Top

Sleep and Breathing

Published in:

01-06-2019 | Sleep Breathing Physiology and Disorders • Original Article

Catestatin serum levels are increased in male patients with obstructive sleep apnea

Authors: Josip A. Borovac, Zoran Dogas, Daniela Supe-Domic, Tea Galic, Josko Bozic

Published in: Sleep and Breathing | Issue 2/2019

Abstract

Purpose

Obstructive sleep apnea (OSA) is a complex sleep disorder associated with autonomic and sympathetic dysregulation. To the contrary, catestatin, an endogenous pleiotropic peptide cleaved from chromogranin A, is known for its inhibitory effects on catecholamine release and sympathetic activity. The aims of the study were to determine catestatin serum levels among male OSA patients compared to healthy control subjects and to explore associations of catestatin with anthropometric, polysomnographic, and lipid profile parameters.

Methods

Seventy-eight male OSA patients aged 50.3 ± 8.8 years and 51 age/sex/BMI-matched control subjects aged 50.4 ± 7.8 years were enrolled in the study. Catestatin serum levels were determined by an enzyme-linked immunosorbent assay (ELISA).

Results

Catestatin serum levels were significantly higher among OSA patients compared to control subjects (2.9 ± 1.2 vs. 1.5 ± 1.1 ng/mL, p < 0.001). Serum catestatin levels significantly correlated with apnea-hypopnea index (AHI) among non-obese OSA subjects (r = 0.466, p = 0.016; β = 0.448, p = 0.026), while in whole OSA population, catestatin levels significantly correlated with neck circumference (r = 0.318, p < 0.001; β = 0.384, p < 0.001) and high-density lipoprotein (HDL) cholesterol (r = − 0.320, p < 0.001; β = − 0.344, p < 0.001). In multivariate-adjusted regression model, serum catestatin was significant and independent predictor of OSA status (OR 4.98, 95% CI 2.17–11.47, p < 0.001).

Conclusions

Catestatin serum levels are significantly increased in male OSA population and positively correlate with disease severity in non-obese patients. OSA status is independently predicted by catestatin levels; however, this finding is restricted to patients with moderate-to-severe disease. Further studies are necessary to elucidate the mechanistic role of catestatin in the complex pathophysiology of OSA.

Lévy P, Kohler M, McNicholas WT, Barbé F, McEvoy RD, Somers VK, Lavie L, Pépin J-L (2015) Obstructive sleep apnoea syndrome. Nat Rev Dis Primers 1:15015. https://doi.org/10.1038/nrdp.2015.15 CrossRefPubMed

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 (2008, Circulation) 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). 118(10):1080–1111. https://doi.org/10.1161/CIRCULATIONAHA.107.189375

Galic T, Bozic J, Ivkovic N, Gunjaca G, Ticinovic TK, Dogas Z (2016) Effects of mandibular advancement device treatment on arterial stiffness and glucose metabolism in patients with mild to moderate obstructive sleep apnea: a prospective 1 year study. Sleep Breath 20(1):69–77. https://doi.org/10.1007/s11325-015-1186-y CrossRefPubMed

Kent BD, McNicholas WT, Ryan S (2015) Insulin resistance, glucose intolerance and diabetes mellitus in obstructive sleep apnoea. J Thorac Dis 7(8):1343–1357. https://doi.org/10.3978/j.issn.2072-1439.2015.08.11 CrossRefPubMedPubMedCentral

Bozic J, Galic T, Supe-Domic D, Ivkovic N, Ticinovic Kurir T, Valic Z, Lesko J, Dogas Z (2016) Morning cortisol levels and glucose metabolism parameters in moderate and severe obstructive sleep apnea patients. Endocrine 53(3):730–739. https://doi.org/10.1007/s12020-016-0925-6 CrossRefPubMed

Adedayo AM, Olafiranye O, Smith D, Hill A, Zizi F, Brown C, Jean-Louis G (2014) Obstructive sleep apnea and dyslipidemia: evidence and underlying mechanism. Sleep Breath 18(1):13–18. https://doi.org/10.1007/s11325-012-0760-9 CrossRefPubMed

Nadeem R, Singh M, Nida M, Waheed I, Khan A, Ahmed S, Naseem J, Champeau D (2014) Effect of obstructive sleep apnea hypopnea syndrome on lipid profile: a meta-regression analysis. J Clin Sleep Med 10(5):475–489. https://doi.org/10.5664/jcsm.3690 CrossRefPubMedPubMedCentral

Galic T, Bozic J, Pecotic R, Ivkovic N, Valic M, Dogas Z (2016) Improvement of cognitive and psychomotor performance in patients with mild to moderate obstructive sleep apnea treated with mandibular advancement device: a prospective 1-year study. J Clin Sleep Med 12(2):177–186. https://doi.org/10.5664/jcsm.5480 CrossRefPubMedPubMedCentral

Troger J, Theurl M, Kirchmair R, Pasqua T, Tota B, Angelone T, Cerra MC, Nowosielski Y, Matzler R, Troger J, Gayen JR, Trudeau V, Corti A, Helle KB (2017) Granin-derived peptides. Prog Neurobiol 154:37–61. https://doi.org/10.1016/j.pneurobio.2017.04.003 CrossRefPubMed

10.

Mahata SK, O'Connor DT, Mahata M, Yoo SH, Taupenot L, Wu H, Gill BM, Parmer RJ (1997) Novel autocrine feedback control of catecholamine release. A discrete chromogranin a fragment is a noncompetitive nicotinic cholinergic antagonist. J Clin Invest 100(6):1623–1633. https://doi.org/10.1172/jci119686 CrossRefPubMedPubMedCentral

11.

Mahata SK, Mahata M, Fung MM, O'Connor DT (2010) Catestatin: a multifunctional peptide from chromogranin A. Regul Pept 162(1–3):33–43. https://doi.org/10.1016/j.regpep.2010.01.006 CrossRefPubMedPubMedCentral

12.

Kojima M, Ozawa N, Mori Y, Takahashi Y, Watanabe-Kominato K, Shirai R, Watanabe R, Sato K, Matsuyama TA, Ishibashi-Ueda H, Koba S, Kobayashi Y, Hirano T, Watanabe T (2018) Catestatin prevents macrophage-driven atherosclerosis but not arterial injury-induced neointimal hyperplasia. Thromb Haemost 118(1):182–194. https://doi.org/10.1160/th17-05-0349 CrossRefPubMed

13.

Durakoglugil ME, Ayaz T, Kocaman SA, Kirbas A, Durakoglugil T, Erdogan T, Cetin M, Sahin OZ, Cicek Y (2015) The relationship of plasma catestatin concentrations with metabolic and vascular parameters in untreated hypertensive patients: influence on high-density lipoprotein cholesterol. Anatol J Cardiol 15(7):577–585. https://doi.org/10.5152/akd.2014.5536 CrossRefPubMed

14.

Bandyopadhyay GK, Mahata SK (2017) Chromogranin A regulation of obesity and peripheral insulin sensitivity. Front Endocrinol (Lausanne) 8:20. https://doi.org/10.3389/fendo.2017.00020 CrossRef

15.

O'Connor DT, Kailasam MT, Kennedy BP, Ziegler MG, Yanaihara N, Parmer RJ (2002) Early decline in the catecholamine release-inhibitory peptide catestatin in humans at genetic risk of hypertension. J Hypertens 20(7):1335–1345CrossRefPubMed

16.

Li J, Thorne LN, Punjabi NM, Sun CK, Schwartz AR, Smith PL, Marino RL, Rodriguez A, Hubbard WC, O'Donnell CP, Polotsky VY (2005) Intermittent hypoxia induces hyperlipidemia in lean mice. Circ Res 97(7):698–706. https://doi.org/10.1161/01.RES.0000183879.60089.a9 CrossRefPubMed

17.

Li J, Grigoryev DN, Ye SQ, Thorne L, Schwartz AR, Smith PL, O'Donnell CP, Polotsky VY (2005) Chronic intermittent hypoxia upregulates genes of lipid biosynthesis in obese mice. J Appl Physiol (1985) 99(5):1643–1648. https://doi.org/10.1152/japplphysiol.00522.2005 CrossRefPubMed

18.

Qian Y, Yi H, Zou J, Meng L, Tang X, Zhu H, Yu D, Zhou H, Su K, Guan J, Yin S (2016) Independent association between sleep fragmentation and dyslipidemia in patients with obstructive sleep apnea. Sci Rep 6:26089. https://doi.org/10.1038/srep26089 CrossRefPubMedPubMedCentral

19.

Drager LF, Togeiro SM, Polotsky VY, Lorenzi-Filho G (2013) Obstructive sleep apnea: a cardiometabolic risk in obesity and the metabolic syndrome. J Am Coll Cardiol 62(7):569–576. https://doi.org/10.1016/j.jacc.2013.05.045 CrossRefPubMedPubMedCentral

20.

Kim J, Lee S, Bhattacharjee R, Khalyfa A, Kheirandish-Gozal L, Gozal D (2010) Leukocyte telomere length and plasma catestatin and myeloid-related protein 8/14 concentrations in children with obstructive sleep apnea. Chest 138(1):91–99. https://doi.org/10.1378/chest.09-2832 CrossRefPubMedPubMedCentral

21.

Kapur VK, Auckley DH, Chowdhuri S, Kuhlmann DC, Mehra R, Ramar K, Harrod CG (2017) Clinical practice guideline for diagnostic testing for adult obstructive sleep apnea: an American Academy of sleep medicine clinical practice guideline. J Clin Sleep Med 13(3):479–504. https://doi.org/10.5664/jcsm.6506 CrossRefPubMedPubMedCentral

22.

Bassetti CL, Đogaš Z, Peigneux P (2014) European Sleep Research Society (ESRS) European sleep medicine textbook. European Sleep Research Society

23.

Chung F, Abdullah HR, Liao P (2016) STOP-Bang questionnaire: a practical approach to screen for obstructive sleep apnea. Chest 149(3):631–638. https://doi.org/10.1378/chest.15-0903 CrossRef

24.

Pecotic R, Dodig IP, Valic M, Ivkovic N, Dogas Z (2012) The evaluation of the Croatian version of the Epworth sleepiness scale and STOP questionnaire as screening tools for obstructive sleep apnea syndrome. Sleep Breath 16(3):793–802CrossRefPubMed

25.

Fischer J, Dogas Z, Bassetti CL, Berg S, Grote L, Jennum P, Levy P, Mihaicuta S, Nobili L, Riemann D, Puertas Cuesta FJ, Raschke F, Skene DJ, Stanley N, Pevernagie D (2012) Standard procedures for adults in accredited sleep medicine centres in Europe. J Sleep Res 21(4):357–368. https://doi.org/10.1111/j.1365-2869.2011.00987.x CrossRefPubMed

26.

Epstein L, Kristo D, Strollo P Jr, Friedman N, Malhotra A, Patil S, Ramar K, Rogers R, Schwab R, Weaver E (2009) Adult obstructive sleep apnea task force of the American Academy of sleep medicine. Clinical guideline for the evaluation, management and long-term care of obstructive sleep apnea in adults. J Clin Sleep Med 5(3):263–276

27.

Narkiewicz K, Somers VK (2003) Sympathetic nerve activity in obstructive sleep apnoea. Acta Physiol Scand 177(3):385–390. https://doi.org/10.1046/j.1365-201X.2003.01091.x CrossRefPubMed

28.

Mahata SK, Kiranmayi M, Mahapatra NR (2018) Catestatin: a master regulator of cardiovascular functions. Curr Med Chem 25(11):1352–1374. https://doi.org/10.2174/0929867324666170425100416 CrossRefPubMed

29.

Meng L, Ye XJ, Ding WH, Yang Y, Di BB, Liu L, Huo Y (2011) Plasma catecholamine release-inhibitory peptide catestatin in patients with essential hypertension. J Cardiovasc Med (Hagerstown) 12(9):643–647. https://doi.org/10.2459/JCM.0b013e328346c142 CrossRef

30.

Schillaci G, De Vuono S, Pucci G (2011) An endogenous brake on the sympathetic nervous system: the emerging role of catestatin in hypertension. J Cardiovasc Med (Hagerstown) 12(9):609–612. https://doi.org/10.2459/JCM.0b013e328348d925 CrossRef

31.

Liu L, Ding W, Li R, Ye X, Zhao J, Jiang J, Meng L, Wang J, Chu S, Han X, Peng F (2013) Plasma levels and diagnostic value of catestatin in patients with heart failure. Peptides 46:20–25. https://doi.org/10.1016/j.peptides.2013.05.003 CrossRefPubMed

32.

Romero-Corral A, Caples SM, Lopez-Jimenez F, Somers VK (2010) Interactions between obesity and obstructive sleep apnea: implications for treatment. Chest 137(3):711–719. https://doi.org/10.1378/chest.09-0360 CrossRefPubMedPubMedCentral

33.

Ernst G, Bosio M, Salvado A, Dibur E, Nigro C, Borsini E (2016) Difference between apnea-hypopnea index (AHI) and oxygen desaturation index (ODI): proportional increase associated with degree of obesity. Sleep Breath 20(4):1175–1183. https://doi.org/10.1007/s11325-016-1330-3 CrossRefPubMed

34.

Bandyopadhyay GK, Vu CU, Gentile S, Lee H, Biswas N, Chi NW, O'Connor DT, Mahata SK (2012) Catestatin (chromogranin A(352-372)) and novel effects on mobilization of fat from adipose tissue through regulation of adrenergic and leptin signaling. J Biol Chem 287(27):23141–23151. https://doi.org/10.1074/jbc.M111.335877 CrossRefPubMedPubMedCentral

35.

Gaede AH, Pilowsky PM (2012) Catestatin, a chromogranin A-derived peptide, is sympathoinhibitory and attenuates sympathetic barosensitivity and the chemoreflex in rat CVLM. Am J Physiol Regul Integr Comp Physiol 302(3):R365–R372. https://doi.org/10.1152/ajpregu.00409.2011 CrossRefPubMed

36.

Smith JC, Ellenberger HH, Ballanyi K, Richter DW, Feldman JL (1991) Pre-Botzinger complex: a brainstem region that may generate respiratory rhythm in mammals. Science 254(5032):726–729CrossRefPubMedPubMedCentral

37.

Gaede AH, Pilowsky PM (2010) Catestatin in rat RVLM is sympathoexcitatory, increases barosensitivity, and attenuates chemosensitivity and the somatosympathetic reflex. Am J Physiol Regul Integr Comp Physiol 299(6):R1538–R1545. https://doi.org/10.1152/ajpregu.00335.2010 CrossRefPubMed

38.

Tan KC, Chow WS, Lam JC, Lam B, Wong WK, Tam S, Ip MS (2006) HDL dysfunction in obstructive sleep apnea. Atherosclerosis 184(2):377–382. https://doi.org/10.1016/j.atherosclerosis.2005.04.024 CrossRefPubMed

39.

Kawano Y, Tamura A, Kadota J (2012) Association between the severity of obstructive sleep apnea and the ratio of low-density lipoprotein cholesterol to high-density lipoprotein cholesterol. Metabolism 61(2):186–192. https://doi.org/10.1016/j.metabol.2011.06.004 CrossRefPubMed

40.

Verghese PB, Arrese EL, Soulages JL (2007) Stimulation of lipolysis enhances the rate of cholesterol efflux to HDL in adipocytes. Mol Cell Biochem 302(1–2):241–248. https://doi.org/10.1007/s11010-007-9447-0 CrossRefPubMed

Title: Catestatin serum levels are increased in male patients with obstructive sleep apnea
Authors: Josip A. Borovac
Zoran Dogas
Daniela Supe-Domic
Tea Galic
Josko Bozic
Publication date: 01-06-2019
Publisher: Springer International Publishing
Published in: Sleep and Breathing / Issue 2/2019
Print ISSN: 1520-9512
Electronic ISSN: 1522-1709
DOI: https://doi.org/10.1007/s11325-018-1703-x

ACC 2024 Congress Coverage

Heart Failure Video

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Catestatin serum levels are increased in male patients with obstructive sleep apnea

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 2/2019

Interrater agreement between American and Chinese sleep centers according to the 2014 AASM standard

Sleep quality in survivors of critical illness: practical shortcomings resolved

Predictors of cognitive behavioral therapy outcomes for insomnia in veterans with post-traumatic stress disorder

The use of mandibular advancement devices in obstructive sleep apnea: a proven and effective therapy

Overexpression of filamin c in chronic intermittent hypoxia-induced cardiomyocyte apoptosis is a potential cardioprotective target for obstructive sleep apnea

Associations between objectively assessed physical fitness levels and sleep quality in community-dwelling elderly people in South China

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