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

ABSTRACT

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 µg/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 µg/g cr) with the lowest (median 0.20 µg/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.