Introduction

Stroke is an acute neurological disorder characterized by focal dysfunction resulting from the cerebral artery blockage and insufficient blood supply to the brain. This condition initiates a cascade of pathophysiological events, including an inflammatory response, excitotoxicity, calcium overload, and oxidative stress1. Clinical symptoms include hemiplegia, aphasia, depression, dysphagia, and cognitive impairment2. Globally affecting approximately 17.95 million people and causing an estimated 630,000 stroke-related deaths annually, stroke ranks as the second leading cause of mortality and the third largest contributor to disability-adjusted life years (DALYs) lost worldwide3,4. Consequently, it presents a significant public health challenge that severely threatens human health.

In stroke prevention and treatment, prognostic indicators serve as crucial tools for enhancing risk stratification and predicting patient survival outcomes. The National Institutes of Health Stroke Scale (NIHSS), while widely used for neurological assessment5, demonstrates suboptimal prognostic accuracy in ischemic stroke (73.7% sensitivity, 74.1% specificity)6. The Glasgow Coma Scale (GCS) evaluates consciousness but proves inadequate for sedated/intubated patients7, whereas the Barthel Index quantifies daily living functionality while neglecting post-stroke cognitive impacts8. Similarly, the SF-36 quality-of-life tool suffers from significant floor/ceiling effects limiting clinical utility9 While conventional neurological assessment tools primarily evaluate consciousness and physical function, their efficacy remains operator-dependent and is compromised by patient cooperation, with a limited capacity for dynamic acute-phase monitoring. In contrast, inflammation- and nutrition-related biomarkers derived from routine laboratory data objectively quantify the severity of neural injury while providing critical insights into inflammatory responses, immune competence, and coagulation status, thus enabling a comprehensive characterization of disease progression.

Stroke is a multifactorial pathology characterized by inflammation as a central mediator, with elevated inflammatory markers correlating with increased incidence and mortality10,11,12. Stroke typically triggers inflammatory responses, including the release of cytokines and chemokines, which initiate pathological processes such as vascular endothelial injury and thrombosis, ultimately resulting in brain tissue damage. Chronic inflammation can induce insulin resistance through inflammatory factors like tumor necrosis factor and C-reactive protein (CRP)13,14 leading to decreased serum albumin levels and body weight12,15. Previous studies have established strong associations between albumin levels16,17,18 and body mass index (BMI)19 with stroke severity and functional outcomes. Inflammation directly influences stroke prognosis and does so indirectly through the modulation of albumin and body weight. The interdependence among nutritional, immune, and prognostic parameters underscores the necessity for multidimensional indicator panels to enable a comprehensive assessment.

Immunonutrition is an emergent and interdisciplinary subject since it comprises various aspects related to nutrition, immunity, infections, inflammation, injury, or tissue damage20. The systemic immune-inflammation index (SII), nutritional risk index (NRI), and the Naples prognostic score (NPS) are biomarkers used to assess immunonutritional status in various disease conditions. Elevated SII correlates with increased mortality, recurrence risk, and functional impairment severity in stroke patients21. Lower NRI is associated with adverse outcomes in stroke patients, including higher mortality rates, prolonged hospitalization, and increased complications19. The NPS is a novel scoring system that combines inflammatory and nutritional assessments, initially developed for prognostic evaluation in colorectal cancer22. These indices are calculated using the following parameters: lymphocyte, neutrophil, and monocyte counts, serum albumin (ALB), total cholesterol (TC), height, and weight. These parameters offer advantages such as low cost, ease of acquisition, high accuracy, and good reproducibility, demonstrating significant potential for broad clinical application across various diseases.

Currently, evidence regarding the immunonutritional status and all-cause mortality in stroke patients is limited, and the prognostic significance of immunonutritional indicators remains unclear. This study aims to address these gaps by utilizing data from the National Health and Nutrition Examination Survey (NHANES) from 2005 to 2018, in conjunction with National Death Index (NDI) records up to December 31, 2019. The research investigates five immunonutritional indicators (NPS, NRI, SII, ALB, and TC) in stroke patients and their association with all-cause mortality. The objective is to identify prognostic assessment indicators for stroke with greater predictive value, thereby enhancing risk stratification and providing theoretical support for the development of prevention and treatment strategies.

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