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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.

Methods

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, =0.022), while those with hyperlipidemia showed poorer preservation (OR=2.429, 95% CI=1.027-7.747, =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, =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, =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, =0.044), while elevated Lp(a) levels reduced this likelihood (OR=0.075, 95% CI=0.007-0.848, =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.

Conclusion

ApoA1 and Lp(a) are promising biomarkers for identifying AIS patients eligible for “penumbra freezing,” suggesting the potential to extend the treatment window.

© 2025 The Author(s). Published by Bentham Science Publishers.
This is an open access article published under CC BY 4.0 https://creativecommons.org/licenses/by/4.0/legalcode
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2025-10-02
2026-02-23

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Apolipoprotein A1 and Lipoprotein(a) as Biomarkers for the “Penumbra Freezing” in Acute Ischemic Stroke: Insights From a Case-Control and Mendelian Randomization Study
Bentham Science Publishers ; https://doi.org/10.2174/0109298673374444250901100551
/content/journals/cmc/10.2174/0109298673374444250901100551
/content/journals/cmc/10.2174/0109298673374444250901100551
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  • Article Type:     Review Article
Keywords: penumbra freezing ; lipid test ; biomarkers ; acute ischemic stroke ; Apolipoprotein A1 ; Lipoprotein(a)

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