Peripheral endothelial dysfunction in myalgic encephalomyelitis/chronic fatigue syndrome

Abstract

AIMS: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a complex multisystem disease. Evidence for disturbed vascular regulation comes from  various studies showing cerebral hypoperfusion and orthostatic intolerance. The  peripheral endothelial dysfunction (ED) has not been sufficiently investigated in  patients with ME/CFS. The aim of the present study was to examine peripheral  endothelial function in patients with ME/CFS. METHODS AND RESULTS: Thirty-five  patients [median age 40 (range 18-70) years, mean body mass index 23.8 ± 4.2  kg/m(2) , 31% male] with ME/CFS were studied for peripheral endothelial function  assessed by peripheral arterial tonometry (EndoPAT2000). Clinical diagnosis of  ME/CFS was based on Canadian Criteria. Nine of these patients with elevated  antibodies against β2-adrenergic receptor underwent immunoadsorption, and  endothelial function was measured at baseline and 3, 6, and 12 months follow-up.  ED was defined by reactive hyperaemia index ≤1.81. Twenty healthy subjects of  similar age and body mass index were used as a control group. Peripheral ED was  found in 18 of 35 patients (51%) with ME/CFS and in 4 healthy subjects (20%, P <  0.05). Patients with ED, in contrast to patients with normal endothelial  function, reported more severe disease according to Bell score (31 ± 12 vs. 40 ±  16, P = 0.04), as well as more severe fatigue-related symptoms (8.62 ± 0.87 vs.  7.75 ± 1.40, P = 0.04) including a higher demand for breaks [9.0 (interquartile  range 7.0-10.0) vs. 7.5 (interquartile range 6.0-9.25), P = 0.04]. Peripheral ED  showed correlations with more severe immune-associated symptoms (r = -0.41, P =  0.026), such as sore throat (r = -0.38, P = 0.038) and painful lymph nodes (r =  -0.37, P = 0.042), as well as more severe disease according to Bell score (r =  0.41, P = 0.008) and symptom score (r = -0.59, P = 0.005). There were no  differences between the patient group with ED and the patient group with normal  endothelial function regarding demographic, metabolic, and laboratory parameters.  Further, there was no difference in soluble vascular cell adhesion molecule and  soluble intercellular adhesion molecule levels. At baseline, peripheral ED was  observed in six patients who underwent immunoadsorption. After 12 months,  endothelial function had improved in five of these six patients (reactive  hyperaemia index 1.58 ± 0.15 vs. 2.02 ± 0.46, P = 0.06). CONCLUSIONS: Peripheral  ED is frequent in patients with ME/CFS and associated with disease severity and  severity of immune symptoms. As ED is a risk factor for cardiovascular disease,  it is important to elucidate if peripheral ED is associated with increased  cardiovascular morbidity and mortality in ME/CFS.