title: Multivariate analysis of the relation between diet and warfarin dose.
abstract: OBJECTIVE
  The vitamin K antagonist (VKA) warfarin is effective for the prevention of thromboembolisms. Maintenance doses differ greatly among patients and are known to be primarily determined by genetic polymorphisms. The relative impact of dietary vitamin K intake is still a matter of debate. We hypothesize that a multivariate model is more suitable for exploring the relation between dietary intake of vitamin K and warfarin dose than conventional uni- or bivariate analyses.
  
  
  METHODS
  In a cross-sectional study, we interviewed 244 patients in the maintenance phase of warfarin therapy and detected polymorphisms in the VKORC1 and CYP2C9 genes. Dietary vitamin K intake was estimated from food frequency questionnaires.
  
  
  RESULTS
  A univariate correlation analysis and the regression coefficient from the multivariate model showed a small but significant negative relation between vitamin K intake and warfarin dose. A loading plot of the partial least squares regression model illustrated this counter-intuitive observation, which might be explained by the latent structure between variables. The variation in warfarin dose could be divided into two significant latent variables, the so-called components. In component one, pharmacogenetics explained 52% of dose variation. Component two described health-related behavior (diet, physical activity and body weight) and explained 8% of dose variation. Here, vitamin K intake positively correlated with warfarin dose.
  
  
  CONCLUSIONS
  This study highlights the importance of choosing a statistical method that reflects the complexity of data for interpretation of results from observational studies. The multivariate model appears to be well suited to describe the complex relationship between vitamin K intake and VKA dose.
authors.affiliation: Department of Food Science/Quality and Technology, Faculty of Life Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Morten Arendt
authors.initials: MA
authors.lastname: Rasmussen
authors.forename: Jane
authors.initials: J
authors.lastname: Skov
authors.forename: Else-Marie
authors.initials: EM
authors.lastname: Bladbjerg
authors.forename: Johannes J
authors.initials: JJ
authors.lastname: Sidelmann
authors.forename: Marianne
authors.initials: M
authors.lastname: Vamosi
authors.forename: Jørgen
authors.initials: J
authors.lastname: Jespersen
mesh_terms: D000368:Aged; D000925:Anticoagulants / Q000008:administration & dosage*; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics*; D003430:Cross-Sectional Studies; D065729:Cytochrome P-450 CYP2C9; D004032:Diet; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D006899:Mixed Function Oxygenases / Q000235:genetics*; D015999:Multivariate Analysis; D020641:Polymorphism, Single Nucleotide; D013923:Thromboembolism / Q000235:genetics / Q000517:prevention & control; D014812:Vitamin K / Q000008:administration & dosage* / Q000037:antagonists & inhibitors; D064417:Vitamin K Epoxide Reductases; D014815:Vitamins / Q000008:administration & dosage* / Q000037:antagonists & inhibitors; D014859:Warfarin / Q000008:administration & dosage*
chemical_list: D000925:Anticoagulants; D014815:Vitamins; D014812:Vitamin K; D014859:Warfarin; D006899:Mixed Function Oxygenases; C450260:CYP2C9 protein, human; D065729:Cytochrome P-450 CYP2C9; D001189:Aryl Hydrocarbon Hydroxylases; C578523:VKORC1 protein, human; D064417:Vitamin K Epoxide Reductases