Novel Subgroups in Subarachnoid Hemorrhage and Their Association With Outcomes-A Systematic Review and Meta-Regression

Abstract

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.

Keywords: cohort studies; follow up risk time points; related-risk factors disease; risk factors; subgroup subarachnoid hemorrhage.

Figure 1

Different risk factors combined with clinical SAH improve accuracy of predicting models for a-SAH, na-SAH. (A,B) Receiver operator characteristic (ROC) curves for different risk factors along in a-SAH subtype (A) and na-SAH subtype (B). The value the AUC (the area under the ROC curve) and 95% CI. (A) Receiver operator characteristic (ROC) curves for different risk factors along in a-SAH subtype. ROC curve showing the sensitivity and specificity of a-SAH subgroup classification. (B) Receiver operator characteristic (ROC) curves for different risk factors along in na-SAH subtype. ROC curve showing the sensitivity and specificity of na-SAH subgroup classification. (C) Survival ratio for individual a-SAH subgroup categorized based on follow-up time after 60 and 120 months. Significant difference in a-SAH subgroup. (D) Survival ratio for individual na-SAH subgroup categorized based on follow-up time after 60 and 120 months. Significant difference in na-SAH subgroup.

Figure 2

The Kaplan-Meier survival curve analysis of differ follow-up timepoint for SAH subtype stratified by disease-related or probable causes. (1) (A) the aSAH-S subgroup, (B) the a-d-SAH subgroup, (C) the aSAH-T subgroup, (D) the aSAH-N subgroup, (E) the aSAH-V subgroup, (F) the aSAH-I subgroup, (G) the a-bd-SAH subgroup, (H) aSAH-subgroup total figure. (2) (I) the na-pmSAH subgroup, (J) the na-ni-ivl-SAH subgroup, (K) the na-t-SAH subgroup, (L) the na-ne-SAH subgroup, (M) the na-d-SAH subgroup, (N) naSAH-subgroup total figure.

Figure 3

Risk of bias and applicability concerns graph: review author's judgements about each risk of bias item for each include randomized controlled study (RCT), cohort original studies and case series/case-control original studies (domain presented as percentages across included studies). (A) Case-control original studies, (B) Case-cohort original studies, (C) Case series report studies, (D) RCT.

Figure 4

Risk of bias and applicability concerns summary: review author's judgements about each risk of bias item for each included RCT.