The journal of nutrition, health & aging

, Volume 22, Issue 8, pp 965–974 | Cite as

The Relationship Between Anaemia and Frailty: A Systematic Review and Meta-Analysis of Observational Studies

  • Katie PalmerEmail author
  • D. L. Vetrano
  • A. Marengoni
  • A. M. Tummolo
  • E. R. Villani
  • N. Acampora
  • R. Bernabei
  • G. Onder
  • WP4 of the Joint Action Advantage



There is increasing evidence that frailty may play a role in chronic diseases, but the associations with specific chronic disorders are still unclear.


To conduct a systematic review and meta-analysis assessing the association of anaemia and frailty in observational studies.


The review was performed according to PRISMA guidelines. We searched PubMed, Web of Science, and Embase from 01/01/2002-10/09/2017. Pooled estimates were obtained through random effect models and Mantel-Haenszel weighting. Homogeneity was assessed with the I2 statistic. Publication bias was assessed with Egger’s and Begg’s tests.


Nineteen studies were included; two longitudinal, seventeen cross-sectional. All studies except three reported an association between anaemia and frailty. The pooled prevalence of prefrailty in individuals with anaemia was 49% (95% CI=38-59%; I2=89.96%) and 24% (95% CI=17-31%; I2= 94.78%) for frailty. Persons with anaemia had more than a twofold odds of frailty (pooled OR=2.24 95% CI=1.53-3.30; I2=91.8%). Only two studies longitudinally examined the association between anaemia and frailty, producing conflicting results.


Frailty and prefrailty are common in anaemic persons. Older persons with anaemia have more than a two-fold increased odds of frailty. These results may have clinical implications, as they identify the need to assess frailty in anaemic people and investigate any potential negative effects associated with the co-occurrence of both conditions. Longitudinal research that examines temporal changes in anaemia and effect of treatment are needed to further clarify the relationship between anaemia and frailty.

Key words

Frail hemoglobin chronic diseases vulnerable ageing anemic 


  1. 1.
    Fried LP, Tangen CM, Walston J, Newman AB, Hirsch C, Gottdiener J, Seeman T, Tracy R, Kop WJ, Burke G, McBurnie MA, Cardiovascular Health Study Collaborative Research G. Frailty in older adults: evidence for a phenotype. J Gerontol A Biol Sci Med Sci 2001;56:M146–156.CrossRefPubMedGoogle Scholar
  2. 2.
    Beard JR, Officer A, de Carvalho IA, Sadana R, Pot AM, Michel JP, Lloyd-Sherlock P, Epping-Jordan JE, Peeters G, Mahanani WR, Thiyagarajan JA, Chatterji S. The World report on ageing and health: a policy framework for healthy ageing. Lancet 2016;387:2145–2154. doi: 10.1016/s0140-6736(15)00516-4.CrossRefPubMedGoogle Scholar
  3. 3.
    Clegg A, Young J, Iliffe S, Rikkert MO, Rockwood K. Frailty in elderly people. Lancet 2013;381:752–762. doi: 10.1016/s0140-6736(12)62167-9.CrossRefPubMedGoogle Scholar
  4. 4.
    Hajek A, Bock J-O, Saum K-U, Matschinger H, Brenner H, Holleczek B, Haefeli WE, Heider D, König H-H. Frailty and healthcare costs—longitudinal results of a prospective cohort study. Age Ageing 2017;1–9. doi: 10.1093/ageing/afx157.Google Scholar
  5. 5.
    Dent E, Kowal P, Hoogendijk EO. Frailty measurement in research and clinical practice: A review. Eur J Int Med 2016;31:3–10. doi: CrossRefGoogle Scholar
  6. 6.
    Rockwood K, Song X, MacKnight C, Bergman H, Hogan DB, McDowell I, Mitnitski A. A global clinical measure of fitness and frailty in elderly people. CMAJ 2005;173:489–495. doi: 10.1503/cmaj.050051.CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Collard RM, Boter H, Schoevers RA, Oude Voshaar RC. Prevalence of frailty in community-dwelling older persons: a systematic review. J Am Geriatr Soc 2012;60:1487–1492. doi: 10.1111/j.1532-5415.2012.04054.x.CrossRefPubMedGoogle Scholar
  8. 8.
    Santos-Eggimann B, Cuenoud P, Spagnoli J, Junod J. Prevalence of frailty in middleaged and older community-dwelling Europeans living in 10 countries. J Gerontol A Biol Sci Med Sci 2009;64:675–681. doi: 10.1093/gerona/glp012.CrossRefPubMedGoogle Scholar
  9. 9.
    Marengoni A, Vetrano DL, Manes-Gravina E, Bernabei R, Onder G, Palmer K. The relationship between chronic obstructive pulmonary disease and frailty: a systematic review and meta-analysis of observational studies. 2018;Chest doi: 10.1016/j.chest.2018.02.014.Google Scholar
  10. 10.
    Mukhopadhyay D, Mohanaruban K. Iron deficiency anaemia in older people: investigation, management and treatment. Age Ageing 2002;31:87–91.CrossRefPubMedGoogle Scholar
  11. 11.
    Patel KV, Harris TB, Faulhaber M, Angleman SB, Connelly S, Bauer DC, Kuller LH, Newman AB, Guralnik JM. Racial variation in the relationship of anemia with mortality and mobility disability among older adults. Blood. 2007;109:4663–4670. doi: 10.1182/blood-2006-10-055384.CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Luengo-Fernandez R, Burns R, Leal J. Economic burden of non-malignant blood disorders across Europe: a population-based cost study. Lancet Haematol 3:e371–e378. doi: 10.1016/S2352-3026(16)30061-8.Google Scholar
  13. 13.
    Roy CN. Anemia in frailty. Clin Geriatr Med 2011;27:67–78. doi: 10.1016/j. cger.2010.08.005.CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Liberati A, Altman DG, Tetzlaff J, Mulrow C, Gotzsche PC, Ioannidis JP, Clarke M, Devereaux PJ, Kleijnen J, Moher D. The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate healthcare interventions: explanation and elaboration. BMJ 2009;339:b2700. doi: 10.1136/bmj.b2700.CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Stang A. Critical evaluation of the Newcastle-Ottawa scale for the assessment of the quality of nonrandomized studies in meta-analyses. Eur J Epidemiol 2010;25:603–605. doi: 10.1007/s10654-010-9491-z.CrossRefPubMedGoogle Scholar
  16. 16.
    Zulfiqar AA, Sui Seng X, Gillibert A, Kadri N, Doucet J. Anemia and frailty in the elderly hospitalized in an acute unit: Preliminary results. Eur J Intern Med 2017;38:e8–e9. doi: 10.1016/j.ejim.2016.10.022.CrossRefPubMedGoogle Scholar
  17. 17.
    Liotta G, O’Caoimh R, Gilardi F, Proietti MG, Rocco G, Alvaro R, Scarcella P, Molloy DW, Orlando S, Mancinelli S, Palombi L, Stievano A, Marazzi MC. Assessment of frailty in community-dwelling older adults residents in the Lazio region (Italy): A model to plan regional community-based services. Arch Gerontol Geriatr 2017;68:1–7. doi: 10.1016/j.archger.2016.08.004.CrossRefPubMedGoogle Scholar
  18. 18.
    Leng S, Chaves P, Koenig K, Walston J. Serum interleukin-6 and hemoglobin as physiological correlates in the geriatric syndrome of frailty: a pilot study. J Am Geriatr Soc 2002;50:1268–1271.CrossRefPubMedGoogle Scholar
  19. 19.
    Serra-Prat M, Papiol M, Vico J, Palomera E, Sist X, Cabré M. Factors associated with frailty in community-dwelling elderly population. A cross-sectional study. Eur Geriatr Med 2016;7:531–537. doi: 10.1016/j.eurger.2016.09.005.CrossRefGoogle Scholar
  20. 20.
    Schoufour JD, Echteld MA, Boonstra A, Groothuismink ZM, Evenhuis HM. Biochemical measures and frailty in people with intellectual disabilities. Age Ageing 2016;45:142–148. doi: 10.1093/ageing/afv152.CrossRefPubMedGoogle Scholar
  21. 21.
    Zilinski J, Zillmann R, Becker I, Benzing T, Schulz RJ, Roehrig G. Prevalence of anemia among elderly inpatients and its association with multidimensional loss of function. Ann Hematol 2014;93:1645–1654. doi: 10.1007/s00277-014-2110-4.CrossRefPubMedGoogle Scholar
  22. 22.
    Chang SS, Weiss CO, Xue QL, Fried LP. Patterns of comorbid inflammatory diseases in frail older women: the Women’s Health and Aging Studies I and II. J Gerontol A Biol Sci Med Sci 2010;65:407–413. doi: 10.1093/gerona/glp181.CrossRefPubMedGoogle Scholar
  23. 23.
    Chaves PHM, Semba RD, Leng SX, Woodman RC, Ferrucci L, Guralnik JM, Fried LP. Impact of anemia and cardiovascular disease on frailty status of communitydwelling older women: The Women’s Health and Aging Studies I and II. J Gerontol A Biol Sci Med Sci 2005;729–735.Google Scholar
  24. 24.
    Corona LP, Andrade FCD, Duarte YAD, Lebrao ML. The relationship between anemia, hemoglobin concentration and frailty in Brazilian older adults. J Nutr Health Aging 2015;19:935–940. doi: 10.1007/s12603-015-0502-3.CrossRefGoogle Scholar
  25. 25.
    Juarez-Cedillo T, Basurto-Acevedo L, Vega-Garcia S, Manuel-Apolinar L, Cruz-Tesoro E, Rodriguez-Perez JM, Garcia-Hernandez N, Perez-Hernandez N, Fragoso JM. Prevalence of anemia and its impact on the state of frailty in elderly people living in the community: SADEM study. Ann Hematol 2014;93:2057–2062. doi: 10.1007/s00277-014-2155-4.CrossRefPubMedGoogle Scholar
  26. 26.
    Llibre Jde J, Lopez AM, Valhuerdi A, Guerra M, Llibre-Guerra JJ, Sanchez YY, Bosch R, Zayas T, Moreno C. Frailty, dependency and mortality predictors in a cohort of Cuban older adults, 2003–2011. MEDICC Rev 2014;16:24–30.PubMedGoogle Scholar
  27. 27.
    Lahousse L, Maes B, Ziere G, Loth DW, Verlinden VJA, Zillikens MC, Uitterlinden AG, Rivadeneira F, Tiemeier H, Franco OH, Ikram MA, Hofman A, Brusselle GG, Stricker BH. Adverse outcomes of frailty in the elderly: The Rotterdam Study. Eur J Epidemiol 2014;29:419–427. doi: 10.1007/s10654-014-9924-1.CrossRefPubMedGoogle Scholar
  28. 28.
    Fried LP, Xue QL, Cappola AR, Ferrucci L, Chaves P, Varadhan R, Guralnik JM, Leng SX, Semba RD, Walston JD, Blaum CS, Bandeen-Roche K. Nonlinear multisystem physiological dysregulation associated with frailty in older women: implications for etiology and treatment. J Gerontol A Biol Sci Med Sci 2009;64:1049–1057. doi: 10.1093/gerona/glp076.CrossRefPubMedGoogle Scholar
  29. 29.
    Hirani V, Cumming RG, Blyth F, Naganathan V, Le Couteur DG, Waite LM, Handelsman DJ, Seibel MJ. Cross-sectional and longitudinal associations between the active vitamin D metabolite (1,25 dihydroxyvitamin D) and haemoglobin levels in older Australian men: the Concord Health and Ageing in Men Project. Age 2015;37:1–13. doi: 10.1007/s11357-015-9749-1.CrossRefGoogle Scholar
  30. 30.
    Trevisan C, Veronese N, Maggi S, Baggio G, Toffanello ED, Zambon S, Sartori L, Musacchio E, Perissinotto E, Crepaldi G, Manzato E, Sergi G. Factors Influencing Transitions Between Frailty States in Elderly Adults: The Progetto Veneto Anziani Longitudinal Study. J Am Geriatr Soc 2017;65:179–184. doi: 10.1111/jgs.14515.CrossRefPubMedGoogle Scholar
  31. 31.
    Khandelwal D, Goel A, Kumar U, Gulati V, Narang R, Dey AB. Frailty is associated with longer hospital stay and increased mortality in hospitalized older patients. J Nutr Health Aging 2012;16:732–735. doi: 10.1007/s12603-012-0369-5.CrossRefPubMedGoogle Scholar
  32. 32.
    Jha SR, Hannu MK, Chang S, Montgomery E, Harkess M, Wilhelm K, Hayward CS, Jabbour A, Spratt PM, Newton P, Davidson PM, Macdonald PS. The Prevalence and Prognostic Significance of Frailty in Patients With Advanced Heart Failure Referred for Heart Transplantation. Transplant 2016;100:429–436. doi: 10.1097/tp.0000000000000991.CrossRefGoogle Scholar
  33. 33.
    Jha SR, Ha HS, Hickman LD, Hannu M, Davidson PM, Macdonald PS, Newton PJ. Frailty in advanced heart failure: a systematic review. Heart Fail Rev 2015;20:553–560. doi: 10.1007/s10741-015-9493-8.CrossRefPubMedGoogle Scholar
  34. 34.
    Rohrig G. Anemia in the frail, elderly patient. Clin Interv Aging. 2016;11:319–326. doi: 10.2147/cia.s90727.CrossRefPubMedPubMedCentralGoogle Scholar
  35. 35.
    Nemeth E, Ganz T. Anemia of inflammation. Hematol Oncol Clin North Am 2014;28:671–681, vi. doi: 10.1016/j.hoc.2014.04.005.CrossRefPubMedPubMedCentralGoogle Scholar
  36. 36.
    Soysal P, Stubbs B, Lucato P, Luchini C, Solmi M, Peluso R, Sergi G, Isik AT, Manzato E, Maggi S, Maggio M, Prina AM, Cosco TD, Wu YT, Veronese N. Inflammation and frailty in the elderly: A systematic review and meta-analysis. Ageing Res Rev 2016;31:1–8. doi: 10.1016/j.arr.2016.08.006.CrossRefPubMedGoogle Scholar
  37. 37.
    Zhang X, Meng X, Chen Y, Leng SX, Zhang H. The Biology of Aging and Cancer: Frailty, Inflammation, and Immunity. Cancer J 2017;23:201–205. doi: 10.1097/ppo.0000000000000270.PubMedGoogle Scholar
  38. 38.
    Ben-Hadj-Mohamed M, Khelil S, Ben Dbibis M, Khlifi L, Chahed H, Ferchichi S, Bouajina E, Miled A. Hepatic Proteins and Inflammatory Markers in Rheumatoid Arthritis Patients. Iranian J Public Health 2017;46:1071–1078.Google Scholar
  39. 39.
    Le Calve S, Somme D, Prud’homm J, Corvol A. Blood transfusion in elderly patients with chronic anemia: a qualitative analysis of the general practitioners’ attitudes. BMC Fam Pract 2017;18:76. doi: 10.1186/s12875-017-0647-8.CrossRefPubMedPubMedCentralGoogle Scholar
  40. 40.
    De Franceschi L, Iolascon A, Taher A, Cappellini MD. Clinical management of iron deficiency anemia in adults: Systemic review on advances in diagnosis and treatment. Eur J Intern Med 2017;42:16–23. doi: 10.1016/j.ejim.2017.04.018.CrossRefPubMedGoogle Scholar
  41. 41.
    Simon GI, Craswell A, Thom O, Fung YL. Outcomes of restrictive versus liberal transfusion strategies in older adults from nine randomised controlled trials: a systematic review and meta-analysis. Lancet Haematol 4:e465–e474. doi: 10.1016/S2352-3026(17)30141-2.Google Scholar
  42. 42.
    Ekerstad N, Bylin K, Karlson BW. Early rehospitalizations of frail elderly patients -the role of medications: a clinical, prospective, observational trial. Drug Healthc Patient Saf 2017;9:77–88. doi: 10.2147/dhps.s139237.CrossRefPubMedPubMedCentralGoogle Scholar
  43. 43.
    Palmer K, Marengoni A, Forjaz MJ, Jureviciene E, Laatikainen T, Mammarella F, Muth C, Navickas R, Prados-Torres A, Rijken M, Rothe U, Souchet L, Valderas J, Vontetsianos T, Zaletel J, Onder G. Multimorbidity care model: Recommendations from the consensus meeting of the Joint Action on Chronic Diseases and Promoting Healthy Ageing across the Life Cycle (JA-CHRODIS). Health Policy 2017;doi: 10.1016/j.healthpol.2017.09.006.Google Scholar
  44. 44.
    Onder G, Cesari M, Maggio M, Palmer K. Defining a care pathway for patients with multimorbidity or frailty. Eur J Intern Med 2017;38:1–2. doi: 10.1016/j. ejim.2017.01.013.CrossRefPubMedGoogle Scholar
  45. 45.
    Ng TP, Feng L, Nyunt MS, Larbi A, Yap KB. Frailty in older persons: multisystem risk factors and the Frailty Risk Index (FRI). J Am Med Dir Assoc 2014;15:635–642. doi: 10.1016/j.jamda.2014.03.008.CrossRefPubMedGoogle Scholar
  46. 46.
    Nadruz W, Jr., Kitzman D, Windham BG, Kucharska-Newton A, Butler K, Palta P, Griswold ME, Wagenknecht LE, Heiss G, Solomon SD, Skali H, Shah AM. Cardiovascular Dysfunction and Frailty Among Older Adults in the Community: The ARIC Study. J Gerontol A Biol Sci Med Sci 2017;72:958–964. doi: 10.1093/gerona/glw199.PubMedGoogle Scholar
  47. 47.
    Silva JC, de Moraes ZV, da Silva CA, Mazon SD, Guariento ME, Neri AL, Fattori A. Understanding red blood cell parameters in the context of the frailty phenotype: interpretations of the FIBRA (Frailty in Brazilian Seniors) study. Arch Gerontol Geriatr 2014;59:636–641. doi: 10.1016/j.archger.2014.07.014.CrossRefPubMedGoogle Scholar

Copyright information

© Serdi and Springer-Verlag France SAS, part of Springer Nature 2018

Authors and Affiliations

  • Katie Palmer
    • 1
    • 5
    Email author
  • D. L. Vetrano
    • 2
    • 3
  • A. Marengoni
    • 3
  • A. M. Tummolo
    • 3
  • E. R. Villani
    • 3
  • N. Acampora
    • 3
  • R. Bernabei
    • 3
  • G. Onder
    • 3
  • WP4 of the Joint Action Advantage
    • 4
  1. 1.San Camillo Hospital IRCCSVeniceItaly
  2. 2.Aging Research CenterKarolinska Institutet and Stockholm UniversityStockholmSweden
  3. 3.Department of Geriatrics, Centro Medicina dell’InvecchiamentoUniversità Cattolica del Sacro CuoreMilanItaly
  4. 4.Department of Clinical and Experimental SciencesUniversity of BresciaBresciaItaly
  5. 5.Fondazione Ospedale San Camillo IRCCSVeniceItaly

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