Cardiovascular Risk Factors Associated with Venous Thromboembolism

John Gregson, Stephen Kaptoge, Thomas Bolton, Lisa Pennells, Peter Willeit, Stephen Burgess, Steven Bell, Michael Sweeting, Eric B. Rimm, Christopher Kabrhel, Bengt Zöller, Gerd Assmann, Vilmundur Gudnason, Aaron R. Folsom, Volker Arndt, Astrid Fletcher, Paul E. Norman, Børge G. Nordestgaard, Akihiko Kitamura, Bakhtawar K. MahmoodiPeter H. Whincup, Matthew Knuiman, Veikko Salomaa, Christa Meisinger, Wolfgang Koenig, Maryam Kavousi, Henry Völzke, Jackie A. Cooper, Toshiharu Ninomiya, Edoardo Casiglia, Beatriz Rodriguez, Yoav Ben-Shlomo, Jean Pierre Després, Leon Simons, Elizabeth Barrett-Connor, Cecilia Björkelund, Marlene Notdurfter, Daan Kromhout, Jackie Price, Susan E. Sutherland, Johan Sundström, Jussi Kauhanen, John Gallacher, Joline W.J. Beulens, Rachel Dankner, Cyrus Cooper, Simona Giampaoli, Jason F. Deen, Agustín Gómez De La Cámara, Lewis H. Kuller, Annika Rosengren, Peter J. Svensson, Dorothea Nagel, Carlos J. Crespo, Hermann Brenner, Juan R. Albertorio-Diaz, Robert Atkins, Eric J. Brunner, Martin Shipley, Inger Njølstad, Deborah A. Lawlor, Yvonne T. Van Der Schouw, Randi Marie Selmer, Maurizio Trevisan, W. M.Monique Verschuren, Philip Greenland, Sylvia Wassertheil-Smoller, Gordon D.O. Lowe, Angela M. Wood, Adam S. Butterworth, Simon G. Thompson, John Danesh, Emanuele Di Angelantonio*, Tom Meade

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

65 Citations (Scopus)

Abstract

Importance: It is uncertain to what extent established cardiovascular risk factors are associated with venous thromboembolism (VTE). Objective: To estimate the associations of major cardiovascular risk factors with VTE, ie, deep vein thrombosis and pulmonary embolism. Design, Setting, and Participants: This study included individual participant data mostly from essentially population-based cohort studies from the Emerging Risk Factors Collaboration (ERFC; 731728 participants; 75 cohorts; years of baseline surveys, February 1960 to June 2008; latest date of follow-up, December 2015) and the UK Biobank (421537 participants; years of baseline surveys, March 2006 to September 2010; latest date of follow-up, February 2016). Participants without cardiovascular disease at baseline were included. Data were analyzed from June 2017 to September 2018. Exposures: A panel of several established cardiovascular risk factors. Main Outcomes and Measures: Hazard ratios (HRs) per 1-SD higher usual risk factor levels (or presence/absence). Incident fatal outcomes in ERFC (VTE, 1041; coronary heart disease [CHD], 25131) and incident fatal/nonfatal outcomes in UK Biobank (VTE, 2321; CHD, 3385). Hazard ratios were adjusted for age, sex, smoking status, diabetes, and body mass index (BMI). Results: Of the 731728 participants from the ERFC, 403396 (55.1%) were female, and the mean (SD) age at the time of the survey was 51.9 (9.0) years; of the 421537 participants from the UK Biobank, 233699 (55.4%) were female, and the mean (SD) age at the time of the survey was 56.4 (8.1) years. Risk factors for VTE included older age (ERFC: HR per decade, 2.67; 95% CI, 2.45-2.91; UK Biobank: HR, 1.81; 95% CI, 1.71-1.92), current smoking (ERFC: HR, 1.38; 95% CI, 1.20-1.58; UK Biobank: HR, 1.23; 95% CI, 1.08-1.40), and BMI (ERFC: HR per 1-SD higher BMI, 1.43; 95% CI, 1.35-1.50; UK Biobank: HR, 1.37; 95% CI, 1.32-1.41). For these factors, there were similar HRs for pulmonary embolism and deep vein thrombosis in UK Biobank (except adiposity was more strongly associated with pulmonary embolism) and similar HRs for unprovoked vs provoked VTE. Apart from adiposity, these risk factors were less strongly associated with VTE than CHD. There were inconsistent associations of VTEs with diabetes and blood pressure across ERFC and UK Biobank, and there was limited ability to study lipid and inflammation markers. Conclusions and Relevance: Older age, smoking, and adiposity were consistently associated with higher VTE risk.

Original languageEnglish
Pages (from-to)163-173
Number of pages11
JournalJAMA Cardiology
Volume4
Issue number2
DOIs
Publication statusPublished - Feb 2019
Externally publishedYes

Bibliographical note

Funding Information:
conducted using the UK Biobank resource under Application Number 26865. This work was supported by underpinning grants from the UK Medical Research Council (grant G0800270), the British Heart Foundation (grant SP/09/002), the British Heart Foundation Cambridge Cardiovascular Centre of Excellence, UK National Institute for Health Research Cambridge Biomedical Research Centre, European Research Council (grant 268834) , the European Commission Framework Programme 7 (grant HEALTH-F2-2012-279233), and Health Data Research UK. Dr Danesh holds a British Heart Foundation Personal Chair and a National Institute for Health Research Senior Investigator Award.

Funding Information:
received grants from AstraZeneca and BioSensors as well as personal fees from BioSensors, Edwards Lifesciences, and MvRX. Dr Kaptoge has received grants from the British Heart Foundation and the UK Medical Research Council paid to the Department of Public Health and Primary Care of the University of Cambridge. Dr Kabrhel has received grant HL116854 from the National Heart, Lung, and Blood Institute as well as grants from Diagnostica Stago, Janssen Pharmaceuticals, and Siemens Healthcare Diagnostics. Dr Salomaa has received personal fees from Novo Nordisk. Dr Koenig has received grants and nonfinancial support from Abbott, Beckmann, Roche Diagnostics, and Singulex as well as personal fees from AstraZeneca, Novartis, Pfizer, The Medicines Company, GlaxoSmithKline, DalCor, Kowa, and Amgen for consulting and from AstraZeneca, Sanofi, and Berlin-Chernie for lectures. Dr Lawlor has received grants from the UK Medical Research Council, UK Economic and Social Science Research Council, British Heart Foundation, Diabetes UK, European Research Council, and National Institute for Health as well as funds in kind from Medtronic and Roche Diagnostics paid to the University of Bristol. Dr Butterworth has received grants from AstraZeneca, Biogen, Merck, Novartis, and Pfizer. Dr Thompson has received grants from British Heart Foundation and the UK Medical Research Council. No other disclosures were reported.

Publisher Copyright:
© 2019 American Medical Association. All rights reserved.

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