title: Prospective study of seasonal patterns in hemostatic factors in older men and their relation to excess winter coronary heart disease deaths.
abstract: BACKGROUND
  In England and Wales, approximately 20% extra deaths from coronary heart disease (CHD) occur between December and March, among older people. Circulating concentrations of tissue plasminogen activator (t-PA), von Willebrand factor (VWF) and fibrin D-dimer are associated with arterial disease, and tend to peak in winter. The potential contributions of these hemostatic activation measures to excess winter mortality are unknown.
  
  
  OBJECTIVE
  To estimate contributions of hemostatic factors to excess winter mortality.
  
  
  METHODS
  Seasonal patterns in t-PA, VWF and D-dimer were investigated in 4088 men aged 60-79 years from 24 British towns. Data on established coronary risk factors were collected by questionnaire, physical examination and blood sampling. The adjusted mean increase in hemostatic markers during winter months, after adjustment for a range of coronary risk factors, was combined with associations of each marker with CHD mortality obtained from 9 years' follow-up of participants, to predict degree of excess CHD winter mortality. Associations of hemostatic markers with CHD incidence from large meta-analyses were also used.
  
  
  RESULTS
  All three markers showed peaks in winter; the adjusted mean increases during winter months were 0.21, 0.15 and 0.12 standard deviations for t-PA, VWF and log(D-dimer), respectively. Predicted excess hazard ratios for winter CHD mortality were 3.0%, 2.4% and 3.1%, respectively, in combination, representing an 8.6% excess. This increased to 14% when applying meta-analysis estimates.
  
  
  CONCLUSIONS
  Seasonal patterns in three hemostatic markers predict at least 8.6% excess CHD mortality in winter in Great Britain, potentially accounting for over half the excess observed in recent years.
authors.affiliation: Wolfson Institute of Preventive Medicine, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK.
authors.forename: M A
authors.initials: MA
authors.lastname: Ghebre
authors.forename: S G
authors.initials: SG
authors.lastname: Wannamethee
authors.forename: A
authors.initials: A
authors.lastname: Rumley
authors.forename: P H
authors.initials: PH
authors.lastname: Whincup
authors.forename: G D O
authors.initials: GD
authors.lastname: Lowe
authors.forename: R W
authors.initials: RW
authors.lastname: Morris
mesh_terms: D000367:Age Factors; D000368:Aged; D015415:Biomarkers / Q000097:blood; D001780:Blood Coagulation Tests; D003327:Coronary Disease / Q000097:blood* / Q000401:mortality*; D005338:Fibrin Fibrinogen Degradation Products / Q000032:analysis; D006487:Hemostasis; D006801:Humans; D015994:Incidence; D016014:Linear Models; D008297:Male; D015201:Meta-Analysis as Topic; D008875:Middle Aged; D015999:Multivariate Analysis; D016017:Odds Ratio; D016016:Proportional Hazards Models; D011446:Prospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D012621:Seasons; D012737:Sex Factors; D013997:Time Factors; D010959:Tissue Plasminogen Activator / Q000097:blood; D006113:United Kingdom / Q000453:epidemiology; D015854:Up-Regulation; D014841:von Willebrand Factor / Q000032:analysis
chemical_list: D015415:Biomarkers; D005338:Fibrin Fibrinogen Degradation Products; C036309:fibrin fragment D; D014841:von Willebrand Factor; D010959:Tissue Plasminogen Activator