Skip to main content

Advertisement

Log in

Anemia of aging and obstructive sleep apnea

  • Original Article
  • Published:
Sleep and Breathing Aims and scope Submit manuscript

Abstract

Introduction

World Health Organization defined anemia of aging (AOA) when men and women greater than 65 years, respectively, have unexplained hemoglobin (Hgb) less than 13 and 12 g/dl. Recent evidence suggests that this is likely a chronic inflammatory process involving interleukins (IL) 6, 12, and C-reactive protein. Among elderly with obstructive sleep apnea (OSA), hypoxic stimulation of erythropoiesis may obscure AOA. Treatment of OSA may paradoxically restore AOA. We sought to identify OSA and AOA coexistence and OSA treatment AOA interaction.

Methods

Records of 101 successive patients older than 65 years and with OSA who were treated with continuous positive airway pressure were analyzed retrospectively. Differences among pre/post-treatment of OSA hemograms were assessed using paired two-tailed Student’s t test. Hemogram changes were compared to apnea–hypopnea index (AHI), respiratory effort related arousals (RERA), and duration patients slept with oxyhemoglobin saturation <89% (hypoxic time (HT)) and were assessed for correlative significance using Pearson coefficient correlation.

Results

Eighty-two of one hundred one patients (27 men, 55 women; average age 71 years) had charted all the study data variables cited above. Mean pre-treatment and mean 1-year post-treatment of OSA Hgb/hematocrit (Hct) for men and women, respectively, were 13 g/dl/40.7% to 12.7 g/dl/39.1% and 12.1 g/dl/38.1% to 11.9 g/dl/37.6%. Hct changed significantly among both men and women (p < 0.05). Among 56% and 30% of the 82 patient study cohort, 1-year post-treatment of OSA, Hct declined (mean 4.8%) and increased (mean 3.7%), respectively; both changes were statistically significant (p < 0.01). These changes did not correlate significantly with AHI, RERA, or HT.

Discussion

Among the entire cohort for both men and women, we did not see AOA before OSA treatment and we did see AOA 1 year after OSA treatment. However, post-treatment of OSA Hct distributed bimodally, with significant increases and declines of Hct. While these Hct changes did not correlate significantly with selected sleep-breathing variables, we remain intrigued by a possible AOA-OSA interaction. AOA and OSA share common inflammatory processes. We believe OSA inflammatory processes interact with OSA hypoxia-induced erythropoiesis. The balance of these sets of processes determines the effect of OSA and OSA treatment on AOA.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

Abbreviations

AOA:

anemia of aging

Hgb:

hemoglobin

OSA:

obstructive sleep apnea

IL:

interleukins

HT:

hypoxic time

CPAP:

continuous positive airway pressure

References

  1. Nandigam V, Nandigam K, Badhe BA, Dutta TK (2004) Is adult definition of anemia applicable to a geriatric population? Study of erythrocyte parameters in Indian geriatric inpatients. J Am Geriatr Soc 52:1589–1590

    Article  PubMed  Google Scholar 

  2. Guralnik JM, Eisenstaedt RS, Ferrucci L, Klein HG, Woodman RC (2004) Prevalence of anemia in persons 65 years and older in the United States: evidence for a high rate of unexplained anemia. Blood 104:2263–2268

    Article  CAS  PubMed  Google Scholar 

  3. Eisenstaedt R, Penninx BW, Woodman RC (2006) Anemia in the elderly: current understanding and emerging concepts. Blood Rev 20(4):213–226

    Article  PubMed  Google Scholar 

  4. Nemeth E, Valore EV, Territo M, Schiller G, Lichtenstein A, Ganz T (2003) Hepcidin, a putative mediator of anemia of inflammation, is a type II acute-phase protein. Blood 101(7):2461–2463

    Article  CAS  PubMed  Google Scholar 

  5. Shamsuzzaman AS, Winnicki M, Lanfranchi P (2002) Elevated C-reactive protein in patients with obstructive sleep apnea. Circulation 105:2462–2464

    Article  CAS  PubMed  Google Scholar 

  6. Yokoe T, Minoguchi K, Matsuo H (2003) Elevated levels of C-reactive protein and interleukin-6 in patients with obstructive sleep apnea syndrome are decreased by nasal continuous positive airway pressure. Circulation 107:1129–1134

    Article  CAS  PubMed  Google Scholar 

  7. Rechtschaffen A, Kales A (1968) eds. A manual of standardized terminology, techniques, and scoring system for sleep stages of human subjects. US Department of Health, Education, and Welfare Public Health Service–NIH/NIND

  8. American Academy of Sleep Medicine Task Force (1999) Sleep-related breathing disorders in adults: recommendations for syndrome definition and measurement techniques in clinical research. Sleep 22:667–689

    Google Scholar 

  9. Kikuchi M, Inagaki T, Shinagawa N (2001) Five-year survival of older people with anemia: variation with hemoglobin concentration. J Am Geriatr Soc 49(9):1226–1228

    Article  CAS  PubMed  Google Scholar 

  10. Wu WC, Rathore SS, Wang Y, Radford MJ, Krumholz HM (2001) Blood transfusion in elderly patients with acute myocardial infarction. N Engl J Med 345(17):1230–1236

    Article  CAS  PubMed  Google Scholar 

  11. Amin MG, Tighiouart H, Weiner DE, Stark PC, Griffith JL, MacLeod B, Salem DN, Sarnak MJ (2004) Hematocrit and left ventricular mass: the Framingham Heart study. J Am Coll Cardiol 43(7):1276–1282

    Article  PubMed  Google Scholar 

  12. Dharmarajan TS, Norkus EP (2004) Mild anemia and the risk of falls in older adults from nursing homes and the community. J Am Med Dir Assoc 5(6):395–400

    Article  CAS  PubMed  Google Scholar 

  13. Penninx BW, Guralnik JM, Onder G, Ferrucci L, Wallace RB, Pahor M (2003) Anemia and decline in physical performance among older persons. Am J Med 115(2):104–110

    Article  PubMed  Google Scholar 

  14. Dharmarajan TS, Pais W, Norkus EP (2005) Does anemia matter? Anemia, morbidity, and mortality in older adults: need for greater recognition. Geriatrics 60(12):22–29

    CAS  PubMed  Google Scholar 

  15. Goring K, Collop N (2008) Sleep disordered breathing in hospitalized patients. J Clin Sleep Med 4(2):105–110

    PubMed  Google Scholar 

  16. Weiss G, Goodnough LT (2005) Anemia of chronic disease. N Engl J Med 352:1011–1023

    Article  CAS  PubMed  Google Scholar 

  17. Tilg H, Ulmer H, Kaser A, Weiss G (2002) Role of IL-10 for induction of anemia during inflammation. J Immunol 169:2204–2209

    CAS  PubMed  Google Scholar 

  18. Faquin WC, Schneider TJ, Goldberg MA (1992) Effect of inflammatory cytokines on hypoxia-induced erythropoietin production. Blood 79:1987–1994

    CAS  PubMed  Google Scholar 

  19. Nordstrom D, Lindroth Y, Marsal L, Hafstrom I, Henrich C, Rantapaa-Dahlqvist S (1997) Availability of iron and degree of inflammation modifies the response to recombinant human erythropoietin when treating anemia of chronic disease in patients with rheumatoid arthritis. Rheumatol Int 17:67–73

    Article  CAS  PubMed  Google Scholar 

  20. Weinstein DA, Roy CN, Fleming MD, Loda MF, Wolfsdorf JI, Andrews NC (2002) Inappropriate expression of hepcidin is associated with iron refractory anemia: implications for the anemia of chronic disease. Blood 100:3776–3781

    Article  CAS  PubMed  Google Scholar 

  21. Roy CN, Weinstein DA, Andrews NC, Mead E (2003) Johnson Award for Research in Pediatrics Lecture: the molecular biology of the anemia of chronic disease: a hypothesis. Pediatr Res 53:507–512

    Article  PubMed  Google Scholar 

  22. Jongen-Lavrencic M, Peeters HR, Wognum A, Vreugdenhil G, Breedveld FC, Swaak AJ (1997) Elevated levels of inflammatory cytokines in bone marrow of patients with rheumatoid arthritis and anemia of chronic disease. J Rheumatol 24:1504–1509

    CAS  PubMed  Google Scholar 

  23. Papadaki HA, Kritikos HD, Valatas V, Boumpas DT, Eliopoulos GD (2002) Anemia of chronic disease in rheumatoid arthritis is associated with increased apoptosis of bone marrow erythroid cells: improvement following anti-tumor necrosis factor-alpha antibody therapy. Blood 100:474–482

    Article  CAS  PubMed  Google Scholar 

  24. Vgontzas AN, Papanicolaou DA, Bixler EO (1997) Elevation of plasma cytokines in disorders of excessive daytime sleepiness: role of sleep disturbance and obesity. J Clin Endocrinol Metab 82:1313–1316

    CAS  PubMed  Google Scholar 

  25. Vgontzas AN, Papanicolaou DA, Bixler EO (2000) Sleep apnea and daytime sleepiness and fatigue: relation to visceral obesity, insulin resistance, and hypercytokinemia. J Clin Endocrinol Metab 85:1151–1158

    CAS  PubMed  Google Scholar 

  26. Entzian P, Linnemann K, Schlaak M (1996) Obstructive sleep apnea and circadian rhythms of hormones and cytokines. Am J Respir Crit Care Med 153:1080–1086

    Article  CAS  PubMed  Google Scholar 

  27. Schulz R, Mahmoudi S, Hattar K (2000) Enhanced release of superoxide from polymorphonuclear neutrophils in obstructive sleep apnea. Am J Respir Crit Care Med 162:566–570

    Article  CAS  PubMed  Google Scholar 

  28. Dyugovskaya L, Lavie P, Lavie L (2002) Increased adhesion molecules expression and production of reactive oxygen species in leukocytes of sleep apnea patients. Am J Respir Crit Care Med 165:934–939

    Article  PubMed  Google Scholar 

  29. Hui Y, Funk CD (2002) Cysteinyl leukotriene receptors. Biochem Pharmacol 64:1549–1557

    Article  CAS  PubMed  Google Scholar 

  30. 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

    Article  CAS  PubMed  Google Scholar 

  31. Malhotra A, White DP (2002) Obstructive sleep apnoea. Lancet 360(9328):237–245

    Article  PubMed  Google Scholar 

  32. Wolk R, Somers VK (2003) Cardiovascular consequences of obstructive sleep apnea. Clin Chest Med 24(2):195–205

    Article  PubMed  Google Scholar 

  33. McGown AD, Makker H, Elwell C, Al Rawi PG, Valipour A, Spiro SG (2003) Measurement of changes in cytochrome oxidase redox state during obstructive sleep apnea using near-infrared spectroscopy. Sleep 26(6):710–716

    PubMed  Google Scholar 

  34. Schulz R, Mahmoudi S, Hattar K, Sibelius U, Olschewski H, Mayer K, Seeger W, Grimminger F (2000) Enhanced release of superoxide from polymorphonuclear neutrophils in obstructive sleep apnea. Impact of continuous positive airway pressure therapy. Am J Respir Crit Care Med 162(2 Pt 1):566–570

    Article  CAS  PubMed  Google Scholar 

  35. Fitzpatrick MF, Mackay T, Whyte KF, Allen M, Tam RC, Dore CJ, Henley M, Cotes PM, Douglas NJ (1993) Nocturnal desaturation and serum erythropoietin: a study in patients with chronic obstructive pulmonary disease and in normal subjects. Clin Sci (Lond) 84(3):319–324

    CAS  Google Scholar 

  36. Moore-Gillon JC, Cameron IR (1985) Right ventricular hypertrophy and polycythaemia in rats after intermittent exposure to hypoxia. Clin Sci (Lond) 69(5):595–599

    CAS  Google Scholar 

  37. Wedzicha JA, Cotes PM, Empey DW, Newland AC, Royston JP, Tam RC (1985) Serum immunoreactive erythropoietin in hypoxic lung disease with and without polycythaemia. Clin Sci (Lond) 69(4):413–422

    CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Amir M. Khan.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Khan, A.M., Ashizawa, S., Hlebowicz, V. et al. Anemia of aging and obstructive sleep apnea. Sleep Breath 15, 29–34 (2011). https://doi.org/10.1007/s11325-010-0326-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11325-010-0326-7

Keywords

Navigation