Introduction:
Cadmium is a widespread toxic metal with potential cardiovascular effects, but establishing cadmium as a cardiovascular risk factor has been limited by the lack of data on its association with incident cardiovascular events.
Hypothesis:
We tested the hypothesis that urine cadmium concentrations would be associated with cardiovascular disease mortality and incidence.
Methods:
Prospective cohort study of 3,347 American Indian adults 45-74 years old without prevalent cardiovascular disease from Arizona, Oklahoma and North and South Dakota who participated in the Strong Heart Study (SHS) in 1989-91 and had urine cadmium measures available. Urine cadmium was measured using inductively coupled plasma mass spectrometry. Follow-up extended through December 30
th
2007.
Results:
We identified 1,028 cardiovascular events, including 372 deaths. After adjustment for known cardiovascular risk factors, the hazard ratios (95% CI) for cardiovascular and coronary heart disease mortality, comparing the 80
th
to the 20
th
percentiles of urine cadmium concentrations, were 1.43 (1.21, 1.69) and 1.33 (1.09, 1.62), respectively. The corresponding hazard ratios for incident cardiovascular disease, coronary heart disease, stroke, and heart failure were 1.16 (1.04, 1.29), 1.11 (0.98, 1.27), 1.50 (1.01, 2.22) and 1.22 (1.01, 1.47), respectively. The associations were similar in different study subgroups, including never-smokers. The figure shows increasing dose-response relations between urine cadmium concentrations and all cardiovascular disease mortality and incidence endpoints except for incident stroke.
Conclusions:
Urine cadmium, a biomarker of long-term exposure, was positively and consistently associated with cardiovascular disease mortality and incidence, overall and across subgroups. These findings support that cadmium exposure is a cardiovascular risk factor irrespective of the source of exposure. Efforts to reduce cadmium exposure in the population are needed.
All-Cause Morality and Cardiovascular Disease Mortality in Three American Indian Populations, Aged 45-74 Years, 1984-1988: The Strong Heart Study