Cadmium, Carotid Atherosclerosis, and Incidence of Ischemic Stroke

BACKGROUND Exposure to cadmium has been associated with carotid plaques, inflammation in carotid plaques, and increased risk of ischemic stroke. This study examined the separate and interacting effects of blood cadmium levels and carotid plaques on the risk of incident ischemic stroke. METHODS AND RESULTS Cadmium levels were measured in 4156 subjects (39.2% men; mean±SD age 57.3±5.9 years) without history of stroke, from the Malmö Diet and Cancer cohort. The right carotid artery was examined using B-mode ultrasound examination at baseline. Incidence of ischemic stroke was monitored over a mean follow-up of 16.7 years. Carotid plaque was present in 34.5% of participants. Cadmium was significantly higher in subjects with plaque (mean±SD: 0.53±0.58 μg/L versus 0.42±0.49 μg/L; P<0.001). A total of 221 subjects had ischemic stroke during the follow-up. Incidence of ischemic stroke was associated both with carotid plaque (hazard ratio 1.44, 95% confidence interval, 1.09-1.90, P=0.009) and cadmium (hazard ratio for quartile [Q] 4 versus Q1-3: 1.95, confidence interval, 1.33-2.85, P=0.001), after adjustment for risk factors. There was a significant interaction between cadmium and plaque with respect to risk of ischemic stroke (P=0.011). Adjusted for risk factors, subjects with plaque and cadmium in Q4 had a hazard ratio of 2.88 (confidence interval, 1.79-4.63) for ischemic stroke, compared with those without plaque and cadmium in Q1 to Q3. CONCLUSIONS Cadmium was associated with incidence of ischemic stroke, both independently and in synergistic interaction with carotid plaques. This supports the hypothesis that cadmium promotes vulnerability of carotid plaques, thereby increasing the risk of rupture and ischemic stroke.