Skip to main content
Top
Published in: Neurotherapeutics 4/2018

01-10-2018 | Original Article

Decreased Concentration of Irisin Is Associated with Poor Functional Outcome in Ischemic Stroke

Authors: Wen-Jun Tu, Han-Cheng Qiu, Jian-Lei Cao, Qiang Liu, Xian-Wei Zeng, Ji-Zong Zhao

Published in: Neurotherapeutics | Issue 4/2018

Login to get access

Abstract

Irisin was discovered as a PGC-1a-activated messenger of myocytes that links sedentary lifestyle, obesity, and diabetes. In this study, we investigated the short-term prognostic value of early measurement of irisin concentration in 1530 Han Chinese patients with acute ischemic stroke (AIS) from three stroke centers. The subjects were the first-ever AIS patients who were hospitalized at three stroke centers during the period from January 2015 to December 2016. Clinical information and stroke severity were collected at admission. Neurological evaluations were conducted at the 6-month follow-up. Serum levels of irisin, National Institutes of Health Stroke Scale (NIHSS), and conventional risk factors were evaluated to determine their value to predict functional outcome and mortality within 6 months. Multivariate analyses were performed using logistic regression models. During follow-up, a poor functional outcome was found in 588 patients (38.4%; 95% confidence interval (CI), 36.0–40.9%), and 325 patients died (21.2%; 95% CI, 19.2–23.3%). The stroke patients included in the study were divided into four groups according to irisin quartiles (first is the lowest level). Poor outcome across the irisin quartiles ranged from 54.5% (first quartile) to 21.7% (fourth quartile), and mortality rate ranged from 39.3% (first quartile) to 6.3% (fourth quartile). In a multivariate model using the first quartile (Q1) of irisin vs. Q2–Q4 together with the clinical variables, the marker displayed prognostic information and increased odds ratios of poor outcome by 58% (OR for Q1, 1.58 [95% CI, 1.12–2.43]) and mortality by 185% (OR for Q1, 2.85 [95% CI, 1.79–4.02]). In addition, a model containing known risk factors plus irisin compared with a model containing known risk factors without irisin showed a greater discriminatory ability to predict poor outcome (the area under the curve (AUC) with an increase from 0.73 to 0.75 [95% CI, 0.70–0.81]) and mortality (the AUC increased from 0.80 to 0.83 [95% CI, 0.78–0.87]). Irisin is a novel, independent prognostic marker improving currently used risk stratification of stroke patients. Further studies are needed to confirm this association, which may pave the way to new therapeutic options. Trial registration: ChiCTR-OPC-17013501
Literature
1.
go back to reference Boström P, Wu J, Jedrychowski MP, Korde A, Ye L, Lo JC, et al. A PGC1-a-dependent myokine that drives brown-fat-like development of white fat and thermogenesis. Nature 2012; 481:463–468.CrossRefPubMedPubMedCentral Boström P, Wu J, Jedrychowski MP, Korde A, Ye L, Lo JC, et al. A PGC1-a-dependent myokine that drives brown-fat-like development of white fat and thermogenesis. Nature 2012; 481:463–468.CrossRefPubMedPubMedCentral
2.
go back to reference Huh J Y, Mougios V, Kabasakalis A, et al. Exercise-induced irisin secretion is independent of age or fitness level and increased irisin may directly modulate muscle metabolism through AMPK activation. The Journal of Clinical Endocrinology & Metabolism, 2014, 99(11): E2154–E2161.CrossRef Huh J Y, Mougios V, Kabasakalis A, et al. Exercise-induced irisin secretion is independent of age or fitness level and increased irisin may directly modulate muscle metabolism through AMPK activation. The Journal of Clinical Endocrinology & Metabolism, 2014, 99(11): E2154–E2161.CrossRef
3.
go back to reference Aydin S, Aydin S. Irisin Concentrations as a Myocardial Biomarker. Biomarkers in Cardiovascular Disease, 2016: 489–504. Aydin S, Aydin S. Irisin Concentrations as a Myocardial Biomarker. Biomarkers in Cardiovascular Disease, 2016: 489–504.
4.
go back to reference Ferrer-Martínez A, Ruiz-Lozano P, Chien KR. Mouse PeP: a novel peroxisomal protein linked to myoblast differentiation and development. Dev Dyn. 2002; 224:154–167.CrossRefPubMed Ferrer-Martínez A, Ruiz-Lozano P, Chien KR. Mouse PeP: a novel peroxisomal protein linked to myoblast differentiation and development. Dev Dyn. 2002; 224:154–167.CrossRefPubMed
5.
go back to reference Panagiotou G, Mu L, Na B, et al. Circulating irisin, omentin-1, and lipoprotein subparticles in adults at higher cardiovascular risk. Metabolism, 2014, 63(10): 1265–1271.CrossRefPubMedPubMedCentral Panagiotou G, Mu L, Na B, et al. Circulating irisin, omentin-1, and lipoprotein subparticles in adults at higher cardiovascular risk. Metabolism, 2014, 63(10): 1265–1271.CrossRefPubMedPubMedCentral
6.
go back to reference Moreno-Navarrete JM, Ortega F, Serrano M, Guerra E, Pardo G, Tinahones F, et al. Irisin is expressed and produced by human muscle and adipose tissue in association with obesity and insulin resistance. J Clin Endocrinol Metab 2013;98: E769–778.CrossRefPubMed Moreno-Navarrete JM, Ortega F, Serrano M, Guerra E, Pardo G, Tinahones F, et al. Irisin is expressed and produced by human muscle and adipose tissue in association with obesity and insulin resistance. J Clin Endocrinol Metab 2013;98: E769–778.CrossRefPubMed
7.
go back to reference Crujeiras AB, Zulet MA, Lopez-Legarrea P, de la Iglesia R, Pardo M, Carreira MC, et al. Association between circulating irisin levels and the promotion of insulin resistance during the weight maintenance period after a dietary weight-lowering programin obese patients. Metabolism 2014; 63:520–31.CrossRefPubMed Crujeiras AB, Zulet MA, Lopez-Legarrea P, de la Iglesia R, Pardo M, Carreira MC, et al. Association between circulating irisin levels and the promotion of insulin resistance during the weight maintenance period after a dietary weight-lowering programin obese patients. Metabolism 2014; 63:520–31.CrossRefPubMed
8.
go back to reference Choi YK, Kim MK, Bae KH, Seo HA, Jeong JY, Lee WK, et al. Serum irisin levels in new-onset type 2 diabetes. Diabetes Res Clin Pract 2013; 100:96–101.CrossRefPubMed Choi YK, Kim MK, Bae KH, Seo HA, Jeong JY, Lee WK, et al. Serum irisin levels in new-onset type 2 diabetes. Diabetes Res Clin Pract 2013; 100:96–101.CrossRefPubMed
9.
go back to reference Jang H B, Kim H J, Kang J H, et al. Association of circulating irisin levels with metabolic and metabolite profiles of Korean adolescents. Metabolism, 2017; 73:100–108CrossRefPubMed Jang H B, Kim H J, Kang J H, et al. Association of circulating irisin levels with metabolic and metabolite profiles of Korean adolescents. Metabolism, 2017; 73:100–108CrossRefPubMed
10.
go back to reference Wang S, Pan J. Irisin ameliorates depressive-like behaviors in rats by regulating energy metabolism. Biochemical and Biophysical Research Communications, 2016, 474(1): 22–28.CrossRefPubMed Wang S, Pan J. Irisin ameliorates depressive-like behaviors in rats by regulating energy metabolism. Biochemical and Biophysical Research Communications, 2016, 474(1): 22–28.CrossRefPubMed
11.
go back to reference Kuloglu T, Aydin S, Eren MN, et al. Irisin: a potentially candidate marker for myocardial infarction. Peptides. 2014; 55:85–91.CrossRefPubMed Kuloglu T, Aydin S, Eren MN, et al. Irisin: a potentially candidate marker for myocardial infarction. Peptides. 2014; 55:85–91.CrossRefPubMed
12.
go back to reference Endres M, Gertz K, Lindauer U, et al. Mechanisms of stroke protection by physical activity [J]. Annals of Neurology, 2003, 54(5): 582–590.CrossRefPubMed Endres M, Gertz K, Lindauer U, et al. Mechanisms of stroke protection by physical activity [J]. Annals of Neurology, 2003, 54(5): 582–590.CrossRefPubMed
13.
go back to reference Aronis K N, Moreno M, Polyzos S A, et al. Circulating irisin levels and coronary heart disease: association with future acute coronary syndrome and major adverse cardiovascular events [J]. International Journal of Obesity, 2015, 39(1): 156–162.CrossRefPubMed Aronis K N, Moreno M, Polyzos S A, et al. Circulating irisin levels and coronary heart disease: association with future acute coronary syndrome and major adverse cardiovascular events [J]. International Journal of Obesity, 2015, 39(1): 156–162.CrossRefPubMed
14.
go back to reference Tu W J, Qiu H C, Liu Q, et al. Decreased level of irisin, a skeletal muscle cell-derived myokine, is associated with post-stroke depression in the ischemic stroke population [J]. Journal of Neuroinflammation, 2018, 15(1): 133.CrossRefPubMedPubMedCentral Tu W J, Qiu H C, Liu Q, et al. Decreased level of irisin, a skeletal muscle cell-derived myokine, is associated with post-stroke depression in the ischemic stroke population [J]. Journal of Neuroinflammation, 2018, 15(1): 133.CrossRefPubMedPubMedCentral
15.
go back to reference Sims, JR, Gharai, LR, Schaefer, PW, Vangel M, Rosenthal ES. ABC/2 for rapid clinical estimate of infarct, perfusion, and mismatch volumes. Neurology 2009; 72: 2104–2110.CrossRefPubMedPubMedCentral Sims, JR, Gharai, LR, Schaefer, PW, Vangel M, Rosenthal ES. ABC/2 for rapid clinical estimate of infarct, perfusion, and mismatch volumes. Neurology 2009; 72: 2104–2110.CrossRefPubMedPubMedCentral
16.
go back to reference Bonita R BR. Modification of Rankin Scale: recovery of motor function after stroke. Stroke 1988; 19: 1497–1500.CrossRef Bonita R BR. Modification of Rankin Scale: recovery of motor function after stroke. Stroke 1988; 19: 1497–1500.CrossRef
17.
go back to reference Tu W J, Zeng X W, Deng A, et al. Circulating FABP4 (Fatty Acid–Binding Protein 4) Is a Novel Prognostic Biomarker in Patients with Acute Ischemic Stroke. Stroke, 2017; 48:1531–1538.CrossRefPubMed Tu W J, Zeng X W, Deng A, et al. Circulating FABP4 (Fatty Acid–Binding Protein 4) Is a Novel Prognostic Biomarker in Patients with Acute Ischemic Stroke. Stroke, 2017; 48:1531–1538.CrossRefPubMed
18.
go back to reference Pencina MJ, D’Agostino RB Sr, D’Agostino RB Jr, Vasan RS. Evaluating the added predictive ability of a new marker: from area under the ROC curve to reclassification and beyond. Stat Med 2008; 27:157–172.CrossRefPubMed Pencina MJ, D’Agostino RB Sr, D’Agostino RB Jr, Vasan RS. Evaluating the added predictive ability of a new marker: from area under the ROC curve to reclassification and beyond. Stat Med 2008; 27:157–172.CrossRefPubMed
19.
go back to reference Park KH, Zaichenko L, Brinkoetter M, Thakkar B, Sahin-Efe A, Joung KE, et al. Circulating irisin in relation to insulin resistance and the metabolic syndrome. J Clin Endocrinol Metab 2013;98:4899–4907CrossRefPubMed Park KH, Zaichenko L, Brinkoetter M, Thakkar B, Sahin-Efe A, Joung KE, et al. Circulating irisin in relation to insulin resistance and the metabolic syndrome. J Clin Endocrinol Metab 2013;98:4899–4907CrossRefPubMed
20.
go back to reference Efe T H, Açar B, Ertem A G, et al. Serum irisin level can predict the severity of coronary artery disease in patients with stable angina [J]. Korean Circulation Journal, 2017, 47(1): 44–49.CrossRefPubMed Efe T H, Açar B, Ertem A G, et al. Serum irisin level can predict the severity of coronary artery disease in patients with stable angina [J]. Korean Circulation Journal, 2017, 47(1): 44–49.CrossRefPubMed
21.
go back to reference Shen S, Gao R, Bei Y, et al. Serum Irisin Predicts Mortality Risk in Acute Heart Failure Patients [J]. Cellular Physiology and Biochemistry, 2017; 42(2): 615–622.CrossRefPubMed Shen S, Gao R, Bei Y, et al. Serum Irisin Predicts Mortality Risk in Acute Heart Failure Patients [J]. Cellular Physiology and Biochemistry, 2017; 42(2): 615–622.CrossRefPubMed
22.
go back to reference Yan J, Liu H J, Guo W C, et al. Low serum concentrations of Irisin are associated with increased risk of hip fracture in Chinese older women [J]. Joint Bone Spine 2018; 85(3): 353–358.CrossRefPubMed Yan J, Liu H J, Guo W C, et al. Low serum concentrations of Irisin are associated with increased risk of hip fracture in Chinese older women [J]. Joint Bone Spine 2018; 85(3): 353–358.CrossRefPubMed
23.
go back to reference Chang JS, Kim TH, Nguyen TT, et al. Circulating irisin levels as a predictive biomarker for sarcopenia: A cross-sectional community-based study [J]. Geriatrics & Gerontology International, 2017; 17(11): 2266–2273.CrossRef Chang JS, Kim TH, Nguyen TT, et al. Circulating irisin levels as a predictive biomarker for sarcopenia: A cross-sectional community-based study [J]. Geriatrics & Gerontology International, 2017; 17(11): 2266–2273.CrossRef
24.
go back to reference Liu B W, Yin F Z, Qi X M, et al. The Levels of Serum Irisin as a Predictor of Insulin Resistance in Han Chinese Adults with Metabolically Healthy Obesity [J]. Clinical Laboratory, 2017, 63(5–6): 881–886.PubMed Liu B W, Yin F Z, Qi X M, et al. The Levels of Serum Irisin as a Predictor of Insulin Resistance in Han Chinese Adults with Metabolically Healthy Obesity [J]. Clinical Laboratory, 2017, 63(5–6): 881–886.PubMed
25.
go back to reference Sugiyama Y, Asai K, Yamada K, et al. Decreased levels of irisin, a skeletal muscle cell-derived myokine, are related to emphysema associated with chronic obstructive pulmonary disease [J]. International Journal of Chronic Obstructive Pulmonary Disease, 2017, 12: 765–772.CrossRefPubMedPubMedCentral Sugiyama Y, Asai K, Yamada K, et al. Decreased levels of irisin, a skeletal muscle cell-derived myokine, are related to emphysema associated with chronic obstructive pulmonary disease [J]. International Journal of Chronic Obstructive Pulmonary Disease, 2017, 12: 765–772.CrossRefPubMedPubMedCentral
26.
go back to reference Yang S, Xiao F, Pan L, et al. Association of serum irisin and body composition with chronic kidney disease in obese Chinese adults: a cross-sectional study. BMC Nephrology, 2015, 16(1): 16.CrossRefPubMedPubMedCentral Yang S, Xiao F, Pan L, et al. Association of serum irisin and body composition with chronic kidney disease in obese Chinese adults: a cross-sectional study. BMC Nephrology, 2015, 16(1): 16.CrossRefPubMedPubMedCentral
27.
go back to reference Ebert T, Focke D, Petroff D, et al. Serum levels of the myokine irisin in relation to metabolic and renal function [J]. European Journal of Endocrinology, 2014, 170(4): 501–506.CrossRefPubMed Ebert T, Focke D, Petroff D, et al. Serum levels of the myokine irisin in relation to metabolic and renal function [J]. European Journal of Endocrinology, 2014, 170(4): 501–506.CrossRefPubMed
28.
go back to reference Brondani LA, Boelter G, Assmann TS, Leitao CB, Canani LH, Crispim D. Irisin-encoding gene (FNDC5) variant is associated with changes in blood pressure and lipid profile in type 2 diabetic women but not in men. Metabolism 2015; 64:952–957.CrossRefPubMed Brondani LA, Boelter G, Assmann TS, Leitao CB, Canani LH, Crispim D. Irisin-encoding gene (FNDC5) variant is associated with changes in blood pressure and lipid profile in type 2 diabetic women but not in men. Metabolism 2015; 64:952–957.CrossRefPubMed
29.
go back to reference Zhu D, Wang H, Zhang J, Zhang X, Xin C, Zhang F, et al. Irisin improves endothelial function in type 2 diabetes through reducing oxidative/nitrative stresses. J Mol Cell Cardiol 2015; 87:138–147.CrossRefPubMed Zhu D, Wang H, Zhang J, Zhang X, Xin C, Zhang F, et al. Irisin improves endothelial function in type 2 diabetes through reducing oxidative/nitrative stresses. J Mol Cell Cardiol 2015; 87:138–147.CrossRefPubMed
30.
go back to reference Han F, Zhang S, Hou N, Wang D, Sun X. Irisin improves endothelial function in obese mice through the AMPK-eNOS pathway. Am J Physiol Heart Circ Physiol 2015;309:H1501–H1508.CrossRefPubMed Han F, Zhang S, Hou N, Wang D, Sun X. Irisin improves endothelial function in obese mice through the AMPK-eNOS pathway. Am J Physiol Heart Circ Physiol 2015;309:H1501–H1508.CrossRefPubMed
31.
go back to reference Lu J, Xiang G, Liu M, Mei W, Xiang L, Dong J. Irisin protects against endothelial injury and ameliorates atherosclerosis in apolipoprotein E-null diabetic mice. Atherosclerosis 2015; 243:438–448.CrossRefPubMed Lu J, Xiang G, Liu M, Mei W, Xiang L, Dong J. Irisin protects against endothelial injury and ameliorates atherosclerosis in apolipoprotein E-null diabetic mice. Atherosclerosis 2015; 243:438–448.CrossRefPubMed
32.
go back to reference Polyzos S A, Kountouras J, Shields K, et al. Irisin: a renaissance in metabolism? [J]. Metabolism-Clinical and Experimental, 2013, 62(8): 1037–1044.CrossRefPubMed Polyzos S A, Kountouras J, Shields K, et al. Irisin: a renaissance in metabolism? [J]. Metabolism-Clinical and Experimental, 2013, 62(8): 1037–1044.CrossRefPubMed
33.
go back to reference Iglesia R, Lopez-Legarrea P, Crujeiras A B, et al. Plasma irisin depletion under energy restriction is associated with improvements in lipid profile in metabolic syndrome patients [J]. Clinical Endocrinology, 2014, 81(2): 306–311.CrossRefPubMed Iglesia R, Lopez-Legarrea P, Crujeiras A B, et al. Plasma irisin depletion under energy restriction is associated with improvements in lipid profile in metabolic syndrome patients [J]. Clinical Endocrinology, 2014, 81(2): 306–311.CrossRefPubMed
34.
go back to reference Xin C, Liu J, Zhang J, et al. Irisin improves fatty acid oxidation and glucose utilization in type 2 diabetes by regulating the AMPK signaling pathway [J]. International Journal of Obesity, 2016, 40(3): 443–451.CrossRefPubMed Xin C, Liu J, Zhang J, et al. Irisin improves fatty acid oxidation and glucose utilization in type 2 diabetes by regulating the AMPK signaling pathway [J]. International Journal of Obesity, 2016, 40(3): 443–451.CrossRefPubMed
35.
go back to reference Xiong X Q, Chen D, Sun H J, et al. FNDC5 overexpression and irisin ameliorate glucose/lipid metabolic derangements and enhance lipolysis in obesity [J]. Biochimica et Biophysica Acta (BBA)-Molecular Basis of Disease, 2015, 1852(9): 1867–1875.CrossRef Xiong X Q, Chen D, Sun H J, et al. FNDC5 overexpression and irisin ameliorate glucose/lipid metabolic derangements and enhance lipolysis in obesity [J]. Biochimica et Biophysica Acta (BBA)-Molecular Basis of Disease, 2015, 1852(9): 1867–1875.CrossRef
36.
go back to reference Desilles J P, Meseguer E, Labreuche J, et al. Diabetes Mellitus, Admission Glucose, and Outcomes After Stroke Thrombolysis [J]. Stroke, 2013, 44(7): 1915–1923.CrossRefPubMed Desilles J P, Meseguer E, Labreuche J, et al. Diabetes Mellitus, Admission Glucose, and Outcomes After Stroke Thrombolysis [J]. Stroke, 2013, 44(7): 1915–1923.CrossRefPubMed
38.
go back to reference Wang H, Zhang X, Chen W, et al. Relationship between serum irisin levels and urinary albumin excretion in patients with type 2 diabetes. Journal of Diabetes and Its Complications, 2015, 29(3): 384–389.CrossRefPubMed Wang H, Zhang X, Chen W, et al. Relationship between serum irisin levels and urinary albumin excretion in patients with type 2 diabetes. Journal of Diabetes and Its Complications, 2015, 29(3): 384–389.CrossRefPubMed
39.
go back to reference Santos-García D, Blanco M, Serena J, et al. Brachial arterial flow mediated dilation in acute ischemic stroke [J]. European Journal of Neurology, 2009, 16(6): 684–690.CrossRefPubMed Santos-García D, Blanco M, Serena J, et al. Brachial arterial flow mediated dilation in acute ischemic stroke [J]. European Journal of Neurology, 2009, 16(6): 684–690.CrossRefPubMed
40.
go back to reference Hou N, Han F, Sun X. The relationship between circulating irisin levels and endothelial function in lean and obese subjects. Clinical Endocrinology, 2015, 83(3): 339–343.CrossRefPubMed Hou N, Han F, Sun X. The relationship between circulating irisin levels and endothelial function in lean and obese subjects. Clinical Endocrinology, 2015, 83(3): 339–343.CrossRefPubMed
41.
go back to reference Targonski P V, Bonetti P O, Pumper G M, et al. Coronary endothelial dysfunction is associated with an increased risk of cerebrovascular events [J]. Circulation, 2003, 107(22): 2805–2809.CrossRefPubMed Targonski P V, Bonetti P O, Pumper G M, et al. Coronary endothelial dysfunction is associated with an increased risk of cerebrovascular events [J]. Circulation, 2003, 107(22): 2805–2809.CrossRefPubMed
42.
go back to reference Li D J, Li Y H, Yuan H B, et al. The novel exercise-induced hormone irisin protects against neuronal injury via activation of the Akt and ERK1/2 signaling pathways and contributes to the neuroprotection of physical exercise in cerebral ischemia [J]. Metabolism, 2017, 68: 31–42.CrossRefPubMed Li D J, Li Y H, Yuan H B, et al. The novel exercise-induced hormone irisin protects against neuronal injury via activation of the Akt and ERK1/2 signaling pathways and contributes to the neuroprotection of physical exercise in cerebral ischemia [J]. Metabolism, 2017, 68: 31–42.CrossRefPubMed
43.
go back to reference Zhao Y T, Du J, Wang H, et al. Irisin Protects Against Hypoxia and Reoxygenation Injury Through Hdac4 [J]. Circulation. 2016; 134: A17980CrossRef Zhao Y T, Du J, Wang H, et al. Irisin Protects Against Hypoxia and Reoxygenation Injury Through Hdac4 [J]. Circulation. 2016; 134: A17980CrossRef
Metadata
Title
Decreased Concentration of Irisin Is Associated with Poor Functional Outcome in Ischemic Stroke
Authors
Wen-Jun Tu
Han-Cheng Qiu
Jian-Lei Cao
Qiang Liu
Xian-Wei Zeng
Ji-Zong Zhao
Publication date
01-10-2018
Publisher
Springer International Publishing
Published in
Neurotherapeutics / Issue 4/2018
Print ISSN: 1933-7213
Electronic ISSN: 1878-7479
DOI
https://doi.org/10.1007/s13311-018-0651-2

Other articles of this Issue 4/2018

Neurotherapeutics 4/2018 Go to the issue