Elsevier

American Heart Journal

Volume 158, Issue 4, October 2009, Pages 659-666
American Heart Journal

Clinical Investigation
Congestive Heart Failure
Red cell distribution width in heart failure: Prediction of clinical events and relationship with markers of ineffective erythropoiesis, inflammation, renal function, and nutritional state

https://doi.org/10.1016/j.ahj.2009.07.024Get rights and content

Objectives

The goal of this study was to independently validate the recent observations on the predictive role of red cell distribution width (RDW) for outcomes in chronic heart failure and to provide epidemiologic data on the biological correlates of RDW in heart failure (HF). Understanding the mechanism underlying this observation is unclear, largely hampered by the lack of epidemiologic studies demonstrating factors that are associated with anisocytosis in cardiovascular diseases.

Methods

One hundred ninety-five patients (145 men, 50 women) with systolic HF were enrolled and followed up for a median of 14.5 months. Primary end points were all-cause mortality and hospital readmission due to worsening HF symptoms. A total of 19 clinical chemistry, hematology, and biochemical variables were considered for analysis together with clinical parameters in Cox proportional hazards and multiple regression models.

Results

Red cell distribution width was found to be an N-terminal pro–brain natriuretic peptide independent predictor of all-cause mortality (adjusted HR 1.61 per 1 SD increase) in our study. Multiple correlations between biomarkers of ineffective erythropoiesis (serum iron, ferritin, and soluble transferrin receptor levels), inflammation and acute-phase reaction (interleukin-6, soluble tumor necrosis factor (TNF) receptor I and soluble TNF receptor II, C-reactive protein, and prealbumin concentrations), undernutrition (total cholesterol and albumin levels), and renal function were observed. In the multiple regression model, the strongest relationship for RDW was obtained with soluble transferrin receptor, soluble TNF receptor I, soluble TNF receptor II, and total cholesterol.

Conclusions

Here we validate the strong, independent prediction of morbidity and mortality in HF by RDW. The described correlations between RDW and inflammation, ineffective erythropoiesis, undernutrition, and impaired renal function may facilitate the understanding why this marker is associated with adverse outcomes in HF.

Section snippets

Patient population

The study was carried out in accordance with the Helsinki Declaration at the 3rd Department of Internal Medicine, Semmelweis University, based on a study protocol approved by the highest Ethical Committee of Hungary. Consecutive patients with clinical suspicion of congestive heart failure (CHF) referred to transthoracic echocardiography were considered for inclusion. All patients with <45% left ventricular ejection fraction who provided written informed consent were included independently of

Population characteristics

Baseline characteristics of the patient population are presented in Table I. All of the patients had left ventricular systolic dysfunction (left ventricular ejection fraction <45%), while New York Heart Association (NYHA) class ranged from I to IV. Nineteen clinical chemistry, biochemical, or hematology variables were considered as potential covariates or predictors of outcome (listed in Table II). To rule out bias by duration of follow-up and to better reflect the association of the predictors

Discussion

This is the first observational prospective study independently validating the original observations of Felker et al9 on the prognostic value of red cell distribution width in patients with chronic heart failure. This finding was observed in a prospective cohort of unselected patients with chronic heart failure characterized by left ventricular systolic dysfunction. Primary outcomes in this study were rehospitalization due to worsening of HF symptoms and/or all-cause mortality. In the final

Acknowledgements

We thank our patients who agreed to participate in this study. We thank Donald Silverberg for critical reading of the manuscript. The skillful technical assistance of Holeczky Rudolfné, Szigeti Antalné, Korponai Gézáné, Piroska Sturmann, and Márta Kókai is acknowledged with many thanks.

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