The WBC/HDL ratio outperforms other lipid profiles in predicting mortality among ischemic stroke patients: a retrospective cohort study using MIMIC-IV data

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The WBC/HDL ratio outperforms other lipid profiles in predicting mortality among ischemic stroke patients: a retrospective cohort study using MIMIC-IV data

Li Zou^†Dong Sun^†Lei ZhangYu XieRenwei ZhangHuagang LiBitang DanYumin Liu^*Bin Mei^*

• Department of Neurology, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, China

Objective: To assess the prognostic value of lipid profiles and their ratios, particularly the white blood cell to high-density lipoprotein (WBC/HDL) ratio, for predicting 28-day and 1-year all-cause mortality in ischemic stroke patients admitted to the ICU.

Methods: A retrospective cohort study was conducted using the MIMIC-IV ICU database, including 2,894 ischemic stroke patients. Lipid profiles—including total cholesterol, triglycerides, low-density lipoprotein, and high-density lipoprotein—and derived ratios were analyzed. Associations with mortality were assessed using Cox proportional hazards models adjusted for demographic and clinical factors. Restricted cubic spline and Kaplan–Meier survival analyses were utilized to explore the relationship between the WBC/HDL ratio and mortality risk.

Results: Traditional lipid profiles and their ratios were not significantly associated with 28-day or 1-year mortality. Conversely, an elevated WBC/HDL ratio was independently associated with increased mortality risk at both 28 days (hazard ratio: 2.198; 95% confidence interval: 1.864–3.225) and 1 year (hazard ratio: 3.163; 95% confidence interval: 2.947–3.334). Restricted cubic spline analysis demonstrated a linear relationship between the WBC/HDL ratio and mortality risk, while Kaplan–Meier analyses indicated significantly poorer survival outcomes for patients with higher WBC/HDL ratios.

Interpretation: The WBC/HDL ratio is a superior prognostic marker for mortality in ischemic stroke patients admitted to the ICU, outperforming traditional lipid profiles. Incorporating this measure into clinical practice may enhance early risk stratification and guide targeted interventions.

1 Introduction

Ischemic stroke (IS) is a leading cause of disability and mortality worldwide, imposing a significant burden on patients, families, and healthcare systems (1). Thrombolysis and endovascular embolectomy have significantly improved the prognosis of ischemic stroke patients; however, many patients continue to experience poor outcomes, particularly those requiring intensive care unit (ICU) admission due to severe neurological deficits or medical complications (2). Identifying high-risk patients early remains essential to enhance postoperative management, optimize therapeutic strategies, and allocate resources effectively within the ICU setting.

Lipid metabolism and inflammation are pivotal in the pathogenesis and progression of IS. Dyslipidemia contributes to atherosclerosis and thrombosis, fundamental mechanisms underlying ischemic events (3). Elevated levels of low-density lipoprotein (LDL) and triglycerides (TG), along with decreased high-density lipoprotein (HDL), have been associated with an increased risk of stroke occurrence (4). In parallel, systemic inflammation plays a critical role in neuronal injury and post-stroke recovery, with elevated inflammatory markers correlating with worse outcomes (5, 6).

Given the interconnected roles of lipid metabolism and inflammation in IS, ratios that integrate these parameters have been proposed as comprehensive prognostic markers. Ratios like LDL/HDL, TC/HDL (total cholesterol to HDL ratio), and TG/HDL aim to reflect the balance between pro-atherogenic lipids and protective HDL (7). The white blood cell to HDL ratio (WBC/HDL), in particular, combines systemic inflammation with lipid status, potentially offering a more holistic assessment of risk (8). Prior studies suggest that these composite ratios may hold stronger prognostic value than individual lipid measures in cardiovascular disease (9, 10), yet their predictive utility in ICU-admitted IS patients remains uncertain. Therefore, critical illness and the body’s acute response can change lipid levels and inflammation markers, which may influence their usefulness for predicting outcomes (11, 12). Understanding whether traditional lipid profiles and their ratios can still reliably predict outcomes in this setting is crucial for identifying effective markers to assess risk and guide treatment in the ICU.

Prior studies suggest that these composite ratios may hold stronger prognostic value than individual lipid measures in cardiovascular disease (9, 10), yet their predictive utility in ICU-admitted IS patients remains uncertain. This study therefore aimed to evaluate two critical questions using the MIMIC-IV database (13): first, whether traditional lipid ratios (LDL/HDL, TC/HDL, TG/HDL) retain prognostic value in critically ill stroke patients experiencing acute metabolic disturbances; and second, whether novel ratios integrating systemic inflammation with lipid profiles (e.g., WBC/HDL) could provide enhanced risk stratification in this population. Through this investigation, we sought to establish evidence-based guidance for prognostic marker selection in neurocritical care settings.

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