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

Cardiovascular Risk Factors Associated With Venous Thromboembolism.

Collaborators (135)

Rosamond W, Whitsel E, Cushman M, Barr EL, Shaw JE, Zimmet PZ, Knuiman M, Whincup PH, Kiechl S, Weger S, Willeit J, Lawlor DA, Amuzu A, Dale C, Casas JP, Gallacher J, Tikhonoff V, Greenland P, Nietert, Tybjærg-Hansen A, Frikke-Schmidt R, Jensen GB, Pablos DL, Navia PC, Simons L, McLachlan S, Schöttker B, Saum KU, Holleczek B, Ariansen I, Meyer HE, Håheim LL, Vartiainen E, Jousilahti P, Harald K, Dankner R, Rosengren A, Wilhelmsen L, Björkelund C, Nagel D, Dennison E, Syddall H, Westbury L, Flicker L, Hankey GJ, Golledge J, Ninomiya T, Doi Y, Kiyohara Y, Rodriguez B, Elders P, Stehouwer C, Kabrhel C, Jensen M, Kitamura A, Iso H, Yamagishi K, Salomaa V, Sudhir K, Tuomainen TP, Salonen JT, Cooper JA, Boer JMA, Blokstra A, Melander O, Nilsson PM, Engström G, Trevisan M, Palmieri L, Vanuzzo D, Giampaoli S, Peters A, Thorand B, Heier M, Fletcher A, Kuller LH, Albertorio-Diaz JR, Rimm EB, Hu FB, Manson JE, Meijer K, Gansevoort RT, Crespo CJ, Assmann G, Schulte H, Sluijs I, Cantin B, Lamarche B, Dagenais GR, McEvoy L, Laughlin G, Daniels LB, Aspelund T, Gudmundsson EF, Thorsson B, Leening MJG, Ikram MA, Franco OH, Tunstall-Pedoe H, Völzke H, Werner A, Devereux R, Jolly S, Smith GD, Can G, Yüksel H, Altay S, Njølstad I, Ingelsson M, Giedraitis V, Brenner H, Claessen H, Rothenbacher D, Parikh NI, Eaton C, Shipley M, Kivimaki M, Brunner EJ, Feskens E, Geleijnse JM, Kromhout D, Bolton T, Spackman S, Walker M, Bolton T, Burgess S, Butterworth AS, Di Angelantonio E, Kaptoge S, Pennells L, Spackman S, Thompson SG, Walker M, Wood AM, Danesh J.

Author information

1
London School of Hygiene and Tropical Medicine, London, United Kingdom.
2
MRC/BHF Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom.
3
National Institute for Health Research Blood and Transplant Research Unit in Donor Health and Genomics, University of Cambridge, Cambridge, United Kingdom.
4
Medical University of Innsbruck, Innsbruck, Austria.
5
MRC Biostatistics Unit, Cambridge University, Cambridge, United Kingdom.
6
Harvard T. H. Chan School of Public Health, Boston, Massachusetts.
7
Massachusetts General Hospital, Boston.
8
Department of Clinical Sciences, Lund University, Malmö, Sweden.
9
Assmann Foundation for Prevention, Münster, Germany.
10
Icelandic Heart Association, Kópavogur, Iceland.
11
University of Minnesota School of Public Health, Minneapolis.
12
Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany.
13
University of Western Australia, Perth, Western Australia, Australia.
14
Department of Clinical Biochemistry, Herlev and Gentofte Hospital, Copenhagen University Hospital, Copenhagen, Denmark.
15
Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
16
Copenhagen City Heart Study, Frederiksberg Hospital, Copenhagen University Hospital, Copenhagen, Denmark.
17
Osaka University, Osaka, Japan.
18
University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
19
St George's, University of London, London, United Kingdom.
20
National Institute for Health and Welfare, Helsinki, Finland.
21
Ludwig Maximilian University of Munich, Munich, Germany.
22
Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany.
23
Deutsches Herzzentrum München, Technische Universität München, Munich, Germany.
24
German Centre for Cardiovascular Research (DZHK), partner site Munich Heart Alliance, Munich, Germany.
25
Department of Internal Medicine II-Cardiology, University of Ulm Medical Center, Ulm, Germany.
26
Erasmus University Medical Center, Erasmus University, Rotterdam, the Netherlands.
27
University of Greifswald, Greifswald, Germany.
28
UCL Medical School, University College London, London, United Kingdom.
29
Kyushu University, Fukuoka, Japan.
30
University of Padova, Padua, Italy.
31
University of Hawaii, Honolulu.
32
Population Health Science, Bristol Medical School, University of Bristol, Bristol, United Kingdom.
33
Institute of Nutraceuticals and Functional Foods, Université Laval, Quebec, Quebec, Canada.
34
The University of New South Wales, Sydney, New South Wales, Australia.
35
University of California, San Diego.
36
University of Gothenburg, Gothenburg, Sweden.
37
Department of Internal Medicine, Bruneck Hospital, Bruneck, Italy.
38
University of Edinburgh, Edinburgh, United Kingdom.
39
Medical University of South Carolina, Charleston.
40
Institute of Public Health and Clinical Nutrition, University of Eastern Finland, Kuopio, Finland.
41
VU University Medical Center Amsterdam, Amsterdam, the Netherlands.
42
Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands.
43
Tel Aviv University, Tel Aviv, Israel.
44
MRC Lifecourse Epidemiology Unit, University of Southampton, Southampton, United Kingdom.
45
National Institute of Health (ISS), Rome, Italy.
46
Center of Health Equity, Diversity and Inclusion, University of Washington School of Medicine, Seattle.
47
Clinical Research and Clinical Trials Unit, Plataforma de Innovación en Tecnologías Médicas y Sanitarias, Madrid, Spain.
48
University of Pittsburgh Graduate School of Public Health, Pittsburgh, Pennsylvania.
49
Portland State University, Portland, Oregon.
50
US Centers for Disease Control and Prevention, Atlanta, Georgia.
51
Monash University, Melbourne, Victoria, Australia.
52
Department of Epidemiology and Public Health, University College London, London, United Kingdom.
53
Norwegian Institute of Public Health, Oslo, Norway.
54
MRC Integrative Epidemiology Unit at the University of Bristol, Bristol, United Kingdom.
55
CUNY School of Medicine, City University of New York, New York.
56
Centre for Nutrition, Prevention and Health Services, National Institute for Public Health and the Environment (RIVM), Bilthoven, the Netherlands.
57
Feinberg School of Medicine, Northwestern University, Chicago, Illinois.
58
Albert Einstein College of Medicine, New York, New York.
59
Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, United Kingdom.

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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