Urinary cadmium concentration and the risk of ischemic stroke

Cheng Chen, Pengcheng Xun, Cari Tsinovoi, Leslie A. McClure, John Brockman, Leslie MacDonald, Mary Cushman, Jianwen Cai, Lisa Kamendulis, Jason Mackey, Ka He

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3 Scopus citations


OBJECTIVES: To examine the association between urinary cadmium levels and the incidence of ischemic stroke and to explore possible effect modifications. METHODS: A case-cohort study was designed nested in the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study, including 680 adjudicated incident cases of ischemic stroke and 2,540 participants in a randomly selected subcohort. Urinary creatinine-corrected cadmium concentration was measured at baseline. Multivariable-adjusted hazard ratios (HRs) and the corresponding 95% confidence intervals (CIs) were estimated with the Barlow weighting method for the Cox proportional hazards regression model. RESULTS: The median urinary cadmium concentration was 0.42 (interquartile range 0.27-0.68) μg/g creatinine. After adjustment for potential confounders, urinary cadmium was associated with increased incidence of ischemic stroke (quintile 5 vs quintile 1: HR 1.50, 95% CI 1.01-2.22, p for trend = 0.02). The observed association was more pronounced among participants in the lowest serum zinc tertile (tertile 3 vs tertile 1: HR 1.82, 95% CI 1.06-3.11, p for trend = 0.004, p for interaction = 0.05) but was attenuated and became nonsignificant among never smokers (tertile 3 vs tertile 1: never smokers: HR 1.27, 95% CI 0.80-2.03, p for trend = 0.29; ever smokers: HR 1.60, 95% CI 1.06-2.43, p for trend = 0.07, p for interaction = 0.51). CONCLUSIONS: Findings from this study suggest that cadmium exposure may be an independent risk factor for ischemic stroke in the US general population. Never smoking and maintaining a high serum zinc level may ameliorate the potential adverse effects of cadmium exposure.

Original languageEnglish (US)
Pages (from-to)e382-e391
Issue number4
StatePublished - Jul 24 2018
Externally publishedYes

ASJC Scopus subject areas

  • Clinical Neurology

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    Chen, C., Xun, P., Tsinovoi, C., McClure, L. A., Brockman, J., MacDonald, L., Cushman, M., Cai, J., Kamendulis, L., Mackey, J., & He, K. (2018). Urinary cadmium concentration and the risk of ischemic stroke. Neurology, 91(4), e382-e391. https://doi.org/10.1212/WNL.0000000000005856