25-Hydroxyvitamin D and symptomatic ischemic stroke: An Original Study and Meta-Analysis

Authors

  • Peter Brøndum-Jacobsen MD,

    1. Department of Clinical Biochemistry, Herlev Hospital, Copenhagen University Hospital
    2. Faculty of Health and Medical Sciences, University of Copenhagen
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  • Børge G. Nordestgaard MD, DMSc,

    1. Department of Clinical Biochemistry, Herlev Hospital, Copenhagen University Hospital
    2. Faculty of Health and Medical Sciences, University of Copenhagen
    3. Copenhagen City Heart Study, Bispebjerg Hospital, Copenhagen University Hospital
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  • Peter Schnohr MD, DMSc,

    1. Copenhagen City Heart Study, Bispebjerg Hospital, Copenhagen University Hospital
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  • Marianne Benn MD, PhD, DMSc

    Corresponding author
    1. Department of Clinical Biochemistry, Herlev Hospital, Copenhagen University Hospital
    2. Faculty of Health and Medical Sciences, University of Copenhagen
    3. Department of Clinical Biochemistry, Gentofte Hospital, Copenhagen University Hospital, Copenhagen, Denmark
    • Department of Clinical Biochemistry, Gentofte Hospital, Niels Andersens vej 65, DK-2900 Hellerup, Denmark
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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 (<25.0nmol/l [<10.0ng/ml]) to individuals with optimal vitamin D status (≥75.0nmol/l [≥30.0ng/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.

Interpretation:

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. ANN NEUROL 2013.

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