Urinary cadmium and mortality from all causes, cancer and cardiovascular disease in the general population: systematic review and meta-analysis of cohort studies

Background: Cadmium is a toxic heavy metal distributed in the environment. We conducted a systematic review and meta-analysis to examine the association between urinary cadmium concentration and mortality from all causes, cancer and cardiovascular disease (CVD) in the general population.

Methods: Studies were identified by searching PubMed and Embase (to 30 March 2015) and the reference lists of retrieved articles. We included prospective studies that reported hazard ratios (HR) with 95% confidence intervals (CI) for the association between urinary cadmium concentration and all-cause, cancer or CVD mortality. A random-effects model was used to combine study-specific results.

Results: Nine cohort studies, including 5600 deaths from all causes, 1332 deaths from cancer and 1715 deaths from CVD, were eligible for inclusion in the meta-analysis. The overall HRs for the highest vs lowest category of urinary cadmium were1.44 (95% CI, 1.25-1.64; I(2 )= 40.5%) for all-cause mortality (six studies), 1.39 (95% CI, 0.96-1.99; I(2 )= 75.9%) for cancer mortality (four studies) and 1.57 (95% CI, 1.27-1.95; I(2 )= 34.0%) for CVD mortality (five studies). In an analysis restricted to six cohort studies conducted in populations with a mean urinary cadmium concentration of ≤1 µg/g creatinine, the HRs were 1.38 (95% CI, 1.17-1.63; I(2 )= 48.3%) for all-cause mortality, 1.56 (95% CI, 0.98-2.47; I(2 )= 81.0%) for cancer mortality and 1.50 (95% CI, 1.18-1.91; I(2 )= 38.2%) for CVD mortality.

Conclusions: Even at low-level exposure, cadmium appears to be associated with increased mortality. Further large prospective studies of cadmium exposure and mortality are warranted.