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European Journal of Epidemiology

, Volume 29, Issue 7, pp 489–498 | Cite as

Anemia in the general population: prevalence, clinical correlates and prognostic impact

  • Andreas MartinssonEmail author
  • Charlotte Andersson
  • Pontus Andell
  • Sasha Koul
  • Gunnar Engström
  • J. Gustav Smith
HEMATOLOGY

Abstract

Low hemoglobin concentration is associated with increased mortality, but there is disagreement with regard to the clinical definition of anemia. We aimed to evaluate the prevalence, clinical correlates and association with total and cause-specific long-term mortality across the hemoglobin distribution and for previously proposed definitions of anemia. Blood hemoglobin concentration and mean corpuscular volume was measured in participants of the Malmö diet and cancer study—a prospective cohort study, and related to baseline characteristics and outcomes during follow-up. Primary endpoints were all-cause mortality, cardiovascular mortality and cancer-related mortality. A U-shaped association of hemoglobin with total mortality was observed in spline regression analyses, with nadir at hemoglobin 150 g/L among men and 130 g/L among women. Mortality increased steeply with more strict definitions of anemia, hazard ratio: 1.36, 1.94 and 2.16 for hemoglobin <140/130 (men/women), 132/122 and 130/120 g/L, respectively. Similar trends were seen for both cancer- and cardiovascular mortality. The incidence of coronary disease and cancer did not differ across groups. Erythrocyte volume was an independent predictor of mortality, with the highest mortality observed for macrocytic anemia, which was less prevalent than microcytic and normocytic anemia. Dietary intake of iron and vitamin B12 were significantly lower and use of antithrombotic medications was significantly higher in subjects with anemia. The World Health Organisation definition of anemia was associated with increased mortality (hazard ratio 2.16) but excess mortality was also observed at higher hemoglobin levels. Of morphological subtypes, anemia with macrocytosis was rare but associated with the highest mortality.

Keywords

Anemia Epidemiology Mean-corpuscular volume Hemoglobin 

Notes

Acknowledgments

The Malmö Diet and Cancer study was made possible by grants from the Swedish Cancer Society, the Swedish Medical Research Council, the Swedish Dairy Association, the Albert Påhlsson and Gunnar Nilsson Foundations and the Malmö city council. J.G.S. was supported by the Swedish Heart–Lung Foundation, governmental funding of clinical research within the Swedish National Health Service, the Ulla Ekdahl foundation, the Thorsten Westerström foundation and Skåne University Hospital in Lund.

Conflict of interest

The authors declare no competing interests. All individuals provided written, informed consent. The regional ethics committee approved of the study.

Supplementary material

10654_2014_9929_MOESM1_ESM.doc (274 kb)
Supplementary material 1 (DOC 273 kb)

References

  1. 1.
    Penninx BW, Pahor M, Cesari M, et al. Anemia is associated with disability and decreased physical performance and muscle strength in the elderly. J Am Geriatr Soc. 2004;52(5):719–24.PubMedCrossRefGoogle Scholar
  2. 2.
    Thomas DR. Anemia and quality of life: unrecognized and undertreated. J Gerontol A Biol Sci Med Sci. 2004;59(3):238–41.PubMedCrossRefGoogle Scholar
  3. 3.
    Hamm CW, Bassand J-P, Agewall S, et al. ESC guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation. Eur Heart J. 2011;32(23):2999–3054.PubMedCrossRefGoogle Scholar
  4. 4.
    Ezekowitz JA, McAlister FA, Armstrong PW. Anemia is common in heart failure and is associated with poor outcomes: insights from a cohort of 12065 patients with new-onset heart failure. Circulation. 2003;107(2):223–5.PubMedCrossRefGoogle Scholar
  5. 5.
    Sabatine MS, Morrow DA, Giugliano RP, et al. Association of hemoglobin levels with clinical outcomes in acute coronary syndromes. Circulation. 2005;111(16):2042–9.PubMedCrossRefGoogle Scholar
  6. 6.
    Bolińska S, Sobkowicz B, Zaniewska J, et al. The significance of anaemia in patients with acute ST-elevation myocardial infarction undergoing primary percutaneous coronary intervention. Kardiologia Polska. 2011;69(1):33–9.PubMedGoogle Scholar
  7. 7.
    Caro JJ, Salas M, Ward A, Goss G. Anemia as an independent prognostic factor for survival in patients with cancer: a systemic, quantitative review. Cancer. 2001;91(12):2214–21.PubMedCrossRefGoogle Scholar
  8. 8.
    Winther SA, Finer N, Sharma AM, Torp-Pedersen C, Andersson C. Association of anemia with the risk of cardiovascular adverse events in overweight/obese patients. Int J Obes (Lond). Prepublished on Jun 18 2013. doi: 10.1038/ijo.2013.111.
  9. 9.
    World Health Organisation. Hemoglobin concentrations for the diagnosis of anaemia and assessment of severity. Geneva: World Health Organization; 2011.Google Scholar
  10. 10.
    World Health Organisation. Nutritional anaemias. Report of a WHO Scientific Group. Geneva: World Health Organisation; 1968.Google Scholar
  11. 11.
    Beutler E, Waalen J. The definition of anemia: what is the lower limit of normal of the blood hemoglobin concentration? Blood. 2006;107(5):1747–50.PubMedCentralPubMedCrossRefGoogle Scholar
  12. 12.
    Culleton BF, Manns BJ, Zhang J, Tonelli M, Klarenbach S, Hemmelgarn BR. Impact of anemia on hospitalization and mortality in older adults. Blood. 2006;107(10):3841–6.PubMedCrossRefGoogle Scholar
  13. 13.
    Izaks GJ, Westendorp RGJ, Knook DL. The definition of anemia in older persons. JAMA. 1999;281(18):1714–7.PubMedCrossRefGoogle Scholar
  14. 14.
    Berglund G, Elmstähl S, Janzon L, Larsson SA. The Malmo diet and cancer study. Design and feasibility. J Intern Med. 1993;233(1):45–51.PubMedCrossRefGoogle Scholar
  15. 15.
    Smith JG, Platonov PG, Hedblad B, Engström G, Melander O. Atrial fibrillation in the Malmö diet and cancer study: a study of occurrence, risk factors and diagnostic validity. Eur J Epidemiol. 2010;25(2):95–102.PubMedCrossRefGoogle Scholar
  16. 16.
    Riboli E, Elmstahl S, Saracci R, Gullberg B, Lindgarde F. The Malmo food study: validity of two dietary assessment methods for measuring nutrient intake. Int J Epidemiol. 1997;26(Suppl 1):161–73.CrossRefGoogle Scholar
  17. 17.
    Wirfalt E, Mattisson I, Johansson U, Gullberg B, Wallstrom P, Berglund G. A methodological report from the Malmo diet and cancer study: development and evaluation of altered routines in dietary data processing. Nutr J. 2002;1:3.PubMedCentralPubMedCrossRefGoogle Scholar
  18. 18.
    Ericson UC, Ivarsson MI, Sonestedt E, et al. Increased breast cancer risk at high plasma folate concentrations among women with the MTHFR 677T allele. Am J Clin Nutr. 2009;90(5):1380–9.PubMedCrossRefGoogle Scholar
  19. 19.
    Manjer J, Carlsson S, Elmståhl S, Gullberg B, Janzon L, Lindström M, Mattisson I, Berglund G. The Malmö diet and cancer study: representativity, cancer incidence and mortality in participants and non-participants. Eur J Cancer Prev. 2001;10(6):489–99.PubMedCrossRefGoogle Scholar
  20. 20.
    Ludvidgsson JF, Otterblad-Olausson P, Pettersson BU, Ekbom A. The Swedish personal identity number: possibilities and pitfalls in healthcare and medical research. Eur J Epidemiol. 2009;24(11):659–67.CrossRefGoogle Scholar
  21. 21.
    Johansson LA, Westerling R. Comparing Swedish hospital discharge records with death certificates: implications for mortality statistics. Int J Epidemiol. 2000;29(3):495–502.PubMedCrossRefGoogle Scholar
  22. 22.
    Ludvigsson JF, Andersson E, Ekbom A, et al. External review and validation of the Swedish national inpatient register. BMC Public Health. 2011;11:450.PubMedCentralPubMedCrossRefGoogle Scholar
  23. 23.
    Dödsorsakstatistik—Historik, metoder och tillförlitlighet. Socialstyrelsen. http://www.socialstyrelsen.se/Lists/Artikelkatalog/Attachments/18019/2010-4-33.pdf (14 May 2014).
  24. 24.
    Johansson LA, Björkenstam C, Westerlin R. Unexplained differences between hospital and mortality data indicated mistakes in death certification: an investigation of 1,094 deaths in Sweden during 1995. J Clin Epidemiol. 2009;62(11):1202–9.PubMedCrossRefGoogle Scholar
  25. 25.
    Kvalitet och innehåll i patientregistret: Utskrivningar från 1964–2007 och besök i specialiserad öppenvård (exklusive primärvårdsbesök) 1997-2007. Socialstyrelsen. http://www.socialstyrelsen.se/Lists/Artikelkatalog/Attachments/8306/2009-125-15_200912515_rev2.pdf (14 May 2014).
  26. 26.
    Valente S, Lazzeri C, Chiostri M, Sori A, Giglioli C, Gensini GF. Prior and new onset anemia in ST-elevation myocardial infarction: a different prognostic role? Intern Emerg Med. 2011;6(4):329–36.PubMedCrossRefGoogle Scholar
  27. 27.
    Aslina F, Mazza JJ, Yale SH. Megaloblastic anemia and other causes of macrocytosis. Clin Med Res. 2006;4(3):236–41.CrossRefGoogle Scholar
  28. 28.
    Beyer I, Compté N, Busuioc A, Cappelle S, Lanoy C, Cytryn E. Anemia and transfusions in geriatric patients: a time for evaluation. Hematology. 2010;15(2):116–21.PubMedCrossRefGoogle Scholar
  29. 29.
    Wu W-C, Rathore SS, Wang Y, Radford MJ, Krumholz HM. Blood transfusion in elderly patients with acute myocardial infarctions. N Engl J Med. 2001;345(17):1230–6.PubMedCrossRefGoogle Scholar
  30. 30.
    Marik PE, Corwin HL. Efficacy of red blood cell transfusion in the critically ill: a systematic review of the literature. Crit Care Med. 2008;36(9):2667–74.PubMedCrossRefGoogle Scholar
  31. 31.
    Mancini DM, Katz SD, Lang CC, LaManca J, Hudaihed A, Androne AS. Effect of erythropoietin on exercise capacity in patients with moderate to severe chronic heart failure. Circulation. 2003;107(2):294–9.PubMedCrossRefGoogle Scholar
  32. 32.
    Silverberg DS, Wexler D, Blum M, et al. The use of subcutaneous erythropoietin and intravenous iron for the treatment of the anemia of severe, resistant congestive heart failure improves cardiac and renal function and functional cardiac class, and markedly reduces hospitalizations. J Am Coll Cardiol. 2000;35(7):1737–44.PubMedCrossRefGoogle Scholar
  33. 33.
    Skali H, Parving H-E, Parfrey PS, et al. Stroke in patients with type 2 diabetes mellitus, chronic kidney disease, and anemia treated with Darbepoetin Alfa. Circulation. 2011;124(25):2903–8.PubMedCrossRefGoogle Scholar
  34. 34.
    Goddard AF, James MW, McIntyre AS, Scott BB. Guidelines for the management of iron deficiency anaemia. Gut. 2000;46(Suppl IV):iv1–iv5.Google Scholar
  35. 35.
    Mahoney DH Jr. Anemia in at-risk populations—what should be our focus? Am J Clin Nutr. 2008;88(6):1457–8.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media Dordrecht 2014

Authors and Affiliations

  • Andreas Martinsson
    • 1
    Email author
  • Charlotte Andersson
    • 2
    • 3
  • Pontus Andell
    • 1
  • Sasha Koul
    • 1
  • Gunnar Engström
    • 4
  • J. Gustav Smith
    • 1
    • 3
    • 4
  1. 1.Department of Cardiology, Clinical SciencesLund UniversityLundSweden
  2. 2.Department of CardiologyCopenhagen University Hospital GentofteHellerupDenmark
  3. 3.Department of Clinical Sciences, Clinical Research CentreSkåne University HospitalMalmöSweden
  4. 4.Cardiovascular Epidemiology, Faculty of MedicineLund UniversityMalmöSweden

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