载脂蛋白E在急性缺血性脑卒中的预测和功能转归评估中的应用

王朋; 音大为; 何野; 胡翀; 孙文; 朱余友

doi:10.16766/j.cnki.issn.1674-4152.003662

载脂蛋白E在急性缺血性脑卒中的预测和功能转归评估中的应用

doi: 10.16766/j.cnki.issn.1674-4152.003662

王朋¹,
音大为¹,
何野¹,
胡翀¹,
孙文²,
朱余友^2, ,

1.
中国科学技术大学附属第一医院(安徽省立医院)医学影像科，安徽合肥 230036
2.
中国科学技术大学附属第一医院(安徽省立医院)神经内科

基金项目:

国家自然科学基金面上项目 62371433

详细信息

通讯作者:
朱余友，E-mail：zhuyuyou2020@126.com

中图分类号: R743.3
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- 被引次数: 0
出版历程
- 收稿日期: 2024-04-04

Application value of apolipoprotein E in predicting acute ischemic death and evaluating functional outcomes

WANG Peng¹,
YIN Dawei¹,
HE Ye¹,
HU Chong¹,
SUN Wen²,
ZHU Yuyou^{2
, ,}

1.
Department of Radiology, the First Affiliated Hospital of University of Science and Technology of China, Hefei, Anhui 230036, China

摘要

摘要: 目的近年来许多研究证明多种疾病与载脂蛋白E(APOE)基因多样性相关，本文旨在探讨APOE基因在颅内血管狭窄引起的急性缺血性卒中的预测价值及评估其预后的作用。方法收集2022年1月—2023年12月中国科学技术大学附属第一医院收治的急性缺血性脑卒中(AIS)患者511例，根据是否有颅内动脉狭窄将其分成颅内动脉狭窄(ICAS)组(317例)和非颅内动脉狭窄(NCAS)组(194例)及6个月随访时根据是否携带APOE-ε4将其分为携带ε4基因(213例)组和非携带ε4(298例)组，分析年龄、性别、合并症、血脂、载脂蛋白E(包括等位基因分型)和脂蛋白a的差异，并进行血管壁高分辨率磁共振成像。术后6个月随访患者的功能转归，随访高清血管壁成像结果。结果 ICAS组的APOE浓度显著低于NCAS组(r=0.481，P < 0.01)。携带APOE-ε4基因的患者中45.54%(97/213)和未携带APOE-ε4基因的患者中16.11%(48/298)在治疗结束6个月随访时预后不良(OR=4.622, 95% CI: 3.512~6.091, P < 0.01)。结论血浆APOE水平低是ICAS引起的急性缺血性卒中的高危因素，携带APOE-ε4基因是AIS患者功能预后不良的高危因素。APOE-ε4基因型联合高分辨率血管壁成像在预测急性缺血性卒中发生及评估功能转归方面具有一定的应用价值。
- 急性缺血性脑卒中 /
- 载脂蛋白E /
- 血管壁高分辨率磁共振成像 /
- 功能评估 /
- 临床价值
Abstract: Objective In recent years, many studies have shown that many diseases are associated with apolipoprotein E (APOE) gene diversity. The aim of this study is to investigate the predictive value of the APOE gene in acute ischemic stroke (AIS) caused by intracranial vascular stenosis and its role in evaluating its prognosis. Methods A total of 511 patients with acute ischemic stroke admitted to the First Affiliated Hospital of the University of Science and Technology of China from January 2022 to December 2023 were collected. According to the presence or absence of intracranial artery stenosis, they were divided into the intracranial artery stenosis (ICAS) group (317 cases) and the non-intracranial artery stenosis (NCAS) group (194 cases). At the 6-month follow-up, According to whether they carried the APOE-ε4 gene or not, they were further divided into ε4 carrier group (213 cases) and non-ε4 carrier group (298 cases). Variable such as age, gender, comorbidities, blood lipids, lipoprotein, apolipoprotein E (including allele typing), and lipoprotein A were analyzed, along with high-resolution magnetic resonance imaging of the vessel wall. Followed up evaluations were conducted 6 months after the operation, with results tracked via high-definition vessel wall imaging. Results The plasma APOE concentration in the ICAS group was significantly lower than that in the non-intracranial artery stenosis group (r=0.481, P < 0.01). Among the ε4 carriers, 97/213 (45.54%) had a poor prognosis, while 48/298 (16.11%) of non-ε4 carriers experienced poor prognosis at the end of treatment and after 6 months of follow-up, with a significant difference (OR=4.622, 95% CI: 3.512-6.091, P < 0.01). Conclusion Low plasma APOE levels are a risk factor for acute ischemic stroke caused by ICAS, and the APOE-ε4 gene is associated with poor functional prognosis in AIS patients. Combining the APOE-ε4 genotype with high-resolution vessel wall imaging may be valuable in predicting acute ischemic stroke and evaluating functional outcomes.
- Acute ischemic stroke /
- Apolipoprotein E /
- High resolution magnetic resonance imaging /
- Functional assessment /
- Clinical value
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图 1 正常颅内动脉血管壁高分辨磁共振图像

注：A为颅内大脑中动脉及其分支的血管壁原始图像；B为血管壁曲面重建后的图像。

Figure 1. High-resolution magnetic resonance imaging of the intracranial arterial vessel wall

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图 2 动脉粥样硬化斑块在磁共振不同序列上的表现

注：A为弥散图像；B为冠状位高分辨血管壁成像；C为平扫的轴位高分辨血管壁成像；D为增强后轴位高分辨血管壁成像；黄色箭头指示病灶位置。

Figure 2. Magnetic resonance plaque characteristics across different sequences

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表 1 ICAS组与NCAS组AIS患者基线特征和生化指标比较

Table 1. Comparison of baseline characteristics and biochemical indices between AIS patients in the ICAS and NCAS groups

组别	例数	年龄(x±s，岁)	性别(男/女，例)	吸烟[例(%)]	糖尿病[例(%)]	高血压[例(%)]	肾功能不全[例(%)]	BMI (x±s)
ICAS	317	65.8±12.5	178/139	189(59.6)	84(26.5)	126(39.7)	22(6.9)	23.5±2.7
NCAS	194	61.5±12.1	118/76	112(57.7)	49(25.2)	89(45.9)	10(5.2)	23.9±3.0
统计量		6.021^a	5.273^b	3.392^b	1.181^b	0.990^b	1.134^b	3.572^a
P值		0.013	0.399	0.807	0.783	0.343	0.258	0.291

组别	例数	总胆固醇(x±s, mg/dL)	TG (x±s, mg/d)	HDL (x±s, mg/d)	LDL (x±s, mg/d)	Lp(a) (x±s, mg/dL)	携带APOE-ε4 (例)	APOE浓度(x±s, μg/mL)
ICAS	317	184.4±4.4	109.3±23.7	45.7±12.0	118.3±32.8	24.1±4.3	117	38.9±15.7
NCAS	194	180.2±33.1	118.5±19.9	45.4±12.3	111.5±32.3	21.9±3.7	113	47.8±21.1
统计量		0.273^a	2.493^a	1.605^a	3.869^a	4.736^a	1.473^b	5.042^a
P值		0.096	0.377	0.996	0.095	0.072	0.571	< 0.001
注：^a为t值，^b为χ²值。

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表 2 ICAS影响因素的多元回归分析

Table 2. Multiple regression analysis to identify factors influencing ICAS

变量	B	SE	Waldχ²	P值	OR值	95% CI
APOE	-0.296	0.231	4.203	0.003	1.654	1.353~2.011
年龄	0.241	0.147	6.272	0.031	1.566	1.122~2.451
注：各变量均以实际值赋值。

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表 3 ICAS的发病风险与APOE浓度相关性

Table 3. Correlation between the risk of ICAS and APOE concentration

组别	分组	OR(95% CI)	r值	P值
Adjust 1	三分位数2(32.7~47.2 μg/mL)	0.642(0.277~1.472)	0.437	< 0.001
	三分位数3(≥47.2 μg/mL)	0.251(0.081~0.573)
Adjust 2	三分位数2(32.7~47.2 μg/mL)	0.558(0.202~1.594)	0.481	< 0.01
	三分位数3(≥47.2 μg/mL)	0.194(0.084~0.581)
注：Adjust 1为调整年龄、性别后的结果；Adjust 2为调整年龄、性别、血脂参数后的结果。以三分位数1(＜32.7 μg/mL)为参照。

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表 4 APOE-ε4携带AIS患者与非APOE4携带AIS患者的基线临床比较

Table 4. Baseline clinical comparison of AIS patients with and without APOE-ε4

组别	例数	年龄(x±s，岁)	性别(男/女)	总胆固醇[M(P₂₅, P₇₅), mg/dL]	TG [M(P₂₅, P₇₅), mg/d]	HDL [M(P₂₅, P₇₅), mg/d]	LDL [M(P₂₅, P₇₅), mg/d]
携带ε4	213	62.82±12.11	136/77	4.57(1.72, 11.75)	1.51(0.46, 13.91)	1.02(0.55, 3.31)	2.67(0.63, 7.07)
非携带ε4	298	64.73±12.32	160/138	4.31(1.94, 19.66)	1.38(0.30, 15.55)	1.19(0.08, 2.83)	2.45(0.65, 7.96)
统计量		3.389^a	1.374^b	0.297^c	2.465^c	1.585^c	3.743^c
P值		0.511	0.533	0.002	0.025	0.722	<0.001
注：^a为t值, ^b为χ²值, ^c为Z值。

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表 5 6个月卒中预后不良(mRS≥2分)的多变量logistic回归分析

Table 5. Multivariable logistic regression analysis of poor stroke prognosis (mRS ≥ 2) at 6 months

变量	B	SE	Waldχ²	P值	OR值	95% CI
年龄	0.507	0.201	12.675	0.031	1.668	1.032~2.015
性别	1.175	1.241	1.809	0.125	3.238	1.743~9.034
是否携带ε4	1.531	0.233	28.351	< 0.001	4.622	3.512~6.091
总胆固醇	1.431	0.822	2.120	0.002	1.539	0.647~2.334
甘油三酯	2.433	0.713	4.785	0.025	11.393	1.562~21.147
高密度脂蛋白	1.624	0.917	1.931	0.036	5.073	2.305~6.884
低密度脂蛋白	0.814	0.253	12.719	< 0.001	2.256	1.524~3.257
注：自变量中年龄和血脂参数均以实际值赋值；携带ε4基因=1，非携带ε4基因=0；男性=1，女性=0。ε4携带与非携带者为对照；性别以女性为对照。

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