Red Cell Distribution Width as a Biomarker for Heart Failure: Still Not Ready for Prime-Time

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Disclosure
The authors have no conflicts of interest to declare.
Correspondence
Sunil Nadar, Department of Medicine, Sultan Qaboos University Hospital, PO Box 31, Al Khoudh, Muscat 123, Oman. E: sunilnadar@gmail.com
Received date
04 November 2019
Accepted date
04 November 2019
DOI
https://doi.org/10.15420/cfr.2019.16.1
Open access
This work is open access under the CC-BY-NC 4.0 License which allows users to copy, redistribute and make derivative works for non-commercial purposes, provided the original work is cited correctly.

Dear Editor,

We would like to thank García-Escobar and Ingelmo for their letter regarding our article on the use of biomarkers in routine clinical care for heart failure.1,2 It was with interest that we read their comments on the use of red cell volume distribution width (RDW) as another biomarker for use in the management of patients with heart failure. As mentioned in their letter, RDW is a measure of heterogeneity of red blood cell (RBC) volume or anisocytosis and not a measure of RBC size or volume itself.3 RDW is a number generated by automated blood count machines. Increased variations in RBC volume – that is, a high RDW, is seen in anaemic states (such as iron deficiency anaemia, sickle cell anaemia, thalassaemia and megaloblastic anaemia), in patients using chemotherapeutic agents, in cardiovascular disease, thyroid disease and myelodysplastic syndromes.3

There has been a considerable amount of research into the use of RDW to assess prognosis in various conditions, given that this variable is readily available. García-Escobar and Ingelmo have extensively reviewed this possibility in their letter. They have also analysed the various studies on RDW and heart failure. We agree that data support the use of RDW as a marker of prognosis in patients with heart failure, other cardiovascular diseases and stroke.4–6 There are various mechanisms that may be involved that could explain how RDW predicts mortality. RDW is a surrogate for iron deficiency and other forms anaemia7 that are known to be associated with a poorer prognosis in heart failure.8 In addition to this, there are correlations between high RDW and inflammation, ineffective erythropoiesis, undernutrition and impaired renal function in patients with heart failure.9 RDW is also a marker of hypoxaemia.10 Patients who are sicker on presentation due to systemic inflammation, chronic anaemia, hypoxia and impaired renal function might therefore have a higher RDW due to the various processes coexisting alongside their heart failure. RDW is thus not a specific test for heart failure but is a non-specific surrogate for the various pathogenetic mechanisms that occur in heart failure or indeed any other chronic disease.11–13 RDW therefore cannot be used for the diagnosis of heart failure and as yet there are no studies demonstrating its role in this capacity.

Similarly, there are limited data that can be used to assess the changes that occur in RDW as a result of treatment for heart failure14 and pulmonary embolism.15 The studies to date are small and the one on heart failure is retrospective. The lifespan of RBCs is 100–120 days and it would probably take this long for the RDW to show any significant change. Indeed, after the successful treatment of iron deficiency anaemia with iron supplements, studies have shown that it takes up to 3 months for the RDW to come down to reference levels.16 Extrapolating this to patients with heart failure, a raised RDW might indicate a process that was prevalent up to 3 months prior to the patient’s presentation, rather than reflecting an acute issue.

In conclusion, we would like to state that RDW is a marker of a chronic disease process and is not specific to heart failure. It appears to predict prognosis in patients with heart failure. Currently, there are no trials showing what specific cut-off values would reflect worse prognosis, we only have studies showing correlations of higher values (even within normal reference ranges) with worse prognosis. We cannot recommend what course of action a treating clinician should take when presented with a RDW value for a patient with heart failure as there are insufficient data. Therefore, although a great research tool, we cannot at present recommend the use of RDW in routine clinical practice.

References
  1. García-Escobar A, Ingelmo JM. Red cell volume distribution width as another biomarker. Card Fail Rev 2019;5:176–9.
    Crossref
  2. Nadar SK, Shaikh MM. Biomarkers in routine heart failure clinical care. Card Fail Rev 2019;5:50–6.
    Crossref | PubMed
  3. Evans TC, Jehle D. The red blood cell distribution width. J Emerg Med 1991;9 Suppl 1:71–4.
    PubMed
  4. Felker GM, Allen LA, Pocock SJ, et al. Red cell distribution width as a novel prognostic marker in heart failure: data from the CHARM Program and the Duke Databank. J Am Coll Cardiol 2007;50:40–7.
    Crossref | PubMed
  5. Tonelli M, Sacks F, Arnold M, et al. Relation between red blood cell distribution width and cardiovascular event rate in people with coronary disease. Circulation 2008;117:163–8.
    Crossref | PubMed
  6. Ani C, Ovbiagele B. Elevated red blood cell distribution width predicts mortality in persons with known stroke. J Neurol Sci 2009;277:103–8.
    Crossref | PubMed
  7. Demir A, Yarali N, Fisgin T, et al. Most reliable indices in differentiation between thalassemia trait and iron deficiency anemia. Pediatr Int 2002;44:612–6.
    Crossref | PubMed
  8. Beedkar A, Parikh R, Deshmukh P. Heart failure and the iron deficiency. J Assoc Physicians India 2017;65:79–80.
    PubMed
  9. Förhécz Z, Gombos T, Borgulya G, et al. Red cell distribution width in heart failure: prediction of clinical events and relationship with markers of ineffective erythropoiesis, inflammation, renal function, and nutritional state. Am Heart J 2009;158:659–66.
    Crossref | PubMed
  10. Ycas JW, Horrow JC, Horne BD. Persistent increase in red cell size distribution width after acute diseases: A biomarker of hypoxemia? Clin Chim Acta 2015;448:107–17.
    Crossref | PubMed
  11. Pehlivanlar KM, Oztuna F, Abul Y, et al. Prognostic value of red cell distribution width and echocardiographic parameters in patients with pulmonary embolism. Adv Respir Med 2019;87:69–76.
    Crossref | PubMed
  12. Shi C, Xie M, Li L, et al. The association and diagnostic value of red blood cell distribution width in colorectal cancer. Medicine (Baltimore) 2019;98:e15560.
    Crossref | PubMed
  13. Wang H, Wang J, Huang R, et al. Red blood cell distribution width for predicting significant liver inflammation in patients with autoimmune hepatitis. Eur J Gastroenterol Hepatol 2019;98:e15560.
    Crossref | PubMed
  14. Muhlestein JB, Lappe DL, Anderson JL, et al. Both initial red cell distribution width (RDW) and change in RDW during heart failure hospitalization are associated with length of hospital stay and 30-day outcomes. Int J Lab Hematol 2016;38:328–37.
    Crossref | PubMed
  15. Yazici S, Kiris T, Sadik CU, et al. Relation between dynamic change of red cell distribution width and 30-day mortality in patients with acute pulmonary embolism. Clin Respir J 2018;12:953–60.
    Crossref | PubMed
  16. Akarsu S, Taskin E, Yilmaz E, et al. Treatment of iron deficiency anemia with intravenous iron preparations. Acta Haematol 2006;116:51–7.
    Crossref | PubMed