title: 25-hydroxyvitamin D and symptomatic ischemic stroke: an original study and meta-analysis.
abstract: OBJECTIVE
  We tested the hypothesis that low plasma concentrations of 25-hydroxyvitamin D are associated with increased risk of symptomatic ischemic stroke in the general population.
  
  
  METHODS
  We measured plasma 25-hydroxyvitamin D in 10,170 individuals from the general population, the Copenhagen City Heart Study. During 21 years of follow-up, 1,256 and 164 persons developed ischemic and hemorrhagic stroke, respectively. In a meta-analysis of ischemic stroke, we included 10 studies, 58,384 participants, and 2,644 events.
  
  
  RESULTS
  Stepwise decreasing plasma 25-hydroxyvitamin D concentrations were associated with stepwise increasing risk of ischemic stroke both as a function of seasonally adjusted percentile categories and as a function of clinical categories of 25-hydroxyvitamin D (p for trend ≤ 2 × 10(-3)). In a Cox regression model comparing individuals with plasma 25-hydroxyvitamin D concentrations between the 1st and 4th percentiles to individuals with 25-hydroxyvitamin D concentrations between the 50th and 100th percentiles, multivariate adjusted hazard ratio of ischemic stroke was 1.82 (95% confidence interval, 1.41-2.34). Comparing individuals with clinical categories of severe vitamin D deficiency (<25.0 nmol/l [<10.0 ng/ml]) to individuals with optimal vitamin D status (≥75.0 nmol/l [≥30.0 ng/ml]), the multivariate adjusted hazard ratio of ischemic stroke was 1.36 (1.09-1.70). 25-Hydroxyvitamin D concentrations were not associated with risk of hemorrhagic stroke. In a meta-analysis comparing lowest versus highest quartile of 25-hydroxyvitamin D concentrations, the multivariate adjusted odds ratio of ischemic stroke was 1.54 (1.43-1.65) with a corresponding hazard ratio of 1.46 (1.35-1.58) in prospective general population studies.
  
  
  CONCLUSIONS
  In this large population-based prospective study, we observed stepwise increasing risk of symptomatic ischemic stroke with decreasing plasma 25-hydroxyvitamin D concentrations. This finding was substantiated in a meta-analysis.
authors.affiliation: Department of Clinical Biochemistry, Herlev Hospital, Copenhagen University Hospital, Denmark.
authors.forename: Peter
authors.initials: P
authors.lastname: Brøndum-Jacobsen
authors.forename: Børge G
authors.initials: BG
authors.lastname: Nordestgaard
authors.forename: Peter
authors.initials: P
authors.lastname: Schnohr
authors.forename: Marianne
authors.initials: M
authors.lastname: Benn
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000097:blood; D002545:Brain Ischemia / Q000097:blood* / Q000175:diagnosis / Q000453:epidemiology*; D003718:Denmark / Q000453:epidemiology; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D011159:Population Surveillance / Q000379:methods; D011446:Prospective Studies; D012307:Risk Factors; D020521:Stroke / Q000097:blood* / Q000175:diagnosis / Q000453:epidemiology*; D014807:Vitamin D / Q000031:analogs & derivatives* / Q000097:blood
chemical_list: D015415:Biomarkers; D014807:Vitamin D; C104450:25-hydroxyvitamin D