Relation between red blood cell distribution width and ischemic stroke: a case-control study


  • Conflict of interest: None declared.
  • Funding: This study was not supported by any funding.

Correspondence: Jose M. Ramírez-Moreno, Neurology Department, Stroke Unit, Hospital Universitario Infanta Cristina, Avenida de Elvas s/n., 06080 Badajoz, Extremadura, Spain.


Dear Editor

Recent studies have showed an association between higher red blood cell distribution width (RDW) and increased risk of death [1, 2] and cardiovascular disease events [3] in middle-aged and older adults. The aim of this study is to determine the strength of association between RDW levels and ischemic stroke.

A case-control study in a single center was conducted. Two hundred twenty-four consecutive patients suffering a first-ever ischemic stroke confirmed by magnetic resonance imaging (MRI) were included. Two hundred twenty-four randomly selected patients, free of the cerebrovascular disease and from the same population as the cases, were chosen as controls. Baseline RDW was considered as a continuous variable and in quartiles. We use Mantel–Haenszel Test for trend to examine the association between RDW levels and stroke risk. In order to identify determinants of RDW, univariate and multivariate analyses were performed. RDW in cases ranged from 12·27% to 26·17% [mean, 14·48%; standard deviation (SD), 1·76] and in controls ranged from 11·30% to 21·70% (mean, 13·91%; SD, 1·43), P = 0·001. Patients in the fourth quartile (RDW > 14·61%) were significantly more like to have a stroke compared with patients in the lower quartile [RDW < 13·27%, odds ratio (OR) 4·50; 95% confidence interval (CI): 2·50–8·01, P < 0·0001]. After adjusting, there remained a stepwise association between RDW levels and risk of stroke; compared with the lowest quartile of RDW: second quartile, OR 2·5 (95% CI, 1·4–4·6); third quartile, OR 3·2 (95% CI, 1·7–5·9); and four quartile, OR 5·9 (95% CI, 3·1–11·4). The analysis for trend was statistically significant by Mantel–Haenszel Test, reflecting a clear dose–response gradient; higher levels of RDW were associated with increased risk of stroke (Xt = 4·69; P < 0·0001) (Fig. 1). In multivariate linear regression analysis, RDW was significantly associated with age (b = 0·121, P = 0·034), atrial fibrillation (b = 0·148, P = 0·009), cancer (b = 0·103, P = 0·063), and hemoglobin (b = −0·141, P = 0·011).

Figure 1.

Risk of stroke by red blood cell distribution width (RDW) according to Mantel–Haenszel Test. Panel shows odds ratio and 95% confidence intervals (error bars).

Case-control studies can be a very efficient way of identifying an association between an exposure and an outcome. If care is taken with definitions, selection of the controls, and reducing the potential for bias, case-control studies can generate valuable information [4]. Based on this study, RDW is a powerful predictor of stroke. The biological mechanisms underlying this association are not clear [5]. Considering that RDW is an inexpensive test, further research is certainly needed to investigate the potential mechanistic role of RDW in stroke occurrence.