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载脂蛋白E ε4与创伤性脑出血患者进行性出血性损伤的关联。

Association of APOE ε4 with progressive hemorrhagic injury in patients with traumatic intracerebral hemorrhage.

作者信息

Wan Xueyan, Gan Chao, You Chao, Fan Ting, Zhang Suojun, Zhang Huaqiu, Wang Sheng, Shu Kai, Wang Xiong, Lei Ting

机构信息

1Department of Neurosurgery and.

2Department of Laboratory Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

出版信息

J Neurosurg. 2019 Jul 19;133(2):496-503. doi: 10.3171/2019.4.JNS183472. Print 2020 Aug 1.

Abstract

OBJECTIVE

The intracranial hematoma volume in patients with traumatic brain injury is a key parameter for the determination of the management approach and outcome. Apolipoprotein E (APOE) ε4 is reported to be a risk factor for larger hematoma volume, which might contribute to a poor outcome. However, whether APOE ε4 is related to progressive hemorrhagic injury (PHI), a common occurrence in the clinical setting, remains unclear. In this study, the authors aimed to investigate the association between the APOE genotype and occurrence of PHI.

METHODS

This prospective study included a cohort of 123 patients with traumatic intracerebral hemorrhage who initially underwent conservative treatment. These patients were assigned to the PHI or non-PHI group according to the follow-up CT scan. A polymerase chain reaction and sequencing method were carried out to determine the APOE genotype. Multivariate logistic regression analysis was applied to identify predictors of PHI.

RESULTS

The overall frequency of the alleles was as follows: E2/2, 0%; E2/3, 14.6%; E3/3, 57.8%; E2/4, 2.4%; E3/4, 22.8%; and E4/4, 2.4%. Thirty-four patients carried at least one allele of ε4. In this study 60 patients (48.8%) experienced PHI, and the distribution of the alleles was as follows: E2/2, 0%; E2/3, 5.7%; E3/3, 22.8%; E2/4, 2.4%; E3/4, 16.3%; and E4/4, 1.6%, which was significantly different from that in the non-PHI group (p = 0.008). Additionally, the late operation rate in the PHI group was significantly higher than that in the non-PHI group (24.4% vs 11.4%, p = 0.002). Multivariate logistic regression identified APOE ε4 (OR 5.14, 95% CI 2.40-11.62), an elevated international normalized ratio (OR 3.57, 95% CI 1.61-8.26), and higher glucose level (≥ 10 mmol/L) (OR 3.88, 95% CI 1.54-10.77) as independent risk factors for PHI. Moreover, APOE ε4 was not a risk factor for the coagulopathy and outcome of the patients with traumatic intracerebral hemorrhage.

CONCLUSIONS

The presence of APOE ε4, an elevated international normalized ratio, and a higher glucose level (≥ 10 mmol/L) are predictors of PHI. Additionally, APOE ε4 is not associated with traumatic coagulopathy and patient outcome.

摘要

目的

创伤性脑损伤患者的颅内血肿体积是决定治疗方法和预后的关键参数。据报道,载脂蛋白E(APOE)ε4是血肿体积较大的一个危险因素,这可能导致不良预后。然而,APOE ε4是否与临床常见的进行性出血性损伤(PHI)相关仍不清楚。在本研究中,作者旨在探讨APOE基因型与PHI发生之间的关联。

方法

这项前瞻性研究纳入了123例最初接受保守治疗的创伤性脑出血患者队列。根据随访CT扫描将这些患者分为PHI组或非PHI组。采用聚合酶链反应和测序方法确定APOE基因型。应用多因素逻辑回归分析来确定PHI的预测因素。

结果

等位基因的总体频率如下:E2/2,0%;E2/3,14.6%;E3/3,57.8%;E2/4,2.4%;E3/4,22.8%;E4/4,2.4%。34例患者携带至少一个ε4等位基因。本研究中60例患者(48.8%)发生了PHI,等位基因分布如下:E2/2,0%;E2/3,5.7%;E3/3,22.8%;E2/4,2.4%;E3/4,16.3%;E4/4,1.6%,与非PHI组有显著差异(p = 0.008)。此外,PHI组的晚期手术率显著高于非PHI组(24.4%对11.4%,p = 0.002)。多因素逻辑回归确定APOE ε4(比值比5.14,95%置信区间2.40 - 11.62)、国际标准化比值升高(比值比3.57,95%置信区间1.61 - 8.26)和较高血糖水平(≥10 mmol/L)(比值比3.88,95%置信区间1.54 - 10.77)为PHI的独立危险因素。此外,APOE ε4不是创伤性脑出血患者凝血障碍和预后的危险因素。

结论

APOE ε4的存在、国际标准化比值升高和较高血糖水平(≥10 mmol/L)是PHI的预测因素。此外,APOE ε4与创伤性凝血障碍和患者预后无关。

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