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

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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.

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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.

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Authors and Affiliations

  1. Department of Public Health and Primary Care, University of Cambridge, Cambridge, CB1 8RN, UK

    Rajiv Chowdhury & Oscar H. Franco

  2. NHS Midlands and East, Cambridge, CB21 5XB, UK

    Sarah Stevens

  3. Department of Epidemiology School of Public Health, Imperial College London, London, UK

    Heather Ward

  4. Foundation for Genomics and Population Health, Cambridge, CB1 8RN, UK

    Susmita Chowdhury

  5. Department of Epidemiology, Erasmus MC, University Medical Center Rotterdam, Office Ee 21–79, PO Box 2040, 3000 CA, Rotterdam, The Netherlands

    Ayesha Sajjad & Oscar H. Franco

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  1. Rajiv Chowdhury
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Correspondence to Oscar H. Franco.

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Appendices

Appendix 1

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Table 2 PRISMA 2009 check-list
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Appendix 2: Literature search strategy

Published studies were identified through electronic searches not limited to the English language using MEDLINE, EMBASE, BIOSIS and the Science Citation Index databases. Electronic searches were supplemented by scanning reference lists of articles identified for all relevant studies (including review articles), by hand searching of relevant journals and by correspondence with study investigators. The computer-based searches combined search terms related to vitamin D, calcium, cerebrovascular disease or stroke without language restriction.

(i) MEDLINE strategy to identify relevant exposures: (“vitamin d”[Mesh] OR “vitamin d”[All Fields] OR “ergocalciferols”[Mesh] OR “ergocalciferols”[All Fields]) OR (“calcium”[Mesh] OR “calcium”[All Fields]) OR “Vitamin D”[Mesh] OR “Vitamin D Deficiency”[Mesh] OR “Calcium”[Mesh]).

(ii) MEDLINE strategy to identify relevant disease outcomes: (“Stroke”[MeSH] OR “cerebrovascular disorders”[MesH] OR “cerebrovascular”[All Fields] OR “Cerebral Infarction”[Mesh] OR “ischaemic stroke” [All Fields] OR “ischemic stroke”[All Fields] OR “Brain Ischemia”[Mesh] OR “Intracranial Arteriosclerosis”[Mesh] OR “intracranial hemorrhages”[MesH] OR “hemorrhagic stroke”[All Fields] OR “ischemic attack, transient”[MeSH]).

Parts (i) and (ii) were combined using ‘AND’ to search MEDLINE. Each part was specifically translated for searching alternative databases.

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Chowdhury, R., Stevens, S., Ward, H. et al. Circulating vitamin D, calcium and risk of cerebrovascular disease: a systematic review and meta-analysis. Eur J Epidemiol 27, 581–591 (2012). https://doi.org/10.1007/s10654-012-9729-z

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