Comorbidities in Heart Failure: Anaemia
By Piotr Ponikowski, MD, PhD, FESC
Anaemia has been recently recognised as a clinically important comorbid condition, that commonly occurs in the syndrome of chronic heart failure (CHF) (1,2). The estimated prevalence ranges widely from 4 – 61% which may well be explained by a lack of consistent definition of anaemia in CHF (1,2). On the other hand the clinical characteristics of the individual population studied may have an impact, since anaemia prevalence increases with CHF severity, advanced age and concomitant renal disease (1,2).
The origin of anaemia in CHF is multifactorial and the most important potential underlying causes include haemodilution, renal dysfunction, malnutrition, chronic inflammation with proinflammatory cytokine overexpression, impaired bone marrow function, and drug therapy with renin-angiotensin inhibitors (1,2). Anaemia itself can be involved in the pathophysiology of the CHF syndrome by worsening left ventricular function, activating neurohormonal systems, deteriorating already compromised renal function which all lead to further progression of the disease.
In CHF, anaemia of even mild-moderate degree is usually associated with substantially decreased aerobic capacity, subjective experience of fatigue and reduced functional status, all of which result in poor quality of life (1-3). Additionally, reduced haemoglobin levels have been consistently shown to be associated with increased risk of hospitalisations and mortality independently of the other prognosticators (1,2).
Whether anaemia correction may become a therapeutic target in CHF has not yet been established. There are no boundaries of optimal haemoglobin levels in CHF which may guide the therapy and previous studies from non-cardiological settings have revealed conflicting results (1,4). Among potential therapies the use of erythropoietin or its analogues usually together with iron to increase red blood cells production seems to be the most promising option (1,5,6). In the seminal studies by the Silverberg group, long-term treatment with erythropoietin in anaemic patients with advanced CHF resulted in a marked improvement in cardiac function, and CHF symptoms, and reduction in hospitalization (5). Manicni et al. (6) in placebo-controlled study demonstrated that 3-month therapy with erythropoietin significantly enhanced exercise capacity and improved quality of life in CHF patients.
We have recently reported the results of double-blind, randomized, placebo-controlled, multi-center study with darbepoetin alfa, a long-acting erythropoiesis stimulating protein, in symptomatic CHF patients with anaemia. Darbepoetin alfa safely increased haemoglobin levels, improved quality of life and a trend toward an increase in exercise capacity was observed (McDonald K et al., presentation at the HFA Meeting, Lisbon 2005). These results have been confirmed in the other study comprising bigger population of 165 CHF anaemic patients (7).
Relatively high prevalence of functional iron deficiency among CHF patients (reaching up 50-60% of those with anaemia) have been recently shown (8). It may well be that the combination of long-acting erythropoiesis stimulating protein with iron i.v. may become the optimal strategy for anaemia treatment in CHF. However, there is still concern about potential side effects and risks related to such therapy. Future, large studies are now needed to address the question whether correction of anaemia would favourably influence morbidity and mortality in CHF.
References and suggested readings:
- 1. Felker GM, Kirkwood F. Adams KF et al. Anemia as a risk factor and therapeutic target in heart failure. J Am Coll Cardiol 2004;44:959 -966.
- 2. Tang YD, Katz SD. Anemia in chronic heart failure. Prevalence, etiology, clinical correlates and treatment options. Circulation 2006;113:2454-61.
- 3. Falk K, Swedberg K, Gaston-Johansson F et al. Fatigue and anaemia in patients with chornic heart failure. Eur J Heart Failure 2006, May 9 (epub ahead of print)
- 4. Besarab A, Bolton WK, Browne JK, et al. The effects of normal as compared with low hematocrit values in patients with cardiac disease who are receiving hemodialysis and epoetin N Engl J Med 1998;339:584-590.
- 5. Silverberg DS, Wexler D, Sheps D, et al. The effect of correction of mild anemia in severe, resistant congestive heart failure using subcutaneous erythropoietin and intravenous iron: a randomized controlled study J Am Coll Cardiol 2001;37:1775-1780.
- 6. Mancini DM, Katz SD, Lamanca J et al. Effect of erythropoietin on exercise capacity in patients with moderate to severe chronic heart failure Circulation 2003;107:294-299.
- 7. van Veldhuisen DJ, Dickstein K, Cohen-Solal A et al. Randomised, double-blind, placebo-controlled study to evaluate the effect of two dosing regimens of darbepoetin alfa on hemoglobin response and symptoms in patients with heart failure and anemia. J Am Coll Cardiol 2006;47:61A (abstract)
- 8. Opasich C, Cazzola M, Scelsi L et al. Blunted erythropoietin production and defective iron supply for erythropoiesis as major causes of anaemia in patients with chronic heart failure. Eur Heart J 2005;26:2232-2237.