Association between the non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio and post-stroke depression in patients with acute ischemic stroke.

Abstract

Objectives: Post-stroke depression (PSD) is a frequent and debilitating complication of acute ischemic stroke (AIS), yet its underlying biochemical predictors remain insufficiently characterized. The non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio (NHHR) has recently emerged as a robust composite metric for assessing the homeostatic imbalance of lipid metabolism and systemic inflammation. This study aimed to evaluate the longitudinal association between admission NHHR levels and the risk of developing PSD at three months post-stroke in patients with AIS.

Methods: We consecutively enrolled 408 patients with AIS from the Department of Neurology at Lixin County People's Hospital between February 2023 and January 2026. Admission NHHR was calculated from fasting lipid panels. Depressive symptoms were evaluated at a 3-month follow-up using the 17-item Hamilton Depression Rating Scale (HAMD-17), with PSD diagnosis confirmed via DSM-V criteria. Participants were stratified into tertiles based on admission NHHR (Q1 ≤7.68; Q2 7.69-10.50; Q3 ≥10.52). Multivariate logistic regression and restricted cubic splines (RCS) were employed to analyze the association between NHHR and PSD risk.

Results: Among the 408 participants, 93 (22.79%) were diagnosed with PSD. Patients in the PSD group exhibited significantly higher admission NHHR levels compared to the non-PSD group (P < 0.001). The prevalence of PSD increased progressively across NHHR tertiles: 10.75% in Q1, 25.81% in Q2, and 63.44% in Q3. After adjusting for age, sex, vascular risk factors, stroke severity (NIHSS), and functional impairment (mRS), the highest NHHR tertile remained a potent independent predictor of PSD (OR 3.240, 95% CI 1.850-5.680, P < 0.001). The admission NHHR level exhibited a robust predictive capacity for PSD, with an AUC of 0.738 (95% CI: 0.681-0.790, P < 0.001). RCS analysis further revealed a statistically significant non-linear relationship (P for non-linearity < 0.001), identifying a vulnerability window between NHHR values of 10 and 15 where the risk of depression escalated most sharply. This association persisted in various subgroup analyses.

Conclusions: Elevated admission NHHR is independently and non-linearly associated with an increased risk of PSD at three months in AIS patients. As an easily accessible biomarker of lipid-driven systemic inflammation, NHHR may serve as a valuable prognostic tool for early risk stratification and targeted psychological intervention in clinical practice.