Department of Biostatistics, University of Kentucky, Lexington, KY, USA.
Department of Neurology, University of Kentucky, Lexington, KY, USA.
J Neuroinflammation. 2024 Aug 17;21(1):205. doi: 10.1186/s12974-024-03201-9.
The Appalachia region of North America is known to have significant health disparities, specifically, worse risk factors and outcomes for stroke. Appalachians are more likely to have comorbidities related to stroke, such as diabetes, obesity, and tobacco use, and are often less likely to have stroke interventions, such as mechanical thrombectomy (MT), for emergent large vessel occlusion (ELVO). As our Comprehensive Stroke Center directly serves stroke subjects from both Appalachian and non-Appalachian areas, inflammatory proteomic biomarkers were identified associated with stroke outcomes specific to subjects residing in Appalachia.
There were 81 subjects that met inclusion criteria for this study. These subjects underwent MT for ELVO, and carotid arterial blood samples acquired at time of intervention were sent for proteomic analysis. Samples were processed in accordance with the Blood And Clot Thrombectomy Registry And Collaboration (BACTRAC; clinicaltrials.gov; NCT03153683). Statistical analyses were utilized to examine whether relationships between protein expression and outcomes differed by Appalachian status for functional (NIH Stroke Scale; NIHSS and Modified Rankin Score; mRS), and cognitive outcomes (Montreal Cognitive Assessment; MoCA).
No significant differences were found in demographic data or co-morbidities when comparing Appalachian to non-Appalachian subjects. However, time from stroke onset to treatment (last known normal) was significantly longer and edema volume significantly higher in patients from Appalachia. Further, when comparing Appalachian to non-Appalachian subjects, there were significant unadjusted differences in the NIHSS functional outcome. A comprehensive analysis of 184 proteins from Olink proteomic (92 Cardiometabolic and 92 Inflammation panels) showed that the association between protein expression outcomes significantly differed by Appalachian status for seven proteins for the NIHSS, two proteins for the MoCA, and three for the mRS.
Our study utilizes an ELVO tissue bank and registry to investigate the intracranial/intravascular proteomic environment occurring at the time of thrombectomy. We found that patients presenting from Appalachian areas have different levels of proteomic expression at the time of MT when compared to patients presenting from non-Appalachian areas. These proteins differentially relate to stroke outcome and could be used as prognostic biomarkers, or as targets for novel therapies. The identification of a disparate proteomic response in Appalachian patients provides initial insight to the biological basis for health disparity. Nevertheless, further investigations through community-based studies are imperative to elucidate the underlying causes of this differential response.
北美洲的阿巴拉契亚地区已知存在显著的健康差距，特别是在中风的风险因素和结果方面更为严重。阿巴拉契亚人更容易出现与中风相关的合并症，如糖尿病、肥胖症和烟草使用，而且他们往往不太可能接受机械血栓切除术 (MT) 等紧急大血管闭塞 (ELVO) 的干预措施。由于我们的综合卒中中心直接为来自阿巴拉契亚和非阿巴拉契亚地区的卒中患者服务，因此确定了与居住在阿巴拉契亚地区的患者特定的卒中结果相关的炎症蛋白组生物标志物。
本研究纳入了 81 名符合纳入标准的患者。这些患者接受了 ELVO 的 MT 治疗，在干预时采集颈动脉动脉血液样本进行蛋白质组分析。样本按照血栓切除术注册和协作研究（BACTRAC；clinicaltrials.gov；NCT03153683）进行处理。利用统计分析来检验蛋白表达与结局之间的关系是否因阿巴拉契亚状态的不同而有所差异，包括功能结局（NIH 卒中量表；NIHSS 和改良 Rankin 评分；mRS）和认知结局（蒙特利尔认知评估；MoCA）。
在比较阿巴拉契亚地区和非阿巴拉契亚地区的患者时，两组在人口统计学数据或合并症方面没有显著差异。然而，阿巴拉契亚地区患者从卒中发作到治疗（最后一次正常）的时间明显更长，水肿体积明显更高。此外，在比较阿巴拉契亚地区和非阿巴拉契亚地区的患者时，NIHSS 功能结局的未调整差异具有统计学意义。来自 Olink 蛋白质组学的 184 种蛋白的综合分析（92 种心脏代谢和 92 种炎症面板）表明，在 NIHSS 方面，蛋白表达结局与阿巴拉契亚状态的关联有 7 种蛋白存在显著差异，MoCA 有 2 种蛋白，mRS 有 3 种蛋白。
本研究利用 ELVO 组织库和注册系统，研究了血栓切除时颅内/血管内的蛋白质组环境。我们发现，与来自非阿巴拉契亚地区的患者相比，来自阿巴拉契亚地区的患者在接受 MT 时的蛋白表达水平存在差异。这些蛋白与卒中结局的相关性不同，可作为预后生物标志物，或作为新型治疗的靶点。在阿巴拉契亚患者中发现的不同的蛋白质组反应提供了对健康差异的生物学基础的初步见解。然而，通过社区研究进行进一步的调查对于阐明这种差异反应的潜在原因至关重要。
