Validation and potential mechanisms of red cell distribution width as a prognostic marker in heart failure

Abstract

Background: Adverse outcomes have recently been linked to elevated red cell distribution width (RDW) in heart failure. Our study sought to validate the prognostic value of RDW in heart failure and to explore the potential mechanisms underlying this association.

Methods and results: Data from the Study of Anemia in a Heart Failure Population (STAMINA-HFP) registry, a prospective, multicenter cohort of ambulatory patients with heart failure supported multivariable modeling to assess relationships between RDW and outcomes. The association between RDW and iron metabolism, inflammation, and neurohormonal activation was studied in a separate cohort of heart failure patients from the United Investigators to Evaluate Heart Failure (UNITE-HF) Biomarker registry. RDW was independently predictive of outcome (for each 1% increase in RDW, hazard ratio for mortality 1.06, 95% CI 1.01-1.12; hazard ratio for hospitalization or mortality 1.06; 95% CI 1.02-1.10) after adjustment for other covariates. Increasing RDW correlated with decreasing hemoglobin, increasing interleukin-6, and impaired iron mobilization.

Conclusions: Our results confirm previous observations that RDW is a strong, independent predictor of adverse outcome in chronic heart failure and suggest elevated RDW may indicate inflammatory stress and impaired iron mobilization. These findings encourage further research into the relationship between heart failure and the hematologic system.

Fig. 1

Unadjusted relationship of red cell distribution width to ad verse outcomes. Kaplan Meier curves for all-cause mortality (A) and hospitalization or mortality (B) by ranges of red cell distribution width.

Fig. 2

Relationship of red cell distribution width to indices of iron metabolism and inflammation. Association of ranges of red cell distribution width with mean corpuscular volume (A), total iron binding capacity (TIBC) saturation (B), and interleukin (IL)-6 (C). Boxes illustrate the 25th, 50th, and 75th percentiles of the distribution. The mean is given by a square, the median by the horizontal line, and the whiskers extend to the 5th and 95th percentiles.