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 = À0.41, P = 0.026), such as sore throat (r = À0.38, P = 0.038) and painful lymph nodes (r = À0.37, P = 0.042), as well as more severe disease according to Bell score (r = 0.41, P = 0.008) and symptom score (r = À0.59, 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.

Effects of Post-Exertional Malaise on Markers of Arterial Stiffness in Individuals with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

“…To the best of our knowledge, this is the first study to assess pre-and-post measures of AIx75 and PWV after a maximal exercise bout in ME/CFS. It has been demonstrated that ME/CFS patients suffer from impaired vascular function, identified from other measures such as the reactive hyperemia scale [ 20 ], markers of inflammation and oxidative stress [ 5 , 10 ], heart rate and blood pressure variability [ 26 ] as well as AIx75 and PWV [ 6 , 27 ]. Expanded research also suggests that completing physical activity may exacerbate ME/CFS symptoms and provoke an increased oxidative and inflammatory response [ 21 , 22 ].…”

“…An increased presence of CRP levels was also found in the CFS cohort compared to controls ( p < 0.01), further implying the correlation of chronic inflammation and artery stiffness in ME/CFS [ 6 ]. Recent research from Scherbakov and associates (2020), expanded upon the theory of vascular dysfunction in ME/CFS cohorts and found that peripheral endothelial dysfunction (ED) was also associated with increased ME/CFS symptom severity [ 20 ]. The pathogenesis of this mechanism is still not understood but can help provide prognostic information to assess cardiovascular morbidity and mortality in ME/CFS populations [ 20 ].…”

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Efficacy of Repeat Immunoadsorption

“…Moreover, an improvement in clinical symptoms could be achieved in seven of the patients, which lasted, in three patients, for more than 12 months [23]. Furthermore, the ME/CFS patients frequently suffer from endothelial dysfunction, which was also improved following IA [26]. These results provided first evidence that IA may be a therapeutic option in ME/CFS patients and the rapid relief from clinical symptoms may be explained by the removal of autoantibodies.…”

Angina Simultaneously Diagnosed with the Recurrence of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

“…In this report, we presented a case of successfully diagnosed angina masked by ME/CFS deterioration. Endothelial dysfunction was previously correlated to ME/CFS and shown to reflect disease severity [ 11 ]. While the pathophysiology of ME/CFS is not yet fully elucidated [ 12 , 13 ], autonomic nervous system dysregulation, immunological disturbance, viral infections, and metabolic changes were proposed as underlying mechanisms of this malady [ 14 , 15 , 16 , 17 ].…”

“…Endothelial dysfunction was reported to reduce cerebral blood flow, which is correlated with disease severity [ 20 , 21 ], and results in further fatigue [ 22 ]. Therefore, endothelial function might be potentially used to assist the diagnosis of ME/CFS, and serve as an indicator of its severity and the risk of complications [ 7 , 11 ]. The early initiation of treatment is important to improve the prognosis in patients with angina [ 23 ].…”