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Objective: The aim of this study was to assess the presence of dysautonomia, as manifested in abnormal cardiovascular reactivity, in patients with familial Mediterranean fever (FMF)., Methods: Fifty-five consecutive patients with FMF and 23 age- and sex-matched healthy controls were evaluated. Cardiovascular reactivity was studied: (1) using recordings of blood pressure (BP) and heart rate (HR) during 10 min of recumbence and 30 min of head-up tilt test to identify clinical endpoints and (2) during tilt-test, identifying parameters acting as independent predictors of FMF reactivity and enabling computation of a cardiovascular reactivity score (CVRS)., Results: Clinically, vasovagal reaction, postural tachycardia syndrome, and/or orthostatic hypotension were observed in ten patients (18.1%). Utilizing a derived equation, the group average CVRS in FMF was 5.83+/-1.78 (healthy group -7.60+/-5.41) ( P=<0.0001). A CVRS of >3.25 was associated with FMF, with 98% sensitivity and 100% specificity., Conclusion: A very high percentage of FMF patients exhibit abnormal cardiovascular reactivity which is clinically occult but can be detected on autonomic challenge and application of the CVRS.

Objective: In studying patients with chronic fatigue syndrome (CFS) we developed a method that confers numerical expression to the degree of blood pressure and heart rate lability, ie, the 'hemodynamic instability score' (HIS). The HIS in CFS patients differed significantly from healthy subjects. The present investigation compares the HIS in CFS, non-CFS chronic fatigue and patients with recurrent syncope., Methods: Patients with CFS (n = 21), non-CFS chronic fatigue (n = 24), syncope of unknown cause (n = 44), and their age and sex-matched healthy controls (n = 21) were evaluated with a standardized head-up tilt test (HUTT). Abnormal reactions (endpoints) on HUTT were classified 'clinical outcomes' (cardioinhibitory or vasodepressor reaction, orthostatic hypotension, postural tachycardia syndrome) and 'HIS endpoint', i.e. HIS >-0.98., Results: The highest incidence of endpoints was noted in patients with CFS (79%), followed by patients with syncope of unknown cause (46%), non-CFS chronic fatigue (35%), and healthy subjects (14%). Presyncope or syncope during tilt occurred in 38% of CFS patients, 21% of patients with non-CFS chronic fatigue, and 43% of patients with recurrent syncope. The average HIS values were: CFS = +2.02 (SD 4.07), non-CFS chronic fatigue = -2.89 (SD 3.64), syncope = -3.2 (SD 3.0), healthy = -2.48 (4.07). The odds ratios for CFS patients to have HIS >-0.98 was 8.8 compared with non-CFS chronic fatigue patients, 14.6 compared with recurrent syncope patients, and 34.8 compared with healthy subjects., Conclusion: The cardiovascular reactivity in patients with CFS has certain features in common with the reactivity in patients with recurrent syncope or non-CFS chronic fatigue, such as the frequent occurrence of vasodepressor reaction, cardioinhibitory reaction, and postural tachycardia syndrome. Apart from to these shared responses, the large majority of CFS patients exhibit a particular abnormality which is characterized by HIS values >-0.98. Thus, HIS >-0.98 lends objective criteria to the assessment of CFS., (Copyright 2002, Elsevier Science (USA). All rights reserved.)

The normal response to postural challenge is characterised by maintenance of relatively stable blood pressure (BP) and heart rate (HR) after 30 sec to 30 min of head-up tilt. The objective of the present study was to determine the degree of instability of cardiovascular responses to postural challenge in normotensive and hypertensive subjects. In the initial phase of the study, two groups of age and sex-matched subjects were assessed: essential hypertension (n = 20) and healthy (n = 37). The BP and HR were recorded at 5-min intervals during the course of the 10-min supine-30-min head-up tilt test (HUTT). We categorised 'BP-change' as the difference between individual BP measurements during HUTT and the last recumbent BP value, divided by latter value. The average and standard deviation (SD) of the recorded BP changes were calculated, and BP changes were plotted along a time curve. A computerised image analyser then calculated the outline ratio (OR) and fractal dimension (FD) values for each of the curves. An identical process evaluated measurements for HR-changes. BP- and HR-changes were then converted into absolute numbers, and the average, SD, OR, and FD were calculated. A multivariate analysis was conducted, evaluating independent predictors of hypertension. Finally, an equation for the calculation of 'haemodynamic instability score' (HIS) was deduced and a cut-off between HIS of hypertensive and normotensive subjects was established. Independent predictors of the cardiovascular response to postural challenge of hypertensives (Group I) vs healthy (Group II) were: a.DIAST-FD, a.HR-AVG, a.HR-SD, a.HR-FD, DIAS-SD and HR-SD and HR-SD. Based on these five predictors, a linear discriminant score was computed and called the Haemodynamic Instability Score (HIS): HIS = 59.4 + (-16.6*a.DIAST-FD) + (-29.0*a.HR-AVG) + (-82.4*a.HR-SD) + (-30.1*a.HR-FD) + (-57.9*DIAS-SD) + (73.4*HR-SD) The HIS values in Group I (hypertensives) were: avg = 3.348, SD = 2.863, and 95% CI for mean = 2.008, 4.688. The HIS values in Group II (healthy) were: avg = -3.394, SD = 2.435, 95% CI for mean = -4.206, -2.582. Values of the HIS > -2.09 were generally observed in hypertensives (sensitivity 95%) and values < or = -2.09 were usually seen in the healthy (specificity 81.1%). The HIS was cross-validated in an additional group of hypertensive patients (n = 73). In the latter group, the HIS values were: avg = -0.456, SD = 4.403, 95% CI for mean = -1.506, 0.593 and 71.4% sensitivity at the proposed cut-off point. In conclusion, the HIS confers numerical expression to the degree of lability of BP and HR during postural challenge. Based on this score, a distinction between the cardiovascular reactivity of hypertensives vs normotensives is drawn. Possible applications of HIS are discussed.

Methods used for the assessment of cardiovascular reactivity are flawed by nonlinear dynamics of the cardiovascular responses to stimuli. In an attempt to address this issue, we utilized a short postural challenge, recorded beat-to-beat heart rate (HR) and pulse transit time (PTT), assessed the data by fractal and recurrence quantification analysis, and processed the obtained variables by multivariate statistics. A 10-min supine phase of the head-up tilt test was followed by recording 600 cardiac cycles on tilt, that is, 5-10 min. Three groups of patients were studied, each including 20 subjects matched for age and gender — healthy subjects, patients with essential hypertension (HT), and patients with chronic fatigue syndrome (CFS). The latter group was studied on account of the well-known dysautonomia of CFS patients, which served as contrast against the cardiovascular reactivity of the healthy population. A total of 52 variables of the HR and PTT were determined in each subject. The multivariate model identified the best predictors for the assessment of reactivity of healthy subjects vs CFS. Based on these predictors, the 'Fractal & Recurrence Analysis-based Score' (FRAS) was calculated: FRAS = 76.2+0.04*HRsupine-DET -12.9*HR-tilt-RIL -0.31*HR-tilt-s.d. -19.27*PTT-tilt-RIL -9.42*PTT-tilt-WAVE. The median values and IQR of FRAS in the groups were: healthy = -1.85 (IQR 1.89), hypertensives = +0.52 (IQR 5.78), and CFS = -24.2 (5.34) (HT vs healthy subjects: P = -0.0036; HT vs CFS: P < 0.0001). Since the FRAS differed significantly between the three groups, it appears likely that the FRAS may recognize phenotypes of cardiovascular reactivity. [ABSTRACT FROM AUTHOR]