Neutrophil to high-density lipoprotein cholesterol ratio and prognosis in acute ischemic stroke: a systematic review and meta-analysis

BACKGROUND: The neutrophil to high-density lipoprotein cholesterol ratio (NHR) is emerging as a potential composite biomarker integrating aspects of inflammation and lipid metabolism in the context of acute ischemic stroke (AIS). However, its clinical utility remains uncertain due to limited and inconsistent evidence across studies. METHODS: A comprehensive systematic search was conducted in PubMed, Embase, and the Cochrane Library up to September 2025 to identify studies examining the association between NHR and adverse outcomes or mortality in AIS patients. Heterogeneity among studies was evaluated through sensitivity and subgroup analyses, and potential publication bias was explored using Egger's test, recognizing the limited power due to the small number of included studies. RESULTS: A meta-analysis including 4,138 patients from five studies suggested a possible association between higher NHR and adverse outcomes in AIS (OR 1.89, 95% CI: 1.18-3.02; I² = 82%), although substantial heterogeneity limits confidence in the pooled estimate. Sensitivity analyses yielded similar trends, but findings should be interpreted cautiously. Subgroup analyses indicated stronger associations for patients undergoing reperfusion therapy (OR 2.80, 95% CI: 1.79-4.38) and at 3-month follow-ups (OR 2.24, 95% CI: 1.51-3.32), while no significant associations were observed with conventional treatment or 1-month follow-ups. The pooled area under the curve (AUC) was 0.63, reflecting limited predictive performance. Only a single study examined mortality, reporting no significant association with NHR (OR 1.5; 95% CI: 0.47-4.74). CONCLUSIONS: Elevated NHR is associated with adverse outcomes in AIS, supporting its potential as a prognostic biomarker. However, evidence for mortality prediction is limited, and further prospective studies are needed.