Calcium Intake and Serum Calcium Level in Relation to the Risk of Ischemic Stroke: Findings from the REGARDS Study

Background and Purpose Data on the association between calcium (Ca) and ischemic stroke are sparse and inconsistent. This study aimed to examine Ca intake and serum Ca levels in relation to risk of ischemic stroke. Methods The primary analysis included 19,553 participants from the Reasons for Geographic And Racial Differences in Stroke (REGARDS) study. A subcohort was randomly selected to create a case-cohort study (n=3,016), in which serum Ca levels were measured. Ischemic stroke cases were centrally adjudicated by physicians based on medical records. Cox proportional hazards regression for the cohort and weighted Cox proportional hazard regression with robust sandwich estimation method for the case-cohort analysis with adjustment for potential confounders were performed. Results During a mean 8.3-year follow-up, 808 incident cases of ischemic stroke were documented. Comparing the highest quintile to the lowest, a statistically significant inverse association was observed between total Ca intake and risk of ischemic stroke (hazard ratio [HR], 0.72; 95% confidence interval [CI], 0.55 to 0.95; Plinear-trend=0.183); a restricted cubic spline analysis indicated a threshold effect like non-linear association of total Ca intake with ischemic stroke (Pnon-linear=0.006). In the case-cohort, serum Ca was inversely associated with the risk of ischemic stroke. Compared to the lowest, the highest quintile of serum Ca had a 27% lower risk of ischemic stroke (HR, 0.73; 95% CI, 0.53 to 0.99; Plinear-trend=0.013). Observed associations were mainly mediated by type 2 diabetes, hypertension, and cholesterol. Conclusions These findings suggest that serum Ca has inverse and Ca intake has threshold effect like association with risk of ischemic stroke.