Peripheral endothelial dysfunction in myalgic encephalomyelitis/chronic fatigue syndrome, 2020, Scherbakov et al

[Andy]

Aims

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a complex multisystem disease. Evidence for disturbed vascular regulation comes from various studies showing cerebral hypoperfusion and orthostatic intolerance. The peripheral endothelial dysfunction (ED) has not been sufficiently investigated in patients with ME/CFS. The aim of the present study was to examine peripheral endothelial function in patients with ME/CFS.

Methods and results
Thirty‐five patients [median age 40 (range 18–70) years, mean body mass index 23.8 ± 4.2 kg/m2, 31% male] with ME/CFS were studied for peripheral endothelial function assessed by peripheral arterial tonometry (EndoPAT2000). Clinical diagnosis of ME/CFS was based on Canadian Criteria.

Nine of these patients with elevated antibodies against β2‐adrenergic receptor underwent immunoadsorption, and endothelial function was measured at baseline and 3, 6, and 12 months follow‐up. ED was defined by reactive hyperaemia index ≤1.81. Twenty healthy subjects of similar age and body mass index were used as a control group.

Peripheral ED was found in 18 of 35 patients (51%) with ME/CFS and in 4 healthy subjects (20%, P < 0.05). Patients with ED, in contrast to patients with normal endothelial function, reported more severe disease according to Bell score (31 ± 12 vs. 40 ± 16, P = 0.04), as well as more severe fatigue‐related symptoms (8.62 ± 0.87 vs. 7.75 ± 1.40, P = 0.04) including a higher demand for breaks [9.0 (interquartile range 7.0–10.0) vs. 7.5 (interquartile range 6.0–9.25), P = 0.04]. Peripheral ED showed correlations with more severe immune‐associated symptoms (r = −0.41, P = 0.026), such as sore throat (r = −0.38, P = 0.038) and painful lymph nodes (r = −0.37, P = 0.042), as well as more severe disease according to Bell score (r = 0.41, P = 0.008) and symptom score (r = −0.59, P = 0.005).

There were no differences between the patient group with ED and the patient group with normal endothelial function regarding demographic, metabolic, and laboratory parameters. Further, there was no difference in soluble vascular cell adhesion molecule and soluble intercellular adhesion molecule levels.

At baseline, peripheral ED was observed in six patients who underwent immunoadsorption. After 12 months, endothelial function had improved in five of these six patients (reactive hyperaemia index 1.58 ± 0.15 vs. 2.02 ± 0.46, P = 0.06).

Conclusions
Peripheral ED is frequent in patients with ME/CFS and associated with disease severity and severity of immune symptoms. As ED is a risk factor for cardiovascular disease, it is important to elucidate if peripheral ED is associated with increased cardiovascular morbidity and mortality in ME/CFS.

Open access, https://onlinelibrary.wiley.com/doi/full/10.1002/ehf2.12633

 

[Snow Leopard]

Endothelial dysfunction is on my short list of possible explanations for the 2 day CPET findings. During exercise there is a fine dance between sympathetic nervous system vasoconstriction to prevent excessive blood pooling in parts of the body that are not being used, yet sufficient vasodilation in the muscle fibre capillaries.


The device costs around $30,000...

Also note that muscle capillarisation is not dictated by oxidative capacity:
https://jeb.biologists.org/content/jexbio/218/21/3377.full.pdf

 

[Marky]

Canadian criteria Time to check if there is a connection between peripheral endothelial dysfunction and cerebral hypoperfusion?

 

[ME/CFS Skeptic]

Hmm the data doesn't look very persuasive.

Why did they choose "A one-tailed P-value of <0.05 was considered statistically significant for clinical scores" I thouht it was standard to use two tailed values. If I understand correctly their choice makes it easier to declare differences as "statistically significant". They also didn't correct for multiple comparisons it seems.

 

[Forbin]

Cort has posted a blog on this today (6/9/20).

https://www.healthrising.org/blog/2...-vessels-arterioles-chronic-fatigue-syndrome/

This does seem interesting, as this kind of thing seems consistent with one of the mechanisms that Dr. Systrom has proposed for the excess oxygen in the RBC's returning to the heart, i.e. that a significant percentage of RBC's are shunting around the capillaries in the periphery (probably because they're too narrow). If you add impaired blood cells deformability into then mix, some kind of cellular hypoxia starts to look like a possibility.

I suppose this could cause weakness and possibly pain in the muscles, but it might be more important to ask what might be going on along these lines in the capillaries of the brain.

[ETA: It might even explain why I just stole @Marky's line of thought just two comments above without realizing it. ]

 

[butter.]

Canadian criteria Time to check if there is a connection between peripheral endothelial dysfunction and cerebral hypoperfusion?

of course there is, I do not understand why it takes them so long, Oaklander talks for 3 years now that SF are important for blood circulation of the brain,... the question is what drives what,... also mitochondria are very important for arterioles function,... we know whats the physical dsyfunction in many already, we do not necessarily need the root cause to treat it,...

 

[butter.]

Cort has posted a blog on this today (6/9/20).

https://www.healthrising.org/blog/2...-vessels-arterioles-chronic-fatigue-syndrome/

This does seem interesting, as this kind of thing seems consistent with one of the mechanisms that Dr. Systrom has proposed for the excess oxygen in the RBC's returning to the heart, i.e. that a significant percentage of RBC's are shunting around the capillaries in the periphery (because they're too narrow). If you add impaired blood cells deformability into then mix, some kind of cellular hypoxia starts to look like a possibility.

I suppose this could cause weakness and possibly pain in the muscles, but it might be more important to ask what might be going on along these lines in the capillaries of the brain.

well they are just f**** for different reasons in different people, there is very unlikely one reason for all patients, what we need is trials with stemcells f.e.