Epidemiology
Higher Lp(a) and lower ApoA1 mark stroke patients whose ischaemic penumbra is preserved beyond the standard treatment window, case-control and Mendelian randomization study finds (Curr Med Chem 2025)
Original title: Apolipoprotein A1 and Lipoprotein(a) as Biomarkers for the "Penumbra Freezing" in Acute Ischemic Stroke: Insights From a Case-Control and Mendelian Randomization Study
This case-control and Mendelian randomization study enrolled 141 acute ischaemic stroke patients presenting beyond the conventional treatment window, using CT perfusion imaging and EXTEND criteria to classify them as showing 'penumbra freezing' (preserved ischaemic penumbra) or not, a state that could extend eligibility for vascular recanalisation treatment. Male sex predicted better penumbra preservation (OR 0.243, 95% CI 0.072-0.813, P = 0.022) while hyperlipidaemia predicted worse preservation (OR 2.429, 95% CI 1.027-7.747, P = 0.043). ApoA1 was significantly lower in the penumbra-freezing group (1.29 vs. 1.42 g/L, P = 0.034), while Lp(a) was significantly higher (304.63 vs. 110.26 mg/L, P = 0.034); higher ApoA1 increased the odds of non-preservation (OR 3.206, P = 0.044) while higher Lp(a) reduced it (OR 0.075, P = 0.036), and Mendelian randomization supported genetic associations for both markers with penumbra status. The authors propose ApoA1 and Lp(a) as candidate biomarkers for identifying late-presenting stroke patients who might still benefit from extended-window treatment, pending validation in larger cohorts.
Original abstract
Introduction: "Penumbra freezing" aims to extend vascular recanalization treatment to acute ischemic stroke (AIS) patients beyond the standard time window by preserving the ischemic penumbra. Efficient biomarkers are crucial for identifying patients eligible for AIS treatment.
Method: This study enrolled 141 AIS patients who exceeded the conventional treatment window. Using CT perfusion imaging, patients were categorized into "penumbra freezing" and "non-penumbra freezing" groups based on the EXTEND criteria. Multiple regression analysis assessed the association of nine baseline factors and five blood lipid indicators with "penumbra freezing." Diagnostic accuracy was evaluated using ROC curves. Mendelian randomization (MR) analysis validated these findings using blood lipid indicators as exposures and penumbra biomarkers as outcomes.
Results: Among AIS patients beyond the treatment window, males exhibited better penumbra preservation (OR=0.243, 95% CI=0.072-0.813, p=0.022), while those with hyperlipidemia showed poorer preservation (OR=2.429, 95% CI=1.027-7.747, p=0.043). In the "penumbra freezing" group, ApoA1 levels were significantly lower (1.29 ± 0.03 g/L) compared to the "non-penumbra freezing" group (1.42 ± 0.06 g/L, p=0.034). Conversely, Lp(a) levels were significantly higher in the "penumbra freezing" group (304.63 ± 52.44 mg/L) than in the "non-penumbra freezing" group (110.26 ± 40.71 mg/L, p=0.034). Higher ApoA1 levels increased the likelihood of "non-penumbra freezing" beyond the time window (OR=3.206, 95% CI=1.034-9.938, p=0.044), while elevated Lp(a) levels reduced this likelihood (OR=0.075, 95% CI=0.007-0.848, p=0.036). MR analysis confirmed genetic associations of ApoA1 and Lp(a) with penumbra biomarkers.
Discussion: ApoA1 and Lp(a) may be linked to ischemic penumbra status, but further validation is needed due to limitations in sample size and study methodology.
Conclusions: ApoA1 and Lp(a) are promising biomarkers for identifying AIS patients eligible for "penumbra freezing," suggesting the potential to extend the treatment window.
Summary written by lp-a.org from the published abstract; figures as published. Page updated 17 August 2026. Methods.