Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2022 Mar 1;10(3):116.
doi: 10.3390/toxics10030116.

Exposure to Metal Mixtures in Association with Cardiovascular Risk Factors and Outcomes: A Scoping Review

Affiliations

Exposure to Metal Mixtures in Association with Cardiovascular Risk Factors and Outcomes: A Scoping Review

Gyeyoon Yim et al. Toxics. .

Abstract

Since the National Institute of Environmental Health Sciences (NIEHS) declared conducting combined exposure research as a priority area, literature on chemical mixtures has grown dramatically. However, a systematic evaluation of the current literature investigating the impacts of metal mixtures on cardiovascular disease (CVD) risk factors and outcomes has thus far not been performed. This scoping review aims to summarize published epidemiology literature on the cardiotoxicity of exposure to multiple metals. We performed systematic searches of MEDLINE (PubMed), Scopus, and Web of Science to identify peer-reviewed studies employing statistical mixture analysis methods to evaluate the impact of metal mixtures on CVD risk factors and outcomes among nonoccupationally exposed populations. The search was limited to papers published on or after 1998, when the first dedicated funding for mixtures research was granted by NIEHS, through 1 October 2021. Twenty-nine original research studies were identified for review. A notable increase in relevant mixtures publications was observed starting in 2019. The majority of eligible studies were conducted in the United States (n = 10) and China (n = 9). Sample sizes ranged from 127 to 10,818. Many of the included studies were cross-sectional in design. Four primary focus areas included: (i) blood pressure and/or diagnosis of hypertension (n = 15), (ii) risk of preeclampsia (n = 3), (iii) dyslipidemia and/or serum lipid markers (n = 5), and (iv) CVD outcomes, including stroke incidence or coronary heart disease (n = 8). The most frequently investigated metals included cadmium, lead, arsenic, and cobalt, which were typically measured in blood (n = 15). The most commonly utilized multipollutant analysis approaches were Bayesian kernel machine regression (BKMR), weighted quantile sum regression (WQSR), and principal component analysis (PCA). To our knowledge, this is the first scoping review to assess exposure to metal mixtures in relation to CVD risk factors and outcomes. Recommendations for future studies evaluating the associations of exposure to metal mixtures with risk of CVDs and related risk factors include extending environmental mixtures epidemiologic studies to populations with wider metals exposure ranges, including other CVD risk factors or outcomes outside hypertension or dyslipidemia, using repeated measurement of metals to detect windows of susceptibility, and further examining the impacts of potential effect modifiers and confounding factors, such as fish and seafood intake.

Keywords: blood pressure; cardiovascular diseases; dyslipidemia; hypertension; metal mixtures; preeclampsia.

PubMed Disclaimer

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Flow chart of literature review and study selection for papers published between 1998 through 1 October 2021.
Figure 2
Figure 2
Number of included studies published by year and multi-pollutant approach. Note: Some studies included multiple cardiovascular disease (CVD) related outcomes or mixture analysis methods.
Figure 3
Figure 3
Heat map of metals and cardiovascular disease (CVD) risk factors or outcomes in the included studies. Numbers represent the number of reviewed publications corresponding to each metal (columns) and CVD risk factors or outcomes (rows). Note: The sum of the numbers presented here exceed the total number of selected studies (n = 29), as each study included a minimum of three metals within their mixtures. Some studies also evaluated more than one CVD-related outcome or risk factor, including stroke, coronary heart disease, and myocardial infarction; blood pressure; diagnosis of hypertension, preeclampsia, and dyslipidemia; and levels of lipid serum or blood lipid markers.

Similar articles

Cited by

References

    1. Cardiovascular Diseases. [(accessed on 9 September 2021)]. Available online: https://www.who.int/westernpacific/health-topics/cardiovascular-diseases.
    1. Cardiovascular Disease, Chronic Kidney Disease, and Diabetes Mortality Burden of Cardio-Metabolic Risk Factors between 1980 and 2010: Comparative Risk Assessment. Lancet Diabetes Endocrinol. 2014;2:634–647. doi: 10.1016/S2213-8587(14)70102-0. - DOI - PMC - PubMed
    1. Briffa J., Sinagra E., Blundell R. Heavy Metal Pollution in the Environment and Their Toxicological Effects on Humans. Heliyon. 2020;6:e04691. doi: 10.1016/j.heliyon.2020.e04691. - DOI - PMC - PubMed
    1. Chowdhury R., Ramond A., O’Keeffe L.M., Shahzad S., Kunutsor S.K., Muka T., Gregson J., Willeit P., Warnakula S., Khan H., et al. Environmental Toxic Metal Contaminants and Risk of Cardiovascular Disease: Systematic Review and Meta-Analysis. BMJ. 2018;362:k3310. doi: 10.1136/bmj.k3310. - DOI - PMC - PubMed
    1. Alissa E.M., Ferns G.A. Heavy Metal Poisoning and Cardiovascular Disease. J. Toxicol. 2011;2011:870125. doi: 10.1155/2011/870125. - DOI - PMC - PubMed

Publication types

LinkOut - more resources