Red cell distribution width, C-reactive protein, the complete blood count, and mortality in patients with coronary disease and a normal comparison population

Abstract

Background

Red cell distribution width (RDW) is associated with morbidity and mortality in coronary artery disease (CAD), but the connection of RDW with chronic inflammation is equivocal.

Methods

In 1,489 patients with CAD and 8.4–15.2 years of follow-up all-cause mortality and RDW were studied using Cox regression. RDW and its associations with inflammation, liver function, renal function, and body mass were assessed. A population of 449 normal (No-CAD) patients also was evaluated.

Results

RDW predicted all-cause mortality in a step-wise manner (HR = 1.37 per quintile; 95% CI = 1.29, 1.46; p-trend < 0.001). A significant but meaningless correlation between RDW and high-sensitivity C-reactive protein (hsCRP) was identified (r = 0.181; p < 0.001). With full adjustment, RDW remained significant (p-trend < 0.001) and the strongest predictor of mortality among all factors included in the model. RDW also strongly predicted all-cause mortality in the normal control population (HR = 1.33 per quintile, CI = 1.15, 1.55; p-trend < 0.001), but hsCRP did not predict mortality among normal controls.

Conclusions

RDW was associated with mortality in patients with CAD and may provide clinically useful prognostication. Although RDW was correlated with hsCRP, they were independent predictors of mortality. RDW has been incorporated into risk prediction tool using data from basic chemistries available at: http://intermountainhealthcare.org/IMRS.

Introduction

The red cell distribution width (RDW) is a readily-available measure of the degree of variation in erythrocyte volume. It is a component of the complete blood count (CBC) and is calculated as a percentage of the standard deviation of the red cell volume divided by the mean corpuscular volume (MCV). Traditionally RDW has been used to differentiate types of anemia; specifically identifying iron-deficiency anemia. However, prior work showed that RDW predicts mortality in patients with coronary artery disease (CAD) [1]. Subsequently it was shown that, independent of hemoglobin or hematocrit, an elevated RDW was associated with increased mortality risk in acute heart failure (HF) patients [2] and in a small population with chronic HF [3]. One study found an elevated RDW to have a stronger association with morbidity and mortality in HF patients than all studied predictors other than age [4]. The RDW associations of Anderson et al. [1] were subsequently confirmed and extended among CAD patients [5] and general medical patients and a general population from NHANES III [6]. Additionally, RDW is associated with elevated troponin levels in patients with acute coronary syndromes and with worse outcomes in patients undergoing percutaneous coronary intervention [7], [8]. RDW also predicts left ventricular ejection fraction (LVEF), HF diagnosis, and readmission for HF among CAD patients, and incident HF among HF-free general cardiovascular patients [9].

Despite these associations, the mechanisms underlying elevated RDW remain unknown. The notion that chronic inflammation may cause RDW elevation is supported by a study of unselected patients in which RDW was correlated with both the erythrocyte sedimentation rate and C-reactive protein (CRP) [10]. In contrast, preliminary evidence from a very small population (N = 226) suggests that this relationship may not exist in cardiovascular disease [11], but mortality outcomes were not studied therein. Another very small study (N = 195) that focused only on chronic HF patients indicated that RDW and CRP independently predict mortality [3]. The relationships between RDW, CRP, and mortality have not been evaluated in a large, general CAD patient population or among individuals free from HF and CAD.