Editors' note: Urinary cadmium concentration and the risk of ischemic stroke

Abstract

In the article “Urinary cadmium concentration and the risk of ischemic stroke,” Drs. Chen et al. reported an increased incidence of ischemic stroke in participants with higher baseline urinary cadmium concentration in a case–cohort study nested with the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study, with the association attenuated among those who never smoked or who had a higher serum zinc level. In response, Dr. Kawada expresses some concerns and an apparent paradox: the lower hazard reported for carotid focal plaque with higher urinary cadmium in a separate study, despite the known increased risk of stroke with carotid atherosclerosis; the need to clarify the dose–response relationship between urinary cadmium and ischemic stroke as modified by smoking status, given that smoking is a major contributor to urinary cadmium levels; and the need to account for kidney function in the analyses. In their reply, while acknowledging the need for further studies of cadmium toxicity, authors He and Chen counter that the inverse correlation between baseline cadmium levels and carotid focal plaque in the separate study was biologically implausible and contrary to the main findings of the study. They also note that sensitivity analyses were performed to address confounding by smoking status and kidney function, and that these yielded similar results. In the article “Urinary cadmium concentration and the risk of ischemic stroke,” Drs. Chen et al. reported an increased incidence of ischemic stroke in participants with higher baseline urinary cadmium concentration in a case–cohort study nested with the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study, with the association attenuated among those who never smoked or who had a higher serum zinc level. In response, Dr. Kawada expresses some concerns and an apparent paradox: the lower hazard reported for carotid focal plaque with higher urinary cadmium in a separate study, despite the known increased risk of stroke with carotid atherosclerosis; the need to clarify the dose–response relationship between urinary cadmium and ischemic stroke as modified by smoking status, given that smoking is a major contributor to urinary cadmium levels; and the need to account for kidney function in the analyses.