BackgroundAnimal studies suggest that high-density lipoprotein cholesterol (HDL-C) protects against reperfusion injury. We hypothesised that higher serum HDL-C levels would have a protective effect against cerebral reperfusion injury in human stroke survivors treated with thrombectomy. MethodsWe included consecutive patients from our prospective anterior circulation large-vessel occlusion (acLVO) registry who underwent thrombectomy between January 2017 and January 2023 at a tertiary stroke centre in Germany in a propensity score-matched analysis. We assessed the association between serum HDL-C levels and imaging indices of post-interventional reperfusion injury according to the Heidelberg Bleeding Classification as well as 90-day functional outcome quantified by the modified Rankin Scale (mRS). We performed sensitivity analyses using multivariable lasso logistic and linear regression adjusted for demographic, clinical and imaging characteristics. ResultsOut of 1702 patients assessed for eligibility, 807 acLVO patients treated with thrombectomy (420 females, median age 77 years [66-84, IQR]) were included. Reperfusion injury reduced the probability of a favourable functional outcome (90-day mRS 0-2) by 14.8% ({beta}=0.15; 95% CI [0.06;0.24]; p=0.001. A serum HDL-C level above the median (1.15 mmol/L) decreased the probability of reperfusion injury by 13.6% ({beta}=-0.14; 95CI% [-0.22; -0.05]; p=0.002) and increased the probability of favourable functional outcome by 13.2% ({beta}=-0.13; 95CI% [-0.22;-0.05]; p=0.003). In sensitivity analyses, higher HDL-C levels were associated with lower odds of reperfusion injury (adjusted OR 0.62; 95% CI [0.43;0.88]; p=0.008) and emerged as a predictor of a favourable functional outcome (adjusted OR 0.60; 95% CI [0.40; 0.90]; p=0.015). ConclusionsIn patients undergoing thrombectomy for acLVO, higher serum levels of HDL-C were associated with a reduced probability of reperfusion injury and favourable functional outcome at 90 days.