Plasma endothelin-1 levels in chronic fatigue syndrome

G. Kennedy, V. Spence, F. Khan and J. J. F. Belch

Vascular Diseases Research Unit, University Department of Medicine, Ninewells Hospital & Medical School, Dundee DD1 9SY, UK

Correspondence to: G. Kennedy. E-mail: g.kirk{at}dundee.ac.uk

SIR, We read with interest the report by Pache et al. [1] showing increased endothelin-1 (ET-1) levels in patients with a diagnosis of fibromyalgia syndrome (FMS) and their conclusion that elevated ET-1 levels might contribute to some of the apparent vascular disturbances that characterize the syndrome. Pache et al. also point to the overlap between the clinical presentation of FMS and other ‘stress-associated disorders including chronic fatigue syndrome (CFS) and depression’. Whether FMS or CFS is stress-induced is a contentious issue in itself, but of equal concern is the view that FMS should be considered to be part of the spectrum of illness under the generic name ‘chronic fatigue syndrome’. Clearly, the symptoms of FMS and CFS have much in common [2, 3] but it has been said that FMS represents an additional burden of suffering among those with CFS [4], those patients meeting the case definitions for both FMS and CFS having a worse course, worse overall health and greater disease impact [2]. Furthermore, while many FMS patients experience fatigue, it has been estimated that only about one-fifth fulfil the specific criteria required for CFS [5]. Clinical similarities apart, there are biological differences between the two; for example, cerebrospinal fluid levels of substance P are elevated in FMS but not in CFS patients [6], and cardiovascular responses to postural challenge are characteristic of many CFS patients but are not apparent in those with FMS [7].

Our group has previously demonstrated that CFS patients have a significantly increased microcirculatory blood flow response to the endothelium-dependent vasodilator acetylcholine (ACh) [8] but not to the endothelium-independent vasodilator sodium nitroprusside (SNP)—a unique phenomenon that we believe may be related to a disturbance of endothelial acetylcholinesterase expression in these patients [9]. Similar experiments carried out by us on patients with FMS [10] and matched control subjects failed to demonstrate any significant difference in either the ACh or SNP responses, nor did these patients show increased baseline vasoconstriction, but the FMS patients did have a significantly elevated resting blood pressure compared with their matched controls.

As part of an investigation into specific vascular risk factors in CFS, we have recently completed a study in our Vascular Diseases Research Unit on 47 patients who, on clinical examination, fulfilled the Centre for Disease Control 1994 criteria for CFS [11], and 34 age- and sex-matched healthy controls. The local ethics committee approved the study and all subjects gave written, informed consent. Supine blood pressure measurements were obtained after a standard rest period of 20 min. ET-1 levels were measured from a morning blood sample, collected in EDTA (ethylenediamine tetraacetate), kept on ice and then centrifuged at 4°C within 5 min. Plasma was separated, aliquoted and stored at –70°C until assayed for ET-1 levels by ELISA (enzyme-linked immunosorbent assay) (R&D Systems, Oxford, UK).

No differences in plasma ET-1 levels were found between CFS patients and their control group (P = 0.30, unpaired t test). CFS patients had a mean ET-1 level of 0.49 pg/ml (range 0.11–1.02) and the control group had a mean ET-1 level of 0.44 pg/ml (range 0.16–0.92). We also found no differences in blood pressure between CFS patients and control subjects. The mean and range for systolic blood pressure were 125 mmHg (90–198) in CFS patients and 123 mmHg (100–180) in controls (P = 0.50); for diastolic blood pressure the results for CFS patients and control subjects were 74 mmHg (50–108) and 72 mmHg (50–88) respectively (P = 0.36).

Taken together, these experimental data challenge the concept that CFS and FMS are part of the same spectrum of illness. Normal ET-1 levels in CFS patients in conjunction with an enhanced endothelial response to ACh may predispose these patients to abnormal cardiovascular responses to orthostatic challenge. While there have been reports of impaired activation of the hypothalamic–pituitary–adrenal (HPA) axis in both CFS and FMS patients that is clearly dissimilar to that seen in depression [12], caution is required about assuming that FMS and CFS are aetiologically analogous disorders of the stress response axis. Our results show no elevation of ET-1 in CFS, in contrast to the data of Pache et al.

The authors have declared no conflicts of interest.

References

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Accepted 13 June 2003





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