Department of Neurology, El Matareya Educational Hospital, Egypt.
Department of Intervention Neurology, Faculty of Medicine, Ain Shams University, Egypt.
Clin Neurol Neurosurg. 2020 Dec;199:106296. doi: 10.1016/j.clineuro.2020.106296. Epub 2020 Oct 7.
This study aims to investigate the genetic predisposition of haptoglobin (Hp) genotype as a predictor for cerebral vasospasm (CV) after acute subarachnoid hemorrhage (aSAH) in the Egyptian population. This permits CV risk factors stratification of patients with aSAH. Hence, it will guide the treatment plan and intensive monitoring for those patients.
The study was carried out at El Matareya Teaching Hospital, Cairo, Egypt. We studied 50 patients with aSAH who were prospectively recruited and followed up by transcranial Doppler (TCD) examination for 14 days following aneurysmal rupture to early detect hemodynamic changes associated with CV and also the occurrence of delayed cerebral ischemia (DCI) as a secondary outcome. In this study, we attempted to analyze Hp genotyping as a potential predictor of CV and DCI during the acute phase of aneurysmal SAH.
As a part of result analyses, among studied patients, 34 patients (68 %) developed CV and 19 patients (38 %) developed DCI. Only history of hypertension [RR = 1.6 (OR = 4)], diabetes mellitus [RR = 1.5 (OR = 3.4)] and smoking [RR = 1.5 (OR = 3.6)] had a significant independent relationship (P < 0.05) with short term risk to develop CV following aSAH. While, Age, sex, hyperlipidemia, cardiovascular disease and peripheral vascular disease, intracranial aneurysm site and size did not achieve significant association for developing CV. Regarding the poor Fisher scale and poor Hunt and Hess score both showed significant association with CV (P < 0.05). Genotyping of Hp protein among our study cohort revealed that the relative distribution of the three haptoglobin genotypes (Hp1-1, HP2-I & HP2-2) among Egyptian patients of aSAH was 14 %, 40 % and 46 %, respectively; (gene proportion being 0.34 for Hp1 and 0.66 for Hp2). Furthermore; Hp 2 allele was associated with radiographic vasospasm detected by TCD among the studied patients (2-2 & 2-1 Vs 1-1: RR = 5.4, OR = 19.8, P < 0.001). In the regression model; Hp genotype expressing Hp-2 allele is predictive for higher risk of development of CV after aSAH. Moreover, searching for the relationship between CV & Hp genotype and the risk for development of DCI; both variables failed to achieve a significant relationship for DCI (P > 0.05).
The Hp genotype may determine the susceptibility to cerebral vasospasm after acute aSAH. This has the potential for use in risk stratification by allowing for the identification of those patients requiring intensive monitoring due to their inherent genetic risk for developing CV allowing for the promising selective application of aggressive treatments to those patients.
本研究旨在探讨结合埃及人群的血红蛋白（Hp）基因型作为急性蛛网膜下腔出血（aSAH）后脑血管痉挛（CV）预测因子的遗传易感性。这使得可以对 aSAH 患者进行 CV 危险因素分层。因此，它将为这些患者指导治疗计划和强化监测。
本研究在埃及开罗的 El Matareya 教学医院进行。我们前瞻性地研究了 50 名 aSAH 患者，通过经颅多普勒（TCD）检查随访 14 天，以早期检测与 CV 相关的血流动力学变化，并作为次要结果检测迟发性脑缺血（DCI）的发生。在这项研究中，我们试图分析 Hp 基因分型作为 aSAH 急性期 CV 和 DCI 的潜在预测因子。
在研究患者中，34 名患者（68%）出现 CV，19 名患者（38%）出现 DCI。只有高血压病史[RR=1.6（OR=4）]、糖尿病病史[RR=1.5（OR=3.4）]和吸烟史[RR=1.5（OR=3.6）]与 aSAH 后短期发生 CV 有显著独立关系（P<0.05）。然而，年龄、性别、血脂异常、心血管疾病和外周血管疾病、颅内动脉瘤部位和大小与 CV 无显著相关性。关于较差的 Fisher 量表和较差的 Hunt 和 Hess 评分，均与 CV 有显著相关性（P<0.05）。在我们的研究队列中，Hp 蛋白的基因分型显示埃及 aSAH 患者的三种血红蛋白基因型（Hp1-1、HP2-I 和 HP2-2）的相对分布分别为 14%、40%和 46%；（基因比例为 Hp1 的 0.34 和 Hp2 的 0.66）。此外；在研究患者中，Hp2 等位基因与 TCD 检测到的放射性血管痉挛有关（2-2 和 2-1 vs 1-1：RR=5.4，OR=19.8，P<0.001）。在回归模型中；表达 Hp-2 等位基因的 Hp 基因型预测 aSAH 后 CV 发生的风险更高。此外，在寻找 CV 与 Hp 基因型之间的关系和 DCI 发生风险之间的关系时，两个变量都与 DCI 没有显著关系（P>0.05）。
Hp 基因型可能决定急性 aSAH 后脑血管痉挛的易感性。这有可能通过允许识别因固有 CV 发生风险而需要强化监测的患者进行风险分层，从而有望选择性地对这些患者应用积极治疗。
