cardiovascular-diseases-(cvds ).&lt;br /&gt;Mokdad, A. H., Bisignano, C., Hsu, J. M., Ababneh, H. S., Abbasgholizadeh, R., Abdelkader, A., &amp; Doan, K. D. (2024). The burden of diseases, injuries, and risk factors by state in the USA, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021. The Lancet, 404(10469), 2314–2340. (PMID: &lt;searchLink fieldCode=&quot;PM&quot; term=&quot;%2210%2E1016%2FS0140-6736%2824%2901446-6%22&quot;&gt;10.1016/S0140-6736(24)01446-6)&lt;/searchLink&gt;&lt;br /&gt;Jin, X., Liu, Y., Jia, W., Xu, R., Guan, X., Cui, M., Zhang, H., Wu, H., Wei, L., &amp; Qi, X. (2025). Association between systemic immune-inflammatory indices and severity of coronary artery lesions in patients with coronary artery disease in different glucose metabolic states. Journal of Inflammation Research, 18, 3295–3309. (PMID: &lt;searchLink fieldCode=&quot;PM&quot; term=&quot;%22400659071189250710%2E2147%2FJIR%2ES507696%22&quot;&gt;400659071189250710.2147/JIR.S507696)&lt;/searchLink&gt;&lt;br /&gt;Wang, X., Ma, H., Li, X., Heianza, Y., Fonseca, V., &amp; Qi, L. (2023). Joint association of loneliness and traditional risk factor control and incident cardiovascular disease in diabetes patients. European Heart Journal, 44(28), 2583–2591. (PMID: &lt;searchLink fieldCode=&quot;PM&quot; term=&quot;%22373856291036100910%2E1093%2Feurheartj%2Fehad306%22&quot;&gt;373856291036100910.1093/eurheartj/ehad306)&lt;/searchLink&gt;&lt;br /&gt;M&#252;nzel, T., Hahad, O., S&#248;rensen, M., Lelieveld, J., Duerr, G. D., Nieuwenhuijsen, M., &amp; Daiber, A. (2022). Environmental risk factors and cardiovascular diseases: A comprehensive expert review. Cardiovascular Research, 118(14), 2880–2902. (PMID: &lt;searchLink fieldCode=&quot;PM&quot; term=&quot;%2234609502964883510%2E1093%2Fcvr%2Fcvab316%22&quot;&gt;34609502964883510.1093/cvr/cvab316)&lt;/searchLink&gt;&lt;br /&gt;Jin, X., Jia, W., Liu, Y., Cui, M., Zhang, H., Wu, H., Li, J., Wei, L., &amp; Qi, X. (2025). Association of platelet to high density lipoprotein cholesterol ratio with coronary lesion severity in middle aged and elderly adults. Scientific Reports, 15(1), 27336. (PMID: &lt;searchLink fieldCode=&quot;PM&quot; term=&quot;%22407171691230147110%2E1038%2Fs41598-025-12981-w%22&quot;&gt;407171691230147110.1038/s41598-025-12981-w)&lt;/searchLink&gt;&lt;br /&gt;Hong, X., Tian, G., Zhu, Y., &amp; Ren T. (2023). Exogeneous metal ions as therapeutic agents in cardiovascular disease and their delivery strategies. Regenerative Biomaterials, 11, Article rbad103. (PMID: &lt;searchLink fieldCode=&quot;PM&quot; term=&quot;%223817377610%2E1093%2Frb%2Frbad103%22&quot;&gt;3817377610.1093/rb/rbad103)&lt;/searchLink&gt;&lt;br /&gt;Wang, Y., Sun, Y., Jie, T., Wang, M., Zhang, S., Yang, H., Jian, W., Dai, D., Xu, R., Yue, B., &amp; Qu, X. (2025). Association between serum copper-zinc-selenium mixture and multiple health outcomes. Bioactive Materials, 50, 432–442. (PMID: &lt;searchLink fieldCode=&quot;PM&quot; term=&quot;%22403092561204176310%2E1016%2Fj%2Ebioactmat%2E2025%2E04%2E004%22&quot;&gt;403092561204176310.1016/j.bioactmat.2025.04.004)&lt;/searchLink&gt;&lt;br /&gt;Pires, J. G. P., Schereider, I. R. G., Cibin, F. W. S., Scorza, F. A., Wiggers, G. A., &amp; Vassallo, D. V. (2025). Metals, cardiovascular risk, and the interplay with oxidative stress: A mini-review. Brazilian Journal of Medical and Biological Research = Revista Brasileira De Pesquisas Medicas E Biologica, 58, e14466.&lt;br /&gt;Lin, B., Alexander, R., Fritzen, R., Mills, S., Stewart, A. J., &amp; McCowan, C. (2025). Abnormal plasma/serum magnesium, copper, and zinc concentrations associate with the future development of cardiovascular diseases. Nutrients, 17(9), Article 1447. (PMID: &lt;searchLink fieldCode=&quot;PM&quot; term=&quot;%22403627561207360710%2E3390%2Fnu17091447%22&quot;&gt;403627561207360710.3390/nu17091447)&lt;/searchLink&gt;&lt;br /&gt;Sun, Z., Xu, Y., Liu, Y., Tao, X., Zhou, P., Feng, H., Weng, Y., Lu, X., Wu, J., Wei, Y., Qu, C., &amp; Liu, Z. (2025). Associations of exposure to 56 serum trace elements with the prevalence and severity of acute myocardial infarction: Omics, mixture, and mediation analysis. Biological Trace Element Research, 203(9), 4466–4478. (PMID: &lt;searchLink fieldCode=&quot;PM&quot; term=&quot;%22398044531231672110%2E1007%2Fs12011-024-04509-6%22&quot;&gt;398044531231672110.1007/s12011-024-04509-6)&lt;/searchLink&gt;&lt;br /&gt;Zhou, R., Zhai, W., Meng, L., Wei, C., &amp; Sun. L. (2025). Serum multi-trace elements and post-stroke cognitive impairment: A prospective observational cohort study. Translational Psychiatry, 15, Article 222. (PMID: &lt;searchLink fieldCode=&quot;PM&quot; term=&quot;%22405934721221688210%2E1038%2Fs41398-025-03420-5%22&quot;&gt;405934721221688210.1038/s41398-025-03420-5)&lt;/searchLink&gt;&lt;br /&gt;Guan, D. X., Yang, C., &amp; Nriagu, J. O. (2024). Editorial: The role of essential trace elements in health and disease. Frontiers in Public Health, 11, Article 1285603. (PMID: &lt;searchLink fieldCode=&quot;PM&quot; term=&quot;%22382397931079516110%2E3389%2Ffpubh%2E2023%2E1285603%22&quot;&gt;382397931079516110.3389/fpubh.2023.1285603)&lt;/searchLink&gt;&lt;br /&gt;Eroglu. B., Eichelmann, F., Kuxhausf, O., Kipp, A. P., Schwerdtle, T., Haase, H., Schomburg, L., &amp; Schulze, M. B. (2025). Trace elements and risk of diabetes-related vascular complications: Results from the EPIC-Potsdam cohort study. Cardiovascular Diabetology, 24, 302. (PMID: &lt;searchLink fieldCode=&quot;PM&quot; term=&quot;%22407078971229152010%2E1186%2Fs12933-025-02861-y%22&quot;&gt;407078971229152010.1186/s12933-025-02861-y)&lt;/searchLink&gt;&lt;br /&gt;Tsvetkov, P., Coy, S., Petrova, B., Dreishpoon, M., Verma, A., Abdusamad, M., Rossen, J., Joesch-Cohen, L., Humeidi, R., Spangler, R. D., Eaton, J. K., Frenkel, E., Kocak, M., Corsello, S. M., Lutsenko, S., Kanarek, N., Santagata, S., &amp; Golub, T. R. (2022). Copper induces cell death by targeting lipoylated TCA cycle proteins. Science (New York, N.Y.), 375(6586), 1254–1261. (PMID: &lt;searchLink fieldCode=&quot;PM&quot; term=&quot;%2235298263927333310%2E1126%2Fscience%2Eabf0529%22&quot;&gt;35298263927333310.1126/science.abf0529)&lt;/searchLink&gt;&lt;br /&gt;Zhang, W., Li, Y., Zheng, K., Li, Y., &amp; Yang, H. (2024). Nonlinear associations between dietary zinc intake and cardiovascular disease risk, a National cross-sectional study based on the NHANES 2005–2018. Preventive Medicine Reports, 45, Article 102830. (PMID: &lt;searchLink fieldCode=&quot;PM&quot; term=&quot;%2210%2E1016%2Fj%2Epmedr%2E2024%2E102830%22&quot;&gt;10.1016/j.pmedr.2024.102830)&lt;/searchLink&gt;&lt;br /&gt;Yang, S., Li, Y., Zhou, L., Wang, X., Liu, L., &amp; Wu, M. (2024). Copper homeostasis and cuproptosis in atherosclerosis: Metabolism, mechanisms and potential therapeutic strategies. Cell Death Discovery, 10(1), 25. (PMID: &lt;searchLink fieldCode=&quot;PM&quot; term=&quot;%22382189411078775010%2E1038%2Fs41420-023-01796-1%22&quot;&gt;382189411078775010.1038/s41420-023-01796-1)&lt;/searchLink&gt;&lt;br /&gt;Escobedo-Monge, M. F., Barrado, E., Parodi-Rom&#225;n, J., Escobedo-Monge, M. A., Torres-Hinojal, M. C., &amp; Marug&#225;n-Miguelsanz, J. M. (2021). Copper and copper/Zn ratio in a series of children with chronic diseases: A cross-sectional study. Nutrients, 13(10), Article 3578. (PMID: &lt;searchLink fieldCode=&quot;PM&quot; term=&quot;%2234684579853799410%2E3390%2Fnu13103578%22&quot;&gt;34684579853799410.3390/nu13103578)&lt;/searchLink&gt;&lt;br /&gt;Bizerea-Moga, T. O., Pitulice, L., Bizerea-Spiridon, O., &amp; Moga, T. V. (2024). Exploring the link between oxidative stress, selenium levels, and obesity in youth. International Journal of Molecular Sciences, 25(13), Article 7276. (PMID: &lt;searchLink fieldCode=&quot;PM&quot; term=&quot;%22390003831124290910%2E3390%2Fijms25137276%22&quot;&gt;390003831124290910.3390/ijms25137276)&lt;/searchLink&gt;&lt;br /&gt;Wen, L., Zhou, L., Zhu, X., &amp; Mei, Y. (2025). Epidemiological profile and determinants of whole blood heavy metal levels in occupationally exposed populations: A cross-sectional study in Hunan Province, China. Frontiers in Public Health, 13, Article 1635236. (PMID: &lt;searchLink fieldCode=&quot;PM&quot; term=&quot;%22407861671233173810%2E3389%2Ffpubh%2E2025%2E1635236%22&quot;&gt;407861671233173810.3389/fpubh.2025.1635236)&lt;/searchLink&gt;&lt;br /&gt;Chen, L. H., Zhong, J. F., Niu, Y. Y., Li, C. P., Li, J., Diao, Z. Q., Yan, H. Y., Xu, M., Huang, W. Q., Xu, Z. T., Su, C., &amp; Liu, D. (2025). Association of dietary choline intake with incidence of frailty: A nationwide prospective cohort study from China. Journal of Cachexia, Sarcopenia and Muscle, 16(2), Article e13796. (PMID: &lt;searchLink fieldCode=&quot;PM&quot; term=&quot;%22401892181197269010%2E1002%2Fjcsm%2E13796%22&quot;&gt;401892181197269010.1002/jcsm.13796)&lt;/searchLink&gt;&lt;br /&gt;Zhang, Y., Song, K., Bi, S., Li, M., &amp; Yao, Z. (2024). Higher remnant cholesterol increases the risk of coronary heart disease and diabetes in postmenopausal women. Frontiers in Endocrinology, 15, Article 1475933. (PMID: &lt;searchLink fieldCode=&quot;PM&quot; term=&quot;%22397171021166365810%2E3389%2Ffendo%2E2024%2E1475933%22&quot;&gt;397171021166365810.3389/fendo.2024.1475933)&lt;/searchLink&gt;&lt;br /&gt;Zhang, Y., Qiu, X., Wu, Z., Li, Y., Shen, X., Wu, J., Cao, P., Sun, Z., &amp; Wang, W. (2025). Comprehensive analysis of the association between volatile organic compound pollutants and chronic kidney disease in hypertensive populations: Insights from multi-omics approaches and identification of potential therapeutic targets. Environmental Research, 282, Article 121966. (PMID: &lt;searchLink fieldCode=&quot;PM&quot; term=&quot;%224044151010%2E1016%2Fj%2Eenvres%2E2025%2E121966%22&quot;&gt;4044151010.1016/j.envres.2025.121966)&lt;/searchLink&gt;&lt;br /&gt;Keil, A. P., Buckley, J. P., O&#39;Brien, K. M., Ferguson, K. K., Zhao, S., &amp; White, A. J. (2020). A quantile-based g-computation approach to addressing the effects of exposure mixtures. Environmental Health Perspectives, 128(4), 047004. (PMID: &lt;searchLink fieldCode=&quot;PM&quot; term=&quot;%2232255670722810010%2E1289%2FEHP5838%22&quot;&gt;32255670722810010.1289/EHP5838)&lt;/searchLink&gt;&lt;br /&gt;Vo, T. T. T., Peng, T. Y., Nguyen, T. H., Bui, T. N. H., Wang, C. S., Lee, W. J., Chen, Y. L., Wu, Y. C., &amp; Lee, I. T. (2024). The crosstalk between copper-induced oxidative stress and cuproptosis: A novel potential anticancer paradigm. Cell Communication and Signaling, 22(1), 353. (PMID: &lt;searchLink fieldCode=&quot;PM&quot; term=&quot;%22389700721122528510%2E1186%2Fs12964-024-01726-3%22&quot;&gt;389700721122528510.1186/s12964-024-01726-3)&lt;/searchLink&gt;&lt;br /&gt;Wu, X., Shi, M., Zhang, H., &amp; Fang, S. (2025). Dietary zinc intake associated with stroke in American adults. Scientific Reports, 15(1), 18301. (PMID: &lt;searchLink fieldCode=&quot;PM&quot; term=&quot;%22404196321210662010%2E1038%2Fs41598-025-03122-4%22&quot;&gt;404196321210662010.1038/s41598-025-03122-4)&lt;/searchLink&gt;&lt;br /&gt;Perek, B., Rzymski, P., Proch, A., Puślecki, M., Poniedziałek, B., Fal, A., Komosa, A., Jemielity, M., &amp; Niedzielski, P. (2025). Exploring the interplay between valvular and serum zinc and copper levels and disease markers in aortic stenosis. Vascular Pharmacology, 159, Article 107497. (PMID: &lt;searchLink fieldCode=&quot;PM&quot; term=&quot;%224027396410%2E1016%2Fj%2Evph%2E2025%2E107497%22&quot;&gt;4027396410.1016/j.vph.2025.107497)&lt;/searchLink&gt;&lt;br /&gt;Zhao, H., Mei, K., Hu, Q., Wu, Y., Xu, Y., Qinling, Yu, P., Deng, Y., Zhu, W., Yan, Z., &amp; Liu, X. (2024). Circulating copper levels and the risk of cardio-cerebrovascular diseases and cardiovascular and all-cause mortality: A systematic review and meta-analysis of longitudinal studies. Environmental Pollution, 340(Pt 2), 122711. (PMID: &lt;searchLink fieldCode=&quot;PM&quot; term=&quot;%223785231210%2E1016%2Fj%2Eenvpol%2E2023%2E122711%22&quot;&gt;3785231210.1016/j.envpol.2023.122711)&lt;/searchLink&gt;&lt;br /&gt;Guo, Q., Cai, J., Qu, Q., Cheang, I., Shi, J., Pang, H., &amp; Li, X. (2024). Association of Blood Trace Elements Levels with Cardiovascular Disease in US Adults: A Cross-Sectional Study from the National Health and Nutrition Examination Survey 2011–2016. Biological Trace Element Research, 202(7), 3037–3050. (PMID: &lt;searchLink fieldCode=&quot;PM&quot; term=&quot;%223789136410%2E1007%2Fs12011-023-03913-8%22&quot;&gt;3789136410.1007/s12011-023-03913-8)&lt;/searchLink&gt;&lt;br /&gt;Kwon, Y. J., Lee, H. S., Park, G., Yang, J., Kim, H. M., &amp; Lee, J. W. (2023). Dietary zinc intake and all-cause and cardiovascular mortality in Korean middle-aged and older adults. Nutrients, 15(2), Article 358. (PMID: &lt;searchLink fieldCode=&quot;PM&quot; term=&quot;%2236678229986293610%2E3390%2Fnu15020358%22&quot;&gt;36678229986293610.3390/nu15020358)&lt;/searchLink&gt;&lt;br /&gt;Zhang, N., Li, Z., Wu, Q., Huang, H., Wang, S., Liu, Y., Chen, J., &amp; Ma, J. (2023). Associations of dietary zinc-vitamin B6 ratio with all-cause mortality and cardiovascular disease mortality based on National Health and Nutrition Examination Survey 1999–2016. Nutrients, 15(2), Article 420. (PMID: &lt;searchLink fieldCode=&quot;PM&quot; term=&quot;%2210%2E3390%2Fnu15020420%22&quot;&gt;10.3390/nu15020420)&lt;/searchLink&gt;&lt;br /&gt;Barrag&#225;n, R., S&#225;nchez-Gonz&#225;lez, C., Aranda, P., Sorl&#237;, J. V., Asensio, E. M., Portol&#233;s, O., Ortega-Azor&#237;n, C., Villamil, L. V., Coltell, O., Llopis, J., Rivas-Garc&#237;a, L., &amp; Corella, D. (2022). Single and combined associations of plasma and urine essential trace elements (Zn, Cu, Se, and Mn) with cardiovascular risk factors in a Mediterranean population. Antioxidants (Basel), 11(10), Article 1991. (PMID: &lt;searchLink fieldCode=&quot;PM&quot; term=&quot;%2236290714959812710%2E3390%2Fantiox11101991%22&quot;&gt;36290714959812710.3390/antiox11101991)&lt;/searchLink&gt;&lt;br /&gt;Ferreira, R. L. U., Sena-Evangelista, K. C. M., de Azevedo, E. P., Pinheiro, F. I., Cobucci, R. N., &amp; Pedrosa, L. F. C. (2021). Selenium in human health and gut microflora: Bioavailability of selenocompounds and relationship with diseases. Frontiers in Nutrition, 8, Article 685317. (PMID: &lt;searchLink fieldCode=&quot;PM&quot; term=&quot;%2234150830821173210%2E3389%2Ffnut%2E2021%2E685317%22&quot;&gt;34150830821173210.3389/fnut.2021.685317)&lt;/searchLink&gt;&lt;br /&gt;Karunakaran, V., Harding, K., Sarnowski, A., &amp; Walter, E. (2025). Trace elements: Clinical perspectives in the critically ill. Journal of the Intensive Care Society, 26(2), 223–236. (PMID: &lt;searchLink fieldCode=&quot;PM&quot; term=&quot;%22399263871180023010%2E1177%2F17511437241305269%22&quot;&gt;399263871180023010.1177/17511437241305269)&lt;/searchLink&gt;&lt;br /&gt;Zhu, D., Zhong, Q., Lin, T., &amp; Song, T. (2023). Higher serum selenium concentration is associated with lower risk of all-cause and cardiovascular mortality among individuals with chronic kidney disease: A population-based cohort study of NHANES. Frontiers in Nutrition, 10, Article 1127188. (PMID: &lt;searchLink fieldCode=&quot;PM&quot; term=&quot;%22370633401010251010%2E3389%2Ffnut%2E2023%2E1127188%22&quot;&gt;370633401010251010.3389/fnut.2023.1127188)&lt;/searchLink&gt;&lt;br /&gt;Gupta, B. G., &amp; Mukhopadhyay, R. (2025). Heavy metal contamination from textile wastewater and its health impacts: A case study from West Bengal with sustainable remediation approaches. Scientific Reports, 15(1), 29578. (PMID: &lt;searchLink fieldCode=&quot;PM&quot; term=&quot;%22407966021234393410%2E1038%2Fs41598-025-13357-w%22&quot;&gt;407966021234393410.1038/s41598-025-13357-w)&lt;/searchLink&gt;&lt;br /&gt;Verma, J., Rao, N., Kulshrestha, M. R., Singh, S., Singh, S., Tiwari, V., &amp; Sharma, M. T. (2026). Exploring the association between potentially toxic elements and chronic kidney disease of unknown etiology in Eastern Uttar Pradesh, India. Biological Trace Element Research, 204(2), 1084–1098. (PMID: &lt;searchLink fieldCode=&quot;PM&quot; term=&quot;%224060380810%2E1007%2Fs12011-025-04731-w%22&quot;&gt;4060380810.1007/s12011-025-04731-w)&lt;/searchLink&gt;&lt;br /&gt;Zhu, K., Zhang, Y., Lu, Q., Geng, T., Li, R., Wan, Z., Zhang, X., Liu, Y., Li, L., Qiu, Z., He, M., Liu, L., Pan, A., &amp; Liu, G. (2022). Associations of exposure to lead and cadmium with risk of all-cause and cardiovascular disease mortality among patients with type 2 diabetes. Environmental Science and Pollution Research International, 29(51), 76805–76815. (PMID: &lt;searchLink fieldCode=&quot;PM&quot; term=&quot;%223567094510%2E1007%2Fs11356-022-21273-z%22&quot;&gt;3567094510.1007/s11356-022-21273-z)&lt;/searchLink&gt;&lt;br /&gt;Verzelloni, P., Urbano, T., Wise, L. A., Vinceti, M., &amp; Filippini, T. (2024). Cadmium exposure and cardiovascular disease risk: A systematic review and dose-response meta-analysis. Environmental Pollution, 345, Article 123462. (PMID: &lt;searchLink fieldCode=&quot;PM&quot; term=&quot;%223829593310%2E1016%2Fj%2Eenvpol%2E2024%2E123462%22&quot;&gt;3829593310.1016/j.envpol.2024.123462)&lt;/searchLink&gt;&lt;br /&gt;Cook, M. K., Zhang, J., &amp; Wei, Y. (2022). Blood lead levels and risk of deaths from cardiovascular disease. The American Journal of Cardiology, 173, 132–138. (PMID: &lt;searchLink fieldCode=&quot;PM&quot; term=&quot;%223535128310%2E1016%2Fj%2Eamjcard%2E2022%2E03%2E002%22&quot;&gt;3535128310.1016/j.amjcard.2022.03.002)&lt;/searchLink&gt;&lt;br /&gt;Y&#252;ksel, D., Yuksel, B., Kalafat, E., Y&#252;ce, T., Katlan, D. C., &amp; Ko&#231;, A. (2022). Assessment of lead and mercury levels in maternal blood, fetal cord blood and placenta in pregnancy with intrauterine growth restriction. Journal of Basic and Clinical Health Sciences, 6(1), 199–205. (PMID: &lt;searchLink fieldCode=&quot;PM&quot; term=&quot;%2210%2E30621%2Fjbachs%2E1008609%22&quot;&gt;10.30621/jbachs.1008609)&lt;/searchLink&gt;&lt;br /&gt;Hua, X., Zhu, L., &amp; Chen, H. (2025). Association between blood heavy metal levels and COPD risk: A cross-sectional study based on NHANES data. Frontiers in Public Health, 13, Article 1494336. (PMID: &lt;searchLink fieldCode=&quot;PM&quot; term=&quot;%22407563961231366710%2E3389%2Ffpubh%2E2025%2E1494336%22&quot;&gt;407563961231366710.3389/fpubh.2025.1494336)&lt;/searchLink&gt;&lt;br /&gt;Guo, X., Li, N., Wang, H., Su, W., Song, Q., Liang, Q., Liang, M., Sun, C., Li, Y., Lowe, S., Bentley, R., Song, E. J., Zhou, Q., Ding, X., &amp; Sun, Y. (2022). Combined exposure to multiple metals on cardiovascular disease in NHANES under five statistical models. Environmental Research, 215(Pt 3), Article 114435. (PMID: &lt;searchLink fieldCode=&quot;PM&quot; term=&quot;%223617476110%2E1016%2Fj%2Eenvres%2E2022%2E114435%22&quot;&gt;3617476110.1016/j.envres.2022.114435)&lt;/searchLink&gt;&lt;br /&gt;Duan, W., Xu, C., Liu, Q., Xu, J., Weng, Z., Zhang, X., Basnet, T. B., Dahal, M., &amp; Gu, A. (2020). Levels of a mixture of heavy metals in blood and urine and all-cause, cardiovascular disease and cancer mortality: A population-based cohort study. Environmental Pollution, 263(Pt A), Article 114630. (PMID: &lt;searchLink fieldCode=&quot;PM&quot; term=&quot;%223361848110%2E1016%2Fj%2Eenvpol%2E2020%2E114630%22&quot;&gt;3361848110.1016/j.envpol.2020.114630)&lt;/searchLink&gt;&lt;br /&gt;Yim, G., Wang, Y., Howe, C. G., &amp; Romano, M. E. (2022). Exposure to metal mixtures in association with cardiovascular risk factors and outcomes: A scoping review. Toxics, 10(3), Article 116. (PMID: &lt;searchLink fieldCode=&quot;PM&quot; term=&quot;%2235324741895563710%2E3390%2Ftoxics10030116%22&quot;&gt;35324741895563710.3390/toxics10030116)&lt;/searchLink&gt;&lt;br /&gt;Udom, G. J., Iyaye, D., Oritsemuelebi, B., Nwanaforo, E., Bede-Ojimadu, O., Abdulai, P. M., Frazzoli, C, &amp; Orisakwe, O. E. (2025). Public health concerns of multifaceted exposures to metal and metalloid mixtures: A systematic review. Environmental Monitoring and Assessment, 197(5), 502. (PMID: &lt;searchLink fieldCode=&quot;PM&quot; term=&quot;%224017270610%2E1007%2Fs10661-025-13963-1%22&quot;&gt;4017270610.1007/s10661-025-13963-1)&lt;/searchLink&gt;&lt;br /&gt;He, Y., Zhou, X., Huang, W., Wu, Y., Zhang, Z., Jin, Y., Li, F., Chen, G., Tao, K., Zhan, Y., Zou, X., Wei, Q., Wei, X., &amp; Qiu, S. (2025). Cadmium exposure and advanced cardiovascular-kidney-metabolic syndrome: An integrated multi-organ perspective based on epidemiology and adverse outcome pathways. Ecotoxicology and Environmental Safety, 303, Article 118885. (PMID: &lt;searchLink fieldCode=&quot;PM&quot; term=&quot;%224081940210%2E1016%2Fj%2Eecoenv%2E2025%2E118885%22&quot;&gt;4081940210.1016/j.ecoenv.2025.118885)&lt;/searchLink&gt;&lt;br /&gt;Ozarde, Y., Purandare, D., Deshmukh, S., &amp; Gadhave, R. (2025). Heavy metals and cardiovascular health: Uncovering links and health challenges. Journal of Trace Elements in Medicine and Biology, 89, Article 127648. (PMID: &lt;searchLink fieldCode=&quot;PM&quot; term=&quot;%224022839910%2E1016%2Fj%2Ejtemb%2E2025%2E127648%22&quot;&gt;4022839910.1016/j.jtemb.2025.127648)&lt;/searchLink&gt;
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              Text: 2026 Oct 03
              Type: published
              Y: 2026
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