Coveney Sarah, McCabe John J, Murphy Sean, Belton Orina, Gray Cleona, Cassidy Tim, Dolan Eamon, de Gaetano Monica, Harbison Joe, Horgan Gillian, Marnane Michael, Merwick Aine, Noone Imelda, Williams David J, Kelly Peter J
Stroke Service, Mater University Hospital and University College Dublin, Dublin, Ireland.
Health Research Board Stroke Clinical Trials Network, Dublin, Ireland.
Cerebrovasc Dis. 2022;51(2):178-187. doi: 10.1159/000517739. Epub 2021 Sep 8.
The 5-year recurrence risk after ischaemic stroke and transient ischaemic attack (TIA) is 25-30%. Although inflammation may be a target for prevention trials, the contribution of plaque inflammation to acute cerebrovascular events remains unclear. We investigated the association of acute inflammatory cytokines and high-sensitivity C-reactive protein (CRP) with recently symptomatic carotid atherosclerosis in a prospective cohort study.
Blood and Imaging markers of TIA BIO-TIA) is a multicentre prospective study of imaging and inflammatory markers in patients with TIA. Exclusion criteria were infection and other co-morbid illnesses associated with inflammation. CRP and serum cytokines (interleukin [IL]-6, IL-1β, IL-8, IL-10, IL-12, interferon-γ [IFN-γ] and tumour necrosis factor-α [TNF-α]) were measured. All patients had carotid imaging.
Two hundred and thirty-eight TIA cases and 64 controls (TIA mimics) were included. Forty-nine (20.6%) cases had symptomatic internal carotid artery stenosis. Pro-inflammatory cytokine levels increased in a dose-dependent manner across controls, TIA without carotid stenosis (CS), and TIA with CS (IL-1β, ptrend = 0.03; IL-6, ptrend < 0.0001; IL-8, ptrend = 0.01; interferon (IFN)-γ, ptrend = 0.005; TNF-α, ptrend = 0.003). Results were unchanged when DWI-positive cases were excluded. On multivariable linear regression, only age (p = 0.01) and CS (p = 0.04) independently predicted log-IL-6. On multivariable Cox regression, CRP was the only independent predictor of 90-day stroke recurrence (adjusted hazard ratio per 1-unit increase 1.03 [95% CI: 1.01-1.05], p = 0.003).
Symptomatic carotid atherosclerosis was associated with elevated cytokines in TIA patients after controlling for other sources of inflammation. High-sensitivity CRP was associated with recurrent ischaemic stroke at 90 days. These findings implicate acute plaque inflammation in the pathogenesis of cerebral thromboembolism and support a rationale for randomized trials of anti-inflammatory therapy for stroke patients, who were excluded from coronary trials.
缺血性中风和短暂性脑缺血发作（TIA）后5年的复发风险为25%-30%。尽管炎症可能是预防试验的一个靶点，但斑块炎症对急性脑血管事件的影响仍不清楚。在一项前瞻性队列研究中，我们调查了急性炎症细胞因子和高敏C反应蛋白（CRP）与近期有症状的颈动脉粥样硬化之间的关联。
TIA生物标志物研究（BIO-TIA）是一项针对TIA患者的影像学和炎症标志物的多中心前瞻性研究。排除标准为感染和其他与炎症相关的合并疾病。检测CRP和血清细胞因子（白细胞介素[IL]-6、IL-1β、IL-8、IL-10、IL-12、干扰素-γ[IFN-γ]和肿瘤坏死因子-α[TNF-α]）。所有患者均进行颈动脉成像。
纳入238例TIA病例和64例对照（TIA模拟病例）。49例（20.6%）病例有症状性颈内动脉狭窄。促炎细胞因子水平在对照组、无颈动脉狭窄（CS）的TIA患者和有CS的TIA患者中呈剂量依赖性增加（IL-1β，趋势p=0.03；IL-6，趋势p<0.0001；IL-8，趋势p=0.01；干扰素（IFN）-γ，趋势p=0.005；TNF-α，趋势p=0.003）。排除DWI阳性病例后结果不变。在多变量线性回归中，只有年龄（p=0.01）和CS（p=0.04）独立预测log-IL-6。在多变量Cox回归中，CRP是90天中风复发的唯一独立预测因子（每增加1个单位的调整风险比为1.03[95%CI：1.01-1.05]，p=0.003）。
在控制其他炎症来源后，有症状的颈动脉粥样硬化与TIA患者细胞因子升高有关。高敏CRP与90天时的缺血性中风复发有关。这些发现提示急性斑块炎症在脑血栓栓塞的发病机制中起作用，并支持对被排除在冠状动脉试验之外的中风患者进行抗炎治疗随机试验的理论依据。
