The Relationship between the Urinary Cadmium Concentration and Cause-Specific Mortality in Subjects without Severe Renal Damage: A 35-Year Follow-Up Study in a Cadmium-Polluted Area of Japan

We evaluated the association between urinary cadmium concentration (uCd, μg/g Cr) and risk of cause-specific mortality according to urinary β2-microglobulin (MG) concentration. Participants were 1383 male and 1700 female inhabitants of the Cd-polluted Kakehashi River basin. The uCd and β2-MG were evaluated in a survey in 1981–1982, where those participants were followed-up over 35 years later. Among the participants with a urinary β2-MG < 1000, the hazard ratios (HRs) (95% confidence interval) for mortality were significantly higher in those with a uCd of ≥ 10.0 compared with < 5.0 for cardiovascular disease [HR 1.92 (1.08–3.40) for men, 1.71 (1.07–2.71) for women], pneumonia or influenza [2.10 (1.10–4.00) for men, 2.22 (1.17–4.19) for women], and digestive diseases [for men; 3.81 (1.49–9.74)]. The uCd was significantly associated with mortality from heart failure in women and digestive diseases in men, after adjustment for other causes of death using the Fine and Gray competing risk regression model. For participants with a urinary β2-MG of ≥ 1000, no significant association was observed between uCd and any major cause of death. In the absence of kidney damage, Cd may increase the risk of death from cardiovascular disease, pneumonia, and digestive diseases.

Urinary cadmium concentration and the risk of ischemic stroke

ObjectivesTo examine the association between urinary cadmium levels and the incidence of ischemic stroke and to explore possible effect modifications.MethodsA 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.ResultsThe 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).ConclusionsFindings 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.