Predictive value of plasma sLRP1 for three-month clinical outcome in acute ischemic stroke and its potential pathophysiological mechanisms: A retrospective and observational study

Abstract

Background & Objective: Acute ischemic stroke (AIS) remains a leading global cause of mortality and disability; thus, accurate early prognosis is critical for guiding personalized management. Soluble low-density lipoprotein receptor-related protein 1 (sLRP1), a circulating protein implicated in neuroinflammatory regulation, has emerged as a potential biomarker in neurodegenerative and vascular pathologies. However, its prognostic significance in AIS remains undefined. This study investigated the prognostic value of admission plasma sLRP1, nuclear factor kappa B p65 subunit (NF- κB p65), and interleukin-6 (IL-6) levels regarding 90-day functional outcomes in AIS patients, while exploring potential underlying pathophysiological interrelationships.

Methods: In this retrospective observational study, we recruited patients with first-ever AIS. Plasma sLRP1, NF-κB p65, and IL-6 levels were quantified from samples obtained at admission. The primary endpoint was poor functional outcome at 90 days, defined as a modified Rankin Scale (mRS) score of 3–6. Prognostic capabilities were assessed using univariate and multivariate logistic regression models and receiver operating characteristic (ROC) curve analyses. Correlations among the biomarkers were also evaluated.

Results: A total of 155 AIS patients were included (median age 68.00 [IQR 60.00–75.00]; 61.29% male). Admission levels of sLRP1, NF-κB p65, and IL-6 were significantly elevated in patients with poor outcomes (all P < 0.01). Multivariate regression identified all three markers as independent predictors of 90-day poor functional outcomes. ROC analysis yielded an area under the curve (AUC) of 0.771 for sLRP1 alone, which improved to 0.839 when combined with NF-κB p65 and IL-6. Furthermore, sLRP1 levels were positively correlated with NF-κB p65 (R = 0.331, P < 0.001) and IL-6 (R = 0.388, P < 0.001), suggesting that sLRP1 may contribute to AIS pathophysiology by mediating cytokine release via the NF-κB inflammatory pathway.

Conclusion: Plasma sLRP1 represents a novel prognostic biomarker for AIS, offering potential advantages over conventional inflammatory markers. The identification of the sLRP1-NF-κB-IL-6 axis highlights a critical neuroinflammatory pathway, positioning sLRP1 as both a predictive tool and a potential therapeutic target. Integrating this biomarker panel into clinical practice could enhance early risk stratification, guide targeted anti-inflammatory interventions, and improve prognostic management in AIS.