Association of Traditional Cardiovascular Risk Factors With Venous Thromboembolism: An Individual Participant Data Meta-Analysis of Prospective Studies

Bakhtawar K Mahmoodi; Mary Cushman; Inger Anne Næss; Matthew A Allison; Willem J Bos; Sigrid K Brækkan; Suzanne C Cannegieter; Ron T Gansevoort; Philimon N Gona; Jens Hammerstrøm; John-Bjarne Hansen; Susan Heckbert; Anders G Holst; Susan G Lakoski; Pamela L Lutsey; JoAnn E Manson; Lisa W Martin; Kunihiro Matsushita; Karina Meijer; Kim Overvad; Eva Prescott; Marja Puurunen; Jacques E Rossouw; Yingying Sang; Marianne T Severinsen; Jur Ten Berg; Aaron R Folsom; Neil A Zakai

doi:10.1161/CIRCULATIONAHA.116.024507

Association of Traditional Cardiovascular Risk Factors With Venous Thromboembolism: An Individual Participant Data Meta-Analysis of Prospective Studies

Circulation. 2017 Jan 3;135(1):7-16. doi: 10.1161/CIRCULATIONAHA.116.024507. Epub 2016 Nov 9.

Authors

Bakhtawar K Mahmoodi¹, Mary Cushman², Inger Anne Næss², Matthew A Allison², Willem J Bos², Sigrid K Brækkan², Suzanne C Cannegieter², Ron T Gansevoort², Philimon N Gona², Jens Hammerstrøm², John-Bjarne Hansen², Susan Heckbert², Anders G Holst², Susan G Lakoski², Pamela L Lutsey², JoAnn E Manson², Lisa W Martin², Kunihiro Matsushita², Karina Meijer², Kim Overvad², Eva Prescott², Marja Puurunen², Jacques E Rossouw², Yingying Sang², Marianne T Severinsen², Jur Ten Berg², Aaron R Folsom², Neil A Zakai²

Affiliations

¹ From Department of Cardiology and Internal Medicine, Sint Antonius Hospital, Nieuwegein, The Netherlands (B.K.M., W.J.B., J.t.B.); Department of Haematology, University Medical Center Groningen, University of Groningen, The Netherlands (B.K.M., K. Meijer); Departments of Medicine and Pathology, University of Vermont, Burlington (M.C., N.A.Z.); Department of Hematology, Trondheim University Hospital, Norway (I.A.N., J.H.); Department of Family and Preventive Medicine, University of California San Diego, La Jolla (M.A.A.); K. G. Jebsen-Thrombosis Research and Expertise Center, Department of Clinical Medicine, University of Tromsø, Norway (S.K.B., J.- B.H.); Department of Clinical Epidemiology, Leiden University Medical Center, University of Leiden, The Netherlands (S.C.C.); Department of Internal Medicine, University Medical Center Groningen, University of Groningen, The Netherlands (R.T.G.); Department of Exercise and Health Sciences, University of Massachusetts, Boston (P.N.G.); Department of Epidemiology and Cardiovascular Health Research Unit, University of Washington, Seattle (S.H.); Laboratory for Molecular Cardiology, Copenhagen University Hospital, Rigshospitalet, Denmark (A.G.H.); Department of Clinical Cancer Prevention and Cardiology, University of Texas MD Anderson Cancer Center, Houston (S.G.L.); Division of Epidemiology and Community Health, University of Minnesota, Minneapolis (P.L.L., A.R.F.); Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA (J.E.M.); Division of Cardiology, George Washington University School of Medicine and Health Sciences, Washington, DC (L.W.M.); Johns Hopkins Bloomberg School of Public Health, Baltimore, MD (K. Matsushita, Y.S.); Department of Public Health, Section for Epidemiology, Aarhus University, and Department of Cardiology, Aalborg University Hospital, Denmark (K.O.); Department of Cardiology, Bispebjerg Hospital, University of Copenhagen, Denmark (E.P.); Framingham Heart Study, Boston University School of Medicine, MA (M.P.); National Heart, Lung, and Blood Institute, Bethesda, MD (J.E.R.); and Department of Hematology, Aalborg University Hospital, Denmark (M.T.S.). b.k.mahmoodi@umcg.nl.
² From Department of Cardiology and Internal Medicine, Sint Antonius Hospital, Nieuwegein, The Netherlands (B.K.M., W.J.B., J.t.B.); Department of Haematology, University Medical Center Groningen, University of Groningen, The Netherlands (B.K.M., K. Meijer); Departments of Medicine and Pathology, University of Vermont, Burlington (M.C., N.A.Z.); Department of Hematology, Trondheim University Hospital, Norway (I.A.N., J.H.); Department of Family and Preventive Medicine, University of California San Diego, La Jolla (M.A.A.); K. G. Jebsen-Thrombosis Research and Expertise Center, Department of Clinical Medicine, University of Tromsø, Norway (S.K.B., J.- B.H.); Department of Clinical Epidemiology, Leiden University Medical Center, University of Leiden, The Netherlands (S.C.C.); Department of Internal Medicine, University Medical Center Groningen, University of Groningen, The Netherlands (R.T.G.); Department of Exercise and Health Sciences, University of Massachusetts, Boston (P.N.G.); Department of Epidemiology and Cardiovascular Health Research Unit, University of Washington, Seattle (S.H.); Laboratory for Molecular Cardiology, Copenhagen University Hospital, Rigshospitalet, Denmark (A.G.H.); Department of Clinical Cancer Prevention and Cardiology, University of Texas MD Anderson Cancer Center, Houston (S.G.L.); Division of Epidemiology and Community Health, University of Minnesota, Minneapolis (P.L.L., A.R.F.); Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA (J.E.M.); Division of Cardiology, George Washington University School of Medicine and Health Sciences, Washington, DC (L.W.M.); Johns Hopkins Bloomberg School of Public Health, Baltimore, MD (K. Matsushita, Y.S.); Department of Public Health, Section for Epidemiology, Aarhus University, and Department of Cardiology, Aalborg University Hospital, Denmark (K.O.); Department of Cardiology, Bispebjerg Hospital, University of Copenhagen, Denmark (E.P.); Framingham Heart Study, Boston University School of Medicine, MA (M.P.); National Heart, Lung, and Blood Institute, Bethesda, MD (J.E.R.); and Department of Hematology, Aalborg University Hospital, Denmark (M.T.S.).

Abstract

Background: Much controversy surrounds the association of traditional cardiovascular disease risk factors with venous thromboembolism (VTE).

Methods: We performed an individual level random-effect meta-analysis including 9 prospective studies with measured baseline cardiovascular disease risk factors and validated VTE events. Definitions were harmonized across studies. Traditional cardiovascular disease risk factors were modeled categorically and continuously using restricted cubic splines. Estimates were obtained for overall VTE, provoked VTE (ie, VTE occurring in the presence of 1 or more established VTE risk factors), and unprovoked VTE, pulmonary embolism, and deep-vein thrombosis.

Results: The studies included 244 865 participants with 4910 VTE events occurring during a mean follow-up of 4.7 to 19.7 years per study. Age, sex, and body mass index-adjusted hazard ratios for overall VTE were 0.98 (95% confidence interval [CI]: 0.89-1.07) for hypertension, 0.97 (95% CI: 0.88-1.08) for hyperlipidemia, 1.01 (95% CI: 0.89-1.15) for diabetes mellitus, and 1.19 (95% CI: 1.08-1.32) for current smoking. After full adjustment, these estimates were numerically similar. When modeled continuously, an inverse association was observed for systolic blood pressure (hazard ratio=0.79 [95% CI: 0.68-0.92] at systolic blood pressure 160 vs 110 mm Hg) but not for diastolic blood pressure or lipid measures with VTE. An important finding from VTE subtype analyses was that cigarette smoking was associated with provoked but not unprovoked VTE. Fully adjusted hazard ratios for the associations of current smoking with provoked and unprovoked VTE were 1.36 (95% CI: 1.22-1.52) and 1.08 (95% CI: 0.90-1.29), respectively.

Conclusions: Except for the association between cigarette smoking and provoked VTE, which is potentially mediated through comorbid conditions such as cancer, the modifiable traditional cardiovascular disease risk factors are not associated with increased VTE risk. Higher systolic blood pressure showed an inverse association with VTE.

Keywords: cardiovascular disease; diabetes mellitus; hyperlipidemia; hypertension; risk factors; smoking; venous thromboembolism.

Publication types

Meta-Analysis

MeSH terms

Age Factors
Blood Pressure
Body Mass Index
Diabetes Complications
Humans
Hyperlipidemias / complications
Hypertension / complications
Lipids / blood
Proportional Hazards Models
Prospective Studies
Pulmonary Embolism / etiology
Risk Factors
Sex Factors
Smoking
Venous Thromboembolism / etiology*
Venous Thrombosis / etiology

Substances

Lipids

Abstract

Publication types

MeSH terms

Substances

Grants and funding