Are serum ferritin and transferrin saturation risk markers for restless legs syndrome in young adults? Longitudinal and cross‐sectional data from the Western Australian Pregnancy Cohort (Raine) Study

Restless legs syndrome has been associated with serum iron deficiency in clinical studies. However, studies investigating this relationship have had inconsistent results and there are no studies in young adults. Therefore, we investigated the relationship between serum measures of iron stores and restless legs syndrome in young adults in the community. Participants in the Western Australian Pregnancy Cohort (Raine) Study answered questions on restless legs syndrome (n = 1,100, 54% female) at age 22 years, and provided serum measures of iron stores (ferritin and transferrin saturation) at ages 17 and 22 years. Restless legs syndrome was diagnosed when four International RLS Study Group criteria were met (urge to move, dysaesthesia, relief by movement, worsening during evening/night) and these symptoms occurred ≥5 times per month. Logistic regression was used to assess associations between serum iron stores and restless legs syndrome, adjusting for potential confounders. The prevalence of restless legs syndrome at age 22 years was 3.0% (n = 33, 70% female). Among those who provided restless legs syndrome and iron data at age 22 years (n = 865), the median (interquartile range) ferritin was not different between the restless legs syndrome (55 [29.5–103.5] µg L^?1) and the non‐restless legs syndrome group (65.0 [35.0–103.3] µg L^?1, p = 0.2), nor were there differences in iron deficiency prevalence (p = 0.36). There was no association between restless legs syndrome (22 years) and iron stores (17, 22 years) before or after adjustment for potential confounders. There was no association between restless legs syndrome at 22 years and iron stores at 17 or 22 years in this cohort. Serum iron stores may not be a useful indicator of restless legs syndrome risk in young adults in the community.     

Respiratory sinus arrhythmia during sleep in children with upper airway obstruction

Upper airway obstruction during adulthood is associated with cardiovascular morbidity; cardiovascular consequences of childhood upper airway obstruction are less well established. This study aimed at investigating the effect of childhood upper airway obstruction on respiratory sinus arrhythmia as a measure of cardiac vagal modulation during night‐time sleep. Overnight polysomnography was conducted in 40 healthy children (20 M; age: 7.5 ± 2.6 years; body mass index percentile: 60.7 ± 26.4%) and 40 children with upper airway obstruction (24 M; age: 7.5 ± 2.7 years; body mass index percentile: 65.8 ± 31.9%). We used the phase‐averaging technique to compute respiratory sinus arrhythmia amplitude and phase delay. To study sleep stage effects and the effect of upper airway obstruction, respiratory sinus arrhythmia was measured during all artefact‐free sleep episodes, and after exclusion of respiratory events. A significant increase in respiratory sinus arrhythmia amplitude and phase delay was observed during stage 4 sleep as compared with rapid eye movement sleep in both groups (amplitude: controls = 0.10 ± 0.03 versus 0.07 ± 0.02 s, P < 0.01, respectively, and upper airway obstruction = 0.07 ± 0.03 versus 0.05 ± 0.03 s, P < 0.05, respectively; phase delay: controls = 3.1 ± 0.1 versus 3.0 ± 0.1 rad, P < 0.05, respectively, and upper airway obstruction = 3.13 ± 0.04 versus 3.04 ± 0.08 rad, P < 0.01, respectively). A significant association between respiratory sinus arrhythmia and apnea/hypopnea index was observed during stage 2 sleep in children with upper airway obstruction. Compared with healthy controls, a significant decrease in respiratory sinus arrhythmia amplitude during stage 2 sleep was observed in children with upper airway obstruction (0.09 ± 0.03 versus 0.06 ± 0.03 s, P < 0.05). However, this difference was not apparent when respiratory events were excluded from analysis. Importantly, respiratory sinus arrhythmia showed a strong negative correlation with body mass index. In conclusion, night‐time respiratory sinus arrhythmia in children is sleep stage dependent and normal during quiet sleep in children with relatively mild upper airway obstruction.     

冠心病患者心率变异性分析

目的研究冠心病患者心率变异（HRV）的变化规律及临床意义。方法选择50例无心律失常冠心病患者（冠心病组）、30例伴心律失常冠心病患者（心率失常组）与52例正常成人自愿者（正常组）进行24h动态心电图HRV指标比较研究。结果与正常组比较,冠心病患者SDNN、SDANN、RMSSD、PNN50和HF指标均降低,LF指标升高,具有显著差异。伴心律失常与无心律失常冠心病患者比较,HRV指标异常变化趋于恶化。结论冠心病患者心脏自主神经调节功能受到损害,迷走神经活性减弱,交感神经活动占优势。     

Should heart rate variability be “corrected” for heart rate? Biological,quantitative, and interpretive considerations

Metrics of heart period variability are widely used in the behavioral and biomedical sciences, although somewhat confusingly labeled as heart rate variability (HRV). Despite their wide use, HRV metrics are usually analyzed and interpreted without reference to prevailing levels of cardiac chronotropic state (i.e., mean heart rate or mean heart period). This isolated treatment of HRV metrics is nontrivial. All HRV metrics routinely used in the literature exhibit a known and positive relationship with the mean duration of the interval between two beats (heart period): as the heart period increases, so does its variability. This raises the question of whether HRV metrics should be “corrected” for the mean heart period (or its inverse, the heart rate). Here, we outline biological, quantitative, and interpretive issues engendered by this question. We provide arguments that HRV is neither uniformly nor simply a surrogate for heart period. We also identify knowledge gaps that remain to be satisfactorily addressed with respect to assumptions underlying existing HRV correction approaches. In doing so, we aim to stimulate further progress toward the rigorous use and disciplined interpretation of HRV. We close with provisional guidance on HRV reporting that acknowledges the complex interplay between the mean and variability of the heart period.     

Diabetic alteration of cardiac vago-sympathetic modulation assessed with tone–entropy analysis

No clear evidence of diabetic alteration of cardiac sympatho-vagal balance has been reported to date. We assessed heart rate variability of diabetic patients with the tone–entropy analysis that has been published elsewhere ( 11 ). Tone reflects the cardiac vago-sympathetic balance and entropy the total autonomic efferent activity. Diabetic influence on tone and entropy was examined in two groups of patients (38–52 years and 60–69 year, total 106) stratified according to the occurrence of impaired glucose tolerance or diabetes mellitus. Ten healthy middle-aged volunteers were also examined as a reference. Electrocardiographic data were collected at rest for 10 min. Tone increased and entropy decreased significantly with severity of diabetic disorders. The alterations were depicted as a curvi-linear relation in tone–entropy space, which superimposed adequately on the standard tone-entropy values obtained in a pharmacological experiment. The results demonstrate that the vago-sympathetic balance is altered with diabetic disorders: vagal predominance is impaired significantly in proportion to a withdrawal of total autonomic efferent activity.     

Cluster Analysis of Extracardiac Control of the Heart Rate in Random-Bred Albino Rats at Rest

Heart rate variability was examined in random-bred albino rats at rest. The rats were clusterized according to activity of autonomic contour of heart rate control. Combination of factor and cluster analyses enhanced informative value of spectrum parameters of the heart rate variability in nonlinear rats grouped by initial neurovegetative status. The contours of central and autonomic regulation describe the most general features of the control influences that realize modulating influences at the heart level via sympathetic and parasympathetic control pathways. Their activity is comprehensively assessed by the normalized power spectrum of variations in the heart rate. Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 147, No. 1, pp. 16–19, January, 2009     

心率变异性分析方法的现状与展望

心率变异(HRV)蕴涵着心血管神经及体液调节的大量信息，心率变异性分析是近年来心电信号处理领域的研究热点，它对于相关疾病的无创检测具有重要的临床意义。本文系统阐述了HRV经典分析方法及其最新研究进展，并提出了今后的研究方向。     

低氧与心率变异性研究进展

高原或运动等生理性低氧或/和临床心血管、呼吸及代谢等疾病病理性缺氧均可改变机体自主神经调节功能,从而导致心率变异性(HRV)变化。HRV对机体功能状态评定、多种疾病的诊断、预后及疗效评价具有重要价值。本综述简要介绍近年来有关低氧与HRV的研究进展。     

Influence of home-based telemonitored Nordic walking training on autonomic nervous system balance in heart failure patients

Introduction

Rehabilitation positively affects the modulation of the autonomic nervous system (ANS). There are no papers evaluating the influence of Nordic walking training (NW) on ANS activity among chronic heart failure (CHF) patients. The aim of study was to assess the influence of NW on ANS activity measured by heart rate variability (HRV) and heart rate turbulence (HRT) in CHF patients and its correlation with physical capacity improvement measured by peak oxygen consumption (peak VO₂ [ml/kg/min]) in the cardiopulmonary exercise treadmill test (CPET).

Material and methods

The study group comprised 111 CHF patients (NYHA class II–III; ejection fraction (EF) ≤ 40%). Patients were randomized (2 : 1) to 8-week NW (five times weekly) at 40–70% of maximal heart rate (training group – TG) (n = 77), or to a control group (CG) (n = 34). The effectiveness of NW was assessed by changes (delta (Δ)) in peak VO₂, HRV and HRT as a result of comparing these parameters from the beginning and the end of the programme.

Results

Eventually, 36 TG patients and 15 CG patients were eligible for HRV and HRT analysis. In the TG low/high frequency ratio (LF/HF) decreased (1.9 ±1.11 vs. 1.7 ±0.63, p = 0.0001) and peak VO₂ increased (16.98 ±4.02 vs. 19.70 ±4.36 ml/kg/min, p < 0.0001). Favourable results in CG were not observed. The differences between TG and CG were significant: Δpeak VO₂ (p = 0.0081); ΔLF/HF (p = 0.0038). An inverse correlation was found between the decrease in ΔLF/HF and the increase in Δpeak VO₂ (R = –0.3830, p = 0.0211) only in the TG. Heart rate variability did not change significantly in either group.

Conclusions

Nordic walking positively affects the parasympathetic-sympathetic balance in CHF patients, which correlates with the improvement in Δpeak VO₂. No significant influence of NW on HRT was observed.     

The effect of change in sympatho-vagal balance on heart rate and blood pressure variability in the foetal lamb

Cardiac and vascular function is mainly under autonomic nervous control within seconds to minutes, although the control is not mature at birth. We studied sympatho-vagal control of heart rate and blood pressure in chronically catheterized foetal lambs in the last trimester of gestation. Power spectral analysis was used to quantitate the frequency-specific heart rate variability (HRV) and blood pressure variability. We performed 15 experiments in seven foetal lambs. These preliminary studies showed that parasympathetic blockade by atropine (eight experiments) had no significant effect on the distribution of HRV to different frequencies. Beta-sympathetic blockade by propranolol (seven experiments) decreased the ratio of low and mid to high frequency (0.025-0.13 to 0.13-1.00 Hz) HRV (P= 0.02). The increased high frequency HRV in the absence of a similar increase in blood pressure variability and tracheal pressure variability suggests enhanced baroreflex responsiveness after propranolol administration. The frequency-specific sympathetic control of HRV in foetal lambs, the change in ratio of low and mid to high frequency HRV, might have clinical implications in estimating the level of foetal sympathetic activation in the follow-up of high-risk pregnancies.     

The Effects of Thoracic Sympathotomy on Heart Rate Variability in Patients with Palmar Hyperhidrosis

Purpose

To observe the evolution of heart rate variability (HRV) in patients with palmar hyperhidrosis before and after endoscopic thoracic sympathotomy and to evaluate the effects of the surgery on the autonomic nervous system.

Materials and Methods

Endoscopic thoracic sympathotomy was performed on 20 patients with palmar hyperhidrosis. The thoracic sympathetic chain at the level of the third to fourth rib (R3-R4) was transected, but the ganglia were left in position without removal. A slightly larger ramus, in comparison to the other rami, that arose laterally from the sympathetic chain was interrupted to achieve adequate sympathetic denervation of the upper extremity. Before and on the day after the surgery, 24-hour Holter Electrocardiograph was performed, obtaining time domain and frequency domain parameters.

Results

Compared with preoperative variables, there was a significant increase in the number of adjacent normal R wave to R wave (R-R) intervals that differed by more than 50 ms, as percent of the total number of normal RR intervals (pNN50); root mean square difference, the square root of the mean of the sum of squared differences between adjacent normal RR intervals over the entire 24-hour recording; standard deviation of the average normal RR interval for all 5-minute segments of a 24-hour recording (SDANN) after thoracic sympathotomy. Low frequencies (LF, 0.04 to 0.15 Hz) decreased significantly. There was no statistical difference in high frequencies (HF, 0.15 to 0.40 Hz), LF/HF ratio (LF/HF), or standard deviation for all normal RR intervals for the entire 24-h recording (SDNN) before and after thoracic sympathotomy.

Conclusion

There was a significant improvement in HRV in patients with palmar hyperhidrosis after thoracic sympathotomy. This may be attributable to an improvement autonomic nervous system balance and parasympathetic predominance in the early postoperative stage.     

Heart rate turbulence in patients with poorly controlled diabetes mellitus type 2

Introduction

Cardiac autonomic neuropathy (CAN) causes substantial morbidity and increased mortality in patients with diabetes mellitus (DM). Besides heart rate variability (HRV), heart rate turbulence (HRT) is an important method of assessment of cardiac autonomic regulation. The aim of the study was to assess the correlation between HRT and diabetic control.

Material and methods

Fifty-nine patients met the inclusion criteria – 38 males and 21 females, age 64.4 ±7.6. The patients included had inadequately controlled DM type 2 defined as glycated haemoglobin (HbA_1c) > 9% (mean 11.8 ±2.7%). In all patients, intensive insulin treatment had been applied for 6 months. After 6 months, HbA_1c was measured. ECG Holter monitoring was performed before and after insulin treatment to evaluate the time domain HRV and HRT parameters (turbulence onset (TO) and turbulence slope (TS)).

Results

After 6 months of intensive insulin treatment, HbA_1c concentrations ranged from 6.3% (45 mmol/mol) to 11.2% (99 mmol/mol) – mean 8.5 ±3.8% (69 ±18 mmol/mol). Significant improvement of TO, TS and SDNN was observed. The TO and TS significantly correlated with HbA_1c (r = 0.35, p = 0.006 and r = –0.31, p = 0.02 respectively). Among analyzed HRV time domain parameters such as SDNN, rMSSD and pNN50, only SDNN correlated with HbA_1c (r = –0.41, p = 0.001). It was further concluded that intensive insulin therapy led to better glycemic control, resulting in improvement of HRT.

Conclusions

Heart rate turbulence may be useful in monitoring changes of the autonomic nervous system functions in patients with DM, similarly to HRV parameters.     

Heart rate variability in overactive bladder experimental model

Introduction

Two main pathophysiological concepts of overactive bladder (OAB) are postulated: the neurogenic and myogenic theories. Autonomic nervous system (ANS) dysfunction is also involved in OAB pathophysiology. The purpose of our study was to estimate ANS activity by heart rate variability (HRV) assessment in two OAB experimental models evoked by cyclophosphamide administration: acute (AOAB) and chronic (COAB) overactive ones.

Material and methods

In the AOAB model, an i.p. dose of cyclophosphamide was administered (200 mg/kg body weight) while the COAB model received 4 times the i.p. administration of cyclophosphamide (75 mg/kg body weight). In each subject, after urethane anaesthesia (1.2 g/kg body weight), 20-minute ECG recordings (PowerLab) were performed with subsequent HRV analysis.

Results

Most of the differences in time domain analysis parameters were insignificant, except those concerning SDNN and rMSSD (p < 0.05). In frequency analysis, a power decrease of all standard spectral components was revealed in both OAB groups. In AOAB, TP (1.43 ±1.21 vs. 7.92 ±6.22 in control; p < 0.05) and VLF (0.95 ±1.08 vs. 6.97 ±5.99 in control; p < 0.05) showed significant power decrease, whereas the COAB group was mostly characterized by LF (0.09 ±0.15 vs. 0.34 ±0.33 in control; p < 0.05) and HF (0.25 ±0.29 vs. 0.60 ±0.41 in control; p < 0.05) decrease.

Conclusions

The ANS disturbances, found as standard spectral parameter abnormalities, were demonstrated in both AOAB and COAB. When this finding is analysed, together with the lack of statistically significant differences in normalized nLF and nHF powers, the VLF changes seem to play an essential role, probably reflecting the progression in bladder inflammatory changes.     

Power spectrum analysis and heart rate variability in Stage 4 and REM sleep: evidence for state-specific changes in autonomic dominance

The present study investigated autonomic activity during NREM and REM sleep stages and wakefulness by spectral analysis of heart rate variability. The results demonstrated that NREM sleep in humans was characterized by a widely different autonomic activation pattern than REM sleep: high parasympathetic activity was found in NREM, while REM was characterized by attenuated vagal tone, and augmented sympathetic activity. The overall pattern during wakefulness showed an intermediate position between NREM and REM patterns; parasympathetic activity was lower than in NREM and higher than in REM, with an opposite trend for sympathetic activity.