Apolipoprotein A1 and Lipoprotein(a) as Biomarkers for the "Penumbra Freezing" in Acute Ischemic Stroke: Insights From a Case-Control and Mendelian Randomization Study.

IF 3.5 4区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Current medicinal chemistry Pub Date : 2025-10-02 DOI:10.2174/0109298673374444250901100551

Jianyu Liu, Zhiyao Xu, Yang Wen, Xing Guo, Xiaoyang Chen, Da Liu, Linyan Li, Hua Liu

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引用次数: 0

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.

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载脂蛋白A1和脂蛋白(a)作为急性缺血性卒中“半暗带冻结”的生物标志物：来自病例对照和孟德尔随机化研究的见解

简介：“半暗带冷冻”旨在通过保留缺血半暗带，将血管再通治疗延长到标准时间窗以外的急性缺血性卒中（AIS）患者。有效的生物标志物对于确定有资格接受AIS治疗的患者至关重要。方法：本研究纳入了141例超过常规治疗窗口期的AIS患者。采用CT灌注成像，根据EXTEND标准将患者分为“半暗区冻结”组和“非半暗区冻结”组。多元回归分析评估了9项基线因素和5项血脂指标与“半暗带冻结”的关系。采用ROC曲线评估诊断准确性。孟德尔随机化（MR）分析证实了这些发现，使用血脂指标作为暴露，半影生物标志物作为结果。结果：在超过治疗窗口期的AIS患者中，男性患者的半暗影保存较好（OR=0.243, 95% CI=0.072 ~ 0.813, p=0.022），高脂血症患者的半暗影保存较差（OR=2.429, 95% CI=1.027 ~ 7.747, p=0.043）。半暗区冷冻组ApoA1水平（1.29±0.03 g/L）显著低于非半暗区冷冻组（1.42±0.06 g/L, p=0.034）。相反，Lp(a)水平在“半影冻结”组（304.63±52.44 mg/L）显著高于“非半影冻结”组（110.26±40.71 mg/L, p=0.034）。较高的ApoA1水平增加了超出时间窗口的“非半影冻结”的可能性（OR=3.206, 95% CI=1.034-9.938, p=0.044），而升高的Lp(a)水平降低了这种可能性（OR=0.075, 95% CI=0.007-0.848, p=0.036）。MR分析证实了ApoA1和Lp(a)与半暗带生物标志物的遗传关联。讨论：ApoA1和Lp(a)可能与缺血半暗带状态有关，但由于样本量和研究方法的限制，需要进一步验证。结论：ApoA1和Lp(a)是鉴别AIS患者是否符合“半暗带冷冻”条件的有希望的生物标志物，表明有可能延长治疗窗口期。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Current medicinal chemistry 医学-生化与分子生物学

CiteScore

8.60

自引率

2.40%

发文量

468

审稿时长

3 months

期刊介绍： Aims & Scope Current Medicinal Chemistry covers all the latest and outstanding developments in medicinal chemistry and rational drug design. Each issue contains a series of timely in-depth reviews and guest edited thematic issues written by leaders in the field covering a range of the current topics in medicinal chemistry. The journal also publishes reviews on recent patents. Current Medicinal Chemistry is an essential journal for every medicinal chemist who wishes to be kept informed and up-to-date with the latest and most important developments.