Levels of Hematopoiesis inhibitor N-acetyl-seryl-aspartyl-lysyl-proline partially explain the occurrence of anemia in heart failure

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.