Reduced Endothelial Function in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome-Results From Open-Label Cyclophosphamide Intervention Study. — CFSMEATLAS
Reduced Endothelial Function in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome-Results From Open-Label Cyclophosphamide Intervention Study.
Sørland, Kari, Sandvik, Miriam Kristine, Rekeland, Ingrid Gurvin et al. · Frontiers in medicine · 2021 · DOI
Quick Summary
This study found that blood vessels in people with ME/CFS don't work as well as they do in healthy people. The researchers measured how blood vessels widen and respond to changes in blood flow, and found these responses were reduced in ME/CFS patients. Interestingly, when patients received a strong immune-suppressing drug called cyclophosphamide, improvements in symptoms didn't match up with improvements in blood vessel function.
Why It Matters
Endothelial dysfunction—impaired regulation of blood flow—could explain key ME/CFS symptoms like orthostatic intolerance and post-exertional malaise. This study provides objective biological evidence of a vascular defect in ME/CFS, supporting the hypothesis that blood vessel dysfunction is a core feature of the disease rather than a secondary effect.
Observed Findings
ME/CFS patients had significantly reduced flow-mediated dilation (FMD 5.9% vs 7.7% in controls, p=0.005), indicating impaired large vessel endothelial function.
Post-occlusive reactive hyperemia (PORH) was significantly reduced in ME/CFS patients (median 1,331 vs 1,886 p.u. in controls, p=0.003), showing small vessel dysfunction.
55% of ME/CFS patients showed clinical improvement after 12 months of cyclophosphamide treatment.
Changes in endothelial function markers from baseline to 12 months did not correlate with clinical response to cyclophosphamide.
Serum biomarkers of endothelial dysfunction were similar between ME/CFS patients and healthy controls.
Inferred Conclusions
Reduced endothelial function affecting both large and small blood vessels is a measurable biological feature of ME/CFS.
Endothelial dysfunction may represent a primary pathological mechanism in ME/CFS distinct from the mechanisms targeted by cyclophosphamide.
Improvement in clinical symptoms after cyclophosphamide does not necessarily indicate restoration of endothelial function, suggesting multiple independent biological defects may occur in ME/CFS.
Remaining Questions
Does endothelial dysfunction directly cause ME/CFS symptoms like orthostatic intolerance and post-exertional malaise, or is it a secondary consequence of other disease processes?
What This Study Does Not Prove
This study does not prove that endothelial dysfunction causes ME/CFS symptoms, only that the two co-exist. The lack of correlation between endothelial function changes and clinical response to cyclophosphamide suggests endothelial dysfunction may not be the primary target of this drug's therapeutic effect, or that other mechanisms drive symptom improvement. The study cannot determine whether restoring endothelial function would improve symptoms.
What causes the endothelial dysfunction in ME/CFS, given that serum biomarkers did not reveal clear differences from controls?
Could therapies specifically targeting endothelial function improve ME/CFS symptoms, and would such improvement occur independently of cyclophosphamide's effects?
Do different ME/CFS patients have different degrees of endothelial dysfunction, and could this variation predict treatment response or symptom severity?