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Comparative Study
. 2019 Feb 1;4(2):163-173.
doi: 10.1001/jamacardio.2018.4537.

Cardiovascular Risk Factors Associated With Venous Thromboembolism

John Gregson  1 , Stephen Kaptoge  2   3 , Thomas Bolton  2   3 , Lisa Pennells  2 , Peter Willeit  2   4 , Stephen Burgess  2   5 , Steven Bell  2   3 , Michael Sweeting  2 , Eric B Rimm  6 , Christopher Kabrhel  7 , Bengt Zöller  8 , Gerd Assmann  9 , Vilmundur Gudnason  10 , Aaron R Folsom  11 , Volker Arndt  12 , Astrid Fletcher  1 , Paul E Norman  13 , Børge G Nordestgaard  14   15   16 , Akihiko Kitamura  17 , Bakhtawar K Mahmoodi  18 , Peter H Whincup  19 , Matthew Knuiman  13 , Veikko Salomaa  20 , Christa Meisinger  21   22 , Wolfgang Koenig  23   24   25 , Maryam Kavousi  26 , Henry Völzke  27 , Jackie A Cooper  28 , Toshiharu Ninomiya  29 , Edoardo Casiglia  30 , Beatriz Rodriguez  31 , Yoav Ben-Shlomo  32 , Jean-Pierre Després  33 , Leon Simons  34 , Elizabeth Barrett-Connor  35 , Cecilia Björkelund  36 , Marlene Notdurfter  37 , Daan Kromhout  18 , Jackie Price  38 , Susan E Sutherland  39 , Johan Sundström  27 , Jussi Kauhanen  40 , John Gallacher  32 , Joline W J Beulens  41   42 , Rachel Dankner  43 , Cyrus Cooper  44 , Simona Giampaoli  45 , Jason F Deen  46 , Agustín Gómez de la Cámara  47 , Lewis H Kuller  48 , Annika Rosengren  36 , Peter J Svensson  8 , Dorothea Nagel  21 , Carlos J Crespo  49 , Hermann Brenner  11 , Juan R Albertorio-Diaz  50 , Robert Atkins  51 , Eric J Brunner  52 , Martin Shipley  52 , Inger Njølstad  53 , Deborah A Lawlor  32   54 , Yvonne T van der Schouw  42 , Randi Marie Selmer  53 , Maurizio Trevisan  55 , W M Monique Verschuren  42   56 , Philip Greenland  57 , Sylvia Wassertheil-Smoller  58 , Gordon D O Lowe  59 , Angela M Wood  2 , Adam S Butterworth  2   3 , Simon G Thompson  2 , John Danesh  2   3 , Emanuele Di Angelantonio  2   3 , Tom Meade  1 ; Emerging Risk Factors Collaboration
Collaborators, Affiliations
Comparative Study

Cardiovascular Risk Factors Associated With Venous Thromboembolism

John Gregson et al. JAMA Cardiol. .

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; 731 728 participants; 75 cohorts; years of baseline surveys, February 1960 to June 2008; latest date of follow-up, December 2015) and the UK Biobank (421 537 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], 25 131) 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 731 728 participants from the ERFC, 403 396 (55.1%) were female, and the mean (SD) age at the time of the survey was 51.9 (9.0) years; of the 421 537 participants from the UK Biobank, 233 699 (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.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Gregson has 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.

Figures

Figure 1.
Figure 1.. Hazard Ratios (HRs) for Venous Thromboembolism (VTE) by 10-Year Age Groups and Fifths of Continuous Factors
All comparisons were adjusted for age, sex, smoking status, history of diabetes, and usual body mass index (BMI; calculated as weight in kilograms divided by height in meters squared) (waist-to-hip ratio and waist circumference were not adjusted for usual BMI). The reference category is age 50 to 59 years for age and is the bottom fifth for all other continuous variables. Associations involve Emerging Risk Factors Collaboration (ERFC) data for fatal VTE and UK Biobank data for VTE. Data on cholesterol and triglyceride levels were unavailable in UK Biobank at the time of analysis. Most UK Biobank participants were aged between 40 and 69 years at baseline. The dotted line indicates the reference value. HDL indicates high-density lipoprotein.
Figure 2.
Figure 2.. Hazard Ratios (HRs) for Venous Thromboembolism (VTE) for Established Cardiovascular Risk Factors
All comparisons were adjusted for age, sex, smoking status, history of diabetes, and usual body mass index (BMI) (waist-to-hip ratio and waist circumference were not adjusted for usual BMI). Associations involve Emerging Risk Factors Collaboration (ERFC) data for fatal VTE and UK Biobank data for VTE. CRP indicates C-reactive protein; HDL, high-density lipoprotein; Lp(a), lipoprotein(a). aHazard ratios are presented per 1-SD higher usual risk factor level unless otherwise indicated.
Figure 3.
Figure 3.. Hazard Ratios (HRs) for Pulmonary Embolism (PE) vs Deep Vein Thrombosis (DVT) for Established Cardiovascular Risk Factors in UK Biobank
All comparisons were adjusted for age, sex, smoking status, history of diabetes, and usual body mass index (BMI) (waist-to-hip ratio and waist circumference were not adjusted for usual BMI). Associations involve UK Biobank data only. aHazard ratios are presented per 1-SD higher usual risk factor level unless otherwise indicated.
Figure 4.
Figure 4.. Hazard Ratios (HRs) for Unprovoked vs Provoked Venous Thromboembolism (VTE) for Established Cardiovascular Risk Factors in UK Biobank
All comparisons were adjusted for age, sex, smoking status, history of diabetes, and usual body mass index (BMI) (waist-to-hip ratio and waist circumference were not adjusted for usual BMI). Associations involve UK Biobank data only. aHazard ratios are presented per 1-SD higher usual risk factor level unless otherwise indicated.
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