Red cell distribution width, C-reactive protein, the complete blood count, and mortality in patients with coronary disease and a normal comparison population☆
Highlights
► Red cell distribution width (RDW) is associated with mortality in CAD patients. ► The etiology of RDW elevation is unknown. ► Elevation of RDW is not due to chronic inflammation as measured by hsCRP. ► RDW is also associated with mortality in controls and is not a coronary disease-specific or heart failure-specific marker. ► Despite an unknown pathophysiology, elevated RDW is a strong predictor of mortality.
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.
Section snippets
Study population
Patients enrolled in the catheterization laboratory registry of the Intermountain Heart Collaborative Study between October, 1993 and August, 2000 were included if they had a baseline CBC, high-sensitivity (hs) CRP, and angiographically-documented CAD (N = 1,489). This study was approved by the Intermountain Healthcare Institutional Review Board.
Coronary angiography was performed for clinical purposes and CAD prospectively assessed as normal (0% to < 10% stenosis), mild/moderate (10% to < 70%
Results
Baseline characteristics for CAD patients are provided in Table 1, stratified by median RDW of 13.0%. Patients with an elevated RDW were slightly older on average and more likely to have hypertension, diabetes, a prior cardiovascular event, and worse renal function. As has been reported previously, patients with an impaired LVEF had a higher RDW. Corresponding with the higher burden of comorbidities, patients with an elevated RDW were more often medically managed for their CAD then patients
Discussion
Among a large CAD patient population, elevated RDW was associated with a strong graded risk of mortality. Even after adjusting for standard and clinical risk factors, an elevated RDW remained a significant independent risk factor for mortality over an average follow-up period of approximately 10 years. Among a CAD-free comparison population, RDW was also independently associated with mortality.
Although hsCRP is known to predict mortality in CAD patients [11], this is the first report of a
Acknowledgments
This work was supported by Internal Institutional funds.
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Clinical trial registration: database registry of the Intermountain Heart Collaborative Study: NCT00406185 (ClinicalTrials.gov).