pii: sp-00422-15
http://dx.doi.org/10.5665/sleep.4960
EDITORIAL
Cardiovascular Consequences in Children with Obstructive Sleep Apnea: Is It Possible to Predict Them? Commentary on Quante et al. The effect of adenotonsillectomy for childhood sleep apnea on cardiometabolic measures. SLEEP 2015;38:1395–1403. Pablo E. Brockmann, MD Department of Pediatric Cardiology and Pulmonology, Sleep Center, School of Medicine, Pontificia Universidad Católica de Chile, Santiago de Chile, Chile
Cardiovascular consequences are frequent in patients with obstructive sleep apnea (OSA).1–6 Adverse cardiovascular outcomes have been less described in children than in adults. However, there is increasing evidence that the deleterious effects of OSA could be starting early in life.7 In this issue of SLEEP, Quante et al.8 present new results from the Childhood Adenotonsillectomy Trial (CHAT) study of health and behavioral outcomes in children with OSAS, randomized to early AT (eAT) or to Watchful Waiting with Supportive Care (WWSC). In their study, cardiometabolic outcomes are described and compared between eAT and WWSC groups. The impact of the treatment of OSA on blood pressure, heart rate during sleep and wakefulness; lipid profiles and glucose; and levels of inflammatory markers were analyzed. They found that these parameters at baseline, as well their changes at follow-up, were correlated with polysomnographic indices and sleep quality. The study included 464 children (aged 5 to 9.9 years). No significant changes of cardiometabolic outcomes were found over the 7- month interval in the eAT group and to the WWSC group. One of the strengths of study by Quante et al. is its large sample size and its outstanding methodological approach. The authors specifically excluded children with severe OSA or hypoxemia. The included children actually had “mild” OSA. On one hand, these inclusion criteria highlight the relevance of considering the apparently milder groups of OSA as vulnerable. On the other hand, exclusion of more severe cases might be an explanation for the lack of significant changes of cardiometabolic outcomes after surgery. The only parameter that was significantly associated with the baseline severity of OSA was heart rate. Heart rate emerged as a potential predictor of OSA severity and a measure of responsiveness to OSA treatment. In this study, heart rate during wakefulness was measured during a one-minute recording of the radial pulse. Average heart rate during sleep was obtained from polysomnographic software (electrocardiogram or pulse oximetry). It has been proposed that heart rate changes are induced by autonomic nervous system activation during sleep.9 In children with OSA this might be associated with the reported risk of Submitted for publication July, 2015 Accepted for publication July, 2015 Address correspondence to: Dr. Pablo E. Brockmann, Department of Pediatric Cardiology and Pulmonology, Sleep Center, School of Medicine, Pontificia Universidad Católica de Chile Lira 85 5to piso, 330074 Santiago de Chile, Chile; Tel: 56.2.23543767; Email: [email protected] SLEEP, Vol. 38, No. 9, 2015
long-term cardiovascular consequences.10 The exact relationship between respiratory events such as apneas (or hypopneas), and pulse rate changes has not been well investigated in children. In the study by Quante et al., a significant association was found between the apnea hypopnea index (AHI) and several heart rate parameters.8 Specifically, heart rate during REM sleep was significantly associated with AHI, SpO2, different sleep stages, and ETCO2. In previous studies, heart rate has been investigated as a predictor of OSA. In one of these studies, heart rate increases by ≥ 6 beats per minute showed 0.70 sensitivity and 0.89 specificity for obstructive respiratory events and 0.72 sensitivity and 0.82 specificity for central respiratory events.11 Heart rate variability (i.e., increases from the baseline) has also been used in previous studies. One of the problems with pulse rate is the lack of an adequate definition for a clinically relevant heart rate change. Also, heart and pulse rate are often considered equal, even if they are obtained by two different methods: electrocardiography and pulse oximetry.12 Previous studies investigating this topic largely concur with the present study’s results.13 Heart rate based on an electrocardiography-based classification system13 achieved acceptable diagnostic test accuracy in a systematic review.14 The study included in that systematic review was of interest, as it used a fully automated system for detection of heart rate.13,14 In addition, heart rate measurement may be recorded easily and is probably well tolerated by children.15 The exact mechanism that links heart rate changes with OSA is not entirely understood. However, data from investigations conducted on this issue suggest that heart rate variability in children with OSA may be related to “autonomic arousal” following airway obstruction in children.16,17 Children suffering from OSA present heart rate changes at the termination of respiratory events that are twice as high as in healthy children.18 Apart from its use as a predictor of OSA, the association of heart rate changes with OSA-related consequences has also been investigated.13,19–24 Heart rate changes seem to be associated with attention problems and enuresis in children.10 Previous studies have associated increased heart rate variability with enuresis, thereby suggesting an autonomic dysregulation as a possible cause.25 A common abnormal autonomic pathway between heart rate changes, and enuresis seems therefore a possible hypothesis.25 Even after adjusting for several confounding factors, a significant association between heart rate changes and symptoms suggesting attention deficit has been demonstrated.10 Taken together, these data strongly suggest the importance of heart rate as a promissory marker of possible cardiovascular
1343
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consequences in children. But what follows from these findings? Basically, there is both good and bad news. The good news is that heart rate seems to be a simple and easy obtainable marker of OSA. Quante et al.8 add to current knowledge by demonstrating that not only heart rate during sleep, but also during wakefulness was associated with health consequences. Hence, one might hypothesize that daytime measurements of heart rate could be developed help as markers. The bad news, however, is the possible “adaptation” to heart rate changes. An autonomic adaptation to repetitive respiratory events may induce a reduced response of heart rate after a time. How would this affect the predictive value of heart rate as marker of OSArelated consequences? This has yet to be proven in long-term follow-up studies. The study by Quante et al. highlights the importance of heart rate and its association with increased cardiovascular risk. This study brings our knowledge a step beyond: its results support the role of a simple parameter like heart rate as a marker of OSA and its consequences. Future studies should investigate the clinical importance of such simple and easily obtainable markers for OSA related consequences in in children. CITATION Brockmann PE. Cardiovascular consequences in children with obstructive sleep apnea: is it possible to predict them? SLEEP 2015;38(9):1343–1344. DISCLOSURE STATEMENT Dr. Brockmann has indicated no financial conflicts of interest. REFERENCES
1. Kaditis A. From obstructive sleep apnea in childhood to cardiovascular disease in adulthood: what is the evidence? Sleep 2010 33:1279–80. 2. Li AM, Au CT, Sung RY, et al. Ambulatory blood pressure in children with obstructive sleep apnoea: a community based study. Thorax 2008;63:803–9. 3. Leung LC, Ng DK, Lau MW, et al. Twenty-four-hour ambulatory BP in snoring children with obstructive sleep apnea syndrome. Chest 2006;130:1009–17. 4. Marcus JA, Pothineni A, Marcus CZ, Bisognano JD. The role of obesity and obstructive sleep apnea in the pathogenesis and treatment of resistant hypertension. Curr Hypertens Rep 2014;16:411. 5. Bhattacharjee R, Gozal D. Cardiovascular disease and sleep disordered breathing: are children vulnerable? Sleep 2009;32:1251–2. 6. Bhattacharjee R, Kheirandish-Gozal L, Pillar G, Gozal D. Cardiovascular complications of obstructive sleep apnea syndrome: evidence from children. Prog Cardiovasc Dis 2009;51:416–33. 7. Gozal D, O’Brien L, Row BW. Consequences of snoring and sleep disordered breathing in children. Pediatr Pulmonol Suppl 2004;26:166–8.
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8. Quante M, Wang R, Weng J, et al. The effect of adenotonsillectomy for childhood sleep apnea on cardiometabolic measures. Sleep 2015;38:1395–403. 9. Noehren A, Brockmann PE, Urschitz MS, Sokollik C, Schlaud M, Poets CF. Detection of respiratory events using pulse rate in children with and without obstructive sleep apnea. Pediatr Pulmonol 2010;45:459–68. 10. Brockmann PE, Urschitz MS, Noehren A, Sokollik C, Schlaud M, Poets CF. Risk factors and consequences of excessive autonomic activation during sleep in children. Sleep Breath 2011;15:409–16. 11. Foo JY, Bradley AP, Wilson SJ, Williams GR, Dakin C, Cooper DM. Screening of obstructive and central apnoea/hypopnoea in children using variability: a preliminary study. Acta Paediatr 2006;95:561–4. 12. Pu Y, Patterson R, Cramerbornemann M. Nocturnal cardiorespiratory indices - a novel screening tool for pediatric obstructive sleep disordered breathing. Conf Proc IEEE Eng Med Biol Soc 2005;3:2575–8. 13. Shouldice RB, O’Brien LM, O’Brien C, de Chazal P, Gozal D, Heneghan C. Detection of obstructive sleep apnea in pediatric subjects using surface lead electrocardiogram features. Sleep 2004;27:784–92. 14. Brockmann PE, Schaefer C, Poets A, Poets CF, Urschitz MS. Diagnosis of obstructive sleep apnea in children: a systematic review. Sleep Med Rev 2013;17:331–40. 15. Foo JY, Lim CS. Development of a home screening system for pediatric respiratory sleep studies. Telemed J E Health 2006;12:698–701. 16. Morielli A, Ladan S, Ducharme FM, Brouillette RT. Can sleep and wakefulness be distinguished in children by cardiorespiratory and videotape recordings? Chest 1996;109:680–7. 17. Gozal D, Hakim F, Kheirandish-Gozal L. Chemoreceptors, baroreceptors, and autonomic deregulation in children with obstructive sleep apnea. Respir Physiol Neurobiol 2012. 18. Noehren A, Brockmann P, Urschitz M, Sokollik C, Schlaud M, Poets C. Detection of respiratory events using pulse rate in children with and without obstructive sleep apnea. Pediatr Pulmonol 2010;45:459–68. 19. Gil E, Vergara JM, Bianchi AM, Laguna P. Obstructive sleep apnea syndrome analysis in children by decreases in the amplitude fluctuations of pulse photoplethysmography: role of recording duration and heart rate variability. Conf Proc IEEE Eng Med Biol Soc 2007;2007:6090–3. 20. Aljadeff G, Gozal D, Schechtman VL, Burrell B, Harper RM, Ward SL. Heart rate variability in children with obstructive sleep apnea. Sleep 1997;20:151–7. 21. Tauman R, O’Brien LM, Mast BT, Holbrook CR, Gozal D. Peripheral arterial tonometry events and electroencephalographic arousals in children. Sleep 2004;27:502–6. 22. Raymond B, Cayton RM, Chappell MJ. Combined index of heart rate variability and oximetry in screening for the sleep apnoea/hypopnoea syndrome. J Sleep Res 2003;12:53–61. 23. Adachi H, Mikami A, Kumano-go T, et al. Clinical significance of pulse rate rise during sleep as a screening marker for the assessment of sleep fragmentation in sleep-disordered breathing. Sleep Med 2003;4:537–42. 24. Pu Y, Patterson R, Cramerbornemann M. Nocturnal cardio-respiratory indices - a novel screening tool for pediatric obstructive sleep disordered breathing. Conf Proc IEEE Eng Med Biol Soc 2005;3:2575–8. 25. Unalacak M, Aydin M, Ermis B, et al. Assessment of cardiac autonomic regulation in children with monosymptomatic nocturnal enuresis by analysis of heart rate variability. Tohoku J Exp Med 2004;204:63–9.
Editorial—Brockmann
http://dx.doi.org/10.5665/sleep.4960
EDITORIAL
Cardiovascular Consequences in Children with Obstructive Sleep Apnea: Is It Possible to Predict Them? Commentary on Quante et al. The effect of adenotonsillectomy for childhood sleep apnea on cardiometabolic measures. SLEEP 2015;38:1395–1403. Pablo E. Brockmann, MD Department of Pediatric Cardiology and Pulmonology, Sleep Center, School of Medicine, Pontificia Universidad Católica de Chile, Santiago de Chile, Chile
Cardiovascular consequences are frequent in patients with obstructive sleep apnea (OSA).1–6 Adverse cardiovascular outcomes have been less described in children than in adults. However, there is increasing evidence that the deleterious effects of OSA could be starting early in life.7 In this issue of SLEEP, Quante et al.8 present new results from the Childhood Adenotonsillectomy Trial (CHAT) study of health and behavioral outcomes in children with OSAS, randomized to early AT (eAT) or to Watchful Waiting with Supportive Care (WWSC). In their study, cardiometabolic outcomes are described and compared between eAT and WWSC groups. The impact of the treatment of OSA on blood pressure, heart rate during sleep and wakefulness; lipid profiles and glucose; and levels of inflammatory markers were analyzed. They found that these parameters at baseline, as well their changes at follow-up, were correlated with polysomnographic indices and sleep quality. The study included 464 children (aged 5 to 9.9 years). No significant changes of cardiometabolic outcomes were found over the 7- month interval in the eAT group and to the WWSC group. One of the strengths of study by Quante et al. is its large sample size and its outstanding methodological approach. The authors specifically excluded children with severe OSA or hypoxemia. The included children actually had “mild” OSA. On one hand, these inclusion criteria highlight the relevance of considering the apparently milder groups of OSA as vulnerable. On the other hand, exclusion of more severe cases might be an explanation for the lack of significant changes of cardiometabolic outcomes after surgery. The only parameter that was significantly associated with the baseline severity of OSA was heart rate. Heart rate emerged as a potential predictor of OSA severity and a measure of responsiveness to OSA treatment. In this study, heart rate during wakefulness was measured during a one-minute recording of the radial pulse. Average heart rate during sleep was obtained from polysomnographic software (electrocardiogram or pulse oximetry). It has been proposed that heart rate changes are induced by autonomic nervous system activation during sleep.9 In children with OSA this might be associated with the reported risk of Submitted for publication July, 2015 Accepted for publication July, 2015 Address correspondence to: Dr. Pablo E. Brockmann, Department of Pediatric Cardiology and Pulmonology, Sleep Center, School of Medicine, Pontificia Universidad Católica de Chile Lira 85 5to piso, 330074 Santiago de Chile, Chile; Tel: 56.2.23543767; Email: [email protected] SLEEP, Vol. 38, No. 9, 2015
long-term cardiovascular consequences.10 The exact relationship between respiratory events such as apneas (or hypopneas), and pulse rate changes has not been well investigated in children. In the study by Quante et al., a significant association was found between the apnea hypopnea index (AHI) and several heart rate parameters.8 Specifically, heart rate during REM sleep was significantly associated with AHI, SpO2, different sleep stages, and ETCO2. In previous studies, heart rate has been investigated as a predictor of OSA. In one of these studies, heart rate increases by ≥ 6 beats per minute showed 0.70 sensitivity and 0.89 specificity for obstructive respiratory events and 0.72 sensitivity and 0.82 specificity for central respiratory events.11 Heart rate variability (i.e., increases from the baseline) has also been used in previous studies. One of the problems with pulse rate is the lack of an adequate definition for a clinically relevant heart rate change. Also, heart and pulse rate are often considered equal, even if they are obtained by two different methods: electrocardiography and pulse oximetry.12 Previous studies investigating this topic largely concur with the present study’s results.13 Heart rate based on an electrocardiography-based classification system13 achieved acceptable diagnostic test accuracy in a systematic review.14 The study included in that systematic review was of interest, as it used a fully automated system for detection of heart rate.13,14 In addition, heart rate measurement may be recorded easily and is probably well tolerated by children.15 The exact mechanism that links heart rate changes with OSA is not entirely understood. However, data from investigations conducted on this issue suggest that heart rate variability in children with OSA may be related to “autonomic arousal” following airway obstruction in children.16,17 Children suffering from OSA present heart rate changes at the termination of respiratory events that are twice as high as in healthy children.18 Apart from its use as a predictor of OSA, the association of heart rate changes with OSA-related consequences has also been investigated.13,19–24 Heart rate changes seem to be associated with attention problems and enuresis in children.10 Previous studies have associated increased heart rate variability with enuresis, thereby suggesting an autonomic dysregulation as a possible cause.25 A common abnormal autonomic pathway between heart rate changes, and enuresis seems therefore a possible hypothesis.25 Even after adjusting for several confounding factors, a significant association between heart rate changes and symptoms suggesting attention deficit has been demonstrated.10 Taken together, these data strongly suggest the importance of heart rate as a promissory marker of possible cardiovascular
1343
Editorial—Brockmann
consequences in children. But what follows from these findings? Basically, there is both good and bad news. The good news is that heart rate seems to be a simple and easy obtainable marker of OSA. Quante et al.8 add to current knowledge by demonstrating that not only heart rate during sleep, but also during wakefulness was associated with health consequences. Hence, one might hypothesize that daytime measurements of heart rate could be developed help as markers. The bad news, however, is the possible “adaptation” to heart rate changes. An autonomic adaptation to repetitive respiratory events may induce a reduced response of heart rate after a time. How would this affect the predictive value of heart rate as marker of OSArelated consequences? This has yet to be proven in long-term follow-up studies. The study by Quante et al. highlights the importance of heart rate and its association with increased cardiovascular risk. This study brings our knowledge a step beyond: its results support the role of a simple parameter like heart rate as a marker of OSA and its consequences. Future studies should investigate the clinical importance of such simple and easily obtainable markers for OSA related consequences in in children. CITATION Brockmann PE. Cardiovascular consequences in children with obstructive sleep apnea: is it possible to predict them? SLEEP 2015;38(9):1343–1344. DISCLOSURE STATEMENT Dr. Brockmann has indicated no financial conflicts of interest. REFERENCES
1. Kaditis A. From obstructive sleep apnea in childhood to cardiovascular disease in adulthood: what is the evidence? Sleep 2010 33:1279–80. 2. Li AM, Au CT, Sung RY, et al. Ambulatory blood pressure in children with obstructive sleep apnoea: a community based study. Thorax 2008;63:803–9. 3. Leung LC, Ng DK, Lau MW, et al. Twenty-four-hour ambulatory BP in snoring children with obstructive sleep apnea syndrome. Chest 2006;130:1009–17. 4. Marcus JA, Pothineni A, Marcus CZ, Bisognano JD. The role of obesity and obstructive sleep apnea in the pathogenesis and treatment of resistant hypertension. Curr Hypertens Rep 2014;16:411. 5. Bhattacharjee R, Gozal D. Cardiovascular disease and sleep disordered breathing: are children vulnerable? Sleep 2009;32:1251–2. 6. Bhattacharjee R, Kheirandish-Gozal L, Pillar G, Gozal D. Cardiovascular complications of obstructive sleep apnea syndrome: evidence from children. Prog Cardiovasc Dis 2009;51:416–33. 7. Gozal D, O’Brien L, Row BW. Consequences of snoring and sleep disordered breathing in children. Pediatr Pulmonol Suppl 2004;26:166–8.
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8. Quante M, Wang R, Weng J, et al. The effect of adenotonsillectomy for childhood sleep apnea on cardiometabolic measures. Sleep 2015;38:1395–403. 9. Noehren A, Brockmann PE, Urschitz MS, Sokollik C, Schlaud M, Poets CF. Detection of respiratory events using pulse rate in children with and without obstructive sleep apnea. Pediatr Pulmonol 2010;45:459–68. 10. Brockmann PE, Urschitz MS, Noehren A, Sokollik C, Schlaud M, Poets CF. Risk factors and consequences of excessive autonomic activation during sleep in children. Sleep Breath 2011;15:409–16. 11. Foo JY, Bradley AP, Wilson SJ, Williams GR, Dakin C, Cooper DM. Screening of obstructive and central apnoea/hypopnoea in children using variability: a preliminary study. Acta Paediatr 2006;95:561–4. 12. Pu Y, Patterson R, Cramerbornemann M. Nocturnal cardiorespiratory indices - a novel screening tool for pediatric obstructive sleep disordered breathing. Conf Proc IEEE Eng Med Biol Soc 2005;3:2575–8. 13. Shouldice RB, O’Brien LM, O’Brien C, de Chazal P, Gozal D, Heneghan C. Detection of obstructive sleep apnea in pediatric subjects using surface lead electrocardiogram features. Sleep 2004;27:784–92. 14. Brockmann PE, Schaefer C, Poets A, Poets CF, Urschitz MS. Diagnosis of obstructive sleep apnea in children: a systematic review. Sleep Med Rev 2013;17:331–40. 15. Foo JY, Lim CS. Development of a home screening system for pediatric respiratory sleep studies. Telemed J E Health 2006;12:698–701. 16. Morielli A, Ladan S, Ducharme FM, Brouillette RT. Can sleep and wakefulness be distinguished in children by cardiorespiratory and videotape recordings? Chest 1996;109:680–7. 17. Gozal D, Hakim F, Kheirandish-Gozal L. Chemoreceptors, baroreceptors, and autonomic deregulation in children with obstructive sleep apnea. Respir Physiol Neurobiol 2012. 18. Noehren A, Brockmann P, Urschitz M, Sokollik C, Schlaud M, Poets C. Detection of respiratory events using pulse rate in children with and without obstructive sleep apnea. Pediatr Pulmonol 2010;45:459–68. 19. Gil E, Vergara JM, Bianchi AM, Laguna P. Obstructive sleep apnea syndrome analysis in children by decreases in the amplitude fluctuations of pulse photoplethysmography: role of recording duration and heart rate variability. Conf Proc IEEE Eng Med Biol Soc 2007;2007:6090–3. 20. Aljadeff G, Gozal D, Schechtman VL, Burrell B, Harper RM, Ward SL. Heart rate variability in children with obstructive sleep apnea. Sleep 1997;20:151–7. 21. Tauman R, O’Brien LM, Mast BT, Holbrook CR, Gozal D. Peripheral arterial tonometry events and electroencephalographic arousals in children. Sleep 2004;27:502–6. 22. Raymond B, Cayton RM, Chappell MJ. Combined index of heart rate variability and oximetry in screening for the sleep apnoea/hypopnoea syndrome. J Sleep Res 2003;12:53–61. 23. Adachi H, Mikami A, Kumano-go T, et al. Clinical significance of pulse rate rise during sleep as a screening marker for the assessment of sleep fragmentation in sleep-disordered breathing. Sleep Med 2003;4:537–42. 24. Pu Y, Patterson R, Cramerbornemann M. Nocturnal cardio-respiratory indices - a novel screening tool for pediatric obstructive sleep disordered breathing. Conf Proc IEEE Eng Med Biol Soc 2005;3:2575–8. 25. Unalacak M, Aydin M, Ermis B, et al. Assessment of cardiac autonomic regulation in children with monosymptomatic nocturnal enuresis by analysis of heart rate variability. Tohoku J Exp Med 2004;204:63–9.
Editorial—Brockmann
