This study aimed to develop a method to distinguish between the cardiovascular reactivity in chronic fatigue syndrome (CFS) and other patient populations. Patients with CFS (n = 23), familial Mediterranean fever (n = 15), psoriatic arthritis (n = 10), generalized anxiety disorder (n = 12), neurally mediated syncope (n = 20), and healthy subjects (n = 20) were evaluated with a shortened head-up tilt test (HUTT). A 10-minute supine phase of the HUTT was followed by recording 600 cardiac cycles on tilt, i. e., 5 to 10 minutes. Beat-to-beat heart rate (HR) and pulse transit time (PTT) were acquisitioned. Data were processed by recurrence plot and fractal analysis. Fifty-two variables were calculated in each subject. On multivariate analysis, the best predictors of CFS were HR-tilt-R/L, PTT-tilt-R/L, HR-supine-DET, PTT-tilt-WAVE, and HR-tilt-SD. Based on these predictors, the 'Fractal & Recurrence Analysis-based Score' (FRAS) was calculated: FRAS = 76.2 + 0.04*HR-supine-DET - 12.9*HR-tilt-R/L - 0.31*HR-tilt-SD - 19.27*PTT-tilt-R/L - 9.42* PTT-tilt-WAVE. The best cut-off differentiating CFS from the control population was FRAS = + 0.22. FRAS > + 0.22 was associated with CFS (sensitivity 70 % and specificity 88 %). The cardiovascular reactivity received mathematical expression with the aid of the FRAS. The shortened HUTT was well tolerated. The FRAS provides objective criteria which could become valuable in the assessment of CFS.

Pathological disturbances may alter cardiovascular reactivity. Our data support the existence of disease-related CVR phenotypes, with implications for pathogenesis and differential diagnosis.

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There is a particular dysautonomia in CFS that differs from dysautonomia in other disorders, characterized by HIS >-0.98. The HIS can reinforce the clinician's diagnosis by providing objective criteria for the assessment of CFS, which until now, could only be subjectively inferred.

Aberrations of CVR (cardiovascular reactivity), an expression of autonomic function, lack specificity for a particular disorder. Recently, a CVR pattern particular to chronic fatigue syndrome has been observed. In the present study, we aimed to develop methodologies for assessing disease-specific CVR patterns. As a prototype, a population of 50 consecutive patients with FMF (familial Mediterranean fever) was studied and compared with control populations. A 10 min supine/30 min head-up tilt test with recording of the heart rate and blood pressure or the pulse transit time was performed. Five studies were conducted applying different methods. In each study, statistical analysis identified independent predictors of CVR in FMF. Based on regression coefficients of these predictors, a linear DS (discriminant score) was computed for every subject. Each study established an equation to assess CVR, calculate DS for FMF and determine the sensitivity and specificity of the DS cut-off. In each of the five studies, abnormal CVR was observed in FMF patients. The best accuracy (88% sensitivity and 90.1% specificity for FMF) was obtained by a method based on beat-to-beat heart rate and pulse transit time recordings. Data was processed by fractal and recurrence quantitative analysis with recordings in FMF patients compared with a mixed control population. Identification of disease-specific CVR patterns was possible with the methodologies described in the present study. In FMF, disease-specific CVR may be explained by the interplay between neuroendocrine loops specific to FMF with cardiovascular homoeostatic mechanisms. Recognition of disease-specific CVR patterns may advance the understanding of homoeostatic mechanisms and have implications in clinical practice.