Department of Neurology Beijing Tiantan Hospital, Capital Medical University Beijing China.
China National Clinical Research Center for Neurological Diseases Beijing China.
J Am Heart Assoc. 2024 Jun 18;13(12):e033616. doi: 10.1161/JAHA.123.033616. Epub 2024 Jun 14.
We aim to identify the distinct lesion patterns and regions associated with functional outcome and inflammation in patients with acute ischemic stroke, and investigate whether the association between lesion patterns and functional outcome was mediated by inflammation.
We performed nonnegative matrix factorization to derived low-dimensional lesion patterns (atoms), and Bayesian linear regression models were applied to explore the associations of lesion patterns with inflammatory factors including high-sensitivity C-reactive protein and interleukin-6, as well as functional outcome (defined as modified Rankin Scale score at 3 months). The difference distribution mean and 95% highest probability density interval (HPDI) were calculated. Mediation analysis was used to examine the mediating effects of inflammation on the relationships between lesion patterns and functional outcome. Seven lesion patterns were derived from 5914 patients with acute ischemic stroke. Lesion patterns distributed in the cortical regions were associated with inflammatory response, including atom 1 (interleukin-6: mean, 0.113 [95% HPDI, 0.073-0.162]; high-sensitivity C-reactive protein: mean, 0.082 [95% HPDI, 0.038-0.123]) and atom 4 (interleukin-6: mean, 0.113 [95% HPDI, 0.071-0.167]; high-sensitivity C-reactive protein: mean, 0.108 [95% HPDI, 0.058-0.165]). These lesion patterns were also significantly associated with functional outcome (atom 1: mean, 1.958 [95% HPDI, 1.538-2.383]; atom 4: mean, 2.245 [95% HPDI, 1.773-2.741]). Mediation analysis suggested that interleukin-6 explained 15.34% and 7.47% in the association of atom 1 and atom 4 with functional outcome, respectively.
Certain lesion patterns that are associated with both inflammation and functional outcome of acute ischemic stroke, especially cortical infarction, may play a role in functional outcome through modulating inflammatory reactions.
本研究旨在确定与急性缺血性脑卒中患者功能结局和炎症相关的独特病变模式和区域，并探讨病变模式与功能结局之间的关联是否通过炎症介导。
我们采用非负矩阵分解（NMF）方法推导出低维病变模式（原子），并应用贝叶斯线性回归模型探讨病变模式与炎症因子（包括高敏 C 反应蛋白和白细胞介素 6）之间的相关性，以及与功能结局（定义为 3 个月时的改良 Rankin 量表评分）的相关性。计算差异分布均值和 95%最高概率密度区间（HPDI）。采用中介分析检验炎症在病变模式与功能结局之间关系中的中介作用。
从 5914 例急性缺血性脑卒中患者中提取出 7 种病变模式。皮质区分布的病变模式与炎症反应相关，包括原子 1（白细胞介素 6：均值，0.113[95% HPDI，0.073-0.162]；高敏 C 反应蛋白：均值，0.082[95% HPDI，0.038-0.123]）和原子 4（白细胞介素 6：均值，0.113[95% HPDI，0.071-0.167]；高敏 C 反应蛋白：均值，0.108[95% HPDI，0.058-0.165]）。这些病变模式与功能结局也显著相关（原子 1：均值，1.958[95% HPDI，1.538-2.383]；原子 4：均值，2.245[95% HPDI，1.773-2.741]）。中介分析表明，白细胞介素 6 分别解释了原子 1 和原子 4 与功能结局关联的 15.34%和 7.47%。
某些与急性缺血性脑卒中炎症和功能结局均相关的病变模式，尤其是皮质梗死，可能通过调节炎症反应在功能结局中发挥作用。
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