Circadian skin temperature rhythm and dysautonomia in [ME/CFS]: ... endothelin-1 in vascular dysregulation, 2023, Cambras et al

Discussion in 'ME/CFS research' started by Samuel, Oct 2, 2022.

  1. Samuel

    Samuel Senior Member (Voting Rights)

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    Post with a link to the final paper here
    ********


    Source: Research Square
    Preprint
    Date: September 21, 2022
    URL: https://www.researchsquare.com/article/rs-2044838/v1


    Circadian skin temperature rhythm and dysautonomia in Myalgic
    Encephalomyelitis/Chronic Fatigue Syndrome: the role of
    endothelin-1 in the vascular dysregulation
    -------------------------------------------------------------
    Trinitat Cambras(1), Maria Fernanda Zeron-Rugerio(1), Antoni
    Diez-Noguera(1), Maria Cleofe Zaragoza(2), Joan Carles Domingo
    (1), Ramon Sanmartin-Sentanes(3), Jose Alegre-Martin(4), Jesus
    Castro-Marrero(5,*)
    1 Universitat de Barcelona
    2 Clinical Research Department, Laboratory Vinas
    3 Vall d'Hebron Hospital Universitari
    4 Hospital Universitari Vall d'Hebron Servei de Medicina Interna
    5 Vall d'Hebron Institut de Recerca
    * Corresponding author. Email: jesus.castro@vhir.org


    Abstract

    Purpose
    There is accumulating evidence of autonomic dysfunction in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS); however, little is known about its association with circadian rhythms and endothelial dysfunction. This study aimed to explore the relationship between autonomic responses using an orthostatic test, skin temperature circadian variations, and circulating endothelial biomarkers in ME/CFS.

    Methods
    Sixty-seven adult female ME/CFS patients and 48 matched healthy controls were enrolled. Demographic and clinical characteristics suggestive of autonomic disturbances were assessed using validated self-reported outcome measures. Postural changes in blood pressure [BP], heart rate [HR], and wrist temperature (WT) were recorded during the orthostatic test. Actigraphy during one week was used to determine the 24-hour profile of peripheral temperature and motor activity. Circulating endothelial biomarkers were also measured as indicators of endothelial functioning.

    Results
    ME/CFS patients showed higher BP and HR values than healthy controls at rest (p<0.05 for both), and also higher amplitude of the circadian activity rhythm (p<0.01). Circulating levels of endothelin-1 (ET-1) and vascular cell adhesion molecule-1 (VCAM-1) were significantly higher in ME/CFS (p<0.05). In ME/CFS, ET-1 levels were associated with the stability and amplitude of the temperature rhythm, (p<0.01), and also with the self-reported questionnaires (p<0.001).

    Conclusions
    ME/CFS patients exhibited alterations in circadian rhythms and hemodynamic measures that are associated with endothelial dysfunction, supporting previous evidence of dysautonomia in ME/CFS. Future investigation in this area is needed to assess vascular tone abnormalities and dysautonomia which may provide therapeutic targets for ME/CFS.

    Keywords: chronic fatigue syndrome, circadian rhythms, endothelin-1, myalgic encephalomyelitis, skin temperature

    --------
    (c) 2022 Research Square


    via m-a fluks.
     
    Last edited by a moderator: Mar 2, 2023
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  2. Hutan

    Hutan Moderator Staff Member

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    Thanks for posting @Samuel. The study is interesting, although the sample sizes are pretty small and there was a problem with measurements not being taken at the same time of day.

    No differences in the occurrence of POT:

    No difference in wrist temperatures:

    This is the finding from the abstract I'm most interested in - the proteins possibly indicating endothelial dysfunction:
    Screen Shot 2022-10-02 at 12.40.21 pm.png
    The authors noted that levels of ET-1 correlated with self-reported symptom severity. I've got to go do something else, but it seems an interesting finding, in proteins that I think have come up in other studies.
     
  3. rvallee

    rvallee Senior Member (Voting Rights)

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    That can't be right. You can't be a healthy control and have POTS. Lots of people with dysautonomia don't even meet the criteria for increased heart rate because it falls short of the threshold. Odd.
     
  4. Hutan

    Hutan Moderator Staff Member

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    Yes, I think for a start they have confused POTS with POT (by which I mean, an incident of orthostatic tachycardia). But yes, the finding does seem very odd and perhaps raises questions about the validity of the whole study.

    On the other hand, is it possible that healthy people do sometimes have orthostatic tachycardia and the incidence of orthostatic tachycardia in ME/CFS is not at all unusual? I'd be very surprised if that (the bit about orthostatic tachycardia in ME/CFS not being abnormal) were true.
     
  5. dreampop

    dreampop Senior Member (Voting Rights)

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    I was only able to get through the first half of the methods paper, but this at least looks like more thorough and earnest attempt from a group I don't know about (in spain).

    Criteria was ICC from a single referral clinic in Barcelona. One important note is the authors say none of the controls were on medications, and for me/cfs no medications were stopped, and there is a long list of symptom management medications.
     
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  6. Creekside

    Creekside Senior Member (Voting Rights)

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    Comparisons with healthy controls are likely to show the differences between 'sick and inactive' people and 'healthy active' people, rather than be ME-specific.

    This morning I was trying to get an old chainsaw to work. There are three adjustments for the carburetor, and they all have to be set correctly to get the engine to run at all intended speeds and loads. Very finicky, and it's hard to know which control to set to which level to get the others to work properly, and the ideal settings are different for each individual engine (and fuel mix, altitude, etc). ME--and long Covid--might be similar to that, with one or more of our internal 'settings' mis-adjusted. Knowing that one factor, such as ET-1, is abnormal, may not be enough to figure the disease out. Still, any information is better than none.
     
  7. Sly Saint

    Sly Saint Senior Member (Voting Rights)

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    Skin Temperature Circadian Rhythms and Dysautonomia in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: The Role of Endothelin-1 in the Vascular Tone Dysregulation



    Abstract:
    There is accumulating evidence of autonomic dysfunction in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS); however, little is known about its association with circadian rhythms and endothelial dysfunction. This study aimed to explore the autonomic responses through an orthostatic test and analysis of the peripheral skin temperature variations and vascular endothelium state in ME/CFS patients.

    Sixty-seven adult female ME/CFS patients and 48 healthy controls were enrolled. Demographic and clinical characteristics were assessed using validated self-reported outcome measures.

    Postural changes in blood pressure, heart rate, and wrist temperature were recorded during the orthostatic test. Actigraphy during one week was used to determine the 24-h profile of peripheral temperature and activity. Circulating endothelial biomarkers were measured as indicators of endothelial functioning.

    Results showed that ME/CFS patients presented higher blood pressure and heart rate values than healthy controls in the supine and standing position (p < 0.05 for both), and also a higher amplitude of the activity rhythm (p < 0.01). Circulating levels of endothelin-1 (ET-1) and vascular cell adhesion molecule-1 (VCAM-1) were significantly higher in ME/CFS (p < 0.05). In ME/CFS, ET-1 levels were associated with the stability of the temperature rhythm (p < 0.01), and also with the self-reported questionnaires (p < 0.001).

    This suggests that ME/CFS patients exhibited modifications in circadian rhythm and hemodynamic measures, which are associated with endothelial biomarkers (ET-1 and VCAM-1). Future investigation in this area is needed to assess dysautonomia and vascular tone abnormalities, which may provide potential therapeutic targets for ME/CFS.

    https://www.mdpi.com/1422-0067/24/5/4835


     
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  8. wigglethemouse

    wigglethemouse Senior Member (Voting Rights)

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    A Bateman Horne Nasa Lean Test study from a few years ago reported 1/3 of healthy controls met the heart rate definition of tachycardia for POTS. I can't find the study but I did find my note of the definition for heart rate limit used.
    " (2) Postural orthostatic tachycardia syndrome (POTS) was defined as an increase of HR >30 bpm at any time during the 10-min NLT."

    The response when I queried this was that you need to confirm that there are abnormal symptoms reported during the test to rule out the healthy controls. In addition, I asked a POTS expert at a dysautonomia conference about this and they had the same answer about symptoms required. In my opinion, no-one has a good answer why so many healthy controls had a 30bpm rise.
     
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  9. Ravn

    Ravn Senior Member (Voting Rights)

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    I've noticed more and more people have started saying that for a POTS diagnosis the HR has to go up and stay up. Just speculating but maybe in the healthy people there's only a brief spike before their HR normalises again?
     
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  10. Sly Saint

    Sly Saint Senior Member (Voting Rights)

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  11. Dolphin

    Dolphin Senior Member (Voting Rights)

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