Reduced Endothelial Function in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome-Results From Open-Label Cyclophosphamide Intervention Study.

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.