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CLINICAL RESEARCH

Red Cell Distribution Width as a Novel Prognostic Marker in Heart Failure

Data From the CHARM Program and the Duke Databank

G. Michael Felker, MD, MHS, FACC^_*,_*, Larry A. Allen, MD^_*, Stuart J. Pocock, PhD, Linda K. Shaw, MS^_*, John J.V. McMurray, MD, FACC, Marc A. Pfeffer, MD, PhD, FACC, Karl Swedberg, MD, PhD, FACC^||, Duolao Wang, PhD, Salim Yusuf, DPhil, FACC^¶, Eric L. Michelson, MD, FACC^#, Christopher B. Granger, MD, FACC^_* for the CHARM Investigators

^_* Duke Clinical Research Institute, Durham, North Carolina
London School of Hygiene and Tropical Medicine, London, United Kingdom
University of Glasgow, Glasgow, United Kingdom
Brigham and Women's Hospital, Boston, Massachusetts
^|| Department of Medicine, Sahlgrenska University Hospital/Östra, Göteburg, Sweden
^¶ McMaster University, Hamilton, Ontario, Canada;
^# AstraZeneca LP, Wilmington, Delaware. The CHARM program was funded by AstraZeneca. Drs. Pfeffer, Swedberg, McMurray, Yusuf, Granger, and Pocock have served as consultants to or received research grants and honoraria from AstraZeneca. Dr. Michelson is an employee of AstraZeneca

Manuscript received January 9, 2007; revised manuscript received February 23, 2007, accepted February 25, 2007.

^_* Reprint requests and correspondence: Dr. G. Michael Felker, Duke Clinical Research Institute, 2400 Pratt Street, Room 0311 Terrace Level, DUMC Box 3850, Durham, North Carolina 27715 (Email: michael.felker{at}duke.edu).

Objectives: The goal of this study was to identify potentially novel laboratory markers of risk in chronic heart failure patients.

Background: Although a variety of prognostic markers have been described in heart failure, a systematic assessment of routine laboratory values has not been reported.

Methods: All 2,679 symptomatic chronic heart failure patients from the North American CHARM (Candesartan in Heart Failure: Assessment of Reduction in Mortality and Morbidity) program had a wide range of laboratory measures performed at a core facility, enabling us to assess the relationship between routine blood tests and outcomes using a Cox proportional hazards model. We then replicated our findings in a cohort of 2,140 heart failure patients from the Duke Databank.

Results: Among 36 laboratory values considered in the CHARM program, higher red cell distribution width (RDW) showed the greatest association with morbidity and mortality (adjusted hazard ratio 1.17 per 1-SD increase, p < 0.001). Higher RDW was among the most powerful overall predictors, with only age and cardiomegaly showing a better independent association with outcome. This finding was replicated in the Duke Databank, in which higher RDW was strongly associated with all-cause mortality (adjusted hazard ratio 1.29 per 1 SD, p < 0.001), second only to age as a predictor of outcome.

Conclusions: In 2 large contemporary heart failure populations, RDW was found to be a very strong independent predictor of morbidity and mortality. Understanding how and why this marker is associated with outcome may provide novel insights into heart failure pathophysiology.

Abbreviations and Acronyms   ACE = angiotensin-converting enzyme   HR = hazard ratio   NYHA = New York Heart Association   RDW = red cell distribution width

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