Top

Sleep and Breathing

Published in:

Open Access 01-12-2018 | Sleep Breathing Physiology and Disorders • Original Article

Obesity modulates the association between sleep apnea treatment and CHI3L1 levels but not CHIT1 activity in moderate to severe OSA: an observational study

Authors: Unnur Dilja Teitsdottir, Erna Sif Arnardottir, Erla Bjornsdottir, Thorarinn Gislason, Petur Henry Petersen

Published in: Sleep and Breathing | Issue 4/2018

Abstract

Purpose

The inflammatory markers chitinase-3-like protein 1 (CHI3L1) and chitotriosidase (CHIT1) have both been associated with cardiovascular complications. The aim of this preliminary observational study was to assess the roles and interaction of obstructive sleep apnea (OSA) severity and body mass index (BMI) with plasma CHI3L1 levels and CHIT1 activity in patients with moderate to severe OSA. The second aim was to assess the roles and interaction of positive airway pressure (PAP) treatment and BMI on the expression of the same proteins.

Methods

The study included 97 OSA patients with an apnea–hypopnea index (AHI) ≥ 15 and full usage of PAP treatment after 4 months. Plasma CHI3L1 levels and CHIT1 activity were measured before and after treatment.

Results

Multiple linear regression analysis demonstrated an independent association of BMI on CHI3L1 levels (p < 0.05) but not on CHIT1 activity. The OSA severity markers (AHI and oxygen desaturation index) did not independently or in interaction with BMI levels associate with CHI3L1 levels or with CHIT1 activity (p > 0.05). A two-way repeated measures ANOVA revealed a significant interaction between PAP treatment effect (before vs. after) and BMI groups (< 35 kg/m² vs. ≥ 35 kg/m²) on CHI3L1 levels (p = 0.03) but not on CHIT1 activity (p = 0.98).

Conclusions

Obesity independently associated with CHI3L1 levels. Association between OSA severity and CHI3L1 levels or CHIT1 activity (independent of or dependent on obesity level) could not be confirmed. However, decrease was observed in CHI3L1 levels after PAP treatment in severely obese OSA patients but not in those less obese.

Available only for authorised users

Marin JM, Carrizo SJ, Vicente E, Agusti AG (2005) Long-term cardiovascular outcomes in men with obstructive sleep apnoea-hypopnoea with or without treatment with continuous positive airway pressure: an observational study, Lancet (London, England). 365(9464):1046–1053. https://doi.org/10.1016/s0140-6736(05)71141-7 CrossRef

Young T, Peppard PE, Gottlieb DJ (2002) Epidemiology of obstructive sleep apnea: a population health perspective. Am J Respir Crit Care Med 165(9):1217–1239CrossRefPubMed

Pack AI, Gislason T (2009) Obstructive sleep apnea and cardiovascular disease: a perspective and future directions. Prog Cardiovasc Dis 51(5):434–451. https://doi.org/10.1016/j.pcad.2009.01.002 CrossRefPubMed

Arnardottir ES, Maislin G, Schwab RJ, Staley B, Benediktsdottir B, Olafsson I, Juliusson S, Romer M, Gislason T, Pack AI (2012) The interaction of obstructive sleep apnea and obesity on the inflammatory markers C-reactive protein and interleukin-6: the Icelandic Sleep Apnea Cohort. Sleep 35(7):921–932. https://doi.org/10.5665/sleep.1952 CrossRefPubMedPubMedCentral

Pak VM, Keenan BT, Jackson N, Grandner MA, Maislin G, Teff K, Schwab RJ, Arnardottir ES, Juliusson S, Benediktsdottir B, Gislason T, Pack AI (2015) Adhesion molecule increases in sleep apnea: beneficial effect of positive airway pressure and moderation by obesity. Int J Obes (2005) 39(3):472–479. https://doi.org/10.1038/ijo.2014.123 CrossRef

Arnardottir ES, Lim DC, Keenan BT, Maislin G, Benediktsdottir B, Juliusson S, Pack AI, Gislason T (2015) Effects of obesity on the association between long-term sleep apnea treatment and changes in interleukin-6 levels: the Icelandic Sleep Apnea Cohort. J Sleep Res 24(2):148–159. https://doi.org/10.1111/jsr.12252 CrossRefPubMed

Jiang H, Schiffer E, Song Z, Wang J, Zurbig P, Thedieck K, Moes S, Bantel H, Saal N, Jantos J, Brecht M, Jeno P, Hall MN, Hager K, Manns MP, Hecker H, Ganser A, Dohner K, Bartke A, Meissner C, Mischak H, Ju Z, Rudolph KL (2008) Proteins induced by telomere dysfunction and DNA damage represent biomarkers of human aging and disease. Proc Natl Acad Sci U S A 105(32):11299–11304. https://doi.org/10.1073/pnas.0801457105 CrossRefPubMedPubMedCentral

Bonneh-Barkay D, Bissel SJ, Wang G, Fish KN, Nicholl GC, Darko SW, Medina-Flores R, Murphey-Corb M, Rajakumar PA, Nyaundi J, Mellors JW, Bowser R, Wiley CA (2008) YKL-40, a marker of simian immunodeficiency virus encephalitis, modulates the biological activity of basic fibroblast growth factor. Am J Pathol 173(1):130–143. https://doi.org/10.2353/ajpath.2008.080045 CrossRefPubMedPubMedCentral

Hakala BE, White C, Recklies AD (1993) Human cartilage gp-39, a major secretory product of articular chondrocytes and synovial cells, is a mammalian member of a chitinase protein family. J Biol Chem 268(34):25803–25810PubMed

10.

Bojesen SE, Johansen JS, Nordestgaard BG (2011) Plasma YKL-40 levels in healthy subjects from the general population. Clin Chim Acta 412(9–10):709–712. https://doi.org/10.1016/j.cca.2011.01.022 CrossRefPubMed

11.

Hempen M, Kopp HP, Elhenicky M, Hobaus C, Brix JM, Koppensteiner R, Schernthaner G, Schernthaner GH (2009) YKL-40 is elevated in morbidly obese patients and declines after weight loss. Obes Surg 19(11):1557–1563. https://doi.org/10.1007/s11695-009-9917-4 CrossRefPubMed

12.

Rathcke CN, Vestergaard H (2009) YKL-40--an emerging biomarker in cardiovascular disease and diabetes. Cardiovasc Diabetol 8:61. https://doi.org/10.1186/1475-2840-8-61 CrossRefPubMedPubMedCentral

13.

Wang X, Xing GH (2014) Serum YKL-40 concentrations are elevated and correlated with disease severity in patients with obstructive sleep apnea syndrome. Scand J Clin Lab Invest 74(1):74–78. https://doi.org/10.3109/00365513.2013.859726 CrossRefPubMed

14.

Jafari B, Elias JA, Mohsenin V (2014) Increased plasma YKL-40/chitinase-3-like-protein-1 is associated with endothelial dysfunction in obstructive sleep apnea. PLoS One 9(5):e98629. https://doi.org/10.1371/journal.pone.0098629 CrossRefPubMedPubMedCentral

15.

Li W, Yu Z, Jiang C (2014) Association of serum YKL-40 with the presence and severity of obstructive sleep apnea syndrome. Lab Med 45(3):220–225. https://doi.org/10.1309/lms98akcxrsl2xor CrossRefPubMed

16.

Bakirci EM, Unver E, Degirmenci H, Kivanc T, Gunay M, Hamur H, Buyuklu M, Ceyhun G, Topal E, Coban TA (2015) Serum YKL-40/chitinase 3-like protein 1 level is an independent predictor of atherosclerosis development in patients with obstructive sleep apnea syndrome. Turk Kardiyoloji Dernegi arsivi : Turk Kardiyoloji Derneginin yayin organidir 43(4):333–339. https://doi.org/10.5543/tkda.2015.56805 CrossRef

17.

Kjaergaard AD, Johansen JS, Bojesen SE, Nordestgaard BG (2016) Role of inflammatory marker YKL-40 in the diagnosis, prognosis and cause of cardiovascular and liver diseases. Crit Rev Clin Lab Sci 53(6):396–408. https://doi.org/10.1080/10408363.2016.1190683 CrossRefPubMed

18.

Mygind ND, Harutyunyan MJ, Mathiasen AB, Ripa RS, Thune JJ, Gotze JP, Johansen JS, Kastrup J (2011) The influence of statin treatment on the inflammatory biomarkers YKL-40 and HsCRP in patients with stable coronary artery disease. Inflamm Res 60(3):281–287. https://doi.org/10.1007/s00011-010-0266-5 CrossRefPubMed

19.

Bonneh-Barkay D, Bissel SJ, Kofler J, Starkey A, Wang G, Wiley CA (2012) Astrocyte and macrophage regulation of YKL-40 expression and cellular response in neuroinflammation. Brain pathology (Zurich, Switzerland) 22(4):530–546. https://doi.org/10.1111/j.1750-3639.2011.00550.x CrossRef

20.

Kanneganti M, Kamba A, Mizoguchi E (2012) Role of chitotriosidase (chitinase 1) under normal and disease conditions. J Epithelial Biol Pharmacol 5:1–9CrossRef

21.

Lungato L, Tamanaha P, Rodrigues MDB, Visniauskas B, Chagas JR, Tufik S, D’Almeida V (2013) Chitotriosidase as a marker of macrophage activation after paradoxical sleep deprivation. Sleep science (Sao Paulo, Brazil) 6(1):5–8

22.

Tamanaha P, D'Almeida V, Calegare BF, Tomita LY, Bittencourt LR, Tufik S (2013) 24 bp duplication of CHIT1 gene and determinants of human chitotriosidase activity among participants of EPISONO, a population-based cross-sectional study, Sao Paulo, Brazil. Clin Biochem 46(12):1084–1088. https://doi.org/10.1016/j.clinbiochem.2013.05.044 CrossRefPubMed

23.

Alanbay I, Ercan CM, Sakinci M, Coksuer H, Ozturk M, Tapan S (2012) A macrophage activation marker chitotriosidase in women with PCOS: does low-grade chronic inflammation in PCOS relate to PCOS itself or obesity? Arch Gynecol Obstet 286(4):1065–1071. https://doi.org/10.1007/s00404-012-2425-0 CrossRefPubMed

24.

Bjornsdottir E, Benediktsdottir B, Pack AI, Arnardottir ES, Kuna ST, Gislason T, Keenan BT, Maislin G, Sigurdsson JF (2016) The prevalence of depression among untreated obstructive sleep apnea patients using a standardized psychiatric interview. J Clin Sleep Med 12(1):105–112. https://doi.org/10.5664/jcsm.5406 CrossRefPubMedPubMedCentral

25.

Arnardottir ES, Verbraecken J, Goncalves M, Gjerstad MD, Grote L, Puertas FJ, Mihaicuta S, McNicholas WT, Parrino L (2016) Variability in recording and scoring of respiratory events during sleep in Europe: a need for uniform standards. J Sleep Res 25(2):144–157. https://doi.org/10.1111/jsr.12353 CrossRefPubMed

26.

Berry RB, Brooks R, Gamaldo C, Harding SM, Lloyd RM, Quan SF, Troester MT, Vaughn BV (2017) AASM scoring manual updates for 2017 (version 2.4). J Clin Sleep Med 13(5):665–666. https://doi.org/10.5664/jcsm.6576 CrossRefPubMedPubMedCentral

27.

Xu L, Han F, Keenan BT, Kneeland-Szanto E, Yan H, Dong X, Chang Y, Zhao L, Zhang X, Li J, Pack AI, Kuna ST (2017) Validation of the Nox-T3 portable monitor for diagnosis of obstructive sleep apnea in Chinese adults. J Clin Sleep Med 13(5):675–683. https://doi.org/10.5664/jcsm.6582 CrossRefPubMedPubMedCentral

28.

Cairns A, Wickwire E, Schaefer E, Nyanjom D (2014) A pilot validation study for the NOX T3(TM) portable monitor for the detection of OSA. Sleep & breathing = Schlaf & Atmung 18(3):609–614. https://doi.org/10.1007/s11325-013-0924-2 CrossRef

29.

Iber C, Medicine AAoS (2007) The AASM manual for the scoring of sleep and associated events: Rules, Terminology and Technical Specifications. American Academy of Sleep Medicine,

30.

Hollak CE, van Weely S, van Oers MH, Aerts JM (1994) Marked elevation of plasma chitotriosidase activity. A novel hallmark of Gaucher disease. J Clin Invest 93 (3):1288–1292. doi:https://doi.org/10.1172/jci117084 CrossRefPubMedPubMedCentral

31.

Kyrgios I, Galli-Tsinopoulou A, Stylianou C, Papakonstantinou E, Arvanitidou M, Haidich AB (2012) Elevated circulating levels of the serum acute-phase protein YKL-40 (chitinase 3-like protein 1) are a marker of obesity and insulin resistance in prepubertal children. Metabolism 61(4):562–568. https://doi.org/10.1016/j.metabol.2011.09.004 CrossRefPubMed

32.

Young T, Palta M, Dempsey J, Skatrud J, Weber S, Badr S (1993) The occurrence of sleep-disordered breathing among middle-aged adults. N Engl J Med 328(17):1230–1235. https://doi.org/10.1056/nejm199304293281704 CrossRefPubMed

33.

Shinohara E, Kihara S, Yamashita S, Yamane M, Nishida M, Arai T, Kotani K, Nakamura T, Takemura K, Matsuzawa Y (1997) Visceral fat accumulation as an important risk factor for obstructive sleep apnoea syndrome in obese subjects. J Intern Med 241(1):11–18CrossRefPubMed

34.

Grunstein R, Wilcox I, Yang TS, Gould Y, Hedner J (1993) Snoring and sleep apnoea in men: association with central obesity and hypertension. Int J Obes Relat Metab Disord 17(9):533–540PubMed

35.

Vincent HK, Taylor AG (2006) Biomarkers and potential mechanisms of obesity-induced oxidant stress in humans. Int J Obes (2005) 30(3):400–418. https://doi.org/10.1038/sj.ijo.0803177 CrossRef

36.

Clement K, Langin D (2007) Regulation of inflammation-related genes in human adipose tissue. J Intern Med 262(4):422–430. https://doi.org/10.1111/j.1365-2796.2007.01851.x CrossRefPubMed

37.

Lavie L (2003) Obstructive sleep apnoea syndrome--an oxidative stress disorder. Sleep Med Rev 7(1):35–51CrossRefPubMed

38.

Tasali E, Ip MS (2008) Obstructive sleep apnea and metabolic syndrome: alterations in glucose metabolism and inflammation. Proc Am Thorac Soc 5(2):207–217. https://doi.org/10.1513/pats.200708-139MG CrossRefPubMed

39.

Curat CA, Wegner V, Sengenes C, Miranville A, Tonus C, Busse R, Bouloumie A (2006) Macrophages in human visceral adipose tissue: increased accumulation in obesity and a source of resistin and visfatin. Diabetologia 49(4):744–747. https://doi.org/10.1007/s00125-006-0173-z CrossRefPubMed

40.

Weisberg SP, McCann D, Desai M, Rosenbaum M, Leibel RL, Ferrante AW Jr (2003) Obesity is associated with macrophage accumulation in adipose tissue. J Clin Invest 112(12):1796–1808. https://doi.org/10.1172/jci19246 CrossRefPubMedPubMedCentral

41.

Hajer GR, van Haeften TW, Visseren FL (2008) Adipose tissue dysfunction in obesity, diabetes, and vascular diseases. Eur Heart J 29(24):2959–2971. https://doi.org/10.1093/eurheartj/ehn387 CrossRefPubMed

42.

Iwata T, Kuwajima M, Sukeno A, Ishimaru N, Hayashi Y, Wabitsch M, Mizusawa N, Itakura M, Yoshimoto K (2009) YKL-40 secreted from adipose tissue inhibits degradation of type I collagen. Biochem Biophys Res Commun 388(3):511–516. https://doi.org/10.1016/j.bbrc.2009.08.024 CrossRefPubMed

43.

Majde JA, Krueger JM (2005) Links between the innate immune system and sleep. J Allergy Clin Immunol 116(6):1188–1198. https://doi.org/10.1016/j.jaci.2005.08.005 CrossRefPubMed

44.

Benca RM, Quintas J (1997) Sleep and host defenses: a review. Sleep 20(11):1027–1037PubMed

45.

Johansen JS, Hvolris J, Hansen M, Backer V, Lorenzen I, Price PA (1996) Serum YKL-40 levels in healthy children and adults. Comparison with serum and synovial fluid levels of YKL-40 in patients with osteoarthritis or trauma of the knee joint. Br J Rheumatol 35(6):553–559CrossRefPubMed

Title: Obesity modulates the association between sleep apnea treatment and CHI3L1 levels but not CHIT1 activity in moderate to severe OSA: an observational study
Authors: Unnur Dilja Teitsdottir
Erna Sif Arnardottir
Erla Bjornsdottir
Thorarinn Gislason
Petur Henry Petersen
Publication date: 01-12-2018
Publisher: Springer International Publishing
Published in: Sleep and Breathing / Issue 4/2018
Print ISSN: 1520-9512
Electronic ISSN: 1522-1709
DOI: https://doi.org/10.1007/s11325-018-1731-6

ACC 2024 Congress Coverage

Heart Failure Video

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Obesity modulates the association between sleep apnea treatment and CHI3L1 levels but not CHIT1 activity in moderate to severe OSA: an observational study

Abstract

Purpose

Methods

Results

Conclusions

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

Incentivised to exercise

New intervention for STEMI-related cardiogenic shock

» View more highlights on the ACC 2024 congress hub page

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

Purpose

Methods

Results

Conclusions

Please log in to get access to this content

Other articles of this Issue 4/2018

Improved follow-up by peripheral arterial tonometry in CPAP-treated patients with obstructive sleep apnea and persistent excessive daytime sleepiness

Comparison of upper airway collapse patterns and its clinical significance: drug-induced sleep endoscopy in patients without obstructive sleep apnea, positional and non-positional obstructive sleep apnea

The independent and combined effects of respiratory events and cortical arousals on the autonomic nervous system across sleep stages

Evaluation of body position in upper airway stimulation for obstructive sleep apnea—is continuous voltage sufficient enough?

Cycle length identifies obstructive sleep apnea and central sleep apnea in heart failure with reduced ejection fraction

Pulmonary functions and sleep-related breathing disorders in lipid storage disease

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

Incentivised to exercise

New intervention for STEMI-related cardiogenic shock

» View more highlights on the ACC 2024 congress hub page