Circulating vitamin D, calcium and risk of cerebrovascular disease: a systematic review and meta-analysis
- 838 Downloads
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.
KeywordsVitamin D Calcium Cerebrovascular disease Meta-analysis
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.
- 1.Committee to Review Dietary Reference Intakes for Vitamin D and Calcium FaNB, Institute of Medicine. Dietary Reference Intakes for Calcium and Vitamin D. Washington: National Academy Press; 2010.Google Scholar
- 3.Gilbert R, Martin RM, Beynon R, Beynon R, Harris R, Savovic J, Zuccolo L, Bekkering GE, Fraser WD, Sterne JA, Metcalfe C. Associations of circulating and dietary vitamin D with prostate cancer risk: a systematic review and dose-response meta-analysis. Cancer Causes Control. 2011;22(3):319–40.PubMedCrossRefGoogle Scholar
- 4.Parker J, Hashmi O, Dutton D, Mavrodaris A, Stranges S, Kandala NB, Clarke A, Franco OH. Levels of vitamin D and cardiometabolic disorders: systematic review and meta-analysis. Maturitas. 2010; 65(3):225–36. Epub 2009 Dec 23.Google Scholar
- 6.Bolland MJ, Grey A, Avenell A, Gamble GD, Reid IR. Calcium supplements with or without vitamin D and risk of cardiovascular events: reanalysis of the women’s health initiative limited access dataset and meta-analysis. BMJ. 2011;19:342.Google Scholar
- 17.Stroup DF, Berlin JA, Morton SC, Olkin I, Williamson GD, Rennie D, Moher D, Becker BJ, Sipe TA, Thacker SB. Meta-analysis of observational studies in epidemiology: a proposal for reporting. Meta-analysis of observational studies in epidemiology (MOOSE) group. JAMA. 2000;283(15):2008–12.PubMedCrossRefGoogle Scholar
- 24.Anderson JL, May HT, Horne BD, Bair TL, Hall NL, Carlquist JF, Lappe DL. Intermountain heart collaborative (IHC) Study group. relation of vitamin D deficiency to cardiovascular risk factors, disease status, and incident events in a general healthcare population. Am J Cardiol. 2010;106(7):963–8.PubMedCrossRefGoogle Scholar
- 25.Drechsler C, Pilz S, Obermayer-Pietsch B, Verduijn M, Tomaschitz A, Krane V, Espe K, Dekker F, Brandenburg V, Marz W, Ritz E, Wanner C. Vitamin D deficiency is associated with sudden cardiac death, combined cardiovascular events, and mortality in haemodialysis patients. Eur Heart J. 2010;31(18):2253–61.PubMedCrossRefGoogle Scholar
- 29.Michos ED, Reiss JP, Post WS, Lutsey PL, Gottesman RF, Mosley TH, Sharrett AR, Melamed ML. 25-Hydroxyvitamin D deficiency is associated with fatal stroke among whites but not blacks: The NHANES-III linked mortality files. Nutrition 2012;1–5.Google Scholar
- 30.Bolland MJ, Bacon CJ, Horne AM, Mason BH, Ames RW, Wang TK, et al. Vitamin D insufficiency and health outcomes over 5 years in older women. Am J Clin Nutr. 2010;91(1):82–9.Google Scholar
- 31.Slinin Y, Blackwell T, Ishani A, Cummings SR, Ensrud KE. Serum calcium, phosphorus and cardiovascular events in post-menopausal women. Int J Cardiol. 2011;149(3):335–40.Google Scholar
- 37.Aihara K, Azuma H, Akaike M, Ikeda Y, Yamashita M, Sudo T, Hayashi H, Yamada Y, Endoh F, Fujimura M, Yoshida T, Yamaguchi H, Hashizume S, Kato M, Yoshimura K, Yamamoto Y, Kato S, Matsumoto T. Disruption of nuclear vitamin D receptor gene causes enhanced thrombogenicity in mice. J Biol Chem. 2004;279:35798–802.PubMedCrossRefGoogle Scholar