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Published in: Heart and Vessels 6/2020

01-06-2020 | Hypoxemia | Original Article

Accumulated nocturnal hypoxemia predict arterial endothelial function in patients with sleep-disordered breathing with or without chronic heart failure

Authors: Hiroyuki Sawatari, Akiko Chishaki, Mari Nishizaka, Mami Miyazono, Tomotake Tokunou, Chie Magota, Umpei Yamamoto, Sakiko Shimizu Handa, Shin-ichi Ando

Published in: Heart and Vessels | Issue 6/2020

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Abtsract

Sleep-disordered breathing (SDB) is often accompanied with the chronic heart failure (CHF). Hypoxemia due to pulmonary congestion from CHF and concurrent SDB might synergistically impair endothelial function and worsen the prognosis. However, the main factors affecting deterioration of endothelial function are unknown and whether the influence of hypoxemia differs in SDB patients with and without CHF remains unclear. Fifty-three patients (CHF group, n = 23; non-CHF group, n = 30) underwent polysomnography to evaluate their SDB and flow-mediated vasodilation (FMD) measurements to assess arterial endothelial function. We examined the relationships between FMD and SDB-related parameters, including our original index of accumulated hypoxemia by SDB throughout one-night sleep: the time desaturation summation index (TDS), calculated as follows: (100% − averaged arterial oxygen saturation during sleep) × total sleep time. The mean age in the CHF and non-CHF groups was 59.0 ± 13.5 and 57.7 ± 11.4 years, respectively. Although the FMD in the 2 groups were not significantly different, well-known adverse factors for FMD such as serum lipid profiles, blood pressure levels, and conventional indices of SDB were worse in the non-CHF group. Only the TDS was not significantly different between 2 groups and associated with FMD as shown by the univariate analysis (CHF: p < 0.05, non-CHF: p < 0.01) and multivariate analysis (CHF: p < 0.05, non-CHF: p < 0.01). Accumulated hypoxemia (TDS) rather than the frequency of hypoxemia might more influence on the endothelial function irrespective of the cardiac state. Removal of accumulation of nocturnal hypoxemia might be a target for treatment equally in the patients with and without CHF.
Literature
1.
go back to reference Brunner H, Cockcroft JR, Deanfield J, Donald A, Ferrannini E, Halcox J, Kiowski W, Luscher TF, Mancia G, Natali A, Oliver JJ, Pessina AC, Rizzoni D, Rossi GP, Salvetti A, Spieker LE, Taddei S, Webb DJ (2005) Endothelial function and dysfunction. Part II: Association with cardiovascular risk factors and diseases. A statement by the Working Group on Endothelins and Endothelial Factors of the European Society of Hypertension. J Hypertens 23(2):233–246CrossRef Brunner H, Cockcroft JR, Deanfield J, Donald A, Ferrannini E, Halcox J, Kiowski W, Luscher TF, Mancia G, Natali A, Oliver JJ, Pessina AC, Rizzoni D, Rossi GP, Salvetti A, Spieker LE, Taddei S, Webb DJ (2005) Endothelial function and dysfunction. Part II: Association with cardiovascular risk factors and diseases. A statement by the Working Group on Endothelins and Endothelial Factors of the European Society of Hypertension. J Hypertens 23(2):233–246CrossRef
2.
go back to reference de Berrazueta JR, Guerra-Ruiz A, Garcia-Unzueta MT, Toca GM, Laso RS, de Adana MS, Martin MAC, Cobo M, LLorca L (2010) Endothelial dysfunction, measured by reactive hyperaemia using strain-gauge plethysmography, is an independent predictor of adverse outcome in heart failure. Eur J Heart Fail 12(5):477–483CrossRef de Berrazueta JR, Guerra-Ruiz A, Garcia-Unzueta MT, Toca GM, Laso RS, de Adana MS, Martin MAC, Cobo M, LLorca L (2010) Endothelial dysfunction, measured by reactive hyperaemia using strain-gauge plethysmography, is an independent predictor of adverse outcome in heart failure. Eur J Heart Fail 12(5):477–483CrossRef
3.
go back to reference Shechter M, Matetzky S, Arad M, Feinberg MS, Freimark D (2009) Vascular endothelial function predicts mortality risk in patients with advanced ischaemic chronic heart failure. Eur J Heart Fail 11(6):588–593CrossRef Shechter M, Matetzky S, Arad M, Feinberg MS, Freimark D (2009) Vascular endothelial function predicts mortality risk in patients with advanced ischaemic chronic heart failure. Eur J Heart Fail 11(6):588–593CrossRef
4.
go back to reference Katz SD, Hryniewicz K, Hriljac I, Balidemaj K, Dimayuga C, Hudaihed A, Yasskiy A (2005) Vascular endothelial dysfunction and mortality risk in patients with chronic heart failure. Circulation 111(3):310–314CrossRef Katz SD, Hryniewicz K, Hriljac I, Balidemaj K, Dimayuga C, Hudaihed A, Yasskiy A (2005) Vascular endothelial dysfunction and mortality risk in patients with chronic heart failure. Circulation 111(3):310–314CrossRef
5.
go back to reference Fang ZY, Marwick TH (2002) Vascular dysfunction and heart failure: epiphenomenon or etiologic agent? Am Heart J 143(3):383–390CrossRef Fang ZY, Marwick TH (2002) Vascular dysfunction and heart failure: epiphenomenon or etiologic agent? Am Heart J 143(3):383–390CrossRef
6.
go back to reference Javaheri S, Barbe F, Campos-Rodriguez F, Dempsey JA, Khayat R, Javaheri S, Malhotra A, Martinez-Garcia MA, Mehra R, Pack AI, Polotsky VY, Redline S, Somers VK (2017) Sleep apnea: types, mechanisms, and clinical cardiovascular consequences. J Am Coll Cardiol 69(7):841–858CrossRef Javaheri S, Barbe F, Campos-Rodriguez F, Dempsey JA, Khayat R, Javaheri S, Malhotra A, Martinez-Garcia MA, Mehra R, Pack AI, Polotsky VY, Redline S, Somers VK (2017) Sleep apnea: types, mechanisms, and clinical cardiovascular consequences. J Am Coll Cardiol 69(7):841–858CrossRef
7.
go back to reference Yumino D, Wang H, Floras JS, Newton GE, Mak S, Ruttanaumpawan P, Parker JD, Bradley TD (2009) Prevalence and physiological predictors of sleep apnea in patients with heart failure and systolic dysfunction. J Card Fail 15(4):279–285CrossRef Yumino D, Wang H, Floras JS, Newton GE, Mak S, Ruttanaumpawan P, Parker JD, Bradley TD (2009) Prevalence and physiological predictors of sleep apnea in patients with heart failure and systolic dysfunction. J Card Fail 15(4):279–285CrossRef
8.
go back to reference Javaheri S (2006) Sleep disorders in systolic heart failure: a prospective study of 100 male patients. The final report. Int J Cardiol 106(1):21–28CrossRef Javaheri S (2006) Sleep disorders in systolic heart failure: a prospective study of 100 male patients. The final report. Int J Cardiol 106(1):21–28CrossRef
9.
go back to reference Bradley TD, Floras JS (2003) Sleep apnea and heart failure: part II: central sleep apnea. Circulation 107(13):1822–1826CrossRef Bradley TD, Floras JS (2003) Sleep apnea and heart failure: part II: central sleep apnea. Circulation 107(13):1822–1826CrossRef
10.
go back to reference Kasai T, Floras JS, Bradley TD (2012) Sleep apnea and cardiovascular disease: a bidirectional relationship. Circulation 126(12):1495–1510CrossRef Kasai T, Floras JS, Bradley TD (2012) Sleep apnea and cardiovascular disease: a bidirectional relationship. Circulation 126(12):1495–1510CrossRef
11.
go back to reference Somers VK, White DP, Amin R, Abraham WT, Costa F, Culebras A, Daniels S, Floras JS, Hunt CE, Olson LJ, Pickering TG, Russell R, Woo M, Young T, American Heart Association Council for High Blood Pressure Research Professional Education Committee CoCC, American Heart Association Stroke C, American Heart Association Council on Cardiovascular N, American College of Cardiology F (2008) Sleep apnea and cardiovascular disease: an American Heart Association/american College of Cardiology Foundation Scientific Statement from the American Heart Association Council for High Blood Pressure Research Professional Education Committee, Council on Clinical Cardiology, Stroke Council, and Council On Cardiovascular Nursing. In collaboration with the National Heart, Lung, and Blood Institute National Center on Sleep Disorders Research (National Institutes of Health). Circulation 118 (10):1080–1111 Somers VK, White DP, Amin R, Abraham WT, Costa F, Culebras A, Daniels S, Floras JS, Hunt CE, Olson LJ, Pickering TG, Russell R, Woo M, Young T, American Heart Association Council for High Blood Pressure Research Professional Education Committee CoCC, American Heart Association Stroke C, American Heart Association Council on Cardiovascular N, American College of Cardiology F (2008) Sleep apnea and cardiovascular disease: an American Heart Association/american College of Cardiology Foundation Scientific Statement from the American Heart Association Council for High Blood Pressure Research Professional Education Committee, Council on Clinical Cardiology, Stroke Council, and Council On Cardiovascular Nursing. In collaboration with the National Heart, Lung, and Blood Institute National Center on Sleep Disorders Research (National Institutes of Health). Circulation 118 (10):1080–1111
12.
go back to reference Hoyos CM, Melehan KL, Liu PY, Grunstein RR, Phillips CL (2015) Does obstructive sleep apnea cause endothelial dysfunction? A critical review of the literature. Sleep Med Rev 20:15–26CrossRef Hoyos CM, Melehan KL, Liu PY, Grunstein RR, Phillips CL (2015) Does obstructive sleep apnea cause endothelial dysfunction? A critical review of the literature. Sleep Med Rev 20:15–26CrossRef
13.
go back to reference Iber C, Ancoli-Israel S, Chesson A, Quan S (2007) The AASM manual for the scoring of sleep and associated events: rules, terminology and technical specifications. American Academy of Sleep Medicine, Westchester, pp 1–49 Iber C, Ancoli-Israel S, Chesson A, Quan S (2007) The AASM manual for the scoring of sleep and associated events: rules, terminology and technical specifications. American Academy of Sleep Medicine, Westchester, pp 1–49
14.
go back to reference Sawatari H, Chishaki A, Nishizaka M, Tokunou T, Adachi S, Yoshimura C, Ohkusa T, Ando SI (2016) Cumulative hypoxemia during sleep predicts vascular endothelial dysfunction in patients with sleep-disordered breathing. Am J Hypertens 29(4):458–463CrossRef Sawatari H, Chishaki A, Nishizaka M, Tokunou T, Adachi S, Yoshimura C, Ohkusa T, Ando SI (2016) Cumulative hypoxemia during sleep predicts vascular endothelial dysfunction in patients with sleep-disordered breathing. Am J Hypertens 29(4):458–463CrossRef
15.
go back to reference Corretti MC, Anderson TJ, Benjamin EJ, Celermajer D, Charbonneau F, Creager MA, Deanfield J, Drexler H, Gerhard-Herman M, Herrington D, Vallance P, Vita J, Vogel R (2002) Guidelines for the ultrasound assessment of endothelial-dependent flow-mediated vasodilation of the brachial artery: a report of the International Brachial Artery Reactivity Task Force. J Am Coll Cardiol 39(2):257–265CrossRef Corretti MC, Anderson TJ, Benjamin EJ, Celermajer D, Charbonneau F, Creager MA, Deanfield J, Drexler H, Gerhard-Herman M, Herrington D, Vallance P, Vita J, Vogel R (2002) Guidelines for the ultrasound assessment of endothelial-dependent flow-mediated vasodilation of the brachial artery: a report of the International Brachial Artery Reactivity Task Force. J Am Coll Cardiol 39(2):257–265CrossRef
16.
go back to reference Nishizaka MK, Zaman MA, Green SA, Renfroe KY, Calhoun DA (2004) Impaired endothelium-dependent flow-mediated vasodilation in hypertensive subjects with hyperaldosteronism. Circulation 109(23):2857–2861CrossRef Nishizaka MK, Zaman MA, Green SA, Renfroe KY, Calhoun DA (2004) Impaired endothelium-dependent flow-mediated vasodilation in hypertensive subjects with hyperaldosteronism. Circulation 109(23):2857–2861CrossRef
17.
go back to reference Inoue S, Takemoto M, Chishaki A, Ide T, Nishizaka M, Miyazono M, Sawatari H, Sunagawa K (2012) Leg heating using far infra-red radiation in patients with chronic heart failure acutely improves the hemodynamics, vascular endothelial function, and oxidative stress. Intern Med 51(17):2263–2270CrossRef Inoue S, Takemoto M, Chishaki A, Ide T, Nishizaka M, Miyazono M, Sawatari H, Sunagawa K (2012) Leg heating using far infra-red radiation in patients with chronic heart failure acutely improves the hemodynamics, vascular endothelial function, and oxidative stress. Intern Med 51(17):2263–2270CrossRef
18.
go back to reference Chung S, Yoon IY, Lee CH, Kim JW (2010) The association of nocturnal hypoxemia with arterial stiffness and endothelial dysfunction in male patients with obstructive sleep apnea syndrome. Respiration 79(5):363–369CrossRef Chung S, Yoon IY, Lee CH, Kim JW (2010) The association of nocturnal hypoxemia with arterial stiffness and endothelial dysfunction in male patients with obstructive sleep apnea syndrome. Respiration 79(5):363–369CrossRef
19.
go back to reference Lui MM, Mak JC, Lai AY, Hui CK, Lam JC, Lam DC, Ip MS (2016) The impact of obstructive sleep apnea and tobacco smoking on endothelial function. Respiration 91(2):124–131CrossRef Lui MM, Mak JC, Lai AY, Hui CK, Lam JC, Lam DC, Ip MS (2016) The impact of obstructive sleep apnea and tobacco smoking on endothelial function. Respiration 91(2):124–131CrossRef
20.
go back to reference Farooqui FA, Sharma SK, Kumar A, Soneja M, Mani K, Radhakrishnan R, Farooqui N (2017) Endothelial function and carotid intima media thickness in obstructive sleep apnea without comorbidity. Sleep Breath 21(1):69–76CrossRef Farooqui FA, Sharma SK, Kumar A, Soneja M, Mani K, Radhakrishnan R, Farooqui N (2017) Endothelial function and carotid intima media thickness in obstructive sleep apnea without comorbidity. Sleep Breath 21(1):69–76CrossRef
21.
go back to reference Gilmartin GS, Lynch M, Tamisier R, Weiss JW (2010) Chronic intermittent hypoxia in humans during 28 nights results in blood pressure elevation and increased muscle sympathetic nerve activity. Am J Physiol Heart Circ Physiol 299(3):H925–H931CrossRef Gilmartin GS, Lynch M, Tamisier R, Weiss JW (2010) Chronic intermittent hypoxia in humans during 28 nights results in blood pressure elevation and increased muscle sympathetic nerve activity. Am J Physiol Heart Circ Physiol 299(3):H925–H931CrossRef
22.
go back to reference Ip MS, Tse HF, Lam B, Tsang KW, Lam WK (2004) Endothelial function in obstructive sleep apnea and response to treatment. Am J Respir Crit Care Med 169(3):348–353CrossRef Ip MS, Tse HF, Lam B, Tsang KW, Lam WK (2004) Endothelial function in obstructive sleep apnea and response to treatment. Am J Respir Crit Care Med 169(3):348–353CrossRef
23.
go back to reference Oldenburg O, Wellmann B, Buchholz A, Bitter T, Fox H, Thiem U, Horstkotte D, Wegscheider K (2016) Nocturnal hypoxaemia is associated with increased mortality in stable heart failure patients. Eur Heart J 37(21):1695–1703CrossRef Oldenburg O, Wellmann B, Buchholz A, Bitter T, Fox H, Thiem U, Horstkotte D, Wegscheider K (2016) Nocturnal hypoxaemia is associated with increased mortality in stable heart failure patients. Eur Heart J 37(21):1695–1703CrossRef
24.
go back to reference Koong AC, Chen EY, Giaccia AJ (1994) Hypoxia causes the activation of nuclear factor kappa B through the phosphorylation of I kappa B alpha on tyrosine residues. Cancer Res 54(6):1425–1430PubMed Koong AC, Chen EY, Giaccia AJ (1994) Hypoxia causes the activation of nuclear factor kappa B through the phosphorylation of I kappa B alpha on tyrosine residues. Cancer Res 54(6):1425–1430PubMed
25.
go back to reference Barnes PJ, Karin M (1997) Nuclear factor-kappaB: a pivotal transcription factor in chronic inflammatory diseases. N Engl J Med 336(15):1066–1071CrossRef Barnes PJ, Karin M (1997) Nuclear factor-kappaB: a pivotal transcription factor in chronic inflammatory diseases. N Engl J Med 336(15):1066–1071CrossRef
26.
go back to reference Garvey JF, Taylor CT, McNicholas WT (2009) Cardiovascular disease in obstructive sleep apnoea syndrome: the role of intermittent hypoxia and inflammation. Eur Respir J 33(5):1195–1205CrossRef Garvey JF, Taylor CT, McNicholas WT (2009) Cardiovascular disease in obstructive sleep apnoea syndrome: the role of intermittent hypoxia and inflammation. Eur Respir J 33(5):1195–1205CrossRef
27.
go back to reference Iida T, Mine S, Fujimoto H, Suzuki K, Minami Y, Tanaka Y (2002) Hypoxia-inducible factor-1alpha induces cell cycle arrest of endothelial cells. Genes Cells 7(2):143–149CrossRef Iida T, Mine S, Fujimoto H, Suzuki K, Minami Y, Tanaka Y (2002) Hypoxia-inducible factor-1alpha induces cell cycle arrest of endothelial cells. Genes Cells 7(2):143–149CrossRef
28.
go back to reference Cai H, Harrison DG (2000) Endothelial dysfunction in cardiovascular diseases: the role of oxidant stress. Circ Res 87(10):840–844CrossRef Cai H, Harrison DG (2000) Endothelial dysfunction in cardiovascular diseases: the role of oxidant stress. Circ Res 87(10):840–844CrossRef
29.
go back to reference Seif F, Patel SR, Walia H, Rueschman M, Bhatt DL, Gottlieb DJ, Lewis EF, Patil SP, Punjabi NM, Babineau DC, Redline S, Mehra R (2013) Association between obstructive sleep apnea severity and endothelial dysfunction in an increased background of cardiovascular burden. J Sleep Res 22(4):443–451CrossRef Seif F, Patel SR, Walia H, Rueschman M, Bhatt DL, Gottlieb DJ, Lewis EF, Patil SP, Punjabi NM, Babineau DC, Redline S, Mehra R (2013) Association between obstructive sleep apnea severity and endothelial dysfunction in an increased background of cardiovascular burden. J Sleep Res 22(4):443–451CrossRef
30.
go back to reference Inoue N, Hirata K, Yamada M, Hamamori Y, Matsuda Y, Akita H, Yokoyama M (1992) Lysophosphatidylcholine inhibits bradykinin-induced phosphoinositide hydrolysis and calcium transients in cultured bovine aortic endothelial cells. Circ Res 71(6):1410–1421CrossRef Inoue N, Hirata K, Yamada M, Hamamori Y, Matsuda Y, Akita H, Yokoyama M (1992) Lysophosphatidylcholine inhibits bradykinin-induced phosphoinositide hydrolysis and calcium transients in cultured bovine aortic endothelial cells. Circ Res 71(6):1410–1421CrossRef
31.
go back to reference Ceriello A, Taboga C, Tonutti L, Quagliaro L, Piconi L, Bais B, Da Ros R, Motz E (2002) Evidence for an independent and cumulative effect of postprandial hypertriglyceridemia and hyperglycemia on endothelial dysfunction and oxidative stress generation: effects of short- and long-term simvastatin treatment. Circulation 106(10):1211–1218CrossRef Ceriello A, Taboga C, Tonutti L, Quagliaro L, Piconi L, Bais B, Da Ros R, Motz E (2002) Evidence for an independent and cumulative effect of postprandial hypertriglyceridemia and hyperglycemia on endothelial dysfunction and oxidative stress generation: effects of short- and long-term simvastatin treatment. Circulation 106(10):1211–1218CrossRef
32.
go back to reference Higashi Y, Kihara Y, Noma K (2012) Endothelial dysfunction and hypertension in aging. Hypertens Res 35(11):1039–1047CrossRef Higashi Y, Kihara Y, Noma K (2012) Endothelial dysfunction and hypertension in aging. Hypertens Res 35(11):1039–1047CrossRef
33.
go back to reference Peller M, Ozieranski K, Balsam P, Grabowski M, Filipiak KJ, Opolski G (2015) Influence of beta-blockers on endothelial function: a meta-analysis of randomized controlled trials. Cardiol J 22(6):708–716CrossRef Peller M, Ozieranski K, Balsam P, Grabowski M, Filipiak KJ, Opolski G (2015) Influence of beta-blockers on endothelial function: a meta-analysis of randomized controlled trials. Cardiol J 22(6):708–716CrossRef
34.
go back to reference Shahin Y, Khan JA, Samuel N, Chetter I (2011) Angiotensin converting enzyme inhibitors effect on endothelial dysfunction: a meta-analysis of randomised controlled trials. Atherosclerosis 216(1):7–16CrossRef Shahin Y, Khan JA, Samuel N, Chetter I (2011) Angiotensin converting enzyme inhibitors effect on endothelial dysfunction: a meta-analysis of randomised controlled trials. Atherosclerosis 216(1):7–16CrossRef
35.
go back to reference Griendling KK, Minieri CA, Ollerenshaw JD, Alexander RW (1994) Angiotensin II stimulates NADH and NADPH oxidase activity in cultured vascular smooth muscle cells. Circ Res 74(6):1141–1148CrossRef Griendling KK, Minieri CA, Ollerenshaw JD, Alexander RW (1994) Angiotensin II stimulates NADH and NADPH oxidase activity in cultured vascular smooth muscle cells. Circ Res 74(6):1141–1148CrossRef
36.
go back to reference Azarbarzin A, Sands SA, Stone KL, Taranto-Montemurro L, Messineo L, Terrill PI, Ancoli-Israel S, Ensrud K, Purcell S, White DP, Redline S, Wellman A (2019) The hypoxic burden of sleep apnoea predicts cardiovascular disease-related mortality: the Osteoporotic Fractures in Men Study and the Sleep Heart Health Study. Eur Heart J 40(14):1149–1157CrossRef Azarbarzin A, Sands SA, Stone KL, Taranto-Montemurro L, Messineo L, Terrill PI, Ancoli-Israel S, Ensrud K, Purcell S, White DP, Redline S, Wellman A (2019) The hypoxic burden of sleep apnoea predicts cardiovascular disease-related mortality: the Osteoporotic Fractures in Men Study and the Sleep Heart Health Study. Eur Heart J 40(14):1149–1157CrossRef
37.
go back to reference Watanabe E, Kiyono K, Matsui S, Somers VK, Sano K, Hayano J, Ichikawa T, Kawai M, Harada M, Ozaki Y (2017) Prognostic importance of novel oxygen desaturation metrics in patients with heart failure and central sleep apnea. J Card Fail 23(2):131–137CrossRef Watanabe E, Kiyono K, Matsui S, Somers VK, Sano K, Hayano J, Ichikawa T, Kawai M, Harada M, Ozaki Y (2017) Prognostic importance of novel oxygen desaturation metrics in patients with heart failure and central sleep apnea. J Card Fail 23(2):131–137CrossRef
38.
go back to reference Freestone B, Chong AY, Nuttall S, Lip GYH (2008) Impaired flow mediated dilatation as evidence of endothelial dysfunction in chronic atrial fibrillation: relationship to plasma von Willebrand factor and soluble E-selectin levels. Thromb Res 122(1):85–90CrossRef Freestone B, Chong AY, Nuttall S, Lip GYH (2008) Impaired flow mediated dilatation as evidence of endothelial dysfunction in chronic atrial fibrillation: relationship to plasma von Willebrand factor and soluble E-selectin levels. Thromb Res 122(1):85–90CrossRef
Metadata
Title
Accumulated nocturnal hypoxemia predict arterial endothelial function in patients with sleep-disordered breathing with or without chronic heart failure
Authors
Hiroyuki Sawatari
Akiko Chishaki
Mari Nishizaka
Mami Miyazono
Tomotake Tokunou
Chie Magota
Umpei Yamamoto
Sakiko Shimizu Handa
Shin-ichi Ando
Publication date
01-06-2020
Publisher
Springer Japan
Published in
Heart and Vessels / Issue 6/2020
Print ISSN: 0910-8327
Electronic ISSN: 1615-2573
DOI
https://doi.org/10.1007/s00380-020-01557-5

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