Abstract
Introduction: Patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) present with a range of symptoms including post-exertional malaise (PEM), orthostatic intolerance, and autonomic dysfunction. Dysfunction of the blood vessel endothelium could be an underlying biological mechanism, resulting in inability to fine-tune regulation of blood flow according to the metabolic demands of tissues. The objectives of the present study were to investigate endothelial function in ME/CFS patients compared to healthy individuals, and assess possible changes in endothelial function after intervention with IV cyclophosphamide.Methods: This substudy to the open-label phase II trial “Cyclophosphamide in ME/CFS” included 40 patients with mild-moderate to severe ME/CFS according to Canadian consensus criteria, aged 18–65 years. Endothelial function was measured by Flow-mediated dilation (FMD) and Post-occlusive reactive hyperemia (PORH) at baseline and repeated after 12 months. Endothelial function at baseline was compared with two cohorts of healthy controls (N = 66 and N = 30) from previous studies. Changes in endothelial function after 12 months were assessed and correlated with clinical response to cyclophosphamide. Biological markers for endothelial function were measured in serum at baseline and compared with healthy controls (N = 30).Results: Baseline FMD was significantly reduced in patients (median FMD 5.9%, range 0.5–13.1, n = 35) compared to healthy individuals (median FMD 7.7%, range 0.7–21, n = 66) (p = 0.005), as was PORH with patient score median 1,331 p.u. (range 343–4,334) vs. healthy individuals 1,886 p.u. (range 808–8,158) (p = 0.003). No significant associations were found between clinical response to cyclophosphamide intervention (reported in 55% of patients) and changes in FMD/PORH from baseline to 12 months. Serum levels of metabolites associated with endothelial dysfunction showed no significant differences between ME/CFS patients and healthy controls.Conclusions: Patients with ME/CFS had reduced endothelial function affecting both large and small vessels compared to healthy controls. Changes in endothelial function did not follow clinical responses during follow-up after cyclophosphamide IV intervention.
Highlights
Patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) present with a range of symptoms including post-exertional malaise (PEM), orthostatic intolerance, and autonomic dysfunction
The purpose of this study was to explore: [1] endothelial function, measured by flow-mediated dilation (FMD) and postocclusive reactive hyperemia (PORH), in a Norwegian cohort of ME/CFS patients compared with healthy individuals, [2] changes in FMD and post-occlusive reactive hyperemia (PORH) from baseline to 12 months, and possible associations between clinical response to cyclophosphamide and changes in FMD/PORH over time
This study was performed as a substudy to the open-label phase II trial “Cyclophosphamide in myalgic encephalomyelitis/chronic fatigue syndrome” [29]
Summary
Patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) present with a range of symptoms including post-exertional malaise (PEM), orthostatic intolerance, and autonomic dysfunction. Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a disease that affects both children and adults and is associated with very low health-related quality of life [1, 2]. Patients present with hallmark symptoms such as post-exertional malaise (PEM), fatigue and lack of adequate restitution from rest or sleep, accompanied by pain, cognitive symptoms and sensory hypersensitivity [3, 4]. Orthostatic intolerance and autonomic dysfunction are frequently reported, and can present with symptoms such as light-headedness, nausea, concentration difficulties, sweating, palpitations, dyspnea, and chest pain after prolonged sitting or standing [6]
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