title: Prime mover or fellow traveller: 25-hydroxy vitamin D's seasonal variation, cardiovascular disease and death in the Scottish Heart Health Extended Cohort (SHHEC).
abstract: BACKGROUND
  Theoretical links between seasonal lack of sunlight, hypovitaminosis D and excess cardiovascular disease and death prompted our adding novel to conventional cohort analyses.
  
  
  METHODS
  We tested three postulates on 13,224 Scottish Heart Health Extended Cohort participants, assayed for 25-hydroxyvitamin D (25OHD) and followed for 22 years. (i) Endpoints enumerated by month of occurrence mirror annual seasonal oscillation in 25OHD. (ii) Endpoint seasonality is increased in people with below median 25OHD. (iii) Low 25OHD predicts endpoints independently of major risk factors.
  
  
  RESULTS
  Baseline median 25OHD level was 36.4 (other quartiles 26.7, 51.7) nmol/l. The March trough was half the August peak, both well after seasonal solstices. (i) There was no demonstrable monthly variation in First Cardiovascular Event (n = 3307). Peaks and troughs for All Death and Cardiovascular Death (n = 2987, 1350) were near the solstices, earlier than extremes of 25OHD. (ii) Endpoint variability showed no difference between those above and below median 25OHD. (iii) Cox model hazard ratios (HR), by decreasing 25OHD, increased modestly and nonspecifically for all endpoints examined, with no threshold, the gradients diminishing by ∼ : 60% following multiple adjustment. For Cardiovascular Disease, HR, by 20 (∼ SD) nmol/l decrease, =1.224 (1.175, 1.275) adjusted for age and sex; additionally adjusted for family history, deprivation index, smoking, systolic blood pressure, total and HDL cholesterol, =1.093 (1.048, 1.139); All Deaths = 1.238 (1.048, 1.139) and 1.098 (1.050, 1.149). 25OHD made no independent contribution to cardiovascular discrimination and reclassification.
  
  
  CONCLUSIONS
  Our analyses challenge vitamin D's alleged role as major prime mover in cardiovascular disease and mortality.
authors.affiliation: Institute of Cardiovascular Research, University of Dundee, Dundee, UK, h.tunstallpedoe@dundee.ac.uk.
authors.forename: Hugh
authors.initials: H
authors.lastname: Tunstall-Pedoe
authors.affiliation: Institute of Cardiovascular Research, University of Dundee, Dundee, UK, Nuffield Department of Public Health, Oxford University, Oxford, UK, George Institute for Global Health, University of Sydney, Sydney, NSW, Australia.
authors.forename: Mark
authors.initials: M
authors.lastname: Woodward
authors.affiliation: UK Clinical Research Collaboration Centre of Excellence for Public Health, Queens University Belfast, Belfast, UK, University Heart Center Hamburg, Clinic for General and Interventional Cardiology, Hamburg, Germany.
authors.forename: Maria
authors.initials: M
authors.lastname: Hughes
authors.affiliation: Centre for Public Health Nutrition Research, University of Dundee, Dundee, UK and.
authors.forename: Annie
authors.initials: A
authors.lastname: Anderson
authors.affiliation: Institute of Cardiovascular Research, University of Dundee, Dundee, UK.
authors.forename: Gwen
authors.initials: G
authors.lastname: Kennedy
authors.affiliation: Institute of Cardiovascular Research, University of Dundee, Dundee, UK.
authors.forename: Jill
authors.initials: J
authors.lastname: Belch
authors.affiliation: National Institute for Health and Welfare, Helsinki, Finland.
authors.forename: Kari
authors.initials: K
authors.lastname: Kuulasmaa
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002318:Cardiovascular Diseases / Q000401:mortality*; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D012307:Risk Factors; D012606:Scotland / Q000453:epidemiology; D012621:Seasons; D014807:Vitamin D / Q000031:analogs & derivatives* / Q000097:blood; D014808:Vitamin D Deficiency / Q000453:epidemiology*
chemical_list: D014807:Vitamin D; C104450:25-hydroxyvitamin D
keywords: Vitamin D; cardiovascular disease; causality; cohort study; mortality; seasonality