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

Samuel

Samuel

Senior Member (Voting Rights)
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
, 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

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(c) 2022 Research Square


via m-a fluks.
 
Last edited by a moderator:
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:
Seven ME/CFS patients had POTS (four in the morning and three in the afternoon) and eight healthy controls (six in the morning and two in the afternoon) also had POTS. Four ME/CFS patients had OH and one healthy control; thus, 16% of ME/CFS patients (11/67) and 13% of healthy controls (6/48) had abnormal cardiovascular responses to position changes after NLT, with no differences between two groups in terms of distribution. No participants had abnormal pulse pressure (PP) (less than 25% SBP). However, although no differences were found between groups in the postural autonomic responses, ME/CFS patients had higher values of BP and HR in both supine and standing position, and in individuals with and without POTS (p < 0.05 in all ANOVA comparisons)
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No difference in wrist temperatures:
Postural WT-related changes could only be measured in 42 ME/CFS patients (15 in the morning and 27 in the afternoon) and in 33 healthy controls (17 in the morning and 16 in the afternoon). Mean WT varied according to the time of the day, and was always higher in the afternoon (WT morning: 28.5±0.37ºC and WT afternoon: 31.5±0.27ºC) but no differences were found between the groups (
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This is the finding from the abstract I'm most interested in - the proteins possibly indicating endothelial dysfunction:
ME/CFS patients showed significantly higher levels of plasma ET-1 and VCAM-1 proteins than healthy controls (p < 0.05 adjusted for both age and BMI). However, no differences were found for ICAM-1 protein (Table 2). We stress that these variables could only be studied in the morning participants due to the circadian rhythm of endothelial biomarkers.
Click to expand...

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.
 
Seven ME/CFS patients had POTS (four in the morning and three in the afternoon) and eight healthy controls (six in the morning and two in the afternoon) also had POTS
Click to expand...
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.
 
rvallee said:
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.
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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.
 
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.
 
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.
 
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


 
rvallee said:
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.
Click to expand...
Hutan said:
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.
Click to expand...

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.
 
wigglethemouse said:
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."
Click to expand...
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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