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Erschienen in: Sleep and Breathing 1/2021

06.04.2020 | Sleep Breathing Physiology and Disorders • Original Article

Serum adropin level is associated with endothelial dysfunction in patients with obstructive sleep apnea and hypopnea syndrome

verfasst von: Ziwen Fan, Yan Zhang, Fangfang Zou, Tengjuan Xu, Pinhua Pan, Chengping Hu, Xiaoli Su

Erschienen in: Sleep and Breathing | Ausgabe 1/2021

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Abstract

Objective

Adropin is a recently discovered peptide hormone that plays a vital role in metabolism and cardiovascular-cerebrovascular function. The purpose of this study is to investigate the role of circulating adropin levels in patients with obstructive sleep apnea-hypopnea syndrome (OSAHS) and further determine the relationship between serum adropin concentration and endothelial dysfunction in patients with OSAHS.

Methods

Forty polysomnography-diagnosed patients with OSAHS and 21 age and sex-matched healthy controls were enrolled in the current study. Serum adropin level, endothelial function parameters including flow-mediated dilatation (FMD) of brachial artery, endothelin-1 (ET-1), and nitric oxide (NO) were measured in all participants.

Results

Serum adropin levels were significantly lower in patients with OSAHS compared to the control subjects. FMD was lower and serum ET-1 levels were higher in patients with OSAHS compared to control subjects. No significant difference was seen in serum NO levels between the two groups. Multivariate linear regression analysis revealed that serum adropin level was positively associated with FMD and negatively correlated with AHI. Additionally, serum adropin levels were lower in patients with OSAHS who had endothelial dysfunction compared with those patients without endothelial dysfunction. The receiver operating characteristic (ROC) analysis showed that area under the curve (AUC) for serum adropin in predicting endothelial dysfunction status in patients with OSAHS was 0.815 (95% CI 0.680–0.951, p = 0.001). The cutoff value of serum adropin level was less than 235.0 pg/mL, which provided the sensitivity and specificity of 81% and 75%, respectively, for the detection of endothelial dysfunction in patients with OSAHS.

Conclusion

Lower circulating adropin levels are closely associated with endothelial dysfunction in patients with OSAHS. Circulating adropin level may serve as an early biomarker to predict the development of endothelial dysfunction before the emergence of clinical symptoms in patients with OSAHS.
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Literatur
1.
Zurück zum Zitat Caples SM, Gami AS, Somers VK (2005) Obstructive sleep apnea. Ann Intern Med 142(3):187–197 CrossRefPubMed Caples SM, Gami AS, Somers VK (2005) Obstructive sleep apnea. Ann Intern Med 142(3):187–197 CrossRefPubMed
3.
Zurück zum Zitat Kokturk O, Ciftci TU, Mollarecep E, Ciftci B (2005) Elevated C-reactive protein levels and increased cardiovascular risk in patients with obstructive sleep apnea syndrome. Int Heart J 46(5):801–809 CrossRefPubMed Kokturk O, Ciftci TU, Mollarecep E, Ciftci B (2005) Elevated C-reactive protein levels and increased cardiovascular risk in patients with obstructive sleep apnea syndrome. Int Heart J 46(5):801–809 CrossRefPubMed
4.
Zurück zum Zitat Gozal D, Kheirandish-Gozal L, Serpero LD, Sans Capdevila O, Dayyat E (2007) Obstructive sleep apnea and endothelial function in school-aged nonobese children: effect of adenotonsillectomy. Circulation. 116(20):2307–2314 CrossRefPubMed Gozal D, Kheirandish-Gozal L, Serpero LD, Sans Capdevila O, Dayyat E (2007) Obstructive sleep apnea and endothelial function in school-aged nonobese children: effect of adenotonsillectomy. Circulation. 116(20):2307–2314 CrossRefPubMed
5.
Zurück zum Zitat 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) 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 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) 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 CrossRefPubMed
6.
Zurück zum Zitat Kato M, Roberts-Thomson P, Phillips BG, Haynes WG, Winnicki M, Accurso V, Somers VK (2000) Impairment of endothelium-dependent vasodilation of resistance vessels in patients with obstructive sleep apnea. Circulation. 102(21):2607–2610 CrossRefPubMed Kato M, Roberts-Thomson P, Phillips BG, Haynes WG, Winnicki M, Accurso V, Somers VK (2000) Impairment of endothelium-dependent vasodilation of resistance vessels in patients with obstructive sleep apnea. Circulation. 102(21):2607–2610 CrossRefPubMed
8.
Zurück zum Zitat Kumar KG, Trevaskis JL, Lam DD, Sutton GM, Koza RA, Chouljenko VN, Kousoulas KG, Rogers PM, Kesterson RA, Thearle M, Ferrante AW Jr, Mynatt RL, Burris TP, Dong JZ, Halem HA, Culler MD, Heisler LK, Stephens JM, Butler AA (2008) Identification of adropin as a secreted factor linking dietary macronutrient intake with energy homeostasis and lipid metabolism. Cell Metab 8(6):468–481 CrossRefPubMedPubMedCentral Kumar KG, Trevaskis JL, Lam DD, Sutton GM, Koza RA, Chouljenko VN, Kousoulas KG, Rogers PM, Kesterson RA, Thearle M, Ferrante AW Jr, Mynatt RL, Burris TP, Dong JZ, Halem HA, Culler MD, Heisler LK, Stephens JM, Butler AA (2008) Identification of adropin as a secreted factor linking dietary macronutrient intake with energy homeostasis and lipid metabolism. Cell Metab 8(6):468–481 CrossRefPubMedPubMedCentral
9.
Zurück zum Zitat Aydin S, Kuloglu T, Aydin S, Eren MN, Yilmaz M, Kalayci M, Sahin I, Kocaman N, Citil C, Kendir Y (2013) Expression of adropin in rat brain, cerebellum, kidneys, heart, liver, and pancreas in streptozotocin-induced diabetes. Mol Cell Biochem 380(1–2):73–81 CrossRefPubMed Aydin S, Kuloglu T, Aydin S, Eren MN, Yilmaz M, Kalayci M, Sahin I, Kocaman N, Citil C, Kendir Y (2013) Expression of adropin in rat brain, cerebellum, kidneys, heart, liver, and pancreas in streptozotocin-induced diabetes. Mol Cell Biochem 380(1–2):73–81 CrossRefPubMed
10.
Zurück zum Zitat Lovren F, Pan Y, Quan A, Singh KK, Shukla PC, Gupta M, Al-Omran M, Teoh H, Verma S (2010) Adropin is a novel regulator of endothelial function. Circulation. 122(11 Suppl):S185–S192 CrossRefPubMed Lovren F, Pan Y, Quan A, Singh KK, Shukla PC, Gupta M, Al-Omran M, Teoh H, Verma S (2010) Adropin is a novel regulator of endothelial function. Circulation. 122(11 Suppl):S185–S192 CrossRefPubMed
11.
Zurück zum Zitat Lian W, Gu X, Qin Y, Zheng X (2011) Elevated plasma levels of adropin in heart failure patients. Intern Med 50(15):1523–1527 CrossRefPubMed Lian W, Gu X, Qin Y, Zheng X (2011) Elevated plasma levels of adropin in heart failure patients. Intern Med 50(15):1523–1527 CrossRefPubMed
12.
Zurück zum Zitat Ganesh Kumar K, Zhang J, Gao S, Rossi J, McGuinness OP, Halem HH, Culler MD, Mynatt RL, Butler AA (2012) Adropin deficiency is associated with increased adiposity and insulin resistance. Obesity (Silver Spring) 20(7):1394–1402 CrossRef Ganesh Kumar K, Zhang J, Gao S, Rossi J, McGuinness OP, Halem HH, Culler MD, Mynatt RL, Butler AA (2012) Adropin deficiency is associated with increased adiposity and insulin resistance. Obesity (Silver Spring) 20(7):1394–1402 CrossRef
13.
Zurück zum Zitat Aydin S, Kuloglu T, Aydin S, Kalayci M, Yilmaz M, Çakmak T, Eren MN (2014) Elevated adropin: a candidate diagnostic marker for myocardial infarction in conjunction with troponin-I. Peptides. 58:91–97 CrossRefPubMed Aydin S, Kuloglu T, Aydin S, Kalayci M, Yilmaz M, Çakmak T, Eren MN (2014) Elevated adropin: a candidate diagnostic marker for myocardial infarction in conjunction with troponin-I. Peptides. 58:91–97 CrossRefPubMed
14.
Zurück zum Zitat Topuz M, Celik A, Aslantas T, Demir AK, Aydin S, Aydin S (2013) Plasma adropin levels predict endothelial dysfunction like flow-mediated dilatation in patients with type 2 diabetes mellitus. J Investig Med 61(8):1161–1164 CrossRefPubMed Topuz M, Celik A, Aslantas T, Demir AK, Aydin S, Aydin S (2013) Plasma adropin levels predict endothelial dysfunction like flow-mediated dilatation in patients with type 2 diabetes mellitus. J Investig Med 61(8):1161–1164 CrossRefPubMed
15.
Zurück zum Zitat Oruc CU, Akpinar YE, Dervisoglu E, Amikishiyev S, Salmaslıoglu A, Gurdol F, Omer B (2017) Low concentrations of adropin are associated with endothelial dysfunction as assessed by flow-mediated dilatation in patients with metabolic syndrome. Clin Chem Lab Med 55(1):139–144 CrossRefPubMed Oruc CU, Akpinar YE, Dervisoglu E, Amikishiyev S, Salmaslıoglu A, Gurdol F, Omer B (2017) Low concentrations of adropin are associated with endothelial dysfunction as assessed by flow-mediated dilatation in patients with metabolic syndrome. Clin Chem Lab Med 55(1):139–144 CrossRefPubMed
16.
Zurück zum Zitat Gozal D, Kheirandish-Gozal L, Bhattacharjee R, Molero-Ramirez H, Tan HL, Bandla HP (2013) Circulating adropin concentrations in pediatric obstructive sleep apnea: potential relevance to endothelial function. J Pediatr 163(4):1122–1126 CrossRefPubMedPubMedCentral Gozal D, Kheirandish-Gozal L, Bhattacharjee R, Molero-Ramirez H, Tan HL, Bandla HP (2013) Circulating adropin concentrations in pediatric obstructive sleep apnea: potential relevance to endothelial function. J Pediatr 163(4):1122–1126 CrossRefPubMedPubMedCentral
18.
Zurück zum Zitat Medical Advisory Secretariat (2006) Polysomnography in patients with obstructive sleep apnea: an evidence-based analysis. Ont Health Technol Assess Ser 6(13):1–38 PubMedCentral Medical Advisory Secretariat (2006) Polysomnography in patients with obstructive sleep apnea: an evidence-based analysis. Ont Health Technol Assess Ser 6(13):1–38 PubMedCentral
19.
Zurück zum Zitat Epstein L, Kristo D, Strollo PJ Jr, Friedman N, Malhotra A, Patil SP, Ramar K, Rogers R, Schwab RJ, Weaver EM, Weinstein MD (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 CrossRefPubMed Epstein L, Kristo D, Strollo PJ Jr, Friedman N, Malhotra A, Patil SP, Ramar K, Rogers R, Schwab RJ, Weaver EM, Weinstein MD (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 CrossRefPubMed
20.
Zurück zum Zitat Johns MW (1991) A new method for measuring daytime sleepiness: the Epworth sleepiness scale. Sleep. 14(6):540–545 CrossRefPubMed Johns MW (1991) A new method for measuring daytime sleepiness: the Epworth sleepiness scale. Sleep. 14(6):540–545 CrossRefPubMed
21.
Zurück zum Zitat Coretti 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) International Brachial Artery Reactivity Task Force. 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):257–265 CrossRef Coretti 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) International Brachial Artery Reactivity Task Force. 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):257–265 CrossRef
23.
Zurück zum Zitat Doshi SN, Naka KK, Payne N et al (2001) Flow-mediated dilatation following wrist and upper arm occlusion in humans: the contribution of nitric oxide. Clin Sci (Lond) 101(6):629–635 CrossRef Doshi SN, Naka KK, Payne N et al (2001) Flow-mediated dilatation following wrist and upper arm occlusion in humans: the contribution of nitric oxide. Clin Sci (Lond) 101(6):629–635 CrossRef
24.
Zurück zum Zitat Celermajer DS, Sorensen KE, Gooch VM, Spiegelhalter DJ, Miller OI, Sullivan ID, Lloyd JK, Deanfield JE (1992) Non-invasive detection of endothelial dysfunction in children and adults at risk of atherosclerosis. Lancet 340(8828):1111–1115 CrossRefPubMed Celermajer DS, Sorensen KE, Gooch VM, Spiegelhalter DJ, Miller OI, Sullivan ID, Lloyd JK, Deanfield JE (1992) Non-invasive detection of endothelial dysfunction in children and adults at risk of atherosclerosis. Lancet 340(8828):1111–1115 CrossRefPubMed
26.
Zurück zum Zitat Alley H, Owens CD, Gasper WJ, Grenon SM (2014) Ultrasound assessment of endothelial-dependent flow-mediated vasodilation of the brachial artery in clinical research. J Vis Exp 92:e52070 Alley H, Owens CD, Gasper WJ, Grenon SM (2014) Ultrasound assessment of endothelial-dependent flow-mediated vasodilation of the brachial artery in clinical research. J Vis Exp 92:e52070
27.
Zurück zum Zitat Goetze JP, Albrethsen J (2014) Adropin: a new regulatory peptide in cardiovascular endocrinology. Regul Pept 190–191:41–42 CrossRefPubMed Goetze JP, Albrethsen J (2014) Adropin: a new regulatory peptide in cardiovascular endocrinology. Regul Pept 190–191:41–42 CrossRefPubMed
29.
Zurück zum Zitat Lamers D, Schlich R, Greulich S et al (2011) Oleic acid and adipokines synergize in inducing proliferation and inflammatory signalling in human vascular smooth muscle cells[J]. J Cell Mol Med 15(5):1177–1188 CrossRefPubMed Lamers D, Schlich R, Greulich S et al (2011) Oleic acid and adipokines synergize in inducing proliferation and inflammatory signalling in human vascular smooth muscle cells[J]. J Cell Mol Med 15(5):1177–1188 CrossRefPubMed
30.
Zurück zum Zitat Lefer DJ, Jones SP, Girod WG et al (1999) Leukocyte-endothelial cell interactions in nitric oxide synthase-deficient mice. Am J Phys 276(6 Pt 2):H1943–H1950 Lefer DJ, Jones SP, Girod WG et al (1999) Leukocyte-endothelial cell interactions in nitric oxide synthase-deficient mice. Am J Phys 276(6 Pt 2):H1943–H1950
33.
Zurück zum Zitat Cockrell A, Laroux FS, Jourd’heuil D, Kawachi S, Gray L et al (1999) Role of inducible nitric oxide synthase in leukocyte extravasation in vivo. Biochem Biophys Res Commun 257(3):684–686 CrossRefPubMed Cockrell A, Laroux FS, Jourd’heuil D, Kawachi S, Gray L et al (1999) Role of inducible nitric oxide synthase in leukocyte extravasation in vivo. Biochem Biophys Res Commun 257(3):684–686 CrossRefPubMed
36.
Zurück zum Zitat Sedgwick JD, Riminton DS, Cryster JG, Körner H (2000) Tumor necrosis factor: a master-regulator of leukocyte movement. Immunol Today 21(3):110–113 CrossRefPubMed Sedgwick JD, Riminton DS, Cryster JG, Körner H (2000) Tumor necrosis factor: a master-regulator of leukocyte movement. Immunol Today 21(3):110–113 CrossRefPubMed
38.
Zurück zum Zitat Cirino G, Fiorucci S, Sessa WC (2003) Endothelial nitric oxide synthase: the Cinderella of inflammation? Trends Pharmacol Sci 24(2):91–95 CrossRefPubMed Cirino G, Fiorucci S, Sessa WC (2003) Endothelial nitric oxide synthase: the Cinderella of inflammation? Trends Pharmacol Sci 24(2):91–95 CrossRefPubMed
40.
Zurück zum Zitat Gu X, Li H, Zhu X, Gu H, Chen J, Wang L, Harding P, Xu W (2015) Inverse correlation between plasma adropin and ET-1 levels in essential hypertension: a cross-sectional study. Medicine (Baltimore) 94(40):e1712 CrossRef Gu X, Li H, Zhu X, Gu H, Chen J, Wang L, Harding P, Xu W (2015) Inverse correlation between plasma adropin and ET-1 levels in essential hypertension: a cross-sectional study. Medicine (Baltimore) 94(40):e1712 CrossRef
41.
Zurück zum Zitat Pernow J, Shemyakin A, Böhm F (2012) New perspectives on endothelin-1 in atherosclerosis and diabetes mellitus. Life Sci 91(13–14):507–516 CrossRefPubMed Pernow J, Shemyakin A, Böhm F (2012) New perspectives on endothelin-1 in atherosclerosis and diabetes mellitus. Life Sci 91(13–14):507–516 CrossRefPubMed
42.
Zurück zum Zitat Ahirwar AK, Jain A, Singh A, Goswami B, Bhatnagar MK, Bhatacharjee J (2015) The study of markers of endothelial dysfunction in metabolic syndrome. Horm Mol Biol Clin Invest 24(3):131–136 Ahirwar AK, Jain A, Singh A, Goswami B, Bhatnagar MK, Bhatacharjee J (2015) The study of markers of endothelial dysfunction in metabolic syndrome. Horm Mol Biol Clin Invest 24(3):131–136
43.
Zurück zum Zitat Butler AA, Tam CS, Stanhope KL, Wolfe BM, Ali MR, O'Keeffe M, St-Onge MP, Ravussin E, Havel PJ (2012) Low circulating adropin concentrations with obesity and aging correlate with risk factors for metabolic disease and increase after gastric bypass surgery in humans. J Clin Endocrinol Metab 97(10):3783–3791 CrossRefPubMedPubMedCentral Butler AA, Tam CS, Stanhope KL, Wolfe BM, Ali MR, O'Keeffe M, St-Onge MP, Ravussin E, Havel PJ (2012) Low circulating adropin concentrations with obesity and aging correlate with risk factors for metabolic disease and increase after gastric bypass surgery in humans. J Clin Endocrinol Metab 97(10):3783–3791 CrossRefPubMedPubMedCentral
44.
Zurück zum Zitat Altincik A, Sayin O (2015) Evaluation of the relationship between serum adropin levels and blood pressure in obese children. J Pediatr Endocrinol Metab 28(9–10):1095–1100 PubMed Altincik A, Sayin O (2015) Evaluation of the relationship between serum adropin levels and blood pressure in obese children. J Pediatr Endocrinol Metab 28(9–10):1095–1100 PubMed
Metadaten
Titel
Serum adropin level is associated with endothelial dysfunction in patients with obstructive sleep apnea and hypopnea syndrome
verfasst von
Ziwen Fan
Yan Zhang
Fangfang Zou
Tengjuan Xu
Pinhua Pan
Chengping Hu
Xiaoli Su
Publikationsdatum
06.04.2020
Verlag
Springer International Publishing
Erschienen in
Sleep and Breathing / Ausgabe 1/2021
Print ISSN: 1520-9512
Elektronische ISSN: 1522-1709
DOI
https://doi.org/10.1007/s11325-020-02072-7

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