Association between Interleukin-6 and Multiple Acute Infarctions in Symptomatic Intracranial Atherosclerotic Disease.

Jinglin Mo, Zimo Chen, Mengxing Wang, Aichun Cheng, Jiejie Li, Yuesong Pan, Yong Jiang, Jing Jing, Yongjun Wang, Yuehua Pu, Zixiao Li
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Abstract

Background: Interleukin-6 (IL-6) plays an important role in the pathophysiology of atherosclerosis. This study aimed to determine whether IL-6 is a crucial biomarker associated with Multiple Acute Infarctions (MAIs), which indicate an important stroke mechanism of artery-to-artery embolism with a high risk of stroke recurrence in symptomatic Intracranial Atherosclerotic Disease (sICAD). We tested the association between circulating IL-6 levels and the presence of MAIs in a prospective population-based registry.

Methods: We included 1,919 patients with sICAD and baseline IL-6 levels from the Third China National Stroke Registry for the current analysis, The baseline IL-6 was centrally measured at Beijing Tiantan Hospital, Images of the brain parenchyma and vascular structures were digitized and then blindly and independently read by two groups of trained readers, The recruited patients were divided into 3 groups according to IL-6 tertiles, The relationship between baseline IL-6 tertile levels and the presence of MAIs was modeled using multivariate logistic regression.

Results: Compared to patients in the first IL-6 tertile those in the second and third tertiles demonstrated a significantly higher proportion of MAIs. The odds ratios were 1.81 [95% Confidence Interval (CI), 1.42-2.30] for the second versus first tertile and 2.15 (95% CI 1.66-2.79) for the third versus first tertile, The proportion of patients with MAIs increased with rising IL-6 tertiles observed at 59.3%, 71.6% and 76.4% for the first, second and third tertiles, respectively (P for trend < 0.001). The association between higher IL-6 tertiles and increased proportion of MAIs was also present in subgroups defined by age < 65 years, age ≥ 65 years, male, and high-sensitivity C-reactive Protein (hs-CRP) ≥ 2 mg/L. Furthermore, a significant interaction was detected for the hs- CRP subgroup (P = 0.038). In sensitivity analyses, the positive correlation between IL-6 levels and the proportion of MAIs remained consistent.

Conclusion: In patients with sICAD, higher IL-6 levels were associated with an increased proportion of MAIs. IL-6 could be used as a biomarker and a potential therapeutic target for future atherosclerosis treatment and prevention in patients with sICAD.

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白细胞介素-6与无症状颅内动脉粥样硬化病多次急性梗死之间的关系
背景:白细胞介素-6(IL-6白细胞介素-6(IL-6)在动脉粥样硬化的病理生理学中起着重要作用。这项研究旨在确定IL-6是否是与多发性急性脑梗塞(MAIs)相关的重要生物标志物,多发性急性脑梗塞表明动脉-动脉栓塞是一种重要的卒中机制,在无症状颅内动脉粥样硬化性疾病(sICAD)中具有很高的卒中复发风险。我们在一项前瞻性人群登记中检验了循环 IL-6 水平与 MAIs 存在之间的关联:北京天坛医院对基线IL-6进行了集中测量,对脑实质和血管结构的图像进行了数字化处理,然后由两组训练有素的阅读者进行独立盲读,并根据IL-6三分位数将所招募的患者分为3组:与 IL-6 第一分位数的患者相比,第二和第三分位数患者的 MAI 比例明显更高。IL-6三分位数越高,MAI患者的比例越高,第一、第二和第三三分位数分别为59.3%、71.6%和76.4%(趋势P<0.001)。在按年龄<65岁、年龄≥65岁、男性和高敏C反应蛋白(hs-CRP)≥2 mg/L定义的亚组中,IL-6三分位数越高与MAI比例增加之间也存在关联。此外,在 hs- CRP 亚组中还发现了明显的交互作用(P = 0.038)。在敏感性分析中,IL-6水平与MAI比例之间的正相关性保持一致:结论:在sICAD患者中,IL-6水平越高,MAI比例越高。IL-6可作为一种生物标志物和潜在的治疗靶点,用于sICAD患者未来的动脉粥样硬化治疗和预防。
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