title: Impact of regular physical activity on weekly warfarin dose requirement.
abstract: Warfarin is an oral anticoagulant agent with a narrow therapeutic index. There is a marked inter- and intra-patient variability in warfarin dose requirement. All factors influencing warfarin response are not known and this study aims to evaluate if regular physical activity (RPA) is a determining factor. RPA level was collected with the Stanford Brief Activity Survey in 1064 incident warfarin users, as part of the Quebec Warfarin Cohort (QWC), and with the Global Physical Activity Questionnaire in 618 patients from the Montreal Heart Institute (MHI) Biobank. Linear regression was performed to model relationship of warfarin dose after 3 months of therapy in the QWC with RPA, while controlling for height, weight, age, CYP2C9 (*2 and *3 alleles) and VKORC1 (*2 allele) genotype. Warfarin dose of prevalent users was modeled in the MHI Biobank for replication. A higher level of physical activity was associated with higher doses of warfarin in both cohorts. In the QWC, physical activity could explain 5.4 % (P < 0.001) and 0.9 % (P = 3.23 × 10(-5)) of variance in dose, in univariate and multivariable models, respectively. Similarly, RPA was found to be associated with 1.7 % (P = 0.0012) and 0.5 % (P = 0.0391) of inter-individual variability in warfarin dose requirement before and after adjustment for other covariables, respectively. RPA is associated with higher warfarin dose requirement. The relevance of clinical recommendations on RPA to maintain a steady response to warfarin should be assessed in further studies.
authors.affiliation: Beaulieu-Saucier Pharmacogenomics Centre, Montreal Heart Institute, Université de Montréal, Montreal, QC, Canada.|Department of Pharmacology, Faculty of Medicine, Université de Montréal, Montreal, QC, Canada.
authors.forename: Étienne
authors.initials: É
authors.lastname: Rouleau-Mailloux
authors.affiliation: Beaulieu-Saucier Pharmacogenomics Centre, Montreal Heart Institute, Université de Montréal, Montreal, QC, Canada.|Faculty of Medicine, Université de Montréal, Montreal, QC, Canada.
authors.forename: Payman
authors.initials: P
authors.lastname: Shahabi
authors.affiliation: Beaulieu-Saucier Pharmacogenomics Centre, Montreal Heart Institute, Université de Montréal, Montreal, QC, Canada.|Faculty of Pharmacy, Université of Montréal, Montreal, QC, Canada.
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Dumas
authors.affiliation: Beaulieu-Saucier Pharmacogenomics Centre, Montreal Heart Institute, Université de Montréal, Montreal, QC, Canada.
authors.forename: Yassamin
authors.initials: Y
authors.lastname: Feroz Zada
authors.affiliation: Beaulieu-Saucier Pharmacogenomics Centre, Montreal Heart Institute, Université de Montréal, Montreal, QC, Canada.
authors.forename: Sylvie
authors.initials: S
authors.lastname: Provost
authors.affiliation: Beaulieu-Saucier Pharmacogenomics Centre, Montreal Heart Institute, Université de Montréal, Montreal, QC, Canada.
authors.forename: Jason
authors.initials: J
authors.lastname: Hu
authors.affiliation: Beaulieu-Saucier Pharmacogenomics Centre, Montreal Heart Institute, Université de Montréal, Montreal, QC, Canada.
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Nguyen
authors.affiliation: Beaulieu-Saucier Pharmacogenomics Centre, Montreal Heart Institute, Université de Montréal, Montreal, QC, Canada.
authors.forename: Nawal
authors.initials: N
authors.lastname: Bouchama
authors.affiliation: Beaulieu-Saucier Pharmacogenomics Centre, Montreal Heart Institute, Université de Montréal, Montreal, QC, Canada.
authors.forename: Ian
authors.initials: I
authors.lastname: Mongrain
authors.affiliation: Beaulieu-Saucier Pharmacogenomics Centre, Montreal Heart Institute, Université de Montréal, Montreal, QC, Canada.|Faculty of Medicine, Université de Montréal, Montreal, QC, Canada.
authors.forename: Mario
authors.initials: M
authors.lastname: Talajic
authors.affiliation: Beaulieu-Saucier Pharmacogenomics Centre, Montreal Heart Institute, Université de Montréal, Montreal, QC, Canada.|Faculty of Medicine, Université de Montréal, Montreal, QC, Canada.
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Tardif
authors.affiliation: Faculty of Pharmacy, Université of Montréal, Montreal, QC, Canada.|Faculty of Medicine, Université de Montréal, Montreal, QC, Canada.
authors.forename: Sylvie
authors.initials: S
authors.lastname: Perreault
authors.affiliation: Beaulieu-Saucier Pharmacogenomics Centre, Montreal Heart Institute, Université de Montréal, Montreal, QC, Canada. marie-pierre.dube@umontreal.ca.|Faculty of Medicine, Université de Montréal, Montreal, QC, Canada. marie-pierre.dube@umontreal.ca.
authors.forename: Marie-Pierre
authors.initials: MP
authors.lastname: Dubé
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015331:Cohort Studies; D065729:Cytochrome P-450 CYP2C9 / Q000235:genetics; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D009043:Motor Activity; D011795:Surveys and Questionnaires; D064417:Vitamin K Epoxide Reductases / Q000235:genetics; D014859:Warfarin / Q000008:administration & dosage*
chemical_list: D014859:Warfarin; C450260:CYP2C9 protein, human; D065729:Cytochrome P-450 CYP2C9; C578523:VKORC1 protein, human; D064417:Vitamin K Epoxide Reductases
keywords: Dose; Interaction; Physical activity; Warfarin