title: Association between the metabolic syndrome, its individual components, and unprovoked venous thromboembolism: results of a patient-level meta-analysis.
abstract: OBJECTIVE
  The metabolic syndrome (MetS) may contribute to the pathogenesis of venous thromboembolism (VTE), but this association requires additional investigation.
  
  
  RESULTS
  We performed a patient-level meta-analysis of case-control and cohort studies that evaluated the role of MetS and risk of unprovoked VTE. For case-control studies, odds ratios and 95% confidence intervals were calculated using logistic regression analysis to estimate the influence of individual variables on the risk of VTE; χ(2) tests for trend were used to investigate the effect of increasing number of components of MetS on the risk of VTE and to explore the influence of abdominal obesity on this relationship. For cohort studies, hazard ratios and 95% confidence interval were calculated using multivariable Cox regression analysis. Six case-control studies were included (908 cases with unprovoked VTE and 1794 controls): in multivariate analysis, MetS was independently associated with VTE (odds ratio, 1.91; 95% confidence interval, 1.57-2.33), and both MetS and abdominal obesity were better predictors of unprovoked VTE than obesity defined by the body mass index. Two prospective cohort studies were included (26,531 subjects and 289 unprovoked VTE events): age, obesity, and abdominal obesity, but not MetS were associated with VTE.
  
  
  CONCLUSIONS
  Case-control but not prospective cohort studies support an association between MetS and VTE. Abdominal adiposity is a strong risk factor for VTE.
authors.affiliation: From the Department of Clinical and Experimental Medicine, University of Insubria, Varese, Italy (W.A., A.S., F.D.); Unit of Cell and Molecular Biology in Cardiovascular Diseases, Centro Cardiologico Monzino, IRCCS, Milan, Italy (M.N.D.D.M.); Department of Experimental and Clinical Medicine, Federico II University, Napoli, Italy (M.N.D.D.M., G.D.M.); Clinical Division of Haematology and Haemostaseology, Department of Medicine I, Medical University of Vienna, Vienna, Austria (C.A., I.P.); Department of Internal Medicine, School of Medicine, CHA University, Seongnam, Korea (M.J.J., D.O.); Department of Clinical Medicine, University of Tromso, Tromso, Norway (J.-B.H., S.K.B.); Division of Epidemiology and Community Health, University of Minnesota School of Public Health, Minneapolis (L.M.S.); Department of Medicine, University of Vermont College of Medicine, Burlington (M.C.); Hemostasis Unit, Service of Clinical Pathology, La Fe University Hospital, Valencia, Spain (A.V., E.B.); and Department of Internal Medicine, Ca' Foncello Hospital, Treviso, Italy (M.R., P.P.). agewal@yahoo.com.
authors.forename: Walter
authors.initials: W
authors.lastname: Ageno
authors.affiliation: From the Department of Clinical and Experimental Medicine, University of Insubria, Varese, Italy (W.A., A.S., F.D.); Unit of Cell and Molecular Biology in Cardiovascular Diseases, Centro Cardiologico Monzino, IRCCS, Milan, Italy (M.N.D.D.M.); Department of Experimental and Clinical Medicine, Federico II University, Napoli, Italy (M.N.D.D.M., G.D.M.); Clinical Division of Haematology and Haemostaseology, Department of Medicine I, Medical University of Vienna, Vienna, Austria (C.A., I.P.); Department of Internal Medicine, School of Medicine, CHA University, Seongnam, Korea (M.J.J., D.O.); Department of Clinical Medicine, University of Tromso, Tromso, Norway (J.-B.H., S.K.B.); Division of Epidemiology and Community Health, University of Minnesota School of Public Health, Minneapolis (L.M.S.); Department of Medicine, University of Vermont College of Medicine, Burlington (M.C.); Hemostasis Unit, Service of Clinical Pathology, La Fe University Hospital, Valencia, Spain (A.V., E.B.); and Department of Internal Medicine, Ca' Foncello Hospital, Treviso, Italy (M.R., P.P.).
authors.forename: Matteo N D
authors.initials: MN
authors.lastname: Di Minno
authors.affiliation: From the Department of Clinical and Experimental Medicine, University of Insubria, Varese, Italy (W.A., A.S., F.D.); Unit of Cell and Molecular Biology in Cardiovascular Diseases, Centro Cardiologico Monzino, IRCCS, Milan, Italy (M.N.D.D.M.); Department of Experimental and Clinical Medicine, Federico II University, Napoli, Italy (M.N.D.D.M., G.D.M.); Clinical Division of Haematology and Haemostaseology, Department of Medicine I, Medical University of Vienna, Vienna, Austria (C.A., I.P.); Department of Internal Medicine, School of Medicine, CHA University, Seongnam, Korea (M.J.J., D.O.); Department of Clinical Medicine, University of Tromso, Tromso, Norway (J.-B.H., S.K.B.); Division of Epidemiology and Community Health, University of Minnesota School of Public Health, Minneapolis (L.M.S.); Department of Medicine, University of Vermont College of Medicine, Burlington (M.C.); Hemostasis Unit, Service of Clinical Pathology, La Fe University Hospital, Valencia, Spain (A.V., E.B.); and Department of Internal Medicine, Ca' Foncello Hospital, Treviso, Italy (M.R., P.P.).
authors.forename: Cihan
authors.initials: C
authors.lastname: Ay
authors.affiliation: From the Department of Clinical and Experimental Medicine, University of Insubria, Varese, Italy (W.A., A.S., F.D.); Unit of Cell and Molecular Biology in Cardiovascular Diseases, Centro Cardiologico Monzino, IRCCS, Milan, Italy (M.N.D.D.M.); Department of Experimental and Clinical Medicine, Federico II University, Napoli, Italy (M.N.D.D.M., G.D.M.); Clinical Division of Haematology and Haemostaseology, Department of Medicine I, Medical University of Vienna, Vienna, Austria (C.A., I.P.); Department of Internal Medicine, School of Medicine, CHA University, Seongnam, Korea (M.J.J., D.O.); Department of Clinical Medicine, University of Tromso, Tromso, Norway (J.-B.H., S.K.B.); Division of Epidemiology and Community Health, University of Minnesota School of Public Health, Minneapolis (L.M.S.); Department of Medicine, University of Vermont College of Medicine, Burlington (M.C.); Hemostasis Unit, Service of Clinical Pathology, La Fe University Hospital, Valencia, Spain (A.V., E.B.); and Department of Internal Medicine, Ca' Foncello Hospital, Treviso, Italy (M.R., P.P.).
authors.forename: Moon Ju
authors.initials: MJ
authors.lastname: Jang
authors.affiliation: From the Department of Clinical and Experimental Medicine, University of Insubria, Varese, Italy (W.A., A.S., F.D.); Unit of Cell and Molecular Biology in Cardiovascular Diseases, Centro Cardiologico Monzino, IRCCS, Milan, Italy (M.N.D.D.M.); Department of Experimental and Clinical Medicine, Federico II University, Napoli, Italy (M.N.D.D.M., G.D.M.); Clinical Division of Haematology and Haemostaseology, Department of Medicine I, Medical University of Vienna, Vienna, Austria (C.A., I.P.); Department of Internal Medicine, School of Medicine, CHA University, Seongnam, Korea (M.J.J., D.O.); Department of Clinical Medicine, University of Tromso, Tromso, Norway (J.-B.H., S.K.B.); Division of Epidemiology and Community Health, University of Minnesota School of Public Health, Minneapolis (L.M.S.); Department of Medicine, University of Vermont College of Medicine, Burlington (M.C.); Hemostasis Unit, Service of Clinical Pathology, La Fe University Hospital, Valencia, Spain (A.V., E.B.); and Department of Internal Medicine, Ca' Foncello Hospital, Treviso, Italy (M.R., P.P.).
authors.forename: John-Bjarne
authors.initials: JB
authors.lastname: Hansen
authors.affiliation: From the Department of Clinical and Experimental Medicine, University of Insubria, Varese, Italy (W.A., A.S., F.D.); Unit of Cell and Molecular Biology in Cardiovascular Diseases, Centro Cardiologico Monzino, IRCCS, Milan, Italy (M.N.D.D.M.); Department of Experimental and Clinical Medicine, Federico II University, Napoli, Italy (M.N.D.D.M., G.D.M.); Clinical Division of Haematology and Haemostaseology, Department of Medicine I, Medical University of Vienna, Vienna, Austria (C.A., I.P.); Department of Internal Medicine, School of Medicine, CHA University, Seongnam, Korea (M.J.J., D.O.); Department of Clinical Medicine, University of Tromso, Tromso, Norway (J.-B.H., S.K.B.); Division of Epidemiology and Community Health, University of Minnesota School of Public Health, Minneapolis (L.M.S.); Department of Medicine, University of Vermont College of Medicine, Burlington (M.C.); Hemostasis Unit, Service of Clinical Pathology, La Fe University Hospital, Valencia, Spain (A.V., E.B.); and Department of Internal Medicine, Ca' Foncello Hospital, Treviso, Italy (M.R., P.P.).
authors.forename: Lyn M
authors.initials: LM
authors.lastname: Steffen
authors.affiliation: From the Department of Clinical and Experimental Medicine, University of Insubria, Varese, Italy (W.A., A.S., F.D.); Unit of Cell and Molecular Biology in Cardiovascular Diseases, Centro Cardiologico Monzino, IRCCS, Milan, Italy (M.N.D.D.M.); Department of Experimental and Clinical Medicine, Federico II University, Napoli, Italy (M.N.D.D.M., G.D.M.); Clinical Division of Haematology and Haemostaseology, Department of Medicine I, Medical University of Vienna, Vienna, Austria (C.A., I.P.); Department of Internal Medicine, School of Medicine, CHA University, Seongnam, Korea (M.J.J., D.O.); Department of Clinical Medicine, University of Tromso, Tromso, Norway (J.-B.H., S.K.B.); Division of Epidemiology and Community Health, University of Minnesota School of Public Health, Minneapolis (L.M.S.); Department of Medicine, University of Vermont College of Medicine, Burlington (M.C.); Hemostasis Unit, Service of Clinical Pathology, La Fe University Hospital, Valencia, Spain (A.V., E.B.); and Department of Internal Medicine, Ca' Foncello Hospital, Treviso, Italy (M.R., P.P.).
authors.forename: Amparo
authors.initials: A
authors.lastname: Vayà
authors.affiliation: From the Department of Clinical and Experimental Medicine, University of Insubria, Varese, Italy (W.A., A.S., F.D.); Unit of Cell and Molecular Biology in Cardiovascular Diseases, Centro Cardiologico Monzino, IRCCS, Milan, Italy (M.N.D.D.M.); Department of Experimental and Clinical Medicine, Federico II University, Napoli, Italy (M.N.D.D.M., G.D.M.); Clinical Division of Haematology and Haemostaseology, Department of Medicine I, Medical University of Vienna, Vienna, Austria (C.A., I.P.); Department of Internal Medicine, School of Medicine, CHA University, Seongnam, Korea (M.J.J., D.O.); Department of Clinical Medicine, University of Tromso, Tromso, Norway (J.-B.H., S.K.B.); Division of Epidemiology and Community Health, University of Minnesota School of Public Health, Minneapolis (L.M.S.); Department of Medicine, University of Vermont College of Medicine, Burlington (M.C.); Hemostasis Unit, Service of Clinical Pathology, La Fe University Hospital, Valencia, Spain (A.V., E.B.); and Department of Internal Medicine, Ca' Foncello Hospital, Treviso, Italy (M.R., P.P.).
authors.forename: Marcello
authors.initials: M
authors.lastname: Rattazzi
authors.affiliation: From the Department of Clinical and Experimental Medicine, University of Insubria, Varese, Italy (W.A., A.S., F.D.); Unit of Cell and Molecular Biology in Cardiovascular Diseases, Centro Cardiologico Monzino, IRCCS, Milan, Italy (M.N.D.D.M.); Department of Experimental and Clinical Medicine, Federico II University, Napoli, Italy (M.N.D.D.M., G.D.M.); Clinical Division of Haematology and Haemostaseology, Department of Medicine I, Medical University of Vienna, Vienna, Austria (C.A., I.P.); Department of Internal Medicine, School of Medicine, CHA University, Seongnam, Korea (M.J.J., D.O.); Department of Clinical Medicine, University of Tromso, Tromso, Norway (J.-B.H., S.K.B.); Division of Epidemiology and Community Health, University of Minnesota School of Public Health, Minneapolis (L.M.S.); Department of Medicine, University of Vermont College of Medicine, Burlington (M.C.); Hemostasis Unit, Service of Clinical Pathology, La Fe University Hospital, Valencia, Spain (A.V., E.B.); and Department of Internal Medicine, Ca' Foncello Hospital, Treviso, Italy (M.R., P.P.).
authors.forename: Ingrid
authors.initials: I
authors.lastname: Pabinger
authors.affiliation: From the Department of Clinical and Experimental Medicine, University of Insubria, Varese, Italy (W.A., A.S., F.D.); Unit of Cell and Molecular Biology in Cardiovascular Diseases, Centro Cardiologico Monzino, IRCCS, Milan, Italy (M.N.D.D.M.); Department of Experimental and Clinical Medicine, Federico II University, Napoli, Italy (M.N.D.D.M., G.D.M.); Clinical Division of Haematology and Haemostaseology, Department of Medicine I, Medical University of Vienna, Vienna, Austria (C.A., I.P.); Department of Internal Medicine, School of Medicine, CHA University, Seongnam, Korea (M.J.J., D.O.); Department of Clinical Medicine, University of Tromso, Tromso, Norway (J.-B.H., S.K.B.); Division of Epidemiology and Community Health, University of Minnesota School of Public Health, Minneapolis (L.M.S.); Department of Medicine, University of Vermont College of Medicine, Burlington (M.C.); Hemostasis Unit, Service of Clinical Pathology, La Fe University Hospital, Valencia, Spain (A.V., E.B.); and Department of Internal Medicine, Ca' Foncello Hospital, Treviso, Italy (M.R., P.P.).
authors.forename: Doyeun
authors.initials: D
authors.lastname: Oh
authors.affiliation: From the Department of Clinical and Experimental Medicine, University of Insubria, Varese, Italy (W.A., A.S., F.D.); Unit of Cell and Molecular Biology in Cardiovascular Diseases, Centro Cardiologico Monzino, IRCCS, Milan, Italy (M.N.D.D.M.); Department of Experimental and Clinical Medicine, Federico II University, Napoli, Italy (M.N.D.D.M., G.D.M.); Clinical Division of Haematology and Haemostaseology, Department of Medicine I, Medical University of Vienna, Vienna, Austria (C.A., I.P.); Department of Internal Medicine, School of Medicine, CHA University, Seongnam, Korea (M.J.J., D.O.); Department of Clinical Medicine, University of Tromso, Tromso, Norway (J.-B.H., S.K.B.); Division of Epidemiology and Community Health, University of Minnesota School of Public Health, Minneapolis (L.M.S.); Department of Medicine, University of Vermont College of Medicine, Burlington (M.C.); Hemostasis Unit, Service of Clinical Pathology, La Fe University Hospital, Valencia, Spain (A.V., E.B.); and Department of Internal Medicine, Ca' Foncello Hospital, Treviso, Italy (M.R., P.P.).
authors.forename: Giovanni
authors.initials: G
authors.lastname: Di Minno
authors.affiliation: From the Department of Clinical and Experimental Medicine, University of Insubria, Varese, Italy (W.A., A.S., F.D.); Unit of Cell and Molecular Biology in Cardiovascular Diseases, Centro Cardiologico Monzino, IRCCS, Milan, Italy (M.N.D.D.M.); Department of Experimental and Clinical Medicine, Federico II University, Napoli, Italy (M.N.D.D.M., G.D.M.); Clinical Division of Haematology and Haemostaseology, Department of Medicine I, Medical University of Vienna, Vienna, Austria (C.A., I.P.); Department of Internal Medicine, School of Medicine, CHA University, Seongnam, Korea (M.J.J., D.O.); Department of Clinical Medicine, University of Tromso, Tromso, Norway (J.-B.H., S.K.B.); Division of Epidemiology and Community Health, University of Minnesota School of Public Health, Minneapolis (L.M.S.); Department of Medicine, University of Vermont College of Medicine, Burlington (M.C.); Hemostasis Unit, Service of Clinical Pathology, La Fe University Hospital, Valencia, Spain (A.V., E.B.); and Department of Internal Medicine, Ca' Foncello Hospital, Treviso, Italy (M.R., P.P.).
authors.forename: Sigrid K
authors.initials: SK
authors.lastname: Braekkan
authors.affiliation: From the Department of Clinical and Experimental Medicine, University of Insubria, Varese, Italy (W.A., A.S., F.D.); Unit of Cell and Molecular Biology in Cardiovascular Diseases, Centro Cardiologico Monzino, IRCCS, Milan, Italy (M.N.D.D.M.); Department of Experimental and Clinical Medicine, Federico II University, Napoli, Italy (M.N.D.D.M., G.D.M.); Clinical Division of Haematology and Haemostaseology, Department of Medicine I, Medical University of Vienna, Vienna, Austria (C.A., I.P.); Department of Internal Medicine, School of Medicine, CHA University, Seongnam, Korea (M.J.J., D.O.); Department of Clinical Medicine, University of Tromso, Tromso, Norway (J.-B.H., S.K.B.); Division of Epidemiology and Community Health, University of Minnesota School of Public Health, Minneapolis (L.M.S.); Department of Medicine, University of Vermont College of Medicine, Burlington (M.C.); Hemostasis Unit, Service of Clinical Pathology, La Fe University Hospital, Valencia, Spain (A.V., E.B.); and Department of Internal Medicine, Ca' Foncello Hospital, Treviso, Italy (M.R., P.P.).
authors.forename: Mary
authors.initials: M
authors.lastname: Cushman
authors.affiliation: From the Department of Clinical and Experimental Medicine, University of Insubria, Varese, Italy (W.A., A.S., F.D.); Unit of Cell and Molecular Biology in Cardiovascular Diseases, Centro Cardiologico Monzino, IRCCS, Milan, Italy (M.N.D.D.M.); Department of Experimental and Clinical Medicine, Federico II University, Napoli, Italy (M.N.D.D.M., G.D.M.); Clinical Division of Haematology and Haemostaseology, Department of Medicine I, Medical University of Vienna, Vienna, Austria (C.A., I.P.); Department of Internal Medicine, School of Medicine, CHA University, Seongnam, Korea (M.J.J., D.O.); Department of Clinical Medicine, University of Tromso, Tromso, Norway (J.-B.H., S.K.B.); Division of Epidemiology and Community Health, University of Minnesota School of Public Health, Minneapolis (L.M.S.); Department of Medicine, University of Vermont College of Medicine, Burlington (M.C.); Hemostasis Unit, Service of Clinical Pathology, La Fe University Hospital, Valencia, Spain (A.V., E.B.); and Department of Internal Medicine, Ca' Foncello Hospital, Treviso, Italy (M.R., P.P.).
authors.forename: Elena
authors.initials: E
authors.lastname: Bonet
authors.affiliation: From the Department of Clinical and Experimental Medicine, University of Insubria, Varese, Italy (W.A., A.S., F.D.); Unit of Cell and Molecular Biology in Cardiovascular Diseases, Centro Cardiologico Monzino, IRCCS, Milan, Italy (M.N.D.D.M.); Department of Experimental and Clinical Medicine, Federico II University, Napoli, Italy (M.N.D.D.M., G.D.M.); Clinical Division of Haematology and Haemostaseology, Department of Medicine I, Medical University of Vienna, Vienna, Austria (C.A., I.P.); Department of Internal Medicine, School of Medicine, CHA University, Seongnam, Korea (M.J.J., D.O.); Department of Clinical Medicine, University of Tromso, Tromso, Norway (J.-B.H., S.K.B.); Division of Epidemiology and Community Health, University of Minnesota School of Public Health, Minneapolis (L.M.S.); Department of Medicine, University of Vermont College of Medicine, Burlington (M.C.); Hemostasis Unit, Service of Clinical Pathology, La Fe University Hospital, Valencia, Spain (A.V., E.B.); and Department of Internal Medicine, Ca' Foncello Hospital, Treviso, Italy (M.R., P.P.).
authors.forename: Paolo
authors.initials: P
authors.lastname: Pauletto
authors.affiliation: From the Department of Clinical and Experimental Medicine, University of Insubria, Varese, Italy (W.A., A.S., F.D.); Unit of Cell and Molecular Biology in Cardiovascular Diseases, Centro Cardiologico Monzino, IRCCS, Milan, Italy (M.N.D.D.M.); Department of Experimental and Clinical Medicine, Federico II University, Napoli, Italy (M.N.D.D.M., G.D.M.); Clinical Division of Haematology and Haemostaseology, Department of Medicine I, Medical University of Vienna, Vienna, Austria (C.A., I.P.); Department of Internal Medicine, School of Medicine, CHA University, Seongnam, Korea (M.J.J., D.O.); Department of Clinical Medicine, University of Tromso, Tromso, Norway (J.-B.H., S.K.B.); Division of Epidemiology and Community Health, University of Minnesota School of Public Health, Minneapolis (L.M.S.); Department of Medicine, University of Vermont College of Medicine, Burlington (M.C.); Hemostasis Unit, Service of Clinical Pathology, La Fe University Hospital, Valencia, Spain (A.V., E.B.); and Department of Internal Medicine, Ca' Foncello Hospital, Treviso, Italy (M.R., P.P.).
authors.forename: Alessandro
authors.initials: A
authors.lastname: Squizzato
authors.affiliation: From the Department of Clinical and Experimental Medicine, University of Insubria, Varese, Italy (W.A., A.S., F.D.); Unit of Cell and Molecular Biology in Cardiovascular Diseases, Centro Cardiologico Monzino, IRCCS, Milan, Italy (M.N.D.D.M.); Department of Experimental and Clinical Medicine, Federico II University, Napoli, Italy (M.N.D.D.M., G.D.M.); Clinical Division of Haematology and Haemostaseology, Department of Medicine I, Medical University of Vienna, Vienna, Austria (C.A., I.P.); Department of Internal Medicine, School of Medicine, CHA University, Seongnam, Korea (M.J.J., D.O.); Department of Clinical Medicine, University of Tromso, Tromso, Norway (J.-B.H., S.K.B.); Division of Epidemiology and Community Health, University of Minnesota School of Public Health, Minneapolis (L.M.S.); Department of Medicine, University of Vermont College of Medicine, Burlington (M.C.); Hemostasis Unit, Service of Clinical Pathology, La Fe University Hospital, Valencia, Spain (A.V., E.B.); and Department of Internal Medicine, Ca' Foncello Hospital, Treviso, Italy (M.R., P.P.).
authors.forename: Francesco
authors.initials: F
authors.lastname: Dentali
mesh_terms: D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D015331:Cohort Studies; D005260:Female; D006801:Humans; D016015:Logistic Models; D008297:Male; D024821:Metabolic Syndrome / Q000150:complications*; D008875:Middle Aged; D056128:Obesity, Abdominal / Q000150:complications; D012307:Risk Factors; D054556:Venous Thromboembolism / Q000453:epidemiology*
keywords: metabolic syndrome X; obesity; pulmonary embolism; venous thromboembolism; venous thrombosis