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(Circulation. 2005;112:1743-1747.)
© 2005 American Heart Association, Inc.

Heart Failure

Levels of Hematopoiesis Inhibitor N-Acetyl-Seryl-Aspartyl-Lysyl-Proline Partially Explain the Occurrence of Anemia in Heart Failure

Peter van der Meer, MD; Erik Lipsic, MD; B. Daan Westenbrink, MD; Ruud M.A. van de Wal, MD; Regien G. Schoemaker, PhD; Edo Vellenga, MD; Dirk J. van Veldhuisen, MD; Adriaan A. Voors, MD; Wiek H. van Gilst, PhD

From the Departments of Cardiology (P.v.d.M., E.L., B.D.W., R.v.d.W., A.A.V., D.J.v.V., W.H.v.G.), Hematology (E.V.), and Clinical Pharmacology (W.H.v.G., R.G.S.), University Medical Center Groningen, Groningen, the Netherlands.

Correspondence to P. van der Meer, Hanzeplein 1, 9700 RB Groningen, The Netherlands. E-mail p.van.der.meer{at}thorax.azg.nl

Received March 15, 2005; revision received April 26, 2005; accepted May 31, 2005.

Background— Anemia is common in patients with chronic heart failure (CHF) and is associated with a poor prognosis. However, only a minority of patients with CHF have impaired renal function or underlying hematinic deficiencies. It has been shown that inhibition of the renin-angiotensin system is associated with the development of anemia. The aim of the present study was to determine possible mechanisms linking anemia to renin-angiotensin system activity in CHF patients.

Methods and Results— We initially evaluated 98 patients with advanced stable CHF who were treated with ACE inhibitors (left ventricular ejection fraction, 28±1%; age, 69±1 years; 80% male), 10 of whom had an unexplained anemia (normal hematinics and no renal failure). These 10 anemic patients were matched with 10 nonanemic patients in terms of age and left ventricular ejection fraction. Serum ACE activity was 73% lower in anemic CHF patients compared with nonanemic CHF patients (P=0.018). Moreover, serum of these patients inhibited in vitro the proliferation of bone marrow–derived erythropoietic progenitor cells of healthy donors by 17% (P=0.003). Levels of the hematopoiesis inhibitor N-acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP), which is almost exclusively degraded by ACE, were significantly higher in anemic CHF patients and were clearly correlated to erythroid progenitor cell proliferation (r=–0.64, P=0.001).

Conclusions— Serum ACE activity is markedly lower in anemic CHF patients, and serum of these patients inhibits hematopoiesis. The clear correlation between Ac-SDKP and proliferation of erythroid progenitor cells suggests an inhibitory role of Ac-SDKP on hematopoiesis in CHF patients, which may explain the observed anemia in patients treated with ACE inhibitors.

Key Words: peptides • anemia • angiotensin • heart failure • hematopoiesis

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