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Original Research: PEDIATRICS |

Changes in Heart Rate Variability After Adenotonsillectomy in Children With Obstructive Sleep Apnea FREE TO VIEW

Hiren V. Muzumdar, MD; Sanghun Sin, MS; Margarita Nikova, PhD; Gregory Gates, PhD; Dongyoun Kim, PhD; Raanan Arens, MD
Author and Funding Information

From the Division of Respiratory and Sleep Medicine (Drs Muzumdar, Nikova, and Arens and Mr Sin), and the Division of Cardiology (Dr Gates), Children’s Hospital at Montefiore; and Albert Einstein College of Medicine (Drs Muzumdar, Gates, and Arens and Mr Sin), Bronx, NY; and the Department of Biomedical Engineering (Dr Kim), College of Health Science, Yonsei University, Seoul, South Korea.

Correspondence to: Raanan Arens, MD, Children’s Hospital at Montefiore, 3415 Bainbridge Ave, Bronx, NY 10467; e-mail: rarens@montefiore.org


For editorial comment see page 977

Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (http://www.chestpubs.org/site/misc/reprints.xhtml).


© 2011 American College of Chest Physicians


Chest. 2011;139(5):1050-1059. doi:10.1378/chest.10-1555
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Background:  Obstructive sleep apnea syndrome (OSAS) is associated with cardiovascular morbidity and mortality, and increased sympathetic activity is considered to be a causative link in this association. Higher levels of sympathetic activity have been reported in children with OSAS. Sympathetic predominance is indicated on heart rate variability (HRV) analysis by increased heart rate (HR) and a higher ratio of low-frequency to high-frequency band power (LF/HF). Improvement in OSAS after adenotonsillectomy (AT) in children with OSAS could, therefore, be associated with reduced HR and reduced LF/HF.

Methods:  Changes in HR and time and frequency components of HRV were retrospectively analyzed in 2-min epochs free of respiratory events during light, deep, and rapid-eye-movement (REM) sleep in children with OSAS who underwent polysomnography before and after AT.

Results:  Eighteen children with OSAS, aged 4.9 ± 2.4 years (mean ± SD) were studied. After AT, the apnea-hypopnea index decreased from 31.9 ± 24.8 events/h to 4.1 ± 3.7 events/h. The HR decreased after AT in all stages of sleep (99.8 ± 16.9 beats/min to 80.7 ± 12.9 beats/min [light sleep]; 100.2 ± 15.4 beats/min to 80.5 ± 12.4 beats/min [deep sleep)]; and 106.9 ± 16.4 beats/min to 87.0 ± 12.1 beats/min [REM sleep]), as did the LF/HF (1.6 ± 2.7 to 0.6 ± 0.5 [light sleep]; 1.2 ± 1.6 to 0.5 ± 0.6 [deep sleep]; and 3.0 ± 5.4 to 1.4 ± 1.7 [REM sleep]).

Conclusions:  The proportion of sympathetic activity of the autonomic nervous system declines in children with OSAS after AT in association with improvement in sleep-disordered breathing.

Figures in this Article

Obstructive sleep apnea syndrome (OSAS) is characterized by recurrent partial or complete upper-airway obstruction during sleep, resulting in disruption of normal ventilation and sleep patterns, neurocognitive deficits, and cardiovascular morbidities.1,2 In adults, OSAS is linked to increased cardiovascular morbidity,3 while in children, there is clear evidence of abnormalities in the regulation of BP, cardiac function, autonomic function, and endothelial function.47

Increased sympathetic neural discharge, potentially mediated by hypoxemia via alteration of carotid body chemoreceptors, has been demonstrated in adults with OSAS.811 Arousals can independently increase sympathetic tone, heart rate (HR), and BP.12,13 Autonomic dysregulation is a proposed mechanism for the increased risk of sudden death and cardiac arrhythmias in adults with OSAS.3,14,15 Increased sympathetic activity has been reported in children with OSAS, as measured by pulse arterial tonometry in response to immersion in cold water and by alterations in baroreceptor gain.16,17

Autonomic balance can be noninvasively estimated using HR and heart rate variability (HRV), which is the oscillation in the interval between consecutive heartbeats and consecutive instantaneous HRs.18 Low-frequency (0.04-0.15 Hz) band power (LF) represents sympathetic and parasympathetic nervous system activity, whereas high-frequency (0.15-0.4 Hz) band power (HF) represents parasympathetic nervous system activity. The ratio of low-frequency to high-frequency band power (LF/HF) represents sympathovagal balance, with an increase in the LF/HF indicating a tilt toward the sympathetic component.

Sympathetic predominance in the form of a higher LF/HF and LF has been demonstrated in children with OSAS.19 However, the effects of reversal or mitigation of OSAS on HRV have not been reported in children.

Adenotonsillectomy (AT) is the first treatment option in children with adenotonsillar hypertrophy and OSAS, and it usually results in a significant improvement in OSAS.20 We hypothesized that improvement in OSAS after AT would be associated with a reduction in HR and the LF/HF. We retrospectively measured changes in HRV in a group of children with OSAS and adenotonsillar hypertrophy who had AT followed by improvement in OSAS, as documented on polysomnography after AT. Some of the results of these studies have been previously reported in an abstract.21

Sequential children who were diagnosed with OSAS on polysomnographic evaluation (the OSAS group) and had a repeat polysomnograph study after AT within 1 year of the first study were retrospectively selected for evaluation. Data extracted included age, sex, height, and weight. Age-, sex-, and BMI-matched children with primary snoring who did not have OSAS on polysomnographic evaluation were selected as a comparison group of children (the control group). All potential subjects were screened for congestive heart failure, cardiac arrhythmia, chronic lung disease, developmental delay, and use of medications likely to affect heart rate, such as propranolol, and were excluded from the study if these criteria were present. Institutional review board approval was obtained for the study (Montefiore Medical Center, FWA 00002558).

Polysomnographic Evaluation

An overnight polysomnograph study (Xltek; Oakville, Ontario, Canada) was performed before and after AT, with measurement of the following parameters: sleep stage, muscle tone, thoracoabdominal movement measured using piezoelectric belts (Sleepmate; Midlothian, Virginia), airflow measured using oronasal thermistors, oxygen saturation measured using pulse oximeters (Masimo; Irvine, California), leg movement, and ECG. All data were sampled at 200 Hz. Sleep staging and scoring of arousals were done per standard criteria by one blinded scorer (M. N.).22 Obstructive apnea was scored when airflow was absent for the duration of two breaths in the presence of thoracoabdominal movement. Central apnea was scored when respiratory effort was absent for at least 20 s or at least two breaths and was associated with bradycardia, oxygen desaturation of at least 3%, or arousal. Hypopnea was defined as a 50% reduction in airflow associated with an arousal of 3% or greater reduction in oxygen saturation. The apnea-hypopnea index (AHI), which is the number of apneas and hypopneas per hour, and the arousal index, which is the number of arousals per hour, were both calculated. OSAS was diagnosed if the obstructive AHI was > 1 event/h or the AHI was > 2 events/h.23 The control group had an obstructive apnea-hypopnea index of < 1 event/h and an AHI < 2 events/h.

HRV Analysis

The ECG signal of the polysomnogram was processed through MATLAB (Mathworks; Natick, Massachusetts) and Labview software (National Instruments; Austin, Texas) to pinpoint RR peaks. The signal was interpolated and resampled at 2.5 Hz. RR intervals > 1,500 milliseconds and < 200 milliseconds were omitted. The ECG signal was processed through Labview, MATLAB, and HRV analog software (Department of Applied Physics, University of Kuopio; Kuopio, Finland) to obtain HRV parameters per consensus guidelines.18 For our main analysis, all 2-min epochs during sleep that were free of respiratory events or movement artifacts were analyzed. We elected to analyze epochs free of respiratory events to evaluate persistent changes in HRV after respiratory events and to provide a more “stationary” background to facilitate HRV analysis.18 For each subject, pre-AT and post-AT HRV parameters were compared in light nonrapid-eye-movement (NREM) sleep (stages N1 and N2), deep NREM sleep (stage N3), and rapid-eye-movement (REM) sleep. Similar analysis was performed for the control group, and these parameters were compared with the OSAS group parameters pre-AT and post-AT. Secondary analysis in the OSAS group included all 5-min epochs free of respiratory events or artifact with no sleep-stage differentiation pre-AT and post-AT. In addition, HRV parameters were compared in the pre-AT and post-AT state after stratification of OSAS children according to (1) residual AHI: mild (AHI < 5 events/h) and moderate (AHI > 5 events/h); and (2) baseline BMI: obese (BMI > 95th percentile) and nonobese (BMI < 95th percentile).

Time-domain analysis measures studied included RR interval and HR, the SD of the average of the normal-to-normal RR intervals (SDANN), the average of the SD of normal-to-normal interval indexes (SDNNI), and the square root of the mean of the sum of the squares of the difference in RR intervals of subsequent beats (RMSSD) Frequency-domain analysis was done using Fast-Fourier transform, and indices included LF, HF, and the LF/HF.

Statistical Analysis

Data are presented as mean and SD; anthropometric and polysomnographic data were tested for significant change using t tests. Normally distributed HRV parameters were compared for change using the paired t test, and nonnormally distributed parameters were compared using the Wilcoxon signed-rank test. Univariable analysis was performed with post-AT differences in HR or the LF/HF as dependent variables and changes arousal index, AHI, and oxygen nadir as independent variables. Baseline LF/HF and HR were added as covariates to the model if a significant change was noted on univariable analysis to correct for regression to the mean. All analysis was done using MATLAB and SPSS software (SPSS; Chicago, Illinois); P values < .05 were considered statistically significant.

Study Population

In all, 2,547 sleep studies from March 2005 to mid-August 2008 were screened, and 25 children without exclusionary criteria were found to have OSAS and had sleep studies before and after AT. After omitting subjects with sleep study intervals > 12 months (n = 3) and those with missing data (n = 4), 18 children were included in the study (OSAS group). Demographic, anthropometric, and polysomnographic data are presented in Table 1. All subjects had at least 50% reduction in the AHI (n = 16) or normalization of the AHI (n = 2). The arousal index declined, and the oxyhemoglobin saturation nadir improved in the second sleep study. The time interval between the two sleep studies was 5.5 ± 3.3 months, and the interval between surgery and the second sleep study was 4.0 ± 2.7 months. The BMI and BMI z scores were not significantly different before and after AT. Ten children with primary snoring were studied in the control group (Table 1). There were no differences between the control group and the OSAS group in terms of age, sex distribution, BMI, BMI percentile, sleep stage distribution, or sleep efficiency. The AHI in the control group was less than it was for the OSAS group before AT; the arousal index in the control group was less than it was for the OSAS group before and after AT (Table 1).

Table Graphic Jump Location
Table 1 —Demographics and Polysomnographic Data

Data presented as mean ± (SD). AHI = apnea-hypopnea index; AT = adenotonsillectomy; M = male; N1,2 = stage N1 and N2 sleep; N3 = stage N3 sleep; OSAS = obstructive sleep apnea syndrome; REM = rapid-eye-movement sleep.

a 

P values compare data for children with OSAS before and after AT.

b 

P value < .05, children with OSAS before AT compared with control subjects.

c 

P value < .05, children with OSAS after AT compared with control subjects.

Time-Domain Analysis

Time domain measures pre-AT and post-AT during various sleep stages are shown in Table 2. Accordingly, we noted a significant decrease in HR after AT in all sleep stages with a reciprocal increase in the RR interval (Fig 1). The SDNNI and RMSSD increased after AT in all stages of sleep. The RR interval, SDNNI, and RMSSD were higher in the control group compared with the pre-AT state of the children with OSAS and were not significantly different from those of the post-AT state of the children with OSAS. The SDANN decreased in light and deep sleep after AT in the children with OSAS and was lower than that in the comparison group.

Table Graphic Jump Location
Table 2 —Time-Domain Indices in Sleep Stages in Children With OSAS Before and After AT and in Children in the Control Group

Data are presented as mean ± SD. Control = control group of children with primary snoring without OSAS; HR = heart rate; post-AT = children with OSAS after AT; pre-AT = children with OSAS before AT; RMSSD = square root of the mean of the sum of the squares of the difference in RR intervals of subsequent beats; SDANN = SD of the average of the normal-to-normal RR intervals; SDNNI = SD of the normal-to-normal interval indexes. See Table 1 for expansion of the other abbreviations.

a 

P < .005, comparing children with OSAS pre-AT and post-AT.

b 

P < .05.

c 

P < .01.

d 

P < .05, control group children compared with children with OSAS pre-AT.

e 

P < .05, control group children compared with children with OSAS post-AT.

Figure Jump LinkFigure 1. Changes in heart rate interval after AT. AT = adenotonsillectomy; N1,2 = stage N1 and N2 sleep; N3 = stage N3 sleep; REM = rapid eye movement. *** = P < .005.Grahic Jump Location
Frequency-Domain Analysis

Frequency-domain measures pre-AT and post-AT during various sleep stages are shown in Table 3. Accordingly, LF and HF significantly increased in all stages of sleep after AT, but the relative increase in HF was greater, as indicated by a decrease in the LF/HF after AT (Fig 2). HF in all stages of sleep and LF in light and deep NREM sleep in the control children were higher than those of the pre-AT state of the children with OSAS. LF in REM sleep in the control children trended toward being higher than that of the pre-AT state of the children with OSAS (P = .051). There were no significant differences between the states of the control group and post-AT children with OSAS in LF, HF, or the LF/HF. An analysis of HRV in 5-min epochs18 in the children with OSAS before and after AT showed similar results (Tables 4, 5).

Table Graphic Jump Location
Table 3 —Frequency-Domain Indices in Sleep Stages in Children With OSAS Before and After AT and in Children in the Control Group

Data presented as mean ± SD. LF = low-frequency (0.04-0.15 Hz) band power; HF = high-frequency (0.15-0.4 Hz) band power; LF/HF = ratio of low-frequency to high-frequency band power. See Tables 1 and 2 for expansion of the other abbreviations.

a 

P < .05.

b 

P < .005, comparing children with OSAS pre-AT and post-AT.

c 

P < .05, control group children compared with children with OSAS pre-AT.

d 

P < .05, control group children compared with children with OSAS post-AT.

e 

P < .01.

Figure Jump LinkFigure 2. Changes in the LF/HF after AT. * = P < .05, *** = P < .005. LF/HF = ratio of low-frequency to high-frequency band power. See Figure 1 legend for expansion of other abbreviations.Grahic Jump Location
Table Graphic Jump Location
Table 4 —Five-Minute Epochs: Time-Domain Indices Before and After AT

Data presented as mean ± SD. See Tables 1 and 2 for expansion of the abbreviations.

a 

P < .005.

b 

P < .01.

c 

P < .05.

Table Graphic Jump Location
Table 5 —Five-Minute Epoch: Frequency-Domain Indices Before and After AT

Data presented as mean ± SD. See Tables 1 and 3 for expansion of the abbreviations.

a 

P < .005.

Children with both mild and moderate residual OSAS had significant reductions in HR after AT; children with mild residual OSAS had reductions in the LF/HF in REM and deep sleep (Tables 6, 7). Stratification of HRV changes by BMI showed reductions in HR in both groups after AT and reductions in the LF/HF in light NREM sleep and REM sleep in the group of children who were obese (Tables 8, 9).

Table Graphic Jump Location
Table 6 —Time-Domain Indices in Children With Mild Residual OSAS and Moderate Residual OSAS After AT

Data presented as mean ± SD. See Tables 1 and 2 for expansion of the abbreviations

a 

Mild residual OSAS, AHI 29.4 ± 28.1 events/h pre-AT reduced to 2.0 ± 1.1 events/h post-AT.

b 

P < .01.

c 

P < .05, comparing children with OSAS pre-AT and post-AT.

d 

Moderate residual OSAS, AHI 37.0 ± 17.7 events/h pre-AT reduced to 8.3 ± 3.1 events/h post-AT.

Table Graphic Jump Location
Table 7 —Frequency-Domain Indices in Children With Mild Residual OSAS and Moderate Residual OSAS After AT

Data presented as mean ± SD. See Tables 1 and 3 for expansion of the abbreviations

a 

Mild residual OSAS, AHI 29.4 ± 28.1 events/h pre-AT reduced to 2.0 ± 1.1 events/h post-AT.

b 

P < .05,comparing children with OSAS pre-AT and Post-AT.

c 

P < .01.

d 

Moderate residual OSAS, AHI 37.0 ± 17.7 events/h pre-AT reduced to 8.3 ± 3.1 events/h post-AT.

Table Graphic Jump Location
Table 8 —Changes in Time-Domain Indices in Children With OSAS, Without Obesity and With Obesity, After AT

One child from the study group was not included because the child’s age was < 2 years and the BMI z score was not available. See Tables 1 and 2 for expansion of the abbreviations.

a 

BMI z score 0.27 ± 0.78; AHI reduced from 22.5 ± 16.5 to 3.9 ± 2.8.

b 

P < .01.

c 

P < .05, comparing children with OSAS pre-AT and post-AT.

d 

BMI z score 2.86 ± 0.53; AHI reduced from 49.7 ± 25.7 to 4.8 ± 4.9.

Table Graphic Jump Location
Table 9 —Changes in Frequency-Domain Indices in Children With OSAS, Without Obesity and With Obesity, After AT

One child from the study group was not included because the child’s age was < 2 years and the BMI z score was not available. See Tables 1 and 3 for expansion of the abbreviations.

a 

BMI z score 0.27 ± 0.78; AHI reduced from 22.5 ± 16.5 to 3.9 ± 2.8.

b 

P < .05, comparing children with OSAS pre-AT and post-AT.

c 

BMI z score 2.86 ± 0.53; AHI reduced from 49.7 ± 25.7 to 4.8 ± 4.9.

Bivariable Analysis

The change in the LF/HF was proportional to the change in the arousal index and AHI on initial bivariable analysis, but these associations were not significant after baseline values of the LF/HF were inserted in the analysis. The change in HR did not correlate with any explanatory variable.

This study demonstrates that improvement in OSAS following AT in children is associated with changes in autonomic balance as shown on HRV analysis. The HR interval, LF, HF, SDNNI, and RMSSD increased, while the LF/HF decreased in all stages of sleep with improvement of OSAS and approached values similar to those of the control group. Together, the decreases in HR and the LF/HF imply a shift in autonomic balance away from the sympathetic component with reductions in OSAS.

The physiologic implications of changes in time-domain parameters are not clear, but the RMSSD is mathematically correlated with HF, and the SDNNI is correlated with the mean of the total power in the epoch.18 The observed increases in the RMSSD and SDNNI along with HF and total power (HF + LF) after AT are in accordance with these correlations. The study also indicated a decrease in the SDANN after AT. The SDANN reflects changes in frequencies at intervals > 2 to 5 min, and the decreased SDNN can reflect the reduction in frequency of apnea, hypopnea, or arousal events after AT.

Analysis of HRV in 5-min epochs was performed because this epoch length can provide a better estimate of LF18; this too suggested a similar shift in autonomic balance. These epochs were analyzed without regard to sleep stage because an adequate number of epochs free of respiratory events were not available in all stages of sleep.

Changes in HR were consistently seen when the children were stratified by residual OSAS status, but changes in the LF/HF were more consistent in the children with mild residual OSAS than in children with moderate OSAS. The level of OSAS below which sympathovagal imbalance is reversed or becomes negligible is not clear and needs further study.

The changes in HR after AT were significant in obese and nonobese children, but the obese group had more consistent reductions in the LF/HF (two out of three sleep stages), suggesting that obese children with OSAS may have greater autonomic imbalance than nonobese children with OSAS.

HR is dependent on antagonistic autonomic inputs from the parasympathetic and sympathetic components,24 while HRV in comparison can provide more insight into the change in autonomic balance between the two components. HF is predominantly determined by parasympathetic output18,25 and is partially related to respiratory activity; parasympathetic blockade with atropine significantly reduces HF.26 LF is related to both sympathetic and parasympathetic activity.27,28

OSAS is associated with higher HR in adults in some studies but not all,29,30 and treatment of OSAS with continuous positive airway pressure (CPAP) and oral appliances can decrease HR.31,32 Studies of HRV in adults with OSAS have shown higher LF/HF compared with subjects without OSAS.29,3234 Treatment of OSAS with CPAP or oral appliances has shown reversal of some of these changes.32,34

In children, Constantin et al35 reported reductions in pulse rate obtained from pulse oximetry after AT in children with OSAS, which is similar to our findings of reduced HR. They also reported a decrease in pulse rate variability (PRV) after treatment of OSAS. PRV was defined as the SD of a 7-s average for pulse rate. PRV is likely similar to SDANN, which also decreased after AT in our study, because it measures the variability of cycles > 2 and 5 min. The autonomic implications of PRV have not been elucidated. Aljadeff et al36 reported alterations in beat-to-beat variability in children with OSAS compared with children with primary snoring, noting a V-shaped form on Poincaré plots in children with OSAS compared with children without OSAS. They did not analyze the time or frequency-domain components of HRV. Baharav et al19 demonstrated consistently higher LF and LF/HF in various stages of sleep in children with OSAS compared to control children, reflecting a relatively greater sympathetic component in children with OSAS. In a large cross-sectional study of children, Liao et al37 reported a lower HF and RMSSD in children with moderate OSAS, which is similar to our findings, but did not find a higher HR or LF/HF in children with OSAS. This may be because of a smaller number of children with an AHI > 5 events/h or because of the inclusion of only the first epoch of the sleep stage in the analysis. In contrast to our findings, Chaicharn et al38 reported a lower LF/HF during the daytime in children with OSAS compared with children with a history of no snoring. However, there were significant differences in methodology; this study was conducted for a relatively short period during the daytime when differences in respiration and anxiety in a small number of children may have significantly impacted the HR and HRV, as pointed out by the authors. Our study, in comparison, studied HRV over a longer period of time, compared changes in various stages of sleep, and had a larger number of subjects. Additionally, with improvement of OSAS, we found a consistent pattern of change in HR and HRV, away from the sympathetic, in all stages of sleep as compared with the group of children without OSAS.

It should be emphasized that HRV is affected by age, sex, genetic factors, time of day (Fig 3), degree of obesity, movement, and individual variability in addition to autonomic function.24,3942 Similarly, HR is partly dependent on nonautonomic factors such as the intrinsic rate of the sinus node, circadian phase, temperature, and exercise.24 Studying the same subject before and after AT, at the same time of day, minimizes the changes in HR and HRV due to factors not related to OSAS and does not require measurement of adherence to treatment, such as is required with CPAP.

Figure Jump LinkFigure 3. Overnight changes in LF and HF before and after AT in a sample subject. HF = high-frequency (0.15-0.4 Hz) band power; LF = low-frequency (0.04-0.15 Hz) band power. See Figure 1 legend for expansion of other abbreviation.Grahic Jump Location

The present study is limited by the retrospective nature of the data, predominance of male subjects, variable interval between sleep studies, and the lack of a comparable group of children with OSAS that did not undergo surgery and were reassessed after a matching time interval. Also, oronasal flow was assessed using thermistors and may have underestimated obstructed breathing. Nevertheless, the overall data are suggestive that resolution or mitigation of OSAS is associated with reduction in sympathetic activity.

HRV and HR have been assessed as predictors of outcome in several prospective studies in adults. A higher HR has been associated with increased mortality in prospective studies4345; lower levels of time-domain indices of HRV (SDNNI, RMSSD) have been linked to an increased risk of mortality from coronary heart disease and all-cause mortality in the general population46; and lower frequency-domain indices (LF, HF, LF/HF) have been associated with increased risk of cardiac events and all-cause mortality.47,48 OSAS itself is considered an independent risk factor for mortality,49 and changes in HR and HRV associated with increased mortality are seen in children with OSAS; these phenomena taken together suggest an association that merits investigation.5054

In summary, we analyzed changes in HRV in children with OSAS after AT and observed evidence of reduction in sympathetic predominance associated with improvement of OSAS. These results also support further investigation of the influence of residual OSAS and baseline obesity on HRV changes.

Author contributions: Dr Muzumdar had full access to the data and will vouch for the integrity of the data.

Dr Muzumdar: contributed to the conception and planning of the study, data collection and analysis, and writing of the manuscript.

Mr Sin: contributed to the conception and planning of the study, data collection and analysis, and writing of the manuscript.

Dr Nikova: contributed to data collection, scoring of the sleep studies, and writing of the manuscript.

Dr Gates: contributed to the planning of the study, data analysis, and writing of the manuscript.

Dr Kim: contributed to the planning of the study, data analysis, and writing of the manuscript.

Dr Arens: contributed to the conception and planning of the study and writing of the manuscript.

Financial/nonfinancial disclosures: The authors have reported to CHEST that no potential conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article.

Other contributions: We would like to acknowledge the invaluable assistance of Swapnil Rajpathak, MBBS, DrPH, with the statistical analysis. All studies were performed at Children’s Hospital at Montefiore, Bronx, NY.

AHI

apnea-hypopnea index

AT

adenotonsillectomy

CPAP

continuous positive airway pressure

HF

high-frequency (0.15-0.4 Hz) band power

HR

heart rate

HRV

heart rate variability

LF

low-frequency (0.04-0.15 Hz) band power

LF/HF

ratio of low-frequency to high-frequency band power

NREM

nonrapid eye movement

OSAS

obstructive sleep apnea syndrome

PRV

pulse rate variability

REM

rapid eye movement

RMSSD

square root of the mean of the sum of the squares of the difference in RR intervals of subsequent beats

SDANN

SD of the average of the normal-to-normal RR intervals

SDNNI

SD of the normal-to-normal interval indexes

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O’Brien LM, Gozal D. Autonomic dysfunction in children with sleep-disordered breathing. Sleep. 2005;286:747-752. [PubMed]
 
Task Force of the European Society of Cardiology and the North American Society of Pacing and ElectrophysiologyTask Force of the European Society of Cardiology and the North American Society of Pacing and Electrophysiology Heart rate variability: standards of measurement, physiological interpretation and clinical use. Circulation. 1996;935:1043-1065. [CrossRef] [PubMed]
 
Baharav A, Kotagal S, Rubin BK, Pratt J, Akselrod S. Autonomic cardiovascular control in children with obstructive sleep apnea. Clin Auton Res. 1999;96:345-351. [CrossRef] [PubMed]
 
Section on Pediatric Pulmonology, Subcommittee on Obstructive Sleep Apnea Syndrome. American Academy of PediatricsSection on Pediatric Pulmonology, Subcommittee on Obstructive Sleep Apnea Syndrome. American Academy of Pediatrics Clinical practice guideline: diagnosis and management of childhood obstructive sleep apnea syndrome. Pediatrics. 2002;1094:704-712. [CrossRef] [PubMed]
 
Muzumdar HV, Sin S, Syamaprasad S, et al. Heart rate variability in children with OSAS before and after tonsilloadenoidectomy [Abstract]. Am J Respir Crit Care Med. 2008;177:A705
 
Iber C, Ancoli-Israel S, Chesson A, Quan SF. for the American Academy of Sleep Medicine. The AASM Manual for the Scoring of Sleep and Associated Events: Rules, Terminology and Technical Specifications. 2007; Westchester, IL American Academy of Sleep Medicine
 
Muzumdar H, Arens R. Diagnostic issues in pediatric obstructive sleep apnea. Proc Am Thorac Soc. 2008;52:263-273. [CrossRef] [PubMed]
 
Lahiri MK, Kannankeril PJ, Goldberger JJ. Assessment of autonomic function in cardiovascular disease: physiological basis and prognostic implications. J Am Coll Cardiol. 2008;5118:1725-1733. [CrossRef] [PubMed]
 
Akselrod S, Gordon D, Ubel FA, Shannon DC, Berger AC, Cohen RJ. Power spectrum analysis of heart rate fluctuation: a quantitative probe of beat-to-beat cardiovascular control. Science. 1981;2134504:220-222. [CrossRef] [PubMed]
 
Challapalli S, Kadish AH, Horvath G, Goldberger JJ. Differential effects of parasympathetic blockade and parasympathetic withdrawal on heart rate variability. J Cardiovasc Electrophysiol. 1999;109:1192-1199. [CrossRef] [PubMed]
 
Malliani A, Pagani M, Lombardi F, Cerutti S. Cardiovascular neural regulation explored in the frequency domain. Circulation. 1991;842:482-492. [CrossRef] [PubMed]
 
Pagani M, Lombardi F, Guzzetti S, et al. Power spectral analysis of heart rate and arterial pressure variabilities as a marker of sympatho-vagal interaction in man and conscious dog. Circ Res. 1986;592:178-193. [CrossRef] [PubMed]
 
Narkiewicz K, Montano N, Cogliati C, van de Borne PJ, Dyken ME, Somers VK. Altered cardiovascular variability in obstructive sleep apnea. Circulation. 1998;9811:1071-1077. [CrossRef] [PubMed]
 
Roche F, Duverney D, Court-Fortune I, et al. Cardiac interbeat interval increment for the identification of obstructive sleep apnea. Pacing Clin Electrophysiol. 2002;258:1192-1199. [CrossRef] [PubMed]
 
Sumi K, Chin K, Takahashi K, et al. Effect of nCPAP therapy on heart rate in patients with obstructive sleep apnoea-hypopnoea. QJM. 2006;998:545-553. [CrossRef] [PubMed]
 
Coruzzi P, Gualerzi M, Bernkopf E, et al. Autonomic cardiac modulation in obstructive sleep apnea: effect of an oral jaw-positioning appliance. Chest. 2006;1305:1362-1368. [CrossRef] [PubMed]
 
Gula LJ, Krahn AD, Skanes A, et al. Heart rate variability in obstructive sleep apnea: a prospective study and frequency domain analysis. Ann Noninvasive Electrocardiol. 2003;82:144-149. [CrossRef] [PubMed]
 
Roche F, Court-Fortune I, Pichot V, et al. Reduced cardiac sympathetic autonomic tone after long-term nasal continuous positive airway pressure in obstructive sleep apnoea syndrome. Clin Physiol. 1999;192:127-134. [CrossRef] [PubMed]
 
Constantin E, McGregor CD, Cote V, Brouillette RT. Pulse rate and pulse rate variability decrease after adenotonsillectomy for obstructive sleep apnea. Pediatr Pulmonol. 2008;435:498-504. [CrossRef] [PubMed]
 
Aljadeff G, Gozal D, Schechtman VL, Burrell B, Harper RM, Ward SL. Heart rate variability in children with obstructive sleep apnea. Sleep. 1997;202:151-157. [PubMed]
 
Liao D, Li X, Rodriguez-Colon SM, et al. Sleep-disordered breathing and cardiac autonomic modulation in children. Sleep Med. 2010;115:484-488. [CrossRef] [PubMed]
 
Chaicharn J, Lin Z, Chen ML, Ward SL, Keens T, Khoo MC. Model-based assessment of cardiovascular autonomic control in children with obstructive sleep apnea. Sleep. 2009;327:927-938. [PubMed]
 
Kaufman CL, Kaiser DR, Steinberger J, Kelly AS, Dengel DR. Relationships of cardiac autonomic function with metabolic abnormalities in childhood obesity. Obesity (Silver Spring). 2007;155:1164-1171. [CrossRef] [PubMed]
 
Singh JP, Larson MG, O’Donnell CJ, Tsuji H, Evans JC, Levy D. Heritability of heart rate variability: the Framingham Heart Study. Circulation. 1999;9917:2251-2254. [CrossRef] [PubMed]
 
Trinder J, Kleiman J, Carrington M, et al. Autonomic activity during human sleep as a function of time and sleep stage. J Sleep Res. 2001;104:253-264. [CrossRef] [PubMed]
 
Molfino A, Fiorentini A, Tubani L, Martuscelli M, Rossi Fanelli F, Laviano A. Body mass index is related to autonomic nervous system activity as measured by heart rate variability. Eur J Clin Nutr. 2009;6310:1263-1265. [CrossRef] [PubMed]
 
Reunanen A, Karjalainen J, Ristola P, Heliövaara M, Knekt P, Aromaa A. Heart rate and mortality. J Intern Med. 2000;2472:231-239. [CrossRef] [PubMed]
 
Kannel WB, Kannel C, Paffenbarger RS Jr, Cupples LA. Heart rate and cardiovascular mortality: the Framingham Study. Am Heart J. 1987;1136:1489-1494. [CrossRef] [PubMed]
 
Jouven X, Empana JP, Schwartz PJ, Desnos M, Courbon D, Ducimetière P. Heart-rate profile during exercise as a predictor of sudden death. N Engl J Med. 2005;35219:1951-1958. [CrossRef] [PubMed]
 
Dekker JM, Crow RS, Folsom AR, et al. Low heart rate variability in a 2-minute rhythm strip predicts risk of coronary heart disease and mortality from several causes: the ARIC Study. Atherosclerosis Risk In Communities. Circulation. 2000;10211:1239-1244. [CrossRef] [PubMed]
 
Tsuji H, Larson MG, Venditti FJ Jr, et al. Impact of reduced heart rate variability on risk for cardiac events. The Framingham Heart Study. Circulation. 1996;9411:2850-2855. [CrossRef] [PubMed]
 
Tsuji H, Venditti FJ Jr, Manders ES, et al. Reduced heart rate variability and mortality risk in an elderly cohort. The Framingham Heart Study. Circulation. 1994;902:878-883. [CrossRef] [PubMed]
 
Punjabi NM, Caffo BS, Goodwin JL, et al. Sleep-disordered breathing and mortality: a prospective cohort study. PLoS Med. 2009;68:e1000132. [CrossRef] [PubMed]
 
Mitchell RB, Kelly J. Outcome of adenotonsillectomy for obstructive sleep apnea in obese and normal-weight children. Otolaryngol Head Neck Surg. 2007;1371:43-48. [CrossRef] [PubMed]
 
Shine NP, Lannigan FJ, Coates HL, Wilson A. Adenotonsillectomy for obstructive sleep apnea in obese children: effects on respiratory parameters and clinical outcome. Arch Otolaryngol Head Neck Surg. 2006;13210:1123-1127. [CrossRef] [PubMed]
 
Tauman R, Gulliver TE, Krishna J, et al. Persistence of obstructive sleep apnea syndrome in children after adenotonsillectomy. J Pediatr. 2006;1496:803-808. [CrossRef] [PubMed]
 
Ievers-Landis CE, Redline S. Pediatric sleep apnea: implications of the epidemic of childhood overweight. Am J Respir Crit Care Med. 2007;1755:436-441. [CrossRef] [PubMed]
 
Capdevila OS, Kheirandish-Gozal L, Dayyat E, Gozal D. Pediatric obstructive sleep apnea: complications, management, and long-term outcomes. Proc Am Thorac Soc. 2008;52:274-282. [CrossRef] [PubMed]
 

Figures

Figure Jump LinkFigure 1. Changes in heart rate interval after AT. AT = adenotonsillectomy; N1,2 = stage N1 and N2 sleep; N3 = stage N3 sleep; REM = rapid eye movement. *** = P < .005.Grahic Jump Location
Figure Jump LinkFigure 2. Changes in the LF/HF after AT. * = P < .05, *** = P < .005. LF/HF = ratio of low-frequency to high-frequency band power. See Figure 1 legend for expansion of other abbreviations.Grahic Jump Location
Figure Jump LinkFigure 3. Overnight changes in LF and HF before and after AT in a sample subject. HF = high-frequency (0.15-0.4 Hz) band power; LF = low-frequency (0.04-0.15 Hz) band power. See Figure 1 legend for expansion of other abbreviation.Grahic Jump Location

Tables

Table Graphic Jump Location
Table 1 —Demographics and Polysomnographic Data

Data presented as mean ± (SD). AHI = apnea-hypopnea index; AT = adenotonsillectomy; M = male; N1,2 = stage N1 and N2 sleep; N3 = stage N3 sleep; OSAS = obstructive sleep apnea syndrome; REM = rapid-eye-movement sleep.

a 

P values compare data for children with OSAS before and after AT.

b 

P value < .05, children with OSAS before AT compared with control subjects.

c 

P value < .05, children with OSAS after AT compared with control subjects.

Table Graphic Jump Location
Table 2 —Time-Domain Indices in Sleep Stages in Children With OSAS Before and After AT and in Children in the Control Group

Data are presented as mean ± SD. Control = control group of children with primary snoring without OSAS; HR = heart rate; post-AT = children with OSAS after AT; pre-AT = children with OSAS before AT; RMSSD = square root of the mean of the sum of the squares of the difference in RR intervals of subsequent beats; SDANN = SD of the average of the normal-to-normal RR intervals; SDNNI = SD of the normal-to-normal interval indexes. See Table 1 for expansion of the other abbreviations.

a 

P < .005, comparing children with OSAS pre-AT and post-AT.

b 

P < .05.

c 

P < .01.

d 

P < .05, control group children compared with children with OSAS pre-AT.

e 

P < .05, control group children compared with children with OSAS post-AT.

Table Graphic Jump Location
Table 3 —Frequency-Domain Indices in Sleep Stages in Children With OSAS Before and After AT and in Children in the Control Group

Data presented as mean ± SD. LF = low-frequency (0.04-0.15 Hz) band power; HF = high-frequency (0.15-0.4 Hz) band power; LF/HF = ratio of low-frequency to high-frequency band power. See Tables 1 and 2 for expansion of the other abbreviations.

a 

P < .05.

b 

P < .005, comparing children with OSAS pre-AT and post-AT.

c 

P < .05, control group children compared with children with OSAS pre-AT.

d 

P < .05, control group children compared with children with OSAS post-AT.

e 

P < .01.

Table Graphic Jump Location
Table 4 —Five-Minute Epochs: Time-Domain Indices Before and After AT

Data presented as mean ± SD. See Tables 1 and 2 for expansion of the abbreviations.

a 

P < .005.

b 

P < .01.

c 

P < .05.

Table Graphic Jump Location
Table 5 —Five-Minute Epoch: Frequency-Domain Indices Before and After AT

Data presented as mean ± SD. See Tables 1 and 3 for expansion of the abbreviations.

a 

P < .005.

Table Graphic Jump Location
Table 6 —Time-Domain Indices in Children With Mild Residual OSAS and Moderate Residual OSAS After AT

Data presented as mean ± SD. See Tables 1 and 2 for expansion of the abbreviations

a 

Mild residual OSAS, AHI 29.4 ± 28.1 events/h pre-AT reduced to 2.0 ± 1.1 events/h post-AT.

b 

P < .01.

c 

P < .05, comparing children with OSAS pre-AT and post-AT.

d 

Moderate residual OSAS, AHI 37.0 ± 17.7 events/h pre-AT reduced to 8.3 ± 3.1 events/h post-AT.

Table Graphic Jump Location
Table 7 —Frequency-Domain Indices in Children With Mild Residual OSAS and Moderate Residual OSAS After AT

Data presented as mean ± SD. See Tables 1 and 3 for expansion of the abbreviations

a 

Mild residual OSAS, AHI 29.4 ± 28.1 events/h pre-AT reduced to 2.0 ± 1.1 events/h post-AT.

b 

P < .05,comparing children with OSAS pre-AT and Post-AT.

c 

P < .01.

d 

Moderate residual OSAS, AHI 37.0 ± 17.7 events/h pre-AT reduced to 8.3 ± 3.1 events/h post-AT.

Table Graphic Jump Location
Table 8 —Changes in Time-Domain Indices in Children With OSAS, Without Obesity and With Obesity, After AT

One child from the study group was not included because the child’s age was < 2 years and the BMI z score was not available. See Tables 1 and 2 for expansion of the abbreviations.

a 

BMI z score 0.27 ± 0.78; AHI reduced from 22.5 ± 16.5 to 3.9 ± 2.8.

b 

P < .01.

c 

P < .05, comparing children with OSAS pre-AT and post-AT.

d 

BMI z score 2.86 ± 0.53; AHI reduced from 49.7 ± 25.7 to 4.8 ± 4.9.

Table Graphic Jump Location
Table 9 —Changes in Frequency-Domain Indices in Children With OSAS, Without Obesity and With Obesity, After AT

One child from the study group was not included because the child’s age was < 2 years and the BMI z score was not available. See Tables 1 and 3 for expansion of the abbreviations.

a 

BMI z score 0.27 ± 0.78; AHI reduced from 22.5 ± 16.5 to 3.9 ± 2.8.

b 

P < .05, comparing children with OSAS pre-AT and post-AT.

c 

BMI z score 2.86 ± 0.53; AHI reduced from 49.7 ± 25.7 to 4.8 ± 4.9.

References

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Schechter MS. Section on Pediatric Pulmonology, Subcommittee on Obstructive Sleep Apnea Syndrome Section on Pediatric Pulmonology, Subcommittee on Obstructive Sleep Apnea Syndrome Technical report: diagnosis and management of childhood obstructive sleep apnea syndrome. Pediatrics. 2002;1094:1-20. [CrossRef] [PubMed]
 
Caples SM, Garcia-Touchard A, Somers VK. Sleep-disordered breathing and cardiovascular risk. Sleep. 2007;303:291-303. [PubMed]
 
Amin R, Somers VK, McConnell K, et al. Activity-adjusted 24-hour ambulatory blood pressure and cardiac remodeling in children with sleep disordered breathing. Hypertension. 2008;511:84-91. [CrossRef] [PubMed]
 
Amin RS, Carroll JL, Jeffries JL, et al. Twenty-four-hour ambulatory blood pressure in children with sleep-disordered breathing. Am J Respir Crit Care Med. 2004;1698:950-956. [CrossRef] [PubMed]
 
Gozal D, Capdevila OS, Kheirandish-Gozal L. Metabolic alterations and systemic inflammation in obstructive sleep apnea among nonobese and obese prepubertal children. Am J Respir Crit Care Med. 2008;17710:1142-1149. [CrossRef] [PubMed]
 
Gozal D, Kheirandish-Gozal L, Serpero LD, Sans Capdevila O, Dayyat E. Obstructive sleep apnea and endothelial function in school-aged nonobese children: effect of adenotonsillectomy. Circulation. 2007;11620:2307-2314. [CrossRef] [PubMed]
 
Somers VK, Dyken ME, Clary MP, Abboud FM. Sympathetic neural mechanisms in obstructive sleep apnea. J Clin Invest. 1995;964:1897-1904. [CrossRef] [PubMed]
 
Narkiewicz K, van de Borne PJ, Pesek CA, Dyken ME, Montano N, Somers VK. Selective potentiation of peripheral chemoreflex sensitivity in obstructive sleep apnea. Circulation. 1999;999:1183-1189. [CrossRef] [PubMed]
 
Somers VK, Mark AL, Abboud FM. Interaction of baroreceptor and chemoreceptor reflex control of sympathetic nerve activity in normal humans. J Clin Invest. 1991;876:1953-1957. [CrossRef] [PubMed]
 
Gates GJ, Bartels MN, Downey JA, De Meersman RE. The effect of chemoreceptor stimulation upon muscle sympathetic nerve activity. Respir Physiol Neurobiol. 2009;1673:268-272. [CrossRef] [PubMed]
 
Morgan BJ, Crabtree DC, Puleo DS, Badr MS, Toiber F, Skatrud JB. Neurocirculatory consequences of abrupt change in sleep state in humans. J Appl Physiol. 1996;805:1627-1636. [PubMed]
 
Sforza E, Pichot V, Cervena K, Barthélémy JC, Roche F. Cardiac variability and heart-rate increment as a marker of sleep fragmentation in patients with a sleep disorder: a preliminary study. Sleep. 2007;301:43-51. [PubMed]
 
Gami AS, Howard DE, Olson EJ, Somers VK. Day-night pattern of sudden death in obstructive sleep apnea. N Engl J Med. 2005;35212:1206-1214. [CrossRef] [PubMed]
 
Mehra R, Benjamin EJ, Shahar E, et al; Sleep Heart Health Study Sleep Heart Health Study Association of nocturnal arrhythmias with sleep-disordered breathing: the Sleep Heart Health Study. Am J Respir Crit Care Med. 2006;1738:910-916. [CrossRef] [PubMed]
 
McConnell K, Somers VK, Kimball T, et al. Baroreflex gain in children with obstructive sleep apnea. Am J Respir Crit Care Med. 2009;1801:42-48. [CrossRef] [PubMed]
 
O’Brien LM, Gozal D. Autonomic dysfunction in children with sleep-disordered breathing. Sleep. 2005;286:747-752. [PubMed]
 
Task Force of the European Society of Cardiology and the North American Society of Pacing and ElectrophysiologyTask Force of the European Society of Cardiology and the North American Society of Pacing and Electrophysiology Heart rate variability: standards of measurement, physiological interpretation and clinical use. Circulation. 1996;935:1043-1065. [CrossRef] [PubMed]
 
Baharav A, Kotagal S, Rubin BK, Pratt J, Akselrod S. Autonomic cardiovascular control in children with obstructive sleep apnea. Clin Auton Res. 1999;96:345-351. [CrossRef] [PubMed]
 
Section on Pediatric Pulmonology, Subcommittee on Obstructive Sleep Apnea Syndrome. American Academy of PediatricsSection on Pediatric Pulmonology, Subcommittee on Obstructive Sleep Apnea Syndrome. American Academy of Pediatrics Clinical practice guideline: diagnosis and management of childhood obstructive sleep apnea syndrome. Pediatrics. 2002;1094:704-712. [CrossRef] [PubMed]
 
Muzumdar HV, Sin S, Syamaprasad S, et al. Heart rate variability in children with OSAS before and after tonsilloadenoidectomy [Abstract]. Am J Respir Crit Care Med. 2008;177:A705
 
Iber C, Ancoli-Israel S, Chesson A, Quan SF. for the American Academy of Sleep Medicine. The AASM Manual for the Scoring of Sleep and Associated Events: Rules, Terminology and Technical Specifications. 2007; Westchester, IL American Academy of Sleep Medicine
 
Muzumdar H, Arens R. Diagnostic issues in pediatric obstructive sleep apnea. Proc Am Thorac Soc. 2008;52:263-273. [CrossRef] [PubMed]
 
Lahiri MK, Kannankeril PJ, Goldberger JJ. Assessment of autonomic function in cardiovascular disease: physiological basis and prognostic implications. J Am Coll Cardiol. 2008;5118:1725-1733. [CrossRef] [PubMed]
 
Akselrod S, Gordon D, Ubel FA, Shannon DC, Berger AC, Cohen RJ. Power spectrum analysis of heart rate fluctuation: a quantitative probe of beat-to-beat cardiovascular control. Science. 1981;2134504:220-222. [CrossRef] [PubMed]
 
Challapalli S, Kadish AH, Horvath G, Goldberger JJ. Differential effects of parasympathetic blockade and parasympathetic withdrawal on heart rate variability. J Cardiovasc Electrophysiol. 1999;109:1192-1199. [CrossRef] [PubMed]
 
Malliani A, Pagani M, Lombardi F, Cerutti S. Cardiovascular neural regulation explored in the frequency domain. Circulation. 1991;842:482-492. [CrossRef] [PubMed]
 
Pagani M, Lombardi F, Guzzetti S, et al. Power spectral analysis of heart rate and arterial pressure variabilities as a marker of sympatho-vagal interaction in man and conscious dog. Circ Res. 1986;592:178-193. [CrossRef] [PubMed]
 
Narkiewicz K, Montano N, Cogliati C, van de Borne PJ, Dyken ME, Somers VK. Altered cardiovascular variability in obstructive sleep apnea. Circulation. 1998;9811:1071-1077. [CrossRef] [PubMed]
 
Roche F, Duverney D, Court-Fortune I, et al. Cardiac interbeat interval increment for the identification of obstructive sleep apnea. Pacing Clin Electrophysiol. 2002;258:1192-1199. [CrossRef] [PubMed]
 
Sumi K, Chin K, Takahashi K, et al. Effect of nCPAP therapy on heart rate in patients with obstructive sleep apnoea-hypopnoea. QJM. 2006;998:545-553. [CrossRef] [PubMed]
 
Coruzzi P, Gualerzi M, Bernkopf E, et al. Autonomic cardiac modulation in obstructive sleep apnea: effect of an oral jaw-positioning appliance. Chest. 2006;1305:1362-1368. [CrossRef] [PubMed]
 
Gula LJ, Krahn AD, Skanes A, et al. Heart rate variability in obstructive sleep apnea: a prospective study and frequency domain analysis. Ann Noninvasive Electrocardiol. 2003;82:144-149. [CrossRef] [PubMed]
 
Roche F, Court-Fortune I, Pichot V, et al. Reduced cardiac sympathetic autonomic tone after long-term nasal continuous positive airway pressure in obstructive sleep apnoea syndrome. Clin Physiol. 1999;192:127-134. [CrossRef] [PubMed]
 
Constantin E, McGregor CD, Cote V, Brouillette RT. Pulse rate and pulse rate variability decrease after adenotonsillectomy for obstructive sleep apnea. Pediatr Pulmonol. 2008;435:498-504. [CrossRef] [PubMed]
 
Aljadeff G, Gozal D, Schechtman VL, Burrell B, Harper RM, Ward SL. Heart rate variability in children with obstructive sleep apnea. Sleep. 1997;202:151-157. [PubMed]
 
Liao D, Li X, Rodriguez-Colon SM, et al. Sleep-disordered breathing and cardiac autonomic modulation in children. Sleep Med. 2010;115:484-488. [CrossRef] [PubMed]
 
Chaicharn J, Lin Z, Chen ML, Ward SL, Keens T, Khoo MC. Model-based assessment of cardiovascular autonomic control in children with obstructive sleep apnea. Sleep. 2009;327:927-938. [PubMed]
 
Kaufman CL, Kaiser DR, Steinberger J, Kelly AS, Dengel DR. Relationships of cardiac autonomic function with metabolic abnormalities in childhood obesity. Obesity (Silver Spring). 2007;155:1164-1171. [CrossRef] [PubMed]
 
Singh JP, Larson MG, O’Donnell CJ, Tsuji H, Evans JC, Levy D. Heritability of heart rate variability: the Framingham Heart Study. Circulation. 1999;9917:2251-2254. [CrossRef] [PubMed]
 
Trinder J, Kleiman J, Carrington M, et al. Autonomic activity during human sleep as a function of time and sleep stage. J Sleep Res. 2001;104:253-264. [CrossRef] [PubMed]
 
Molfino A, Fiorentini A, Tubani L, Martuscelli M, Rossi Fanelli F, Laviano A. Body mass index is related to autonomic nervous system activity as measured by heart rate variability. Eur J Clin Nutr. 2009;6310:1263-1265. [CrossRef] [PubMed]
 
Reunanen A, Karjalainen J, Ristola P, Heliövaara M, Knekt P, Aromaa A. Heart rate and mortality. J Intern Med. 2000;2472:231-239. [CrossRef] [PubMed]
 
Kannel WB, Kannel C, Paffenbarger RS Jr, Cupples LA. Heart rate and cardiovascular mortality: the Framingham Study. Am Heart J. 1987;1136:1489-1494. [CrossRef] [PubMed]
 
Jouven X, Empana JP, Schwartz PJ, Desnos M, Courbon D, Ducimetière P. Heart-rate profile during exercise as a predictor of sudden death. N Engl J Med. 2005;35219:1951-1958. [CrossRef] [PubMed]
 
Dekker JM, Crow RS, Folsom AR, et al. Low heart rate variability in a 2-minute rhythm strip predicts risk of coronary heart disease and mortality from several causes: the ARIC Study. Atherosclerosis Risk In Communities. Circulation. 2000;10211:1239-1244. [CrossRef] [PubMed]
 
Tsuji H, Larson MG, Venditti FJ Jr, et al. Impact of reduced heart rate variability on risk for cardiac events. The Framingham Heart Study. Circulation. 1996;9411:2850-2855. [CrossRef] [PubMed]
 
Tsuji H, Venditti FJ Jr, Manders ES, et al. Reduced heart rate variability and mortality risk in an elderly cohort. The Framingham Heart Study. Circulation. 1994;902:878-883. [CrossRef] [PubMed]
 
Punjabi NM, Caffo BS, Goodwin JL, et al. Sleep-disordered breathing and mortality: a prospective cohort study. PLoS Med. 2009;68:e1000132. [CrossRef] [PubMed]
 
Mitchell RB, Kelly J. Outcome of adenotonsillectomy for obstructive sleep apnea in obese and normal-weight children. Otolaryngol Head Neck Surg. 2007;1371:43-48. [CrossRef] [PubMed]
 
Shine NP, Lannigan FJ, Coates HL, Wilson A. Adenotonsillectomy for obstructive sleep apnea in obese children: effects on respiratory parameters and clinical outcome. Arch Otolaryngol Head Neck Surg. 2006;13210:1123-1127. [CrossRef] [PubMed]
 
Tauman R, Gulliver TE, Krishna J, et al. Persistence of obstructive sleep apnea syndrome in children after adenotonsillectomy. J Pediatr. 2006;1496:803-808. [CrossRef] [PubMed]
 
Ievers-Landis CE, Redline S. Pediatric sleep apnea: implications of the epidemic of childhood overweight. Am J Respir Crit Care Med. 2007;1755:436-441. [CrossRef] [PubMed]
 
Capdevila OS, Kheirandish-Gozal L, Dayyat E, Gozal D. Pediatric obstructive sleep apnea: complications, management, and long-term outcomes. Proc Am Thorac Soc. 2008;52:274-282. [CrossRef] [PubMed]
 
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