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Long Working Hours and Risk of Venous Thromboembolism

Kivimäki, Mika; Nyberg, Solja T.; Batty, G. David; Madsen, Ida E. H.; Tabák, Adam G. for the IPD-Work Consortium

doi: 10.1097/EDE.0000000000000862
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Department of Epidemiology and Public Health, University College London, London, United Kingdom

Clinicum, Faculty of Medicine, University of Helsinki, Helsinki, Finland

Finnish Institute of Occupational Health, Helsinki, Finland, m.kivimaki@ucl.ac.uk

Clinicum, Faculty of Medicine, University of Helsinki, Helsinki, Finland

Department of Epidemiology and Public Health, University College London, London, United Kingdom

National Research Centre for the Working Environment, Copenhagen, Denmark

Department of Epidemiology and Public Health, University College London, London, United Kingdom

Semmelweis University Faculty of Medicine, 1st Department of Medicine, Budapest, Hungary

We are unable to provide direct access to the data from the single studies analyzed here. Code is available on request.

The consortium is supported by NordForsk, the UK Medical Research Council (K013351), the Academy of Finland (311492), and a Helsinki Institute of Life Science fellowship for Kivimäki. Funding bodies for participating cohort studies are listed on their Web sites. The study was conducted independently of funding agencies. None of the funding agencies played an active role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the article; and decision to submit the article for publication.

The authors report no conflicts of interest.

Supplemental digital content is available through direct URL citations in the HTML and PDF versions of this article (www.epidem.com).

* Investigators of the IPD-Work Venous Thromboembolism group include (in alphabetic order): Lars Alfredsson, G. David Batty, Jakob B. Bjorner, Marianne Borritz, Hermann Burr, Nico Dragano, Jane E. Ferrie, Eleonor I. Fransson, Mark Hamer, Katriina Heikkilä, Markus Jokela, Ichiro Kawachi, Anders Knutsson, Mika Kivimäki, Markku Koskenvuo, Ida E. H. Madsen, Martin L. Nielsen, Maria Nordin, Solja T. Nyberg, Tuula Oksanen, Jan H. Pejtersen, Jaana Pentti, Reiner Rugulies, Paula Salo, Archana Singh-Manoux, Sakari B. Suominen, Adam G. Tabak, Töres Theorell, Jussi Vahtera, Marianna Virtanen, Hugo Westerlund, and Peter J. M. Westerholm.

This is an open access article distributed under the Creative Commons Attribution License 4.0 (CCBY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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To the Editor:

Venous thromboembolism (VTE) results from a blood clot that forms within a vein.1 It includes two subtypes: deep-vein thrombosis (a clot in a deepvein, usually in the leg) and pulmonary embolism (a sudden blockage in a lung artery). Studies of people sleeping in deck chairs in air-raid shelters during the second world war and, more recently, those of passengers on long-haul flights have linked extended periods of sitting to increased VTE risk.2 It is also the case that psychological stress can unfavorably influence blood coagulation and viscosity, potentially increasing the risk of VTE.3,4 People working long hours are often characterized by both sedentary behavior and stress, but to our knowledge, no studies are available on the association of this working pattern with VTE. This is therefore the focus of the present analyses.

We drew individual-level data from eight prospective cohort studies participating in the Individual–Participant–Data meta-analysis in Working Populations (“IPD-Work”) Consortium.5 We excluded people not in full-time employment and those with extant disease at study baseline. Working hours and participant characteristics were assessed at baseline (total N = 77,005 to 77,291 depending on the outcome; eAppendix; http://links.lww.com/EDE/B359). All study members were followed up for VTE for a mean of 9.7 years.

As previously,6–8 we defined ≥55 hours/week as long working hours, with a standard working week of 35–40 hours representing the reference category. Incident VTE was ascertained using linkage to electronic records for hospitalizations and deaths in national registers. We defined VTE using International Classification of Disease diagnostic codes (Table). During 830,550 person-years at risk, 539 VTE events were recorded: 350 with deep-vein thrombosis and 258 with pulmonary embolism (69 participants had both).

TABLE

TABLE

In the Table, we show associations between working hours and VTE. The hazard ratio of VTE for individuals working long hours compared with those working standard hours was 1.5 (95% confidence interval [CI] = 1.1, 2.1). The association with deep-vein thrombosis was stronger (hazard ratio = 1.7, 95% CI = 1.1, 2.5), while the association with pulmonary embolism was less robust (hazard ratio = 1.4, 95% CI = 0.8, 2.4). We found no evidence of heterogeneity across studies (I2 = 0.0%). There was no suggestion that these associations were explained by confounding by common vascular risk factors, including smoking, high alcohol intake, BMI, or leisure-time physical inactivity.

Long working hours have been shown to be associated with increased risk of arrhythmias.7 Irregular rhythm—by disrupting the flow of circulation—can cause blood to pool in the left atrial appendage, contributing to clot formation, especially in the presence of hypercoagulability, a condition also underlying VTE.1,2 The clot can then travel from the heart to the brain and result in a stroke.1,2 In agreement with this link is the observation of increased stroke risk in individuals who work long hours.6 The present study completes the picture by reporting an association between long working hours and hypercoagulability on the venous side of the circulation, as indicated by increased risk of VTE, in particularly deep-vein thrombosis.

These results should be viewed with the following limitations in mind. While we took into account a wide array of covariates, including lifestyle variables and occupational group, we did not have data on prior surgery, major trauma, or blood conditions that increase the tendency toward blood clotting, all of which increase the likelihood of VTE.2 Lack of adjustment for these characteristics, given that they are linked with reduced rather than increased working hours, may have led to an underestimation of the association with VTE. Unmeasured variation in working hours over time, if random, may also have attenuated observed associations by increasing exposure misclassification. Despite these concerns, our results nonetheless suggest that individuals who work long hours may experience an elevated risk of VTE.

Mika Kivimäki

Department of Epidemiology and Public Health

University College London

London, United Kingdom

Clinicum, Faculty of Medicine

University of Helsinki

Helsinki, Finland

Finnish Institute of Occupational Health

Helsinki, Finland

m.kivimaki@ucl.ac.uk

Solja T. Nyberg

Clinicum, Faculty of Medicine

University of Helsinki

Helsinki, Finland

G. David Batty

Department of Epidemiology and Public Health

University College London

London, United Kingdom

Ida E. H. Madsen

National Research Centre for the Working Environment

Copenhagen, Denmark

Adam G. Tabák;

for the IPD-Work Consortium*

Department of Epidemiology and Public Health

University College London

London, United Kingdom

Semmelweis University Faculty of Medicine

1st Department of Medicine

Budapest, Hungary

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REFERENCES

1. Di Nisio M, van Es N, Büller HR. Deep vein thrombosis and pulmonary embolism. Lancet. 2016;388:3060–3073.
2. Goldhaber SZ, Bounameaux H. Pulmonary embolism and deep vein thrombosis. Lancet. 2012;379:1835–1846.
3. Fang F, Fall K, Mittleman MA, et al. Suicide and cardiovascular death after a cancer diagnosis. N Engl J Med. 2012;366:1310–1318.
4. Kivimäki M, Steptoe A. Effects of stress on the development and progression of cardiovascular disease. Nat Rev Cardiol. 2018;15:215–229.
5. Kivimäki M, Nyberg ST, Batty GD, et al; IPD-Work Consortium. Job strain as a risk factor for coronary heart disease: a collaborative meta-analysis of individual participant data. Lancet. 2012;380:1491–1497.
6. Kivimäki M, Jokela M, Nyberg ST, et al; IPD-Work Consortium. Long working hours and risk of coronary heart disease and stroke: a systematic review and meta-analysis of published and unpublished data for 603,838 individuals. Lancet. 2015;386:1739–1746.
7. Kivimäki M, Nyberg ST, Batty GD, et al; IPD-Work consortium. Long working hours as a risk factor for atrial fibrillation: a multi-cohort study. Eur Heart J. 2017;38:2621–2628.
8. Sokejima S, Kagamimori S. Working hours as a risk factor for acute myocardial infarction in Japan: case-control study. BMJ. 1998;317:775–780.

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