Association between the hemoglobin-to-red cell distribution width ratio and three-month unfavorable outcome in older acute ischemic stroke patients: a prospective study

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Association between the hemoglobin-to-red cell distribution width ratio and three-month unfavorable outcome in older acute ischemic stroke patients: a prospective study

Luwen Huang^1†Linlin Li^1†Qing-rong Ouyang¹Ping Chen²Ming Yu^1*‡Lei Xu^1*‡

• ¹Department of Neurology, Suining Central Hospital, Suining, Sichuan Province, China
• ²Department of Pharmacy, Suining Central Hospital, Suining, Sichuan Province, China

Objective: Acute ischemic stroke (AIS) is a prevalent acute condition among older individuals. This study is the first investigation of the link between the HRR and unfavorable three-month outcome in older AIS patients.

Methods: This secondary research used data from a sample of 1,470 older AIS patients collected from a South Korean hospital between January 2010 and December 2016. Multiple imputation was applied to account for absent values. Binary logistic regression analysis was used to examine the relationship between the baseline HRR and adverse outcome at three-month. Restricted cubic spline analysis was employed to evaluate the correlation between HRR levels and adverse outcome. Interaction tests were performed to discern variations among subgroups.

Results: At 3 months, the overall incidence of adverse events was 31.43%, with a median HRR of 9.49. Compared to those with a lower HRR (Q1), the adjusted odds ratios (ORs) for the HRR in Q2, Q3, and Q4 were 0.61 (95% CI: 0.41–0.92, p = 0.017), 0.49 (95% CI: 0.31–0.78, p = 0.003), and 0.54 (95% CI: 0.31–0.92, p = 0.025), respectively. The correlation between the HRR and adverse outcome was non-linear (p < 0.05). An inflection point threshold of 10.70 was established via RCS analysis. Each 1-unit increase in HRR on the left side of the infection point was associated with a 24.0% decrease in the likelihood of adverse outcomes (OR = 0.76, 95% CI: 0.66–0.86, p < 0.001). ROC analysis revealed that HRR had the highest AUC (0.64, 95% CI: 0.61–0.67), followed by hs-CRP (0.60, 95% CI: 0.57–0.63), FPG/HbA1c (0.59, 95% CI: 0.55–0.63), and WBC (0.55, 95% CI: 0.51–0.58).

Conclusion: A lower HRR was correlated with a higher risk for adverse outcome in older AIS patients.

1 Introduction

Stroke is the second leading cause of mortality worldwide and the third major contributor to disability in non-communicable diseases; acute ischemic stroke (AIS) constituted approximately 62.4 to 67.7% of all stroke incidents in 2021 (1). AIS is a common illness among the older population. Between 1990 and 2019, the prevalence of ischemic stroke among older adults was markedly greater than that among younger adults worldwide (2). Consequently, it is imperative to determine appropriate and effective clinical indicators to predict AIS prognosis in geriatric patients, guide clinical care, and improve treatment outcome.

Red blood cell distribution width (RDW), which reflects the variability in red blood cell volume, has traditionally been used for the diagnosis and differential diagnosis of anemia (3). Clinical studies have demonstrated that RDW is increasingly acknowledged as an independent risk factor for recurrence, hemorrhagic transformation, in-hospital mortality, and poststroke fatigue in patients with AIS (4–7). Moreover, recent research has identified RDW as a potential inflammatory marker significantly associated with stroke-associated pneumonia (SAP) and as a valuable tool for enhancing SAP risk stratification in thrombolyzed AIS patients when integrated into established prediction models (8). Nevertheless, a study including 1,504 patients indicated that RDW could not predict the severity or functional results of AIS (9). Therefore, novel and dependable markers are needed to predict AIS outcome. These limitations underscore the urgent need for novel, dependable biomarkers to improve AIS outcome prediction.

The hemoglobin-to-red blood cell distribution width ratio (HRR) is a novel biomarker first introduced by Peng et al. in their research on the progression of esophageal squamous cell cancer (10). HRR has demonstrated a strong correlation with inflammatory levels and has been associated with adverse outcomes in various diseases (10–16). Compared to single inflammatory markers such as WBC or hs-CRP, HRR offers a unique advantage by simultaneously reflecting red blood cell metabolism and systemic inflammation. As a simple and easily obtainable parameter, HRR may provide a more comprehensive prediction of unfavorable outcomes in AIS patients. Importantly, studies have also shown a negative association between HRR and poor outcome in AIS patients (17–19).

Nonetheless, the correlation between HRR and negative outcome in elderly AIS patients remains unclear. This study aimed to address this gap by investigating the correlation between HRR and unfavorable outcome. The ultimate goal is to establish HRR as a simple and accessible biomarker that can aid clinicians in early risk stratification, thereby improving patient management and enhancing quality of life.

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