Sandvik, Miriam Kristine, Sørland, Kari, Leirgul, Elisabeth et al. · PloS one · 2023 · DOI
Quick Summary
This study found that people with ME/CFS have problems with how their blood vessels function—both the larger vessels and the smaller ones that deliver oxygen throughout the body. Researchers measured blood vessel response in 39 ME/CFS patients and compared them to healthy people, and found significant differences. Interestingly, when patients were treated over 18 months, their smaller blood vessel function improved slightly, though the larger blood vessels did not change.
Why It Matters
This is one of the few studies systematically measuring both large and small blood vessel function in ME/CFS, providing objective evidence that vascular dysfunction may be a biological feature of the disease. Understanding vascular abnormalities could help explain why ME/CFS patients experience fatigue, exercise intolerance, and post-exertional malaise, and may open new treatment pathways.
Observed Findings
ME/CFS patients had markedly reduced large-vessel endothelial function (FMD: 5.1% vs 8.2% in controls, p<0.0001)
ME/CFS patients had significantly lower small-vessel microvascular regulation (PORH: 1354 vs 2208 PU in controls, p=0.002)
Small-vessel function (PORH) improved over 18 months in the patient group (1354 to 1834 PU, p=0.028), but large-vessel function (FMD) did not
Rituximab treatment showed no differential benefit over placebo on vascular measures
POSH correlated significantly with physical activity (steps per 24 hours) at baseline, but FMD did not
Inferred Conclusions
Reduced macro- and microvascular endothelial function is a measurable biological abnormality in ME/CFS patients
Vascular dysfunction may contribute to the vascular homeostasis impairment underlying ME/CFS clinical presentation
Small-vessel and large-vessel dysfunction may involve different mechanisms, as evidenced by their lack of correlation and differential responses over time
Remaining Questions
What causes the vascular endothelial dysfunction in ME/CFS—is it primary or secondary to another pathological process?
Why does small-vessel function improve over time while large-vessel function does not, and what drives these differential improvements?
What This Study Does Not Prove
This study does not prove that vascular dysfunction causes ME/CFS symptoms—it only shows an association. The lack of correlation between FMD and PORH suggests these may reflect different physiological mechanisms, and it remains unclear which vascular changes are primary drivers of symptoms. The study also cannot determine why rituximab did not improve vascular function despite symptom improvement.
Does improving endothelial function directly improve ME/CFS symptoms, or are they independent manifestations of the underlying disease?
Can vascular dysfunction explain specific symptoms like post-exertional malaise and exercise intolerance, or is it one of multiple contributing factors?