title: Atherosclerotic Risk Factors and Risk of Myocardial Infarction and Venous Thromboembolism; Time-Fixed versus Time-Varying Analyses. The Tromsø Study.
abstract: BACKGROUND
  Single measurements of modifiable risk factors may underestimate associations with outcomes in cohorts. We aimed to compare risk estimates of myocardial infarction (MI) and venous thromboembolism (VTE) by atherosclerotic risk factors during long follow-up using time-fixed analyses without and with correction for regression dilution and time-varying analyses.
  
  
  METHODS
  The study included 5970 subjects enrolled in the fourth survey of the Tromsø Study (1994/95). Blood pressure, lipid levels, body mass index (BMI), diabetes and smoking status were measured at baseline, and subjects still alive at the fifth (2001/02, n = 5179) and sixth (2007/08, n = 4391) survey were re-measured. Incident events of MI (n = 714) and VTE (n = 214) were recorded until December 2010. Time-fixed and time-varying Cox regression models were used to estimate hazard ratios (HR) for MI and VTE adjusted for age and sex.
  
  
  RESULTS
  Variations in BMI, blood pressure and lipid levels were small, and did not alter the risk estimates when time-varying analyses were compared to time-fixed analyses. For MI, variables that changed considerably over time yielded the greatest changes in risk estimates (HR for smoking changed from 1.80 (95% CI 1.55-2.10) to 2.08 (95% CI 1.78-2.42)). For VTE, only BMI was associated with increased risk in both time-fixed and time-varying analysis, but the risk estimates weakened in the time-varying analysis. Correction of time-fixed HRs with Rosner´s method tended to overestimate risk estimates compared to time-varying analysis.
  
  
  CONCLUSIONS
  For MI and VTE, risk estimates based on baseline and repeated measures corresponded well, whereas correction for regression dilution tended to overestimate risks.
authors.affiliation: K.G. Jebsen-Thrombosis Research and Expertise Center (TREC), Department of Clinical Medicine, UiT The Arctic University of Norway, Tromsø, Norway.
authors.forename: Birgit
authors.initials: B
authors.lastname: Småbrekke
authors.affiliation: K.G. Jebsen-Thrombosis Research and Expertise Center (TREC), Department of Clinical Medicine, UiT The Arctic University of Norway, Tromsø, Norway.
authors.forename: Ludvig Balteskard
authors.initials: LB
authors.lastname: Rinde
authors.affiliation: K.G. Jebsen-Thrombosis Research and Expertise Center (TREC), Department of Clinical Medicine, UiT The Arctic University of Norway, Tromsø, Norway.
authors.forename: Kristian
authors.initials: K
authors.lastname: Hindberg
authors.affiliation: K.G. Jebsen-Thrombosis Research and Expertise Center (TREC), Department of Clinical Medicine, UiT The Arctic University of Norway, Tromsø, Norway.|Division of Internal Medicine, University Hospital of North Norway, Tromsø, Norway.
authors.forename: Erin Mathiesen
authors.initials: EM
authors.lastname: Hald
authors.affiliation: K.G. Jebsen-Thrombosis Research and Expertise Center (TREC), Department of Clinical Medicine, UiT The Arctic University of Norway, Tromsø, Norway.|Division of Internal Medicine, University Hospital of North Norway, Tromsø, Norway.
authors.forename: Anders
authors.initials: A
authors.lastname: Vik
authors.affiliation: Epidemiology of Chronic Diseases Research Group, Department of Community Medicine, UiT The Arctic University of Norway, Tromsø, Norway.
authors.forename: Tom
authors.initials: T
authors.lastname: Wilsgaard
authors.affiliation: Epidemiology of Chronic Diseases Research Group, Department of Community Medicine, UiT The Arctic University of Norway, Tromsø, Norway.
authors.forename: Maja-Lisa
authors.initials: ML
authors.lastname: Løchen
authors.affiliation: K.G. Jebsen-Thrombosis Research and Expertise Center (TREC), Department of Clinical Medicine, UiT The Arctic University of Norway, Tromsø, Norway.|Epidemiology of Chronic Diseases Research Group, Department of Community Medicine, UiT The Arctic University of Norway, Tromsø, Norway.
authors.forename: Inger
authors.initials: I
authors.lastname: Njølstad
authors.affiliation: K.G. Jebsen-Thrombosis Research and Expertise Center (TREC), Department of Clinical Medicine, UiT The Arctic University of Norway, Tromsø, Norway.|Brain and Circulation Research Group, Department of Clinical Medicine, UiT The Arctic University of Norway, Tromsø, Norway.|Department of Neurology, University Hospital of North Norway, Tromsø, Norway.
authors.forename: Ellisiv B
authors.initials: EB
authors.lastname: Mathiesen
authors.affiliation: K.G. Jebsen-Thrombosis Research and Expertise Center (TREC), Department of Clinical Medicine, UiT The Arctic University of Norway, Tromsø, Norway.|Division of Internal Medicine, University Hospital of North Norway, Tromsø, Norway.
authors.forename: John-Bjarne
authors.initials: JB
authors.lastname: Hansen
authors.affiliation: K.G. Jebsen-Thrombosis Research and Expertise Center (TREC), Department of Clinical Medicine, UiT The Arctic University of Norway, Tromsø, Norway.|Division of Internal Medicine, University Hospital of North Norway, Tromsø, Norway.
authors.forename: Sigrid
authors.initials: S
authors.lastname: Brækkan
mesh_terms: D000368:Aged; D050197:Atherosclerosis / Q000209:etiology*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000150:complications*; D012307:Risk Factors; D054556:Venous Thromboembolism / Q000209:etiology*