Predictive value of gut metabolites combined with neutrophil to platelet ratio for clinical functional outcome in acute ischemic stroke treated with endovascular therapy

Abstract

Purpose: This study aimed to investigate the associations between gut metabolites Trimethylamine N-Oxide (TMAO), the novel platelet-derived inflammatory ratio index neutrophil-to-platelet ratio (NPR), and the prognosis of patients with acute ischemic stroke (AIS) undergoing endovascular therapy (EVT).

Methods: This study was a retrospective case-control study. Data were collected from 213 AIS patients who underwent EVT at the Stroke Alliance of the Affiliated Hospital of Xuzhou Medical University between October 2022 and December 2024, including baseline characteristics, laboratory results, and gut-derived metabolite levels from the proximal culprit vessel. Functional outcome was assessed using the modified Rankin scale (mRS) at 3 months after EVT. Based on univariable analysis, a multivariable binary logistic regression model was employed to explore the association of gut-derived TMAO and the platelet-derived inflammatory biomarker NPR with poor functional outcomes. The predictive values of TMAO and NPR, both individually and in combination, were quantitatively compared using receiver operating characteristic (ROC) curves integrated with the DeLong test, continuous net reclassification improvement (cNRI), and integrated discrimination improvement (IDI). Finally, both multiplicative and additive interactions between TMAO and NPR regarding poor functional outcomes were evaluated.

Results: A total of 213 eligible patients were divided into the favorable group (mRS ≤ 3, N = 77) and the unfavorable group (mRS > 3, N = 136). After adjusting for confounding factors, multivariable logistic regression analysis revealed that age (OR: 1.065, 95% CI: 1.022-1.109, p = 0.002), baseline National Institutes of Health Stroke Scale (NIHSS) (OR: 1.069, 95% CI: 1.008-1.133, p = 0.025), TMAO (OR: 2.889, 95% CI: 1.563-5.338, p < 0.001), NPR (OR: 1.864, 95% CI: 1.122-3.096, p = 0.016), onset-to-reperfusion time (OTR) (OR: 1.004, 95% CI: 1.002-1.007, p = 0.002), complete recanalization (OR: 0.129, 95% CI: 0.032-0.530, p = 0.004), and hemorrhagic transformation(HT) (OR: 3.271, 95% CI: 1.351-7.918, p = 0.009) were independent predictors of poor functional outcomes. The areas under the curve (AUC) for TMAO, NPR and the combined value of TMAO and NPR in predicting unfavorable outcomes at 3 months after EVT were 0.698, 0.651 and 0.749, respectively. Furthermore, the DeLong test, along with cNRI and IDI analyses, confirmed the significant incremental predictive value of the combined model, and a significant additive interaction between TMAO and NPR was identified.

Conclusion: This study revealed that elevated levels of TMAO and NPR are independently associated with poor functional outcomes in AIS patients after EVT. The combined assessment of TMAO and NPR provides incremental value in predicting the prognosis of these patients.

Keywords: Trimethylamine N-Oxide (TMAO); acute ischemic stroke (AIS); endovascular therapy (EVT); gut metabolites; inflammation; novel platelet-derived inflammatory biomarkers; outcome.