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(Circulation. 2005;112:1121-1127.)
© 2005 American Heart Association, Inc.

Heart Failure

Anemia and Change in Hemoglobin Over Time Related to Mortality and Morbidity in Patients With Chronic Heart Failure

Results From Val-HeFT

Inder S. Anand, MD, FRCP, DPhil; Michael A. Kuskowski, PhD; Thomas S. Rector, PhD; Viorel G. Florea, MD; Robert D. Glazer, MD; Allen Hester, PhD; Yann Tong Chiang, PhD; Nora Aknay, BSc; Aldo P. Maggioni, MD; Cristina Opasich, MD; Roberto Latini, MD; Jay N. Cohn, MD, for the Val-HeFT Investigators

From the VA Medical Center Minneapolis, Minn (I.S.A., M.A.K., T.S.R.); University of Minnesota, Minneapolis (I.S.A., V.G.F., J.N.C.); Novartis Pharmaceuticals Corporation, East Hanover, NJ (R.D.G., A.H., Y.T.C., N.A.); ANMCO Research Center, Florence, Italy (A.P.M.); Ospedale Civile, Udine, Italy (C.O.); and Instituto "Mario Negri," Milano, Italy (R.L.).

Correspondence to Inder S. Anand, MD, FRCP, DPhil (Oxon), VA Medical Center, Cardiology 111-C, One Veterans Dr, Minneapolis, MN 55417. E-mail anand001{at}umn.edu

Received July 21, 2003; de novo received October 8, 2004; revision received May 5, 2005; accepted May 10, 2005.

Background— Anemia is known to be a prognostic marker for patients with heart failure. However, little is known about the prognostic value of changes in hemoglobin (Hgb) over time or about the causes of anemia.

Methods and Results— Retrospective analysis of Valsartan Heart Failure Trial data indicated that the quartile of patients with the biggest average decrease in Hgb over 12 months (from 14.2 to 12.6 g/dL) had significantly (P0.01) increased risk of subsequent hospitalization (hazard ratio [HR], 1.47), morbid events (HR, 1.41), and death (HR, 1.6) compared with the quartile that exhibited little change in Hgb over 12 months (from 13.7 to 13.8 g/dL). Increasing Hgb was significantly associated with lower mortality in patients with (HR, 0.78) and without (HR, 0.79) anemia at baseline. Anemia at baseline and the changes in Hgb were independently associated with serum albumin, blood pressure, glomerular filtration rate, B-type natriuretic peptide, and C-reactive protein. Lack of anemia at baseline and increases in Hgb over 12 months were not associated with smaller left ventricular diameters or higher ejection fractions.

Conclusions— Changes in Hgb over 12 months were inversely associated with subsequent risk of mortality and morbidity, independently of the effects of baseline anemia and other important predictors. Several factors were independently related to anemia at baseline and changes in Hgb, suggesting multiple causes of anemia in patients with heart failure. These findings raise important questions about the optimal level of Hgb in patients with moderate to severe heart failure and how to achieve them.

Key Words: anemia • angiotensin receptor blockers • clinical trials • hemoglobin • natriuretic peptides • norepinephrine • prognosis

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