European Journal of Epidemiology

, Volume 27, Issue 8, pp 581–591 | Cite as

Circulating vitamin D, calcium and risk of cerebrovascular disease: a systematic review and meta-analysis

  • Rajiv Chowdhury
  • Sarah Stevens
  • Heather Ward
  • Susmita Chowdhury
  • Ayesha Sajjad
  • Oscar H. Franco
Review

Abstract

Available literature suggests that both vitamin D and calcium may be associated with a wide range of non-skeletal outcomes. However, epidemiological evidence supporting their individual associations with incident cerebrovascular disease is scarce. We conducted a systematic review and meta-analysis of prospective cohort studies, published before February 2012 and sought from MEDLINE, EMBASE, BIOSIS and the Science Citation Index databases, and reported cerebrovascular disease (defined as any fatal or non-fatal ischemic stroke, hemorrhagic stroke, cerebrovascular accident or transient ischemic attack) by circulating vitamin D (25-hydroxy vitamin D [25(OH)D] as active metabolite) and calcium levels. Two independent investigators abstracted information on 25(OH)D and calcium, cerebrovascular outcomes and other characteristics from selected studies. Relative risks (RRs) were pooled by both random and fixed effects meta-analyses and were further examined under different study-level characteristics. Publication bias was assessed with funnel plots and Egger’s asymmetry test. From 5,778 initial references, nine unique prospective cohort studies met our inclusion criteria. Seven studies (involving 47,809 participants and 926 cerebrovascular events) focused on circulating 25(OH)D and 3 reported on circulating calcium (22,577 participants and 727 events). For 25(OH)D, in a comparison of individuals in the top third versus those in the bottom third at baseline, the combined RR for cerebrovascular disease, adjusted for several conventional risk factors, was 0.60 (95 % CI 0.48, 0.72). The corresponding RR in the prospective studies that reported on baseline circulating calcium levels for cerebrovascular disease was 1.40 (95 % CI 1.19, 1.64). There was no apparent evidence of heterogeneity or publication bias among included studies. Available data indicate that higher circulating level of vitamin D is associated with a decreased risk of cerebrovascular disease. Conversely, higher circulating calcium concentration is associated with an increased risk of cerebrovascular disease.

Keywords

Vitamin D Calcium Cerebrovascular disease Meta-analysis 

Notes

Acknowledgments

Dr Chowdhury has been a recipient of the Gates Cambridge Ph.D. scholarship; and Prof. Franco is the recipient of a grant from Pfizer Nutrition to establish a new center on ageing research focused on nutrition and lifestyle, ErasmusAGE. Dr Sajjad works within ErasmusAGE.

Supplementary material

10654_2012_9729_MOESM1_ESM.docx (24 kb)
Supplementary material 1 (DOC 25 kb)

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Copyright information

© Springer Science+Business Media B.V. 2012

Authors and Affiliations

  • Rajiv Chowdhury
    • 1
  • Sarah Stevens
    • 2
  • Heather Ward
    • 3
  • Susmita Chowdhury
    • 4
  • Ayesha Sajjad
    • 5
  • Oscar H. Franco
    • 1
    • 5
  1. 1.Department of Public Health and Primary CareUniversity of CambridgeCambridgeUK
  2. 2.NHS Midlands and EastCambridgeUK
  3. 3.Department of Epidemiology School of Public HealthImperial College LondonLondonUK
  4. 4.Foundation for Genomics and Population HealthCambridgeUK
  5. 5.Department of Epidemiology, Erasmus MCUniversity Medical Center RotterdamRotterdamThe Netherlands

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