Obstructive sleep apnea and the effect of CPAP treatment on ischemia-modified albumin levels: a multi effect size meta-analysis with diagnostic test accuracy

  • Seshadri Reddy Varikasuvu
  • Naveen Dutt
  • Dibakar Sahu
Sleep Breathing Physiology and Disorders • Original Article



A close association of oxidative stress (OS) and ischemia-modified albumin (IMA) with obstructive sleep apnea (OSA) has been reported in the literature, but the results on IMA are ambiguous. We conducted a meta-analysis to evaluate the association of IMA with OSA and the effect of continuous positive airway pressure (CPAP) therapy on IMA in patients with OSA.


Relevant studies were identified by searching PubMed and other databases in addition to manual searching of cross-references. Using random-effects model, the standardized mean differences (SMDs), pooled correlation coefficients and summary of diagnostic test accuracies were obtained with 95% confidence intervals (CIs). The meta-regression, sub-group and sensitivity analyses were performed to explore heterogeneity. The presence of publication bias was tested using funnel plot analysis followed by Begg’s and Egger’s tests for statistical signidicance.


This meta-analysis finally included nine studies. When comparing with non-OSA controls, the OSA patients showed a significantly increased circulatory IMA levels (SMD = 1.15, p = 0.0001). And, this increase is even more pronounced in severe-OSA group as compared to mild-moderate OSA patients (SMD = 076, p = 0.0006). A decrease in post-CPAP treatment IMA was observed when compared with that of baseline values. Meta-analysis of correlations showed significant associations of IMA with polysomnographic parameters. The pooled diagnostic odds ratio and area under curve were 19.58 and 0.888 (Q* = 0.819), respectively. There was no evidence of publication bias for the association of IMA with OSA.


This meta-analysis suggests that OSA is associated with significantly increased IMA levels which may indicate OS, ischemia and subclinical cardiovascular risk. In the diagnostic test accuracy meta-analysis, IMA showed good accuracy for OSA detection. However, further studies are required to establish its clinical utility.


Sleep Obstructive sleep apnea Ischemia-modified albumin Meta-analysis 



Dr. V. S. Reddy is very much thankful to Prof Tiejun Tong, and Luo Dehui (PhD Scholar), Department of Mathematics, Hong Kong Baptist University for their statistical expertise and help in the methodology. All the authors acknowledge the help received from Pragathi Duggina (Sri Padmavati Mahila Visvavidyalayam, Andhra Pradesh), Neelakant Varma (Gujarat Forensic Sciences University, Gujarat), and Raju CH (Dr. raju’s speciality clinics, Telangana) in literature search after it was initially and independently done by two authors (VSR & ND).


No funding was received for this research.

Compliance with ethical standards

Conflict of interest

All authors certify that they have no affiliations with or involvement in any organization or entity with any financial interest (such as honoraria; educational grants; participation in speakers’ bureaus; membership, employment, consultancies, stock ownership, or other equity interest; and expert testimony or patent-licensing arrangements), or non-financial interest (such as personal or professional relationships, affiliations, knowledge or beliefs) in the subject matter or materials discussed in this manuscript.

Ethical approval

For this type of study, ethical approval is not required.

Informed consent

For this type of study, formal consent is not required.

Supplementary material

11325_2018_1679_MOESM1_ESM.pdf (586 kb)
ESM 1 (PDF 586 kb)


  1. 1.
    Young T, Peppard PE, Gottlieb DJ (2002) Epidemiology of obstructive sleep apnea: a population health perspective. Am J Respir Crit Care Med 165:1217–1239CrossRefPubMedGoogle Scholar
  2. 2.
    Heinzer R, Vat S, Marques-Vidal P, Marti-Soler H, Andries D, Tobback N, Mooser V, Preisig M, Malhotra A, Waeber G, Vollenweider P, Tafti M, Haba-Rubio J (2015) Prevalence of sleep-disordered breathing in the general population: the HypnoLaus study. Lancet Respir Med 3:310–318CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Dewan NA, Nieto FJ, Somers VK (2015) Intermittent hypoxemia and OSA: implications for comorbidities. Chest 147:266–274CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Eisele HJ, Markart P, Schulz R (2015) Obstructive sleep apnea, oxidative stress, and cardiovascular disease: evidence from human studies. Oxidative Med Cell Longev 2015:608438CrossRefGoogle Scholar
  5. 5.
    Bourdon E, Blache D (2001) The importance of proteins in defense against oxidation. Antioxid Redox Signal 3:293–311CrossRefPubMedGoogle Scholar
  6. 6.
    Faure P, Tamisier R, Baguet JP, Favier A, Halimi S, Levy P, Pepin JL (2008) Impairment of serum albumin antioxidant properties in obstructive sleep apnoea syndrome. Eur Respir J 31:1046–1053CrossRefPubMedGoogle Scholar
  7. 7.
    Bar-Or D, Lau E, Winkler JV (2000) A novel assay for cobalt-albumin binding and its potential as a marker for myocardial ischemia—a preliminary report. J Emerg Med 19:311–315CrossRefPubMedGoogle Scholar
  8. 8.
    Roy D, Quiles J, Gaze DC, Collinson P, Kaski JC, Baxter GF (2006) Role of reactive oxygen species on the formation of the novel diagnostic marker ischaemia modified albumin. Heart 92:113–114CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Seneş M, Kazan N, Coşkun O et al (2007) Oxidative and nitrosative stress in acute ischaemic stroke. Ann Clin Biochem 44:43–47PubMedCrossRefGoogle Scholar
  10. 10.
    Turedi S, Gunduz A, Mentese A, Karahan SC, Yilmaz SE, Eroglu O, Nuhoglu I, Turan I, Topbas M (2007) Value of ischemia-modified albumin in the diagnosis of pulmonary embolism. Am J Emerg Med 25:770–773CrossRefPubMedGoogle Scholar
  11. 11.
    Dogan D, Ocal N, Aydogan M, Tasci C, Arslan Y, Tapan S, Yetkin S, Bilgic H (2016) Assessment of the role of serum ischemia-modified albumin in obstructive sleep apnea in comparison with interleukin-6. Postgrad Med 128:603–608CrossRefPubMedGoogle Scholar
  12. 12.
    Gugliucci A, Kotani K, Komada I et al (2010) Serum ischemia modified albumin levels in obstructive sleep apnea patients before and after treatment: a pilot study. Touro University, California 2010; 9th Annual Research Day Abstract Book-Clinical sciences Poster C-13: p38–39. Availbale from: URL: Accessed 2017 Nov 29
  13. 13.
    Karamanli H, Kiyici A, Arik B, Efe D, Akgedik R (2016) Influence of obstructive sleep apnea on ischemia-modified albumin levels and carotid intima-media thickness. J Investig Med 64:1035–1041CrossRefPubMedGoogle Scholar
  14. 14.
    Ozben S, Huseyinoglu N, Hanikoglu F, Guvenc TS, Yildirim BZ, Cort A, Ozdem S, Ozben T (2014) Advanced oxidation protein products and ischaemia-modified albumin in obstructive sleep apnea. Eur J Clin Investig 44:1045–1052CrossRefGoogle Scholar
  15. 15.
    Öztuna F, Gözaçan H, Kiriş G et al (2013) Effect of nasal continuous positive airway pressure on global right ventricular myocardial performance in patients with obstructive sleep apnea syndrome. Turk J Med Sci 43:393–399Google Scholar
  16. 16.
    Sunnetcioglu A, Asker S, Alp HH, Gunbatar H (2016) Increased asymmetric dimethylarginine and ischemia-modified albumin levels in obstructive sleep apnea. Respir Care 61:1038–1043CrossRefPubMedGoogle Scholar
  17. 17.
    Uygur F, Tanriverdi H, Can M et al (2016) The impact of obstructive sleep apnoea and nasal continuous positive airway pressure on circulating ischaemia-modified albumin concentrations. Mediat Inflamm 2016:8907314CrossRefGoogle Scholar
  18. 18.
    Xu Q, Du J, Ling X et al (2017) Evaluation of MIh scoring system in diagnosis of obstructive sleep apnea syndrome. Med Sci Monit 23:4715–4722CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Yang LX, Ma SG, Liu H, Xu W (2013) Influence of obstructive sleep apnea on serum butyrylcholinesterase activity and ischemia-modified albumin levels. Clinics (Sao Paulo) 68:968–973CrossRefGoogle Scholar
  20. 20.
    Hukins CA (2006) Obstructive sleep apnea—management update. Neuropsychiatr Dis Treat 3:309–326CrossRefGoogle Scholar
  21. 21.
    Barceló A, Barbé F, de la Peña M et al (2006) Antioxidant status in patients with sleep apnoea and impact of continuous positive airway pressure treatment. Eur Respir J 27:756–760CrossRefPubMedGoogle Scholar
  22. 22.
    Li W, Ma D, Liu M, Liu H, Feng S, Hao Z, Wu B, Zhang S (2008) Association between metabolic syndrome and risk of stroke: a meta-analysis of cohort studies. Cerebrovasc Dis 25:539–547CrossRefPubMedGoogle Scholar
  23. 23.
    Whiting PF, Rutjes AW, Westwood ME, Mallett S, Deeks JJ, Reitsma JB, Leeflang MM, Sterne JA, Bossuyt PM, QUADAS-2 Group (2011) QUADAS-2: a revised tool for the quality assessment of diagnostic accuracy studies. Ann Intern Med 155:529–536CrossRefPubMedGoogle Scholar
  24. 24.
    He Y, Chen R, Wang J, Pan W, Sun Y, Han F, Wang Q, Liu C (2016) Neurocognitive impairment is correlated with oxidative stress in patients with moderate-to-severe obstructive sleep apnea hypopnea syndrome. Respir Med 120:25–30CrossRefPubMedGoogle Scholar
  25. 25.
    Paz Y, Mar HL, Hazen SL, Tracy RP et al (2016) Effect of continuous positive airway pressure on cardiovascular biomarkers: the sleep apnea stress randomized controlled trial. Chest 150:80–90CrossRefGoogle Scholar
  26. 26.
    Lavie L, Lavie P (2009) Molecular mechanisms of cardiovascular disease in OSAHS: the oxidative stress link. Eur Respir J 33:1467–1484CrossRefPubMedGoogle Scholar
  27. 27.
    Alonso-Fernández A, García-Río F, Arias MA et al (2009) Effects of CPAP on oxidative stress and nitrate efficiency in sleep apnoea: a randomised trial. Thorax 64:581–586CrossRefPubMedGoogle Scholar
  28. 28.
    Paruthi S, Rosen CL, Wang R, Weng J, Marcus CL, Chervin RD, Stanley JJ, Katz ES, Amin R, Redline S (2015) End-tidal carbon dioxide measurement during pediatric polysomnography: signal quality, association with apnea severity, and prediction of neurobehavioral outcomes. Sleep 38:1719–1726CrossRefPubMedPubMedCentralGoogle Scholar
  29. 29.
    Adly AAM, ElSherif NHK, Ismail EAR et al (2017) Ischemia-modified albumin as a marker of vascular dysfunction and subclinical atherosclerosis in β-thalassemia major. Redox Rep 22:430–438CrossRefPubMedGoogle Scholar
  30. 30.
    Sinha MK, Roy D, Gaze DC, Collinson PO, Kaski JC (2004) Role of “ischemia modified albumin”, a new biochemical marker of myocardial ischaemia, in the early diagnosis of acute coronary syndromes. Emerg Med J 21:29–34CrossRefPubMedPubMedCentralGoogle Scholar
  31. 31.
    Baysal T, Alp H, Koç N, Atabek ME, Eklioğlu BS, Karaarslan S (2012) Serum ischemia-modified albumin level and its association with cardiovascular risk factors in obese children and adolescents. J Pediatr Endocrinol Metab 25:935–944CrossRefPubMedGoogle Scholar
  32. 32.
    Reddy VS, Suchitra MM, Pradeep V et al (2015) Ischemia-modified albumin levels in overt and subclinical hypothyroidism. J Endocrinol Investig 38:885–890CrossRefGoogle Scholar
  33. 33.
    Reddy VS, Agrawal P, Sethi S, Gupta N, Garg R, Madaan H, Kumar V (2015) Associations of FPG, A1C and disease duration with protein markers of oxidative damage and antioxidative defense in type 2 diabetes and diabetic retinopathy. Eye (Lond) 29:1585–1593CrossRefGoogle Scholar
  34. 34.
    Ukinc K, Eminagaoglu S, Ersoz HO, Erem C, Karahan C, Hacihasanoglu AB, Kocak M (2009) A novel indicator of widespread endothelial damage and ischemia in diabetic patients: ischemia-modified albumin. Endocrine 36:425–432CrossRefPubMedGoogle Scholar
  35. 35.
    Reddy VS, Sethi S, Agrawal P, Gupta N, Garg R (2015) Ischemia modified albumin (IMA) and albumin adjusted-IMA (AAIMA) as biomarkers for diabetic retinopathy. Nepal J Ophthalmol 7:117–123CrossRefPubMedGoogle Scholar
  36. 36.
    Reddy VS, Bukke S, Munikumar M (2018) Elevated levels of the circulatory ischemia-modified albumin in patients with polycystic ovary syndrome: a meta-analysis. Gynecol Endocrinol:1–7.
  37. 37.
    Cifçi N, Uyar M, Elbek O et al (2010) Impact of CPAP treatment on cardiac biomarkers and pro-BNP in obstructive sleep apnea syndrome. Sleep Breath 14:241–244CrossRefPubMedGoogle Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Faculty of Medicine, Department of BiochemistryMaheshwara Medical College & HospitalHyderabadIndia
  2. 2.Department of Pulmonary MedicineAll India Institute of Medical SciencesJodhpurIndia
  3. 3.Department of Pulmonary MedicineAll India Institute of Medical SciencesRaipurIndia

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