title: Incident venous thromboembolic events in the Prospective Study of Pravastatin in the Elderly at Risk (PROSPER).
abstract: BACKGROUND
  Venous thromboembolic events (VTE), including deep venous thrombosis and pulmonary embolism, are common in older age. It has been suggested that statins might reduce the risk of VTE however positive results from studies of middle aged subjects may not be generalisable to elderly people. We aimed to determine the effect of pravastatin on incident VTE in older people; we also studied the impact of clinical and plasma risk variables.
  
  
  METHODS
  This study was an analysis of incident VTE using data from the Prospective Study of Pravastatin in the Elderly at Risk (PROSPER), a randomized, double-blind, placebo-controlled trial of pravastatin in men and women aged 70-82. Mean follow-up was 3.2 years. Risk for VTE was examined in non-warfarin treated pravastatin (n = 2834) and placebo (n = 2865) patients using a Cox's proportional hazard model, and the impact of other risk factors assessed in a multivariate forward stepwise regression analysis. Baseline clinical characteristics, blood biochemistry and hematology variables, plasma levels of lipids and lipoproteins, and plasma markers of inflammation and adiposity were compared. Plasma markers of thrombosis and hemostasis were assessed in a nested case (n = 48) control (n = 93) study where the cohort was those participants, not on warfarin, for whom data were available.
  
  
  RESULTS
  There were 28 definite cases (1.0%) of incident VTE in the pravastatin group recipients and 20 cases (0.70%) in placebo recipients. Pravastatin did not reduce VTE in PROSPER compared to placebo [unadjusted hazard ratio (95% confidence interval) 1.42 (0.80, 2.52) p = 0.23]. Higher body mass index (BMI) [1.09 (1.02, 1.15) p = 0.0075], country [Scotland vs Netherlands 4.26 (1.00, 18.21) p = 0.050 and Ireland vs Netherlands 6.16 (1.46, 26.00) p = 0.013], lower systolic blood pressure [1.35 (1.03, 1.75) p = 0.027] and lower baseline Mini Mental State Examination (MMSE) score [1.19 (1.01, 1.41) p = 0.034] were associated with an increased risk of VTE, however only BMI, country and systolic blood pressure remained significant on multivariate analysis. In a nested case control study of definite VTE, plasma Factor VIII levels were associated with VTE [1.52 (1.01, 2.28), p = 0.044]. However no other measure of thrombosis and haemostasis was associated with increased risk of VTE.
  
  
  CONCLUSIONS
  Pravastatin does not prevent VTE in elderly people at risk of vascular disease. Blood markers of haemostasis and inflammation are not strongly predictive of VTE in older age however BMI, country and lower systolic blood pressure are independently associated with VTE risk.
  
  
  BACKGROUND
  Not applicable when study undertaken.
authors.affiliation: Centre of Population and Health Sciences, University of Glasgow, Glasgow, UK. Dilys.Freeman@glasgow.ac.uk
authors.forename: Dilys J
authors.initials: DJ
authors.lastname: Freeman
authors.forename: Michele
authors.initials: M
authors.lastname: Robertson
authors.forename: E Ann
authors.initials: EA
authors.lastname: Brown
authors.forename: Ann
authors.initials: A
authors.lastname: Rumley
authors.forename: Edward S
authors.initials: ES
authors.lastname: Tobias
authors.forename: Marijke
authors.initials: M
authors.lastname: Frölich
authors.forename: P Eline
authors.initials: PE
authors.lastname: Slagboom
authors.forename: J Wouter
authors.initials: JW
authors.lastname: Jukema
authors.forename: Anton Jm
authors.initials: AJ
authors.lastname: de Craen
authors.forename: Naveed
authors.initials: N
authors.lastname: Sattar
authors.forename: Ian
authors.initials: I
authors.lastname: Ford
authors.forename: Allan
authors.initials: A
authors.lastname: Gaw
authors.forename: Ian A
authors.initials: IA
authors.lastname: Greer
authors.forename: Gordon D O
authors.initials: GD
authors.lastname: Lowe
authors.forename: David J
authors.initials: DJ
authors.lastname: Stott
mesh_terms: D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D015331:Cohort Studies; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D015994:Incidence; D008297:Male; D017035:Pravastatin / Q000097:blood / Q000627:therapeutic use*; D011446:Prospective Studies; D012307:Risk Factors; D020246:Venous Thrombosis / Q000097:blood / Q000188:drug therapy* / Q000453:epidemiology*
chemical_list: D017035:Pravastatin