title: Interaction of Hereditary Thrombophilia and Traditional Cardiovascular Risk Factors on the Risk of Arterial Thromboembolism: Pooled Analysis of Four Family Cohort Studies.
abstract: BACKGROUND
  Hereditary thrombophilia is associated with a slightly increased risk of arterial thromboembolism (ATE). Whether hereditary thrombophilia interacts with traditional cardiovascular risk factors on the risk of ATE has yet to be established.
  
  
  RESULTS
  A total of 1891 individuals belonging to 4 family cohorts from the Netherlands were included in the analyses. Five hereditary thrombophilic defects, including factor V Leiden, prothrombin G20210A defect, and deficiencies of the natural anticoagulants (ie, antithrombin, protein C, and protein S), were assessed, and data on risk factors and previous ATE were collected. Thrombophilia was associated with elevated risk of ATE (hazard ratio =1.74, 95% confidence interval, 1.18-2.58; P=0.005). Overall, the association of thrombophilia with ATE tended to be stronger in the presence of traditional cardiovascular risk factors, especially the synergistic effect of thrombophilia with diabetes mellitus was striking (hazard ratio of thrombophilia-ATE association was 1.41 in nondiabetics versus 8.11 in diabetics). Moreover, the association of thrombophilia with ATE tended to be stronger in females and before the age of 55 years as compared with males and individuals >55 years of age, respectively.
  
  
  CONCLUSIONS
  Thrombophilia is associated with ATE. This association may be stronger in the presence of traditional cardiovascular risk factors in particular in individuals with diabetes mellitus. Future studies on thrombophilia-ATE risk should focus on high-risk populations with high prevalence of traditional cardiovascular risk factors.
authors.affiliation: Department of Cardiology, Sint Antonius Hospital, Nieuwegein, The Netherlands (B.K.M., J.t.B.); Division of Hemostasis & Thrombosis, Department of Hematology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands (B.K.M., N.J.G.M.V., K.M.); Department of Vascular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands (S.M.); Department of Clinical Epidemiology, Leiden University Medical Center, University of Leiden, Leiden, The Netherlands (W.M.L.); Department of Cardiology, de Sionsberg Hospital, Dokkum, The Netherlands (J.-L.P.B.); and Department of Hematology, Maastricht University Medical Center, University of Maastricht, Maastricht, The Netherlands (K.H.). b.k.mahmoodi@umcg.nl.
authors.forename: Bakhtawar K
authors.initials: BK
authors.lastname: Mahmoodi
authors.affiliation: Department of Cardiology, Sint Antonius Hospital, Nieuwegein, The Netherlands (B.K.M., J.t.B.); Division of Hemostasis & Thrombosis, Department of Hematology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands (B.K.M., N.J.G.M.V., K.M.); Department of Vascular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands (S.M.); Department of Clinical Epidemiology, Leiden University Medical Center, University of Leiden, Leiden, The Netherlands (W.M.L.); Department of Cardiology, de Sionsberg Hospital, Dokkum, The Netherlands (J.-L.P.B.); and Department of Hematology, Maastricht University Medical Center, University of Maastricht, Maastricht, The Netherlands (K.H.).
authors.forename: Nic J G M
authors.initials: NJ
authors.lastname: Veeger
authors.affiliation: Department of Cardiology, Sint Antonius Hospital, Nieuwegein, The Netherlands (B.K.M., J.t.B.); Division of Hemostasis & Thrombosis, Department of Hematology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands (B.K.M., N.J.G.M.V., K.M.); Department of Vascular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands (S.M.); Department of Clinical Epidemiology, Leiden University Medical Center, University of Leiden, Leiden, The Netherlands (W.M.L.); Department of Cardiology, de Sionsberg Hospital, Dokkum, The Netherlands (J.-L.P.B.); and Department of Hematology, Maastricht University Medical Center, University of Maastricht, Maastricht, The Netherlands (K.H.).
authors.forename: Saskia
authors.initials: S
authors.lastname: Middeldorp
authors.affiliation: Department of Cardiology, Sint Antonius Hospital, Nieuwegein, The Netherlands (B.K.M., J.t.B.); Division of Hemostasis & Thrombosis, Department of Hematology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands (B.K.M., N.J.G.M.V., K.M.); Department of Vascular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands (S.M.); Department of Clinical Epidemiology, Leiden University Medical Center, University of Leiden, Leiden, The Netherlands (W.M.L.); Department of Cardiology, de Sionsberg Hospital, Dokkum, The Netherlands (J.-L.P.B.); and Department of Hematology, Maastricht University Medical Center, University of Maastricht, Maastricht, The Netherlands (K.H.).
authors.forename: Willem M
authors.initials: WM
authors.lastname: Lijfering
authors.affiliation: Department of Cardiology, Sint Antonius Hospital, Nieuwegein, The Netherlands (B.K.M., J.t.B.); Division of Hemostasis & Thrombosis, Department of Hematology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands (B.K.M., N.J.G.M.V., K.M.); Department of Vascular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands (S.M.); Department of Clinical Epidemiology, Leiden University Medical Center, University of Leiden, Leiden, The Netherlands (W.M.L.); Department of Cardiology, de Sionsberg Hospital, Dokkum, The Netherlands (J.-L.P.B.); and Department of Hematology, Maastricht University Medical Center, University of Maastricht, Maastricht, The Netherlands (K.H.).
authors.forename: Jan-Leendert P
authors.initials: JL
authors.lastname: Brouwer
authors.affiliation: Department of Cardiology, Sint Antonius Hospital, Nieuwegein, The Netherlands (B.K.M., J.t.B.); Division of Hemostasis & Thrombosis, Department of Hematology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands (B.K.M., N.J.G.M.V., K.M.); Department of Vascular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands (S.M.); Department of Clinical Epidemiology, Leiden University Medical Center, University of Leiden, Leiden, The Netherlands (W.M.L.); Department of Cardiology, de Sionsberg Hospital, Dokkum, The Netherlands (J.-L.P.B.); and Department of Hematology, Maastricht University Medical Center, University of Maastricht, Maastricht, The Netherlands (K.H.).
authors.forename: Jur
authors.initials: J
authors.lastname: Ten Berg
authors.affiliation: Department of Cardiology, Sint Antonius Hospital, Nieuwegein, The Netherlands (B.K.M., J.t.B.); Division of Hemostasis & Thrombosis, Department of Hematology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands (B.K.M., N.J.G.M.V., K.M.); Department of Vascular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands (S.M.); Department of Clinical Epidemiology, Leiden University Medical Center, University of Leiden, Leiden, The Netherlands (W.M.L.); Department of Cardiology, de Sionsberg Hospital, Dokkum, The Netherlands (J.-L.P.B.); and Department of Hematology, Maastricht University Medical Center, University of Maastricht, Maastricht, The Netherlands (K.H.).
authors.forename: Karly
authors.initials: K
authors.lastname: Hamulyák
authors.affiliation: Department of Cardiology, Sint Antonius Hospital, Nieuwegein, The Netherlands (B.K.M., J.t.B.); Division of Hemostasis & Thrombosis, Department of Hematology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands (B.K.M., N.J.G.M.V., K.M.); Department of Vascular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands (S.M.); Department of Clinical Epidemiology, Leiden University Medical Center, University of Leiden, Leiden, The Netherlands (W.M.L.); Department of Cardiology, de Sionsberg Hospital, Dokkum, The Netherlands (J.-L.P.B.); and Department of Hematology, Maastricht University Medical Center, University of Maastricht, Maastricht, The Netherlands (K.H.).
authors.forename: Karina
authors.initials: K
authors.lastname: Meijer
mesh_terms: D000328:Adult; D001798:Blood Proteins / Q000235:genetics*; D015331:Cohort Studies; D005190:Family; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009426:Netherlands; D012307:Risk Factors; D013923:Thromboembolism / Q000235:genetics*; D019851:Thrombophilia / Q000235:genetics*
chemical_list: D001798:Blood Proteins
keywords: arterial thrombosis; cardiovascular disease; epidemiology; factor V Leiden; hereditary thrombophilia; protein C deficiency; protein S deficiency; prothrombin G20210A