Risk of thrombosis: Another reason to avoid sitting?

Today’s guest post comes from PhD student Bethany Howard.  You can find out more about Bethany at the bottom of this post.  The study that she is discussing was recently published in MSSE, and can be found here.  We have discussed earlier findings from this study in the past on Obesity Panacea, available here.

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I am sure by now you have all heard the messages to avoid your chair and the increased risk of premature death it may be kindly bestowing on you. Indeed there are slogans out there such as “your chair is sending you to an early grave”, “make a stand”, “sitting is the new smoking” and big corporations that promote this important rapidly evolving area of research – that is the study of the health consequences of “too much sitting”.

What do we know?

It’s important to appreciate that these messages about the hazards of sitting are not entirely new – as early as the 1950’s physicians were advocating breaks from sitting. Homans (1954) suggested that the “Such matters  are important enough to suggest the advisability of making movement of the toes, feet and lower legs when one is sitting for long periods and of getting up and exercising when opportunity offers.” Such recommendations were drawn from cases of thrombosis – the formation of a blood clot that obstructs blood flow – with prolonged sitting at the theatre, whist watching TV and during travel.

Today the research initiated from such early work is now evident in the recommendations when we fly. For those of you who are avid jetsetters you will be familiar with the announcement to “get up and move around to reduce the risk of deep vein thrombosis (VT)”. There is now evidence to suggest that this increased risk extends to prolonged bus travel and prolonged workplace sitting. But the question we wanted to ask with our experimental study published recently in Medicine & Science and Sports & Exercise was:

What are the potential reasons for this increased risk?

Virchow describes three components that contribute to the risk of VT, known commonly as Virchows Triad: Impaired blood flow, Hyper-coagulation and Disturbed Endothelium. Of these, there is substantial evidence linking sitting to impaired blood flow, limited evidence on hypercoagulation and little or no evidence for possible effects on the endothelium. The majority of studies that have been conducted in this area have focused on air travel. Although high amounts of sitting are present, air travel does not provide the typical environment in which sitting accumulates in our daily lives.

What did we do?

In order to address these knowledge gaps, we used an experimental study design to examine the effects of sitting (uninterrupted) on markers of thrombosis, specifically markers that relate to clot formation (through haemostasis) and blood viscosity. We then compared these effects to interrupted sitting, to assess whether breaks involving walking were indeed effective at reducing thrombotic risk. To do this we undertook an acute randomized cross-over trial design with subjects being their own controls. The trial consisted of 3 conditions all of which lasted for 7 hours:

1)      Uninterrupted sitting

2)      Sitting interrupted by light-intensity walking breaks

3)      Sitting interrupted by moderate-intensity walking breaks

The two different intensity activity break conditions were incorporated into the study design to determine if there is an intensity effect of the breaks. That is, for a benefit to be seen, do the breaks need to be of a higher intensity? Earlier observational work from our group using objective activity monitoring suggested that the intensity wasn’t as important – having breaks, and frequently seemed most important.

What did we find?

For the common blood viscosity markers (plasma volume, hematocrit, hemoglobin, red blood cells) breaks were beneficial irrespective of the intensity. That is, with the introduction of breaks in sitting time blood viscosity appeared to be reduced. This is likely to have improved blood flow, one of three elements of Virchows triad.

The novel finding of our study however, was the impact on thrombotic risk markers. The major thrombotic risk (and also cardiovascular risk) marker is fibrinogen. Fibrinogen is a protein involved in platelet aggregation, clot formation and a key determinant of blood viscosity. Following prolonged uninterrupted sitting fibrinogen increased. This effect was attenuated by light but not moderate-intensity activity breaks in sitting. The attenuation was somewhat small however, there were individuals who responded much more than others, with the greatest difference between the uninterrupted sitting and light breaks being as high as 1g/l (A 1 g/l change in fibrinogen has been linked to an approximate doubling of risk of heart disease and stroke).

As mentioned we did not see a difference (compared to uninterrupted sitting) for fibrinogen with moderate-intensity breaks. In the paper we rationalized this by suggesting that the higher intensity may have caused an acute inflammatory effect. Although, as is the case with exercise this is likely not deleterious.

What does this mean?

Our findings add to the evidence for an increased thrombotic risk when sitting. They suggest that not only may impaired blood flow be involved, but that changes in fibrinogen could contribute. Importantly we found that short, frequent light-intensity walking breaks were effective at reducing the increased thrombotic risk. Such breaks provide a practical and feasible method of reducing sitting time in the many places in which sitting accumulates (in the office, whilst watching TV). Not many people want to work up a sweat every 20 minutes, but a light stroll is something that most people can do comfortably. In addition to getting up on the plane, a simple, somewhat less scary and more truthful message than “your couch is killing you” that we use in our studies and that you can use every day is to “Stand Up, Sit Less, Move More”.

Reference:Impact on Hemostatic Parameters of Interrupting Sitting with Intermittent Activity. Howard BJ, Fraser SF, Sethi P, Cerin E, Hamilton MT, Owen N, Dunstan DW, Kingwell BA. Med Sci Sports Exerc. 2013 Feb 22. [Epub ahead of print]

About the author: Bethany Howard is a PhD student at the Baker IDI in Melbourne Australia and an avid rower. Her current research focuses on sedentary behaviour, with sub-disciplines in vascular physiology and women’s health.

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14 Responses to Risk of thrombosis: Another reason to avoid sitting?

  1. Kurgen says:

    Something about this study does not add up. Some facts to consider:

    • The population prevalence of thrombosis is ~5%.
    • This study suggests that ~7hrs uninterrupted sitting caused an increase in thrombotic risk markers.
    • Objective assessments (via accelermontry) show that an adult typically spends between 8-12hrs of EVERY day sedentary.

    Given the results suggested in Howard et al., 2012, the public health system SHOULD be drowning in thrombotic-related diseases? However, it is clearly not.

    Correlation does not imply causation. A couple of increased biomarkers, so what?

    Also:
    ‘Sitting is the new smoking’…really? This is really stretching it. Have a look who is saying this? Conflict of interest anyone…

    ‘Kindly bestowing on you’…LOL

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    • Travis Saunders, MSc, CEP says:

      Thanks for your comment. A few things…

      You’re right that the average person spends >50% of their day sitting. But that’s not *uninterrupted* sitting. This study, and others using the same dataset, suggest that sitting isn’t so bad when you take frequent breaks (which is likely the case for many of the folks in the general population).

      This study wasn’t looking at correlations, it was an intervention, which gives a good idea of cause and effect. Based on their design, we can be pretty sure that forcing people to sit without interruption is what caused the increases in risk markers. People throw around the correlation vs causation argument a lot, and with good reason, but this is one cause where it does not apply. This study actually helps to explain *why* uninterrupted sitting is associated with increased risk of thrombosis in correlation studies, by shedding light on the underlying mechanisms. It also suggests that frequent standing/walking breaks are probably a way to reduce the risk of thrombosis (again, not a shock, but nice to have the mechanistic evidence).

      As for the “sitting is the new smoking” line, I think you missed the context. Here is the article’s conclusion, which clearly undercuts that message:

      In addition to getting up on the plane, a simple, somewhat less scary and more truthful message than “your couch is killing you” that we use in our studies and that you can use every day is to “Stand Up, Sit Less, Move More”.

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  2. Kurgen says:

    Let’s look at this from another angle.

    The dose in this study = 7hrs of uninterrupted sitting.

    Now, ask yourself a question, does such a dose of sitting occur in free living settings? Although, the daily movement patterns of free-living adults are not well documented, logically this seems excessive. Indeed, apart from long haul flights, when does 7rhs of uninterrupted sitting occur? Even those in highly sedentary jobs (i.e. call centers & data entry) would not spend 7hrs straight sitting.

    The delicious irony here is that if anything the second condition ‘sitting interrupted by light-intensity walking breaks’ more closely replicates ‘typically’ daily movement patterns. Such as, standing up and walking for morning/afternoon tea & lunch, and bathroom breaks.

    Therefore, it is YOU that has missed the context. There is a mismatch between what this experiment showed and what really occurs in a real world setting. Ergo, it is not surprising that they saw elevated bio-markers, because the dose of sitting in non-physiological.

    Don’t get me started on Hamilton’s ‘classic’ rodent hind-limb suspension studies. 4hrs of hind-limb suspension is NOT the same as sitting behaviors in free-living adults. While were on the subject, bed rest studies are NOT the same as the sitting behaviors in free-living adults.

    Exercise physiologists have long know that different exercise bouts have vastly different physiological consequences. For example, you do not compare the physiological consequences of running a 1okm at a slow steady pace to those observed in 400m sprint.

    The same should apply to sitting behaviors. Compare apples with apples.

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  4. Peter Gibson says:

    Kurgen – your criticisms are unbalanced and somewhat naive. The research environment needs to be controlled so that changes can be adequately captured. In some ways such controlled data is MORE informative because it removes all the ‘fuzz’ associated with real life. Some researchers setup studies with the intention of achieving ecological validity (i.e. make things as real life as possible) – which is also useful, however it fails to tease out the biomarkers that can be changed with intervention and clearly representing real life is a tricky business. If you have read the literature recently you will pick up that sedentary behaviour in itself now appears to have unique physiology that is distinct from lack of physical activity. Hamiltons work has been insightful here. If you have criticism over the study design comparing apples with oranges – perhaps you might be better placed to provide some constructive feedback and suggestion for the authors and future researchers working in the field. What would you measure? How would you run the experiment? Clearly you have some ideas that would be of benefit, given your comments.

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    • Kurgen says:

      ‘Kurgen –your criticisms are unbalanced and somewhat naïve’… your opinion.

      Look, I’ll admit to being deliberately provocative in my previous post. My reasons were to spark a debate, not to attack others’ research and methodologies.

      My issue is with the inference that sitting is one of the key ‘bad guys’ in chronic disease development. Moreover, with the unquestioning nature of those who support this hypothesis.

      ‘Fuzz’ associated with real life’…. beautifully said …. In reality, chronic disease development is multi-factorial and complex. Stress, psychological, nutrition and lifestyle factors, genetics/epigenetics and SES all play a role. I’m remain unconvinced that these factors have been properly adjusted for in SB research to date. A tricky task I know, but a necessary one.

      “If you have read the literature’ ….I can assure you, I’ve done my reading.

      “recently you will pick up that sedentary behaviour in itself now appears to have unique physiology that is distinct from lack of physical activity”….

      Ummm, I’m not sure I follow, I did not question this. My point was that the dose of SB is the issue. I agree that controlled experiments are necessary to describe potential mechanisms. But you have to consider the dose. The dose is the key factor in pharmaceutical trials and behavioural modification interventions alike. The same should apply to SB/inactivity physiology experiments.

      I rarely if at all see the authors acknowledge the fact that jacking up the hind legs of a rat for 4hrs, or subjecting a person to 7hrs of uninterrupted sitting may not directly translate to what actually occurs in a real life setting.

      ‘Constructive feedback and suggestion for the authors and future researchers working in the field’

      Ok, I’ll have a go…

      Phase One – ‘what really happens’

      Establish objectively (via accelerometry and inclinometry) the typically movement and SB patterns among free living populations. Choose 3 or 4 of movement and SB patterns ranging from theoretically ‘most harmful’ to theoretically ‘least harmful’.

      Phase Two – ‘is what really happens bad for health’

      To eliminate the ‘fuzz’, test each of these behaviour patterns in a controlled experimental condition whilst monitoring cardio-metabolic biomarkers. Check across all four SB patterns to see if a clear trend occurs. One would need to consider duration (days/weeks) of the experiment and the population group (age, BMI ect)

      A difficult task, but not impossible. Issues such as cost, participant burden and recruitment would be limitations. Nevertheless, such research may put to bed some of the criticisms of the field.

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      • Peter Gibson says:

        Some good comments and suggestions Kurgen – apologies if I came across a little aggressive, but perhaps your latest post is the way you should have started if you wanted to prompt a useful discussion. It is a good point that 7 hours of uninterrupted may not accurately reflect what is actually going on out there. But again to elucidate the health effect it may have this is probably the best way to tease out the mechanisms responsible and their magnitude. I do agree though that the current study is a little extreme and this should be stated in the conclusions, and, at the very least, as a key limitation.

        Interesting points with phase 1, however I think the literature is pretty clear that the key sedentary behaviour is prolonged uninterrupted sitting (i.e. people sit too much and unload their muscles for prolonged periods). It is obviously going to vary between SES, lifestyle, nutrition etc, but these are separate questions in themselves – the question being asked here is targeting prolonged sitting, therefore the other factors surrounding this key intervention need to be controlled for if one is to elucidate the effect of prolonged sitting (or breaking it up throughout the day), while along the way controlling for nutrition, stress etc where feasible. If they come up as important, then comes the new question for future research studies – small steps.

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  5. Jaideep Sidhu says:

    Hi,

    Any idea if shaking one’s leg (or legs) intermittenly has any positive effects?
    Thanks.

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  6. Jaideep Sidhu says:

    Hi,

    Any idea if shaking one’s leg (or legs) intermittenly has any positive effects?
    Thanks.

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    • Travis Saunders, MSc, CEP says:

      Great question. My guess is that it can’t hurt… if the problem is the lack of muscle activity, then more muscle activity should help, even if it’s just in the form of fidgeting/shaking. But it may not help very much… something that someone will hopefully look at in the future!

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      • Jaideep Sidhu says:

        Right, in the least it won’t hurt. Thanks.

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  7. Peter Gibson says:

    P.s. Hamiltons group have also done work with humans (2011). The mouse model uncovers useful questions that cant always be tested in humans. The field is in its infancy experimentally – many questions remain to be seen and tested but one ought to start with basics and do them well. Bed rest has been noted as too extreme to be linjed to sedentary behaviour in recent reviews (by this group i believe) – hence the move/focus towards prolonged sitting.

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  8. Kurgen says:

    Nothing to add Travis?

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    • Travis says:

      Not especially – Peter has brought up pretty much anything I would have mentioned and then some! :)

      I will say that the phases of your suggested research plan (especially phase 1) are already underway (here is one example of many, from my colleague Rachel Colley: http://www.biomedcentral.com/1471-2458/13/200/abstract).

      But there’s no sense waiting for one aspect of research (e.g. characterizing movement patterns) to be 100% complete before beginning on the other phases, and since we have no idea of the dose response between SB and health, I think it makes sense to begin with large doses (e.g. 7 hours) and work our way down to things that are more and more ecologically valid.

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