Association of the Naples Prognostic Score With Functional Outcomes and the Mediating Effects of PhenoAge Acceleration in Patients With Acute Ischemic Stroke or Transient Ischemic Attack: A Nationwide Registry Study

Background The Naples Prognostic Score (NPS), a novel inflammatory and nutritional score, has attracted widespread attention in the prognosis of various diseases but remains unclear in acute ischemic stroke or transient ischemic attack. We aimed to investigate the association between NPS and poor functional outcomes and test whether PhenoAge acceleration (PAA) mediates or jointly contributes to the relationships. Methods This prospective cohort study included patients with acute ischemic stroke or transient ischemic attack from the CNSR‐III (Third China National Stroke Registry). The NPS (range, 0–4) was calculated based on serum albumin, total cholesterol, neutrophil/lymphocyte ratio, and lymphocyte/monocyte ratio, and categorized as low (0), medium (1 or 2), or high (3 or 4). Logistic regression was used to assess the association between NPS and poor functional outcomes (modified Rankin Scale mRS score, 2–6/3–6). Mediation analyses were performed to explore the role of PAA. Results A total of 7932 patients from the CNSR‐III were included in the analysis. High NPS was significantly associated with poor functional outcomes at 3 months (adjusted odds ratio OR, 1.69 95% CI, 1.13–2.52, P =0.010 for mRS 3–6; adjusted OR, 1.31 95% CI, 1.00–1.71, P =0.048 for mRS 2–6). PAA partially mediated the observed association, with mediation proportions of 13.90% and 12.82% for mRS 3 to 6 and 2 to 6 at 3 months, respectively. Patients with both high NPS and PAA ≥0 had the highest risks of poor outcomes (adjusted OR, 2.16 95% CI, 1.73–2.70 for mRS 3–6; adjusted OR, 1.51 95% CI, 1.25–1.84 for mRS 2–6). Similar results were observed at 1 year. Incorporating combined NPS and PAA into the basic model improved predictive performance for short‐ and long‐term poor functional outcomes. Conclusions High NPS was associated with increased risk of poor functional outcomes at 3‐month and 1‐year follow‐ups in patients with acute ischemic stroke or transient ischemic attack. This association was partially mediated and jointly influenced by PAA.