The Global Burden of Disease Report identifies stroke as the second leading cause of worldwide mortality and disability (Krishnamurthi et al., 2020). Mechanical thrombectomy (MT) has emerged as one of the most efficacious therapies for acute ischemic stroke (AIS; Powers et al., 2018, 2019). Timely and effective thrombectomy significantly improves the prognosis for AIS patients. However, complications such as cerebral hemorrhage, vascular re-occlusion, and cerebral edema may occur after MT, and the limited treatment time window presents challenges to treatment efficacy (Kimberly et al., 2018; Luby et al., 2023; Sarraj et al., 2023). Hence, it is crucial to investigate simple, convenient, and effective clinical indicators that can predict the prognosis of AIS, guide clinical decision-making, and enhance treatment outcomes.

Hemoglobin (Hb) and red cell distribution width (RDW) are conventional blood test parameters. Hb levels determine the oxygen-carrying capacity, while RDW quantifies the variation in red blood cell size (Lippi and Plebani, 2014; Salvagno et al., 2015). These parameters not only reflect the balance between hematopoietic function and red blood cell survival but also play a critical role in inflammation, oxidative stress, and the vascular innate immune system (Emans et al., 2011; Patel et al., 2013; Kawabata, 2020). For instance, anemia has been shown to induce the release of interleukin-6 and tumor necrosis factor-α (Feret et al., 2022), and RDW has been linked to inflammatory markers and oxidative stress (Förhécz et al., 2009). Inflammation and oxidative stress can worsen cerebral edema and hemorrhage, delay cerebral ischemia, and contribute to poor prognosis (Zhao et al., 2017; Esposito et al., 2022; Westendorp et al., 2022). These findings suggest that both Hb and RDW, as essential markers of underlying inflammatory processes, may be correlated with the clinical outcome of ischemic stroke. Hb levels have been identified as significant predictors of AIS and coronary heart disease (Kwok et al., 2016; Chang et al., 2020; Zhang et al., 2021). Research has also demonstrated that RDW can predict adverse outcomes in patients with acute myocardial infarction receiving percutaneous coronary intervention (PCI) and in patients with AIS (Feng et al., 2017; Parizadeh et al., 2019; Xiao et al., 2022). Furthermore, RDW, regardless of anemia status, has been associated with stroke severity and adverse outcomes in AIS, thereby improving stroke prediction accuracy (Saliba et al., 2015; Xue et al., 2022).

Recently, the hemoglobin-to-red cell distribution width ratio (HRR) has emerged as a novel biomarker for cardiovascular diseases. It is calculated from Hb and RDW without additional costs (Rahamim et al., 2022; Xiu et al., 2022). HRR has been studied in relation to myocardial infarction stenting and ischemic stroke associated with atrial fibrillation (Qin et al., 2022; Sun et al., 2022). However, further investigation is needed to determine whether HRR can effectively predict the prognosis of AIS patients undergoing thrombectomy. Additionally, various components of the immune system undergo dynamic changes after AIS, which may have varying effects depending on the stage of stroke development. Therefore, our study aims to investigate the association between HRR and the prognosis of AIS patients undergoing thrombectomy, as well as explore the optimal time point at which HRR functions as a prognostic marker.

The purpose of this study was to investigate the association between the novel biomarker HRR and the outcomes of AIS patients who underwent MT. Our findings suggested that HRR at admission and after 24 h may be significantly lower in patients with poor prognosis and death. However, after adjusting for cerebrovascular risk factors, HRR after 24 h remained an independent risk factor for both poor prognosis and death, regardless of whether intravenous thrombolysis was performed prior to MT.

Anemia is a prevalent condition among AIS patients, and its pathogenesis involves various mechanisms such as reduced oxygen-carrying capacity, inflammation, energy imbalance, and hypercoagulation (Chang et al., 2020). Decreased levels of Hb imply a compromised oxygen-carrying capacity, leading to limited oxygen supply and an energy imbalance in the ischemic penumbra (Kimberly et al., 2013; Desai et al., 2023). Moreover, anemia can trigger the release of inflammatory factors like tumor necrosis factor-α (Feret et al., 2022). Recently, the role of inflammatory reactions in the progression of AIS and its association with poor prognosis has been widely recognized (Kehrel and Fender, 2016; Zhao et al., 2017; Shi et al., 2019; Esposito et al., 2022). Studies have indicated that overall poor nutritional status and weakened immune response may contribute to a worse prognosis (Bullock et al., 2020). Furthermore, anemic patients may experience hypercoagulability, further increasing the risk of ischemic events. Evidence suggests that severe anemia substantially raises the likelihood of stent thrombosis (Pilgrim et al., 2012), and lower Hb level was a strong predictor of post-PCI in-stent restenosis (Hu et al., 2021). Several studies have highlighted baseline Hb as a significant predictor of mortality and ischemic events in PCI (Reinecke, 2003; Dutsch et al., 2022). Additionally, a U-shaped association has been found between Hb levels and poor prognosis, all-cause mortality, and stroke severity in ischemic stroke (Chang et al., 2020; Zhang et al., 2021). Another study reported that lower Hb levels and variability were linked to mortality at 3 months in AIS patients undergoing MT (Nisar et al., 2021). In our investigation, AIS patients undergoing MT with poor prognosis and death had lower Hb levels compared to those with good prognosis and survival, although the difference was not statistically significant.

The value of RDW in cardiovascular disease reflects various mechanisms in the pathophysiological process. Firstly, an increased RDW indicates an underlying inflammatory state and impaired maturation of red blood cells (Ridker et al., 2001). RDW has been associated with inflammatory markers such as C-reactive protein with high sensitivity, interleukin-6, and fibrinogen levels (Förhécz et al., 2009). These inflammatory factors can disrupt red blood cell maturation by affecting the homeostasis of red blood cells, impairing iron metabolism, and inhibiting erythropoietin production (Rechavi and Rivella, 2008; Salvagno et al., 2015). Secondly, oxidative stress and microcirculatory damage play a significant role. Red blood cells possess substantial antioxidant capacity, and oxidative damage can lead to decreased cell survival rates (Emans et al., 2011; Lippi and Plebani, 2014). Changes in the morphology of red blood cells are associated with oxidative stress (Friedman et al., 2004). In addition, reduced red blood cell deformability can impede blood flow through the microcirculation, exacerbating ischemic conditions (Patel et al., 2013). Several studies have independently linked higher baseline RDW levels to mortality and adverse cardiovascular events in myocardial infarction patients undergoing PCI (Fatemi et al., 2013; Bujak et al., 2015; Zhao et al., 2015; Xiao et al., 2022). Research has also demonstrated that RDW may serve as a significant prognostic factor in AIS (Feng et al., 2017; Mohindra et al., 2020). Baseline RDW has been proposed as a prospective marker of mortality in AIS patients undergoing intravenous thrombolysis (Pinho et al., 2018; Ye et al., 2020). Similarly, in our study, AIS patients with poor prognosis and mortality tended to have elevated RDW levels 24 h after MT.

Although Hb and RDW have shown prognostic value in AIS patients, these two parameters can be influenced by various factors as mentioned above. Since HRR is calculated from Hb and RDW, it may provide a more effective and stable assessment compared to individual Hb or RDW measurements, objectively reflecting inflammatory and microcirculatory status, thus potentially serving as a superior biomarker. HRR has recently emerged as a crucial indicator for predicting cardiovascular disease mortality and prognosis (Rahamim et al., 2022). Lower HRR is associated with a higher risk of frailty and adverse outcomes in hospitalized older patients with coronary heart disease (Qu et al., 2021). Moreover, HRR may serve as a reliable indicator of mortality risk in patients with coronary artery disease after PCI (Sun et al., 2022; Xiu et al., 2022). Lower HRR levels have been found to increase the risk of death from all causes in AIS patients with atrial fibrillation (Qin et al., 2022). However, no studies have investigated the predictive significance of HRR for clinical outcomes in AIS patients undergoing MT. By excluding the influence of cardiovascular diseases, malignancies, infectious diseases, serious liver and kidney dysfunction, and adjusting for multivariate confounders, our study suggests that lower HRR significantly increases the risk of poor prognosis and death in AIS patients undergoing MT. Additionally, HRR demonstrates superior discriminative accuracy compared to the single parameter RDW. Globally, the NIHSS score is recognized as a valuable prognostic indicator for AIS, and incorporating HRR into the NIHSS enhances its predictive value.

While our study investigated the association between HRR and outcomes in AIS patients undergoing MT, we acknowledge certain limitations. Firstly, we only collected HRR data at admission and after 24 h of MT, precluding analysis of HRR changes throughout the entire stroke process. Secondly, there was a loss to follow-up of 21 patients, potentially introducing bias into our results. Thirdly, this was a retrospective and single-center design study, raising the possibility of selection bias and limiting the generalizability of our findings. It is important to consider these limitations when interpreting the results, and future research should address these issues to provide more robust evidence on the relationship between HRR and outcomes in AIS patients undergoing MT.

Our study indicates that HRR levels after 24 h of MT, as a simple, novel, cost-effective, and valuable biomarker, are an independent predictor of poor prognosis and death for AIS patients undergoing MT. However, further research is necessary to elucidate the underlying biological mechanisms and confirm the clinical utility of HRR.

The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.

The studies involving humans were approved by the ethics committee of Chengdu Second People’s Hospital. The studies were conducted in accordance with the local legislation and institutional requirements. The participants provided their written informed consent to participate in this study.

XF: Methodology, Data curation, Investigation, Writing – original draft, Funding acquisition. YZ: Investigation, Formal Analysis, Writing – review & editing. QL: Formal Analysis, Writing – review & editing, Software, Validation. BW: Writing – review & editing, Validation, Formal Analysis, Software. JS: Validation, Writing – review & editing, Project administration, Conceptualization, Methodology, Resources.