Higher remnant cholesterol and CHG index associated with lower hemorrhagic transformation risk after IV thrombolysis

This study aimed to investigate the independent and joint effects of two novel lipid-derived biomarkers—Remnant cholesterol (RC) and Cholesterol, high-density lipoprotein, and glucose (CHG) index—with hemorrhagic transformation (HT) and poor prognosis in patients with acute ischemic stroke (AIS) after intravenous thrombolysis (IVT). In this dual-center retrospective cohort study, 4403 AIS patients undergoing IVT were analyzed. RC and the CHG index were calculated from routine baseline biochemical measurements. The primary outcome was HT, and the secondary outcome was poor prognosis at 90 days (modified Rankin Scale [mRS] score > 2). Multivariable logistic regression and restricted cubic spline (RCS) models were used to assess linear and non-linear associations. Subgroup and receiver operating characteristic (ROC) analyses were conducted to evaluate robustness and discriminative ability. Mediation analysis explored the potential mediating role of the systemic immune-inflammation index (SII). Patients with HT or a poor prognosis had lower RC and CHG levels. Multivariate logistic regression analysis revealed that both RC and CHG were negatively associated with the risk of HT and with a poor prognosis. The joint effects showed that patients with higher levels of RC and CHG had a significantly lower risk of HT (OR = 0.18, 95% CI: 0.12–0.25) and poor prognosis (OR = 0.40, 95% CI: 0.32–0.49). Subgroup analyses confirmed the consistency of these negative associations across age, sex, baseline NIHSS, and vascular comorbidities. The RCS models showed a non-linear association between RC and poor prognosis (P for non-linearity < 0.05) but a linear trend with HT (P > 0.05). In contrast, CHG showed a U-shaped non-linear association with both outcomes (P < 0.05). Moreover, the combination of RC and CHG had better predictive efficacy for HT (AUC = 0.750, 95% CI: 0.727–0.773, P < 0.001) and poor prognosis (AUC = 0.721, 95% CI: 0.705–0.737, P < 0.001) than alone. Mediation analysis further showed that SII partially mediated these associations. High RC and CHG levels were associated with a lower risk of HT and poor prognosis in AIS patients undergoing IVT. Integrating these biomarkers enhances predictive performance, supporting their potential utility in pre-thrombolysis risk stratification and personalized treatment decision-making.