Serum Zinc Levels and Incidence of Ischemic Stroke The Reasons for Geographic and Racial Differences in Stroke Study

Background and Purpose: Despite zinc's role as an antioxidant and anti-inflammatory agent, prospective studies relating zinc levels to ischemic stroke risk are lacking. To examine the association between serum zinc levels and incidence of ischemic stroke in a US population. Methods: Using a case-cohort study nested within the Reasons for Geographic and Racial Differences in Stroke cohort, participants were randomly selected from the Reasons for Geographic and Racial Differences in Stroke cohort to generate a sub-cohort (n=2346). All incident ischemic stroke cases as of September 2012 (n=660) were included, with 62 incident cases overlapping in the sub-cohort. Serum zinc levels were measured at baseline. Barlow-weighted Cox's proportional hazards regression models were used to calculate multivariable-adjusted hazard ratios and the corresponding 95% CI of ischemic stroke by serum zinc levels. Results: The median zinc level for the sub-cohort was 121.19 mu g/dL (interquartile range, 104.86-140.39 mu g/dL). Serum zinc levels were inversely associated with incidence of ischemic stroke after adjustment for potential confounders (quartile 4 versus quartile 1: hazard ratio, 0.78 [95% CI, 0.61-0.98], P=0.03 for trend). When stratified by prespecified factors (sex, race, region), only sex showed a significant modification (P=0.03 for interaction). The inverse association was more pronounced among females (quartile 4 versus quartile 1: hazard ratio, 0.58 [95% CI, 0.41-0.84], P<0.01 for trend) than males (quartile 4 versus quartile 1: hazard ratio, 1.08 [95% CI, 0.78-1.51], P=0.92 for trend). Conclusions: Serum zinc concentration was inversely associated with incidence of ischemic stroke, especially among women, indicating that low zinc levels may be a risk factor for ischemic stroke.