title: Circulating 25-hydroxy-vitamin D and risk of cardiovascular disease: a meta-analysis of prospective studies.
abstract: BACKGROUND
  Vitamin D status has been linked to the risk of cardiovascular disease (CVD). However, the optimal 25-hydroxy-vitamin D (25[OH]-vitamin D) levels for potential cardiovascular health benefits remain unclear.
  
  
  RESULTS
  We searched MEDLINE and EMBASE from 1966 through February 2012 for prospective studies that assessed the association of 25(OH)-vitamin D concentrations with CVD risk. A total of 24 articles met our inclusion criteria, from which 19 independent studies with 6123 CVD cases in 65 994 participants were included for a meta-analysis. In a comparison of the lowest with the highest 25(OH)-vitamin D categories, the pooled relative risk was 1.52 (95% confidence interval, 1.30-1.77) for total CVD, 1.42 (95% confidence interval, 1.19-1.71) for CVD mortality, 1.38 (95% confidence interval, 1.21-1.57) for coronary heart disease, and 1.64 (95% confidence interval, 1.27-2.10) for stroke. These associations remained strong and significant when analyses were limited to studies that excluded participants with baseline CVD and were better controlled for season and confounding. We used a fractional polynomial spline regression analysis to assess the linearity of dose-response association between continuous 25(OH)-vitamin D and CVD risk. The CVD risk increased monotonically across decreasing 25(OH)-vitamin D below ≈60 nmol/L, with a relative risk of 1.03 (95% confidence interval, 1.00-1.06) per 25-nmol/L decrement in 25(OH)-vitamin D.
  
  
  CONCLUSIONS
  This meta-analysis demonstrated a generally linear, inverse association between circulating 25(OH)-vitamin D ranging from 20 to 60 nmol/L and risk of CVD. Further research is needed to clarify the association of 25(OH)-vitamin D higher than 60 nmol/L with CVD risk and assess causality of the observed associations.
authors.affiliation: Brigham and Women’s Hospital, Boston, MA 02215, USA. luwang@rics.bwh.harvard.edu
authors.forename: Lu
authors.initials: L
authors.lastname: Wang
authors.forename: Yiqing
authors.initials: Y
authors.lastname: Song
authors.forename: Joann E
authors.initials: JE
authors.lastname: Manson
authors.forename: Stefan
authors.initials: S
authors.lastname: Pilz
authors.forename: Winfried
authors.initials: W
authors.lastname: März
authors.forename: Karl
authors.initials: K
authors.lastname: Michaëlsson
authors.forename: Annamari
authors.initials: A
authors.lastname: Lundqvist
authors.forename: Simerjot K
authors.initials: SK
authors.lastname: Jassal
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Barrett-Connor
authors.forename: Cuilin
authors.initials: C
authors.lastname: Zhang
authors.forename: Charles B
authors.initials: CB
authors.lastname: Eaton
authors.forename: Heidi T
authors.initials: HT
authors.lastname: May
authors.forename: Jeffrey L
authors.initials: JL
authors.lastname: Anderson
authors.forename: Howard D
authors.initials: HD
authors.lastname: Sesso
mesh_terms: D015415:Biomarkers / Q000097:blood; D002318:Cardiovascular Diseases / Q000097:blood / Q000453:epidemiology* / Q000401:mortality; D006801:Humans; D016014:Linear Models; D016017:Odds Ratio; D011379:Prognosis; D011446:Prospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D014807:Vitamin D / Q000031:analogs & derivatives* / Q000097:blood; D014808:Vitamin D Deficiency / Q000097:blood / Q000453:epidemiology* / Q000401:mortality
chemical_list: D015415:Biomarkers; D014807:Vitamin D; C104450:25-hydroxyvitamin D