Endovascular treatment (EVT) has become the standard of care for acute ischemic stroke (AIS) due to large vessel occlusion (LVO); however, significant challenges remain (1). A key challenge is that, even with ongoing refinements in EVT techniques yielding successful reperfusion rates as high as 84–88%, a substantial proportion of patients still fail to achieve functional independence at 90 days (2, 3). Accurately predicting which patients will experience functional dependence at 90 days remains an important clinical objective.

Post-stroke inflammation plays a critical role in secondary brain injury, contributing to blood–brain barrier disruption, cerebral edema, and reperfusion injury (4). Neutrophils are among the first immune cells recruited to the ischemic brain and can exacerbate tissue damage through degranulation, oxidative stress, and the formation of neutrophil extracellular traps (NETs) (5–7). In contrast, serum albumin exerts neuroprotective effects by maintaining plasma osmotic pressure, scavenging free radicals, and mitigating inflammatory cascades (8). An integrated index derived from neutrophil and albumin levels reflects both inflammatory activation and nutritional status, and may serve as a sensitive prognostic indicator in patients with AIS. Compared with absolute neutrophil count, neutrophil percentage better reflects the relative dominance of neutrophils within the circulating leukocyte pool and may be less influenced by acute hemodilution. Notably, the neutrophil percentage-to-albumin ratio (NPAR) has recently shown promise as a potential predictor of functional outcomes in both ischemic and hemorrhagic stroke (9–11).

Nevertheless, the prognostic value of perioperative NPAR levels in LVO-AIS patients treated with EVT remains unclear. Moreover, temporal profiling of NPAR following EVT may provide additional insights into its relationship with clinical outcomes in this population, which has not yet been thoroughly investigated (12). Therefore, this study aimed to investigate whether both admission (pre-EVT) and follow-up (within 48 h after EVT) NPAR levels are associated with 3-month clinical outcome in LVO-AIS patients.

Our study shows that a higher NPAR measured 48 h after EVT, as well as its dynamic change, were independent predictors of 3-month poor functional outcomes after EVT for acute anterior circulation large vessel occlusion stroke.

The neutrophil-to-albumin ratio has been associated with cardiovascular disease, sepsis, and intracerebral hemorrhage (17–19). However, these components play distinct roles in inflammation and disease processes. Higher neutrophil levels have been associated with poor prognosis (20–22), whereas higher albumin levels may exert protective effects and are therefore associated with favorable clinical outcomes (8, 23). While separate analyses may fail to capture their opposing effects, a combined assessment may better reflect their interaction and its association with different clinical conditions. NPAR, as an integrated biomarker, has been associated with clinical outcomes in AIS. Two recent retrospective studies found that elevated NPAR at admission was significantly correlated with poor 90-day functional outcomes in patients undergoing EVT (24, 25). Furthermore, Lu et al. (9) reported that higher NPAR was independently associated with increased all-cause mortality at 30 days, 90 days, 1 year, and during hospitalization.

Unlike previous studies, our data have shown no significant association between admission NPAR and 3-month clinical outcomes. One potential explanation is that admission NPAR primarily reflects baseline inflammatory and nutritional status, which may be influenced by comorbidities and variability in time from symptom onset, thereby limiting its predictive value. Within 6–8 h of stroke onset, neutrophils rapidly accumulate around cerebral vessels and initiate tissue infiltration (26). Following endovascular recanalization, neutrophil accumulation in ischemic and reperfused regions occurs at an accelerated rate and has been shown to correlate with poor neurological outcomes and greater brain injury severity (27). Hypoalbuminemia is common in patients with AIS and has been independently associated with poor functional outcomes, particularly in those undergoing EVT (28). Therefore, dynamic assessment of NPAR may provide stronger prognostic value than single measurements, and data on dynamic NPAR changes in patients undergoing EVT remain limited.

Our findings regarding the associations of 48-h NPAR and its dynamic changes with poor functional outcomes in patients with LVO-AIS may be explained by several mechanisms. One potential explanation is that 48-h NPAR may act as an alternative inflammatory biomarker reflecting peak inflammatory responses after EVT. Previous studies have shown that, during the first 48 h after stroke onset, impaired distal perfusion may promote endothelial inflammation, resulting in tissue injury and early blood–brain barrier disruption (15), while neutrophil infiltration typically peaks approximately at days 1–3 (16). In the context of EVT, prior studies have reported that vascular recanalization is accompanied by accelerated neutrophil recruitment in ischemic regions, which is associated with unfavorable outcomes (27). Substantial evidence demonstrates that proinflammatory responses are closely associated with poor clinical outcomes, particularly in patients treated with EVT (29–31). In addition, neutrophils are recognized as an inflammatory biomarker associated with stroke outcomes (32), whereas albumin exhibits anti-inflammatory properties with neuroprotective effects (33). Another potential explanation is that a high 48-h NPAR level may contribute to the no-reflow phenomenon, thereby increasing the likelihood of futile recanalization. El Amki et al. (20) demonstrated that, even after successful thrombolytic recanalization, cortical perfusion may fail to be restored due to neutrophil-mediated microvascular obstruction. Furthermore, excessive neutrophil accumulation promotes the release of proinflammatory mediators that disrupt endothelial integrity and increase blood–brain barrier permeability, leading to post-ischemic edema (34), while albumin exerts neuroprotective effects by suppressing inflammatory responses and oxidative stress (35), inhibiting platelet aggregation (36), and reducing cytokine-mediated adhesion within the postcapillary microcirculation (37).

Our present study has several limitations. First, despite the prospective design of the DETECT2-CHINA registry, the present study is retrospective and observational, which may introduce confounding bias. Although multivariable analyses were performed to adjust for measured confounders, residual confounding from unmeasured or unknown factors cannot be entirely excluded; for example, infarct volume, a well-established predictor of clinical outcome, was not adjusted for in the analyses. Moreover, as the data were obtained from a single comprehensive stroke center participating in the DETECT2-CHINA registry, the findings may be subject to selection bias and limited external validity. Second, as this was an exploratory analysis with a limited number of outcome events, the multivariable models may be subject to overfitting and imprecision, and the estimated effect sizes should be interpreted with caution, despite sensitivity analyses demonstrating directionally consistent associations. Third, the strong associations of 48-h NPAR and its dynamic changes with poor functional outcome may reflect temporal alterations in post-ischemic inflammation described in prior studies; however, this interpretation remains speculative in the absence of direct physiological or imaging correlations. Finally, NPAR data collection was obtained only at admission and 48 h post-procedure. Serial measurements at multiple time points after EVT could provide a more comprehensive understanding of the prognostic value of NPAR in this population.

In conclusion, this study demonstrated that elevated 48-h NPAR levels and dynamic increases in NPAR from admission to 48-h were associated with poor functional outcomes in patients with LVO-AIS undergoing EVT. These findings need to be validated in future studies.