The endothelium – a thin layer of cells lining every blood vessel – plays a pivotal role in regulating the dilation and constriction of blood vessels, blood clotting, and inflammatory responses.
Emerging theories propose that post-viral conditions, including ME/CFS and long COVID, involve damage to the endothelium. The resulting endothelial dysfunction may lead to the formation of microclots which block capillaries, reducing tissue blood flow and oxygenation, and potentially driving symptoms such as fatigue, cognitive impairment and pain.
Endothelial dysfunction is also characterised by reduced nitric oxide production. In a healthy endothelium, increased blood flow triggers nitric oxide release which aids blood vessel dilation, allowing more blood to flow through. This physiological response is referred to as flow-mediated dilation, and can be assessed in order to gauge whether or not the endothelium is functioning properly.
Through assessing flow-mediated dilation, Dr Marie Mclaughlin and colleagues found that individuals with ME/CFS and those with long COVID displayed notable and similarly impaired endothelial function. This highlights potential vascular (blood vessel-related) involvement in the pathogenesis of these conditions.
What did the study do?
The study aimed to compare flow-mediated dilation between individuals with ME/CFS, those with long COVID, and healthy controls. The rationale behind selecting these patient groups was that, while vascular function impairments have been reported in people with ME/CFS and those with long COVID, they have never been compared directly in the same study, despite considerable overlap between the conditions.
Recruited via social media, the study included 51 participants in total – 17 with ME/CFS, 17 with long COVID, and 17 healthy controls. The paper does not mention whether ME/CFS diagnoses were confirmed or, if so, which diagnostic/research criteria were used. Whilst the healthy controls were matched with the disease cohorts in terms of age, there were some substantial differences in body mass index (BMI), blood pressure, and heart rate between the groups.
The authors mention that to “reduce participant burden, participants were not advised to fast before the test”. Yet, they acknowledge that dietary intake immediately prior to flow-mediated dilation assessment can have a potentially confounding effect on the results.
Assessment of flow-mediated dilation involved four main steps:
- Ultrasound scans of the brachial artery (a major blood vessel in the arm) were taken to obtain baseline measurements of blood vessel diameter and blood flow.
- A pressure cuff around the upper forearm was inflated, temporarily blocking blood flow to the lower arm.
- After five minutes, the cuff was deflated, allowing a rush of blood to flow through the brachial artery. Once again ultrasound scans were used to monitor blood vessel diameter and blood flow.
- Any increase in blood vessel diameter following cuff release indicates dilation. The extent of flow-mediated dilation for each participant was taken as the highest percentage increase in vessel diameter compared to baseline.
What did they find?
The study demonstrated significantly impaired endothelial function in both ME/CFS and long COVID groups in comparison to healthy controls as assessed by flow-mediated dilation. However, the effect size of these differences was relatively small. The smaller the effect size, the less the practical significance of results (their real-world impact), and vice versa.
As mentioned in the paper, it might be hypothesised that individuals with ME/CFS would have poorer vascular function than people with long COVID, due to a longer duration of post-viral illness and ‘multi-system deconditioning’ (which is known to reduce flow-mediated dilation). Yet, interestingly, there was no difference in flow-mediated dilation between participants with ME/CFS and those with long COVID. The authors state this could suggest that endothelial damage is experienced in the early post-viral phase, without a further reduction in flow-mediated dilation after this initial reduction, and that impairment in flow-mediated dilation is unlikely to be due to deconditioning.
It is also worth noting that there was a large spread of the data, meaning that some individuals with ME/CFS or long COVID had “very severely impaired endothelial function, whereas others had comparable flow-mediated dilation to that of the controls”. According to the authors, this suggests “endothelial dysfunction may not be ubiquitous in post-viral conditions” with potentially different disease trajectories and symptomology on an individual level.
In summary, the study found that participants with either ME/CFS or long COVID had significantly impaired endothelial function in comparison to controls as assessed by flow-mediated dilation. Also, there were no significant differences in endothelial function between the ME/CFS and long COVID groups, further highlighting the overlap between the two conditions.
However, there may be questions about the practical significance of the results given the often small effect sizes, in addition to a large spread of data making it challenging to generalise findings. Furthermore, the study had major limitations which go beyond the common issue of having a small sample size.
Not providing details of criteria used or whether participants had a confirmed diagnosis of ME/CFS or long COVID limits our ability to draw conclusions and compare findings with other research. As post-exertional malaise (PEM) is a cardinal feature of ME/CFS, it would have at least been useful to mention if any of the participants experienced this symptom. Additionally, the participants were not matched for BMI or blood pressure despite knowledge that both variables can affect flow-mediated dilation.
While the researchers mention that expert consensus guidelines for flow-mediated dilation assessment were followed where possible, they did not adhere to recommendations for fasting. Certain foods, such as those rich in nitric oxide precursors, can affect blood vessel diameter. Therefore, the lack of fasting prior to the study may have had a confounding effect on the results.
Although this study provides interesting insights into endothelial function in ME/CFS and long COVID, further research with improved methodology is necessary to understand the implications for cardiovascular health in these conditions and to explore potential interventions.
- Read our previous article on endothelial dysfunction in ME/CFS
- Read our two-part series exploring the heart and circulation in ME/CFS: