Long-term cadmium exposure and fractures, cardiovascular disease, and mortality in a prospective cohort of women

Background: Cadmium (Cd) is a toxic metal, which the non-smoking population is mainly exposed to through diet. Current health-based guidance values are based on renal toxicity; however, emerging evidence suggests that bone and the cardiovascular system might be more sensitive to Cd exposure. Objective: To assess the association of urinary Cd (U-Cd) with incidence of fractures, myocardial infarction, heart failure, ischemic stroke and mortality in postmenopausal women. Methods: We used data from 4024 women, aged 56-85 in the population-based prospective Swedish Mammography Cohort-Clinical. U-Cd was measured by ICP-MS at baseline (2004-2009) and categorized into tertiles. Incident cases of the outcomes were ascertained via register linkage through 2019. Multivariable-adjusted hazard ratios (HR) and 95% confidence intervals (CI) were estimated using Cox regression. Results: The median U-Cd at baseline was 0.33 mu g/g creatinine (cr) (5-95 percentiles 0.15-0.77). We ascertained the following incident cases: 903 first fracture of any type, 149 myocardial infarction, 174 heart failure, 162 ischemic stroke and 545 total deaths during the approximately 11 years of follow-up. U-Cd was dose-dependently associated with risk of any fracture (HR: 1.20, 95% CI: 1.01 to 1.43, ptrend: 0.04) and all-cause mortality (HR: 1.38, 95% CI: 1.10 to 1.74, ptrend: <0.01) when comparing the highest tertile of U-Cd (median 0.54 mu g/g cr) with the lowest (median 0.20 mu g/g cr). No clear associations were observed for myocardial infarction, heart failure or stroke. Discussion: Long-term Cd exposure might be associated with risk of fractures and all-cause mortality at lower levels than previously suggested.