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Association between environmental cadmium exposure and increased mortality in the U.S. National Health and Nutrition Examination Survey (1999–2018)

Journal of Exposure Science & Environmental Epidemiology volume 33, pages 874–882 (2023)Cite this article

Abstract

Background

Cadmium (Cd) is toxic to human health and increases overall mortality. In this study, we investigated the association between Cd exposure and all-cause, cardiovascular (CVD), and cancer mortality in the general population and the mediating effect of smoking on these association.

Methods

We used data from U.S. National Health and Nutrition Examination Survey for 1999–2018. To evaluate the hazard ratio (HR) for mortality, a multiple Cox regression analysis was conducted by adjusting for age, sex, race/ethnicity, body mass index, smoking, alcohol, hypertension, diabetes, hyperlipidemia, and history of CVD and cancer. A causal mediation analysis was performed to estimate the effects of smoking.

Results

Among the 31,637 subjects, 5452 (12.3%) died. Blood Cd concentrations were significantly associated with all-cause (HR 1.473, 95% confidence interval [CI] 1.403–1.546, p < 0.001), CVD (HR 1.445, 95% CI 1.344–1.554, p < 0.001), and cancer (HR 1.496, 95% CI 1.406–1.592, p < 0.001) mortality. Urinary Cd concentrations were also significantly associated with them. Using feature selection via machine learning, the importance of Cd in all-cause and cancer mortality was second only to age. The association between Cd concentrations and all-cause mortality was significant in both ever-smokers and never-smokers. The mediating effect of smoking was estimated at 32%, whereas a large proportion (68%) remained a direct effect of Cd. In a subgroup analysis of subjects with cancer history, blood Cd concentrations were significantly associated with cancer-related deaths in those with a history of breast, gastrointestinal, and skin cancers.

Conclusion

High Cd exposure is an important risk factor for all-cause, CVD, and cancer mortality among the general population. Cd exposure increased the risk of death even in never-smokers, and its effects unrelated to smoking were substantial, suggesting the importance of regulating other sources of Cd exposure such as food and water.

Impact Statement

Using national large-scale data, we found that low-level environmental exposure to cadmium significantly increased the risk of all-cause, cardiovascular, and cancer mortality in the general population even after adjusting for several risk factors. Although smoking is a major source of cadmium exposure, cadmium was nevertheless significantly associated with all-cause mortality in never-smokers, and the mediating effect of smoking on this association was only 32%. Hence, other sources of cadmium exposure such as food and water may be important.

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Fig. 1: Blood/urinary Cd concentrations and mortality.
Fig. 2: Feature importance on all-cause, CVD, and cancer mortality.

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Data availability

The dataset supporting the conclusions of this article is available in the CDC repository [National Health and Nutrition Examination Survey in https://www.cdc.gov/nchs/nhanes/index.htm].

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Funding

This research was supported by a grant from the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (grant number: HI19C1194).

Author information

Authors and Affiliations

  1. Division of Endocrinology and Metabolism, Department of Internal Medicine, Hallym University College of Medicine, Chuncheon, Republic of Korea

    Shinje Moon, Junghoon Lee & Jae Myung Yu

  2. Department of Internal Medicine, Chung-Ang University College of Medicine, Seoul, Republic of Korea

    Hoonsung Choi

  3. Department of Environmental Health Sciences, Soonchunhyang University, Asan, Republic of Korea

    Sohyeon Choi & Jeongim Park

  4. Graduate School of Public Health, Seoul National University, Seoul, Republic of Korea

    Kyungho Choi, Ejin Kim & Ho Kim

  5. Institute of Health and Environment, Graduate School of Public Health, Seoul National University, Seoul, Republic of Korea

    Kyungho Choi, Ejin Kim & Ho Kim

  6. Seoul National University Hospital Healthcare System Gangnam Center, Seoul, Republic of Korea

    Min Joo Kim

  7. Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea

    Min Joo Kim & Young Joo Park

  8. Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, Seoul National University, Seoul, Republic of Korea

    Young Joo Park

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Contributions

SM was responsible for conceptualization, methodology, validation, formal analysis, investigation, resources, data curation, visualization, writing—original draft, and writing—review and editing. JL was responsible for methodology, data curation, and visualization. JMY was responsible for methodology, validation, and supervision. HC was responsible for methodology, data curation, and visualization. SC was responsible for methodology, data curation, and visualization. JP was responsible for methodology, data curation, and visualization. KC was responsible for methodology, validation, supervision, and funding acquisition. EK was responsible for data curation and visualization. HC was responsible for methodology, validation, supervision, and funding acquisition. MJK was responsible for methodology, validation, supervision, writing- original draft, writing- review and editing, and project administration. YJP was responsible for methodology, validation, supervision, project administration, and funding acquisition.

Corresponding author

Correspondence to Min Joo Kim.

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The authors declare no competing interests.

Ethical approval

All U.S. NHANES protocols were approved by the Research Ethics Review Board of the National Center for Health Statistics, U.S. Centers for Disease Control and Prevention (NCHS IRB/ERB Protocol Number: 1999–2004, Protocol #98–12; 2005–2010, Protocol #2005–06; 2011–2016, Protocol #2011–17). All patients provided written informed consent.

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Moon, S., Lee, J., Yu, J.M. et al. Association between environmental cadmium exposure and increased mortality in the U.S. National Health and Nutrition Examination Survey (1999–2018). J Expo Sci Environ Epidemiol 33, 874–882 (2023). https://doi.org/10.1038/s41370-023-00556-8

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