Data_Sheet_4_Novel Subgroups in Subarachnoid Hemorrhage and Their Association With Outcomes—A Systematic Review and Meta-Regression.DOCX

Background and Purpose: Subarachnoid hemorrhage (SAH) has long been classified into two main forms, aneurysmal SAH (aSAH) and non-aneurysmal SAH (naSAH), but the related risk factors for aSAH and naSAH are heterogeneous. Our objective was to determine the risk factors for SAH of known or unknown origin with respect to diagnostic evaluation in a large patient cohort. We sought to determine whether our classification system can further predict middle long-term stroke and death.
Methods: We performed a systematic review and meta-analysis to identify risk factors for each SAH subtype. The discovery phase analyzed 11 risk factors from case studies in the literature. Kruskal-Wallis, Cox regression, logistic regression, and Kaplan-Meier analyses were used to compare the two groups.
Results: A total of 14,904 (34.53%) male and 22,801 (52.84%) female patients were eligible for this study. At a median follow-up of 45.6 months, the 5-years overall survival was 97.768% (95% CI: 0.259–0.292) for aSAH patients and 87.904% (95% CI: 1.459–1.643) for naSAH patients. The 10-years survival rate was 93.870% (95% CI: 2.075–3.086) and 78.115% (95% CI: 2.810–3.156), respectively. Multi-risk factor subgroups showed significant intergroup differences. We identified eight risk factors (drugs, trauma, neoplastic, vessels lesion, inflammatory lesion, blood disease, aneurysm, peri-mesencephalic hemorrhage) using logistic regression, which were optimally differentiated among the aSAH [aSAH-S (AUC: 1), a-d-SAH (AUC: 0.9998), aSAH-T (AUC: 0.9199), aSAH-N (AUC: 0.9433), aSAH-V (AUC: 1), aSAH-I (AUC: 0.9954), a-bd-SAH (AUC: 0.9955)] and naSAH [na-pmSAH (AUC: 0.9979), na-ni-ivl-SAH (AUC: 1), na-t-SAH (AUC: 0.9997), na-ne-SAH (AUC: 0.9475), na-d-SAH (AUC: 0.7676)] subgroups. These models were applied in a parallel cohort, showing eight risk factors plus survival rates to predict the prognosis of SAH.
Conclusions: The classification of risk factors related to aSAH and naSAH is helpful in the diagnosis and prediction of the prognosis of aSAH and naSAH patients. Further validation is needed in future clinical applications.

背景与目的：蛛网膜下腔出血（Subarachnoid hemorrhage, SAH）长期以来被分为动脉瘤性蛛网膜下腔出血（aneurysmal SAH, aSAH）与非动脉瘤性蛛网膜下腔出血（non-aneurysmal SAH, naSAH）两大主要类型，但aSAH与naSAH的相关危险因素存在异质性。本研究旨在针对大型患者队列的诊断评估情况，明确已知或不明起源SAH的危险因素；同时探讨本研究的分类体系能否进一步预测中远期卒中与死亡事件。
方法：本研究通过系统评价与荟萃分析，明确各SAH亚型的危险因素。探索阶段对文献中病例研究的11项危险因素进行分析。采用克鲁斯卡尔-沃利斯检验、Cox回归、逻辑回归及Kaplan-Meier分析对两组患者进行比较。
结果：本研究共纳入符合标准的患者14904例男性（占34.53%）与22801例女性（占52.84%）。中位随访时间为45.6个月时，aSAH患者的5年总生存率为97.768%（95%置信区间（Confidence Interval, CI）：0.259~0.292），naSAH患者的5年总生存率为87.904%（95%置信区间（Confidence Interval, CI）：1.459~1.643）；10年生存率分别为93.870%（95%置信区间（Confidence Interval, CI）：2.075~3.086）与78.115%（95%置信区间（Confidence Interval, CI）：2.810~3.156）。多危险因素亚组分析显示组间存在显著差异。通过逻辑回归分析，我们明确了8项危险因素（药物、创伤、肿瘤性病变、血管病变、炎性病变、血液系统疾病、动脉瘤、中脑周围出血），其可在aSAH亚组[aSAH-S（曲线下面积（Area Under the Curve, AUC）：1）、a-d-SAH（AUC：0.9998）、aSAH-T（AUC：0.9199）、aSAH-N（AUC：0.9433）、aSAH-V（AUC：1）、aSAH-I（AUC：0.9954）、a-bd-SAH（AUC：0.9955）]与naSAH亚组[na-pmSAH（AUC：0.9979）、na-ni-ivl-SAH（AUC：1）、na-t-SAH（AUC：0.9997）、na-ne-SAH（AUC：0.9475）、na-d-SAH（AUC：0.7676）]中实现最优区分。将上述模型应用于平行队列后，结果显示8项危险因素联合生存率可用于预测SAH患者的预后。
结论：针对aSAH与naSAH的危险因素分类体系，有助于aSAH与naSAH患者的诊断及预后预测。未来临床应用中仍需开展进一步验证工作。