Physical activity and risk of venous thromboembolism: systematic review and meta-analysis of prospective cohort studies

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Abstract

The inverse association between physical activity and arterial thrombotic disease is well established. Evidence on the association between physical activity and venous thromboembolism (VTE) is divergent. We conducted a systematic review and meta-analysis of published observational prospective cohort studies evaluating the associations of physical activity with VTE risk. MEDLINE, Embase, Web of Science, and manual search of relevant bibliographies were systematically searched until 26 February 2019. Extracted relative risks (RRs) with 95% confidence intervals (CIs) for the maximum versus minimal amount of physical activity groups were pooled using random effects meta-analysis. Twelve articles based on 14 unique prospective cohort studies comprising of 1,286,295 participants and 23,753 VTE events were eligible. The pooled fully-adjusted RR (95% CI) of VTE comparing the most physically active versus the least physically active groups was 0.87 (0.79–0.95). In pooled analysis of 10 studies (288,043 participants and 7069 VTE events) that reported risk estimates not adjusted for body mass index (BMI), the RR (95% CI) of VTE was 0.81 (0.70–0.93). The associations did not vary by geographical location, age, sex, BMI, and methodological quality of studies. There was no evidence of publication bias among contributing studies. Pooled observational prospective cohort studies support an association between regular physical activity and low incidence of VTE. The relationship does not appear to be mediated or confounded by BMI.

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Most cited references 40

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2014 ESC guidelines on the diagnosis and management of acute pulmonary embolism.

Stavros V Konstantinides, Adam Torbicki, Giancarlo Agnelli … (2014)

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Explaining heterogeneity in meta-analysis: a comparison of methods.

S G Thompson, S J Sharp (1999)

Exploring the possible reasons for heterogeneity between studies is an important aspect of conducting a meta-analysis. This paper compares a number of methods which can be used to investigate whether a particular covariate, with a value defined for each study in the meta-analysis, explains any heterogeneity. The main example is from a meta-analysis of randomized trials of serum cholesterol reduction, in which the log-odds ratio for coronary events is related to the average extent of cholesterol reduction achieved in each trial. Different forms of weighted normal errors regression and random effects logistic regression are compared. These analyses quantify the extent to which heterogeneity is explained, as well as the effect of cholesterol reduction on the risk of coronary events. In a second example, the relationship between treatment effect estimates and their precision is examined, in order to assess the evidence for publication bias. We conclude that methods which allow for an additive component of residual heterogeneity should be used. In weighted regression, a restricted maximum likelihood estimator is appropriate, although a number of other estimators are also available. Methods which use the original form of the data explicitly, for example the binomial model for observed proportions rather than assuming normality of the log-odds ratios, are now computationally feasible. Although such methods are preferable in principle, they often give similar results in practice. Copyright 1999 John Wiley & Sons, Ltd.

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Cardiovascular risk factors and venous thromboembolism: a meta-analysis.

Walter Ageno, Cecilia Becattini, Timothy Brighton … (2008)

The concept that venous thromboembolism (VTE) and atherosclerosis are 2 completely distinct entities has recently been challenged because patients with VTE have more asymptomatic atherosclerosis and more cardiovascular events than control subjects. We performed a meta-analysis to assess the association between cardiovascular risk factors and VTE. Medline and EMBASE databases were searched to identify studies that evaluated the prevalence of major cardiovascular risk factors in VTE patients and control subjects. Studies were selected using a priori defined criteria, and each study was reviewed by 2 authors who abstracted data on study characteristics, study quality, and outcomes. Odds ratios or weighted means and 95% confidence intervals (CIs) were then calculated and pooled using a random-effects model. Statistical heterogeneity was evaluated through the use of chi2 and I2 statistics. Twenty-one case-control and cohort studies with a total of 63 552 patients met the inclusion criteria. Compared with control subjects, the risk of VTE was 2.33 for obesity (95% CI, 1.68 to 3.24), 1.51 for hypertension (95% CI, 1.23 to 1.85), 1.42 for diabetes mellitus (95% CI, 1.12 to 1.77), 1.18 for smoking (95% CI, 0.95 to 1.46), and 1.16 for hypercholesterolemia (95% CI, 0.67 to 2.02). Weighted mean high-density lipoprotein cholesterol levels were significantly lower in VTE patients, whereas no difference was observed for total and low-density lipoprotein cholesterol levels. Significant heterogeneity among studies was present in all subgroups except for the diabetes mellitus subgroup. Higher-quality studies were more homogeneous, and significant associations remained unchanged. Cardiovascular risk factors are associated with VTE. This association is clinically relevant with respect to individual screening, risk factor modification, and primary and secondary prevention of VTE. Prospective studies should further investigate the underlying mechanisms of this relationship.

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Author and article information

Contributors

Setor K. Kunutsor:

ORCID: http://orcid.org/0000-0002-2625-0273

skk31@cantab.net

Journal

Journal ID (nlm-ta): Eur J Epidemiol

Journal ID (iso-abbrev): Eur. J. Epidemiol

Title: European Journal of Epidemiology

Publisher: Springer Netherlands (Dordrecht )

ISSN (Print): 0393-2990

ISSN (Electronic): 1573-7284

Publication date (Electronic): 14 November 2019

Publication date PMC-release: 14 November 2019

Publication date (Print): 2020

Volume: 35

Issue: 5

Pages: 431-442

Affiliations

[1 ]GRID grid.410421.2, ISNI 0000 0004 0380 7336, National Institute for Health Research Bristol Biomedical Research Centre, , University Hospitals Bristol NHS Foundation Trust and University of Bristol, ; Bristol, UK

[2 ]GRID grid.5337.2, ISNI 0000 0004 1936 7603, Musculoskeletal Research Unit, Translational Health Sciences, Bristol Medical School, , University of Bristol, ; Learning and Research Building (Level 1), Southmead Hospital, Bristol, BS10 5NB UK

[3 ]GRID grid.412326.0, ISNI 0000 0004 4685 4917, Division of Cardiology, Department of Internal Medicine, , Oulu University Hospital, ; Oulu, Finland

[4 ]GRID grid.412934.9, ISNI 0000 0004 0400 6629, Leicester Diabetes Centre, , Leicester General Hospital, ; Gwendolen Road, Leicester, LE5 4WP UK

[5 ]Diabetes Research Centre, University of Leicester, Leicester General Hospital, Gwendolen Road, Leicester, LE5 4WP UK

[6 ]Exercise Medicine Clinic, Rio de Janeiro, Brazil

[7 ]GRID grid.8652.9, ISNI 0000 0004 1937 1485, University of Ghana Hospital, ; Legon, Ghana

[8 ]GRID grid.9668.1, ISNI 0000 0001 0726 2490, Institute of Public Health and Clinical Nutrition, , University of Eastern Finland, ; Kuopio, Finland

[9 ]GRID grid.9681.6, ISNI 0000 0001 1013 7965, Faculty of Sport and Health Sciences, , University of Jyväskylä, ; Jyvaskyla, Finland

[10 ]GRID grid.460356.2, ISNI 0000 0004 0449 0385, Department of Medicine, , Central Finland Health Care District, ; Jyvaskyla, Finland

Author information

Setor K. Kunutsor http://orcid.org/0000-0002-2625-0273

Article

Publisher ID: 579

DOI: 10.1007/s10654-019-00579-2

PMC ID: 7250794

PubMed ID: 31728878

SO-VID: 43a5e0c1-fa62-4ec1-b911-32cc16ff5295

License:

Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.

History

Date received : 26 March 2019

Date accepted : 5 November 2019

Funding

Funded by: FundRef http://dx.doi.org/10.13039/501100000272, National Institute for Health Research;

Award ID: BRC-1215-20011

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ScienceOpen disciplines: Public health

Keywords: physical activity,venous thromboembolism,cohort study,risk factor,systematic review,meta-analysis

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ScienceOpen disciplines: Public health

Keywords: physical activity, venous thromboembolism, cohort study, risk factor, systematic review, meta-analysis

Physical activity and risk of venous thromboembolism: systematic review and meta-analysis of prospective cohort studies

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Most cited references 40

2014 ESC guidelines on the diagnosis and management of acute pulmonary embolism.

Explaining heterogeneity in meta-analysis: a comparison of methods.

Cardiovascular risk factors and venous thromboembolism: a meta-analysis.

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