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Metal mixture exposures and serum lipid levels in childhood: the Rhea mother-child cohort in Greece

Journal of Exposure Science & Environmental Epidemiology (2024)Cite this article

Abstract

Background

Growing evidence suggests that cardiovascular disease develops over the lifetime, often beginning in childhood. Metal exposures have been associated with cardiovascular disease and important risk factors, including dyslipidemia, but prior studies have largely focused on adult populations and single metal exposures.

Objective

To investigate the individual and joint impacts of multiple metal exposures on lipid levels during childhood.

Methods

This cross-sectional study included 291 4-year-old children from the Rhea Cohort Study in Heraklion, Greece. Seven metals (manganese, cobalt, selenium, molybdenum, cadmium, mercury, and lead) were measured in whole blood using inductively coupled plasma mass spectrometry. Serum lipid levels included total cholesterol, triglycerides, high-density lipoprotein (HDL) cholesterol, and low-density lipoprotein (LDL) cholesterol. To determine the joint and individual impacts of child metal exposures (log2-transformed) on lipid levels, Bayesian kernel machine regression (BKMR) was employed as the primary multi-pollutant approach. Potential effect modification by child sex and childhood environmental tobacco smoke exposure was also evaluated.

Results

BKMR identified a positive association between the metal mixture and both total and LDL cholesterol. Of the seven metals examined, selenium (median 90.6 [IQR = 83.6, 96.5] µg/L) was assigned the highest posterior inclusion probability for both total and LDL cholesterol. A difference in LDL cholesterol of 8.22 mg/dL (95% CI = 1.85, 14.59) was observed when blood selenium was set to its 75th versus 25th percentile, holding all other metals at their median values. In stratified analyses, the positive association between selenium and LDL cholesterol was only observed among boys or among children exposed to environmental tobacco smoke during childhood.

Impact statement

Growing evidence indicates that cardiovascular events in adulthood are the consequence of the lifelong atherosclerotic process that begins in childhood. Therefore, public health interventions targeting childhood cardiovascular risk factors may have a particularly profound impact on reducing the burden of cardiovascular disease. Although growing evidence supports that both essential and nonessential metals contribute to cardiovascular disease and risk factors, such as dyslipidemia, prior studies have mainly focused on single metal exposures in adult populations. To address this research gap, the current study investigated the joint impacts of multiple metal exposures on lipid concentrations in early childhood.

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Fig. 1: Joint associations of the metals with low-density lipoprotein at 4 years of age, estimated by BKMR (n = 291).

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Data availability

The datasets generated and analyzed during the current study are not publicly available due to the privacy of individuals that participated in the study. The data will be available on reasonable request to the Rhea Cohort Study.

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Acknowledgements

The Rhea project was financially supported by Horizon 2020—European Framework Programme for Research and Innovation, ATHLETE, the European Union (grant numbers EU FP6–2003-Food-3-NewGeneris, EU FP6. STREP Hiwate, EU FP7 ENV.2007.1.2.2.2. Project No 211250 Escape, EU FP7–2008-ENV-1.2.1.4 Envirogenomarkers, EU FP7-HEALTH-2009- single stage CHICOS, EU FP7 ENV.2008.1.2.1.6. Proposal No 226285 ENRIECO, EU- FP7- HEALTH-2012 Proposal No 308333 HELIX), and the Greek Ministry of Health. The present study was also funded by Karolinska Institutet and the Swedish Research Council (Project No. 2015-03655). LC was financially supported by NIEHS (grant numbers R01ES030691, R01ES029944, R01 ES030364, P30ES007048, R01ES016813), CGH is supported by a NIH Pathway to Independence Award (R00 ES030400). We would like to thank the Rhea cohort study participants, as well as our colleagues, medical, nursing, and research staff, for their contributions to this study.

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  1. These authors contributed equally: Leda Chatzi, Caitlin G. Howe.

Authors and Affiliations

  1. Department of Epidemiology, Geisel School of Medicine at Dartmouth, Dartmouth College, Lebanon, NH, USA

    Gyeyoon Yim, Megan E. Romano & Caitlin G. Howe

  2. Clinic of Preventive Medicine and Nutrition, Faculty of Medicine, University of Crete, Heraklion, Greece

    Katerina Margetaki

  3. Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden

    Maria Kippler

  4. Department of Social Medicine, Faculty of Medicine, University of Crete, Heraklion, Greece

    Marina Vafeiadi, Theano Roumeliotaki & Vicky Bempi

  5. Department of Population and Public Health Sciences, Division of Environmental Health, University of Southern California, Los Angeles, CA, USA

    Shohreh F. Farzan & Leda Chatzi

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Contributions

GY: Formal analysis, Visualization, Writing—original draft. KM: Data curation, Writing—review & editing. MER: Writing—review & editing. MK: Writing—review & editing. MV: Writing—review & editing. TR: Data curation, Writing—review & editing. VB: Investigation, Writing—review & editing. SFF: Conceptualization, Writing—review & editing. LC: Supervision, Funding acquisition, Writing—review & editing. CGH: Conceptualization, Supervision, Writing—review & editing.

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Yim, G., Margetaki, K., Romano, M.E. et al. Metal mixture exposures and serum lipid levels in childhood: the Rhea mother-child cohort in Greece. J Expo Sci Environ Epidemiol (2024). https://doi.org/10.1038/s41370-024-00674-x

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