Acute ischemic stroke (AIS) is a leading cause of disability and mortality worldwide [1]. Clinical trials have proved that endovascular treatment (EVT) improves functional outcomes for large arterial occlusion patients regardless of prior intravenous thrombolysis (IVT) [2, 3, 4]. The patient’s prognosis with similar characteristics may differ substantially. Indeed, futile recanalization, defined as poor clinical outcome despite early recanalization of an occluded artery, remains a significant challenge [5]. It could be associated to microvascular injury, poor collateral circulation and brain autoregulation [6].

As the peripheral blood index, red cell distribution width (RDW) is well-known to be a risk marker for vessel wall injury and cardiovascular disease [7, 8]. Increased RDW correlates with increased risk for carotid atherosclerosis, which in turn promotes the incidence of stroke [9]. High RDW was found to be related to unfavorable outcomes in AIS patients [10]. So far, the relationship between poor outcome and RDW in AIS patients through complete recanalization remains unclear [11]. Therefore, this work aims to study whether RDW could be a risk indicator for futile recanalization in AIS patients following EVT.

Following excluding 23 patients, the present work had 188 subjects (Fig. 1), with 70 median years old (IQR 60–77), while 39.4% were female patients. The mean RDW value was 13.0 $\pm$ 1.26. The median baseline NIHSS score was 16 (IQR 10–19). Almost 51.9 % (86/188) had good collateral flow (ASPECTS 8-10) to a certain degree [20]. The sites of obstruction including: ICA in 66 patients (35.1%), ICA-T in 4 patients (2.1%), MCA M1 in 86 patients (45.7%), MCA M2 in 31 patients (16.5%), and ACA in 1 patient (0.5%). Overall, 111 out of 188 (59.0%) patients finally had poor functional outcome at 3 months. All patients’ clinical and baseline characteristics are given below in Table 1.

Fig. 1.

Flowchart of inclusion and exclusion.

Age (p = 0.017), ASPECTS 8-10 (p 0.001), the NIHSS score (p 0.001), and HT (p 0.001), as well as the subtype of stroke (p = 0.012), were all substantially different when comparing the two groups. In comparison with the significant recanalization group, the futile recanalization patients exhibited higher systolic blood pressure (p = 0.007), blood glucose (p = 0.011), and RDW value (13.4 $\pm$ 1.33 vs 12.5 $\pm$ 0.72; p 0.001). The OTR time was not substantially associated with a 3-month futile recanalization (p = 0.591).

The binary logistic regression analyses included variables with a p 0.05 in the univariate analysis, as shown in Table 2. Systolic blood pressure (odds ratio (OR), 1.028; 95% confidence interval (CI), 1.008–1.049; p = 0.028), hemorrhagic transformation (OR, 5.701; 95% CI, 1.991–16.324; p = 0.001), NIHSS score (OR, 1.106; 95% CI, 1.017–1.203; p = 0.019), ASPECTS 8–10 (OR, 0.045; 95% CI, 0.016–0.128; p 0.001) were all important risk factors. The higher RDW (OR = 5.233, 95% CI: 2.656–10.307, p 0.001) patients, even after complete recanalization, there is a considerably increased probability of a poor 3-month outcome.

As shown with ROC analysis (Fig. 2), the RDW was found as a respective predictor of futile recanalization, having an AUC of 0.798 and an optimal cut-off value of 13.25 (specificity 87% and sensitivity 60%). Variables discovered through regression analysis were incorporated into an integrated model. The combined model had a significantly higher AUC compared with the RDW alone model (0.944 vs 0.798; p 0.001). Thus, it was more effective significantly.

Fig. 2.

ROC curve of RDW-combined, without RDW and RDW alone model.

The clinical impact of EVT in treating AIS patients has been documented; however, not all fully recanalized patients will be capable of achieving premorbid functionality. Futile recanalization eventually brings physical disability as well as broader pressure to stroke survivors. The prediction of recanalization is pivotal to select patients prior to EVT. In clinical settings, RDW is a readily available and easily assessed blood parameter. Several studies have linked higher RDW levels with ischemic stroke morbidity and mortality [21, 22, 23]. In addition, recent investigations have revealed the importance of RDW as a risk marker of long-term survival in AIS patients receiving IVT [24]. In our prior study, we observed the association between RDW and the 1-year prognosis of anterior circulation ischemic stroke patients following EVT, yet, the respect to futile recanalization remains unclear.

This retrospective observational research showed that RDW could independently contributed to 3-month poor outcome. The model integrating RDW with other risk markers plays a significant role in determining unfavorable functional outcome in AIS patients with successful recanalization.

Different factors have been found to increase the risk of the stroke prognosis such as hyperglycemia, oxidative stress, inflammation, or alterations in brain perfusion [11, 25]. Abnormal elevated RDW indicates the damage of microcirculatory blood flow being implicated as a key pathological feature of stroke [26]. This may account for its association with the severity of vascular lesions partially, which results in futile recanalization following EVT. The association of oxidation with RDW has also been found in an animal model [27]. An imbalance between anti-oxygen implicated in ischemic stroke lesions and the oxygen-free radical production systems causes lipid peroxidative damage [28]. The level of RDW was associated with C-reactive protein (CRP) level in a large population study, suggesting RDW’s fundamental function in increasing inflammatory stress [29]. In turn, inflammation may influence erythrocyte deformability, erythrocyte circulatory half-life, and erythropoiesis, promoting anisocytosis and increasing RDW level [30]. Interestingly, our study observed no statistical difference in WBC counts between two groups. The latent link of inflammation and oxidative stress with RDW may explain the results.

Consistent with our results, RDW in the futile recanalization group were significantly higher than in the successful recanalization group. In addition, the logistic regression analysis observed RDW as a risk indicator of poor prognosis in AIS patients following EVT. These findings support the notion that inflammation plays a central contributor to the stroke pathology and can influence the clinical prognosis [31].

According to ROC curves analysis, we found that the admission RDW had a significant prognostic ability of poor 3-month outcome, having an AUC of 0.798 and the optimal cut-off value of 13.25 (specificity 87% and sensitivity 60%). The primary novel creation was developing a model that combined the RDW with other risk factors. The integrated model outperformed the RDW-only model in terms of predictive value. It could be helpful to take RDW value into account during the preoperative evaluation.

This study was based on actual clinical practice, nevertheless, it has also some limitations. The retrospective single center data collection could have influenced the results, the discriminative value of RDW in terms of specificity and sensitivity was relatively low. Besides, no dynamic changes in RDW were seen, suggesting that the evolution of RDW values over time rather than at a single time, maybe more predictive of prognosis in patients after EVT.

In this study, we demonstrated that RDW is an independent indicator of futile recanalization in anterior circulation AIS patients following EVT. Further prospective longitudinal multicenter trials should be performed to corroborate these findings.

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

Conceptualizing and designing the study—YL and ZW. Extracting, analyzing and interpreting the data, Tables and Figures—ZW. Drafting the manuscript—ZW. Critical revision of the manuscript—YL and ZW. Supervision—YL and ZW. All authors contributed to editorial changes in the manuscript. All authors read and approved the final manuscript. All authors have participated sufficiently in the work and agreed to be accountable for all aspects of the work.

Jiangsu Taizhou People’s Hospital issued approval KY_2022_005_01. Due to the retrospective nature of this study, no written informed consent was obtained.

We thank all the participants in the study.

This research received no external funding.

The authors declare no conflict of interest.