Health Research Board (HRB) Stroke Clinical Trials Network Ireland (SCTNI), Dublin, Ireland (J.J.M., C.W., S.G., P.J.K.).
School of Medicine, University College Dublin (UCD), Ireland (J.J.M., S.G., P.J.K.).
Stroke. 2023 May;54(5):1289-1299. doi: 10.1161/STROKEAHA.122.040529. Epub 2023 Apr 7.
Anti-inflammatory therapies reduce recurrent vascular events in coronary disease. Existing studies have reported highly conflicting findings for the association of blood inflammatory markers with vascular recurrence after stroke leading to uncertainty about the potential of anti-inflammatory therapies after stroke and no consensus about the utility of measurement of inflammatory markers in current guidelines.
We investigated the association between hsCRP (high-sensitivity C-reactive protein), IL-6 (interluekin-6), and recurrent major adverse cardiovascular events (MACE), and stroke from individual participant data from 8420 patients with ischemic stroke/transient ischemic attack from 10 prospective studies. We did within-study multivariable regression analyses and then combined adjusted risk ratio (RR) by random-effects meta-analysis.
During 18 920 person-years of follow-up, 1407 (16.7% [95% CI, 15.9-17.5]) patients had MACE and 1191 (14.1% [95% CI, 13.4-14.9]) patients had recurrent stroke. On bivariate analysis, baseline IL-6 was associated with MACE (RR, 1.26 [95% CI, 1.10-1.43]) and recurrent stroke (RR, 1.18 [95% CI, 1.05-1.32]), per unit increase logIL-6. Similar associations were observed for hsCRP (MACE RR, 1.19 [95% CI, 1.09-1.29]; recurrent stroke RR, 1.12 [95% CI, 1.04-1.21], per unit increase loghsCRP). After adjustment for vascular risk factors and treatment, independent associations remained with MACE (IL-6, RR, 1.12 [95% CI, 1.04-1.21]; hsCRP, RR, 1.09 [95% CI, 1.04-1.15]) and recurrent stroke (IL-6, RR, 1.09 [95% CI, 1.00-1.19]; hsCRP, RR, 1.05 [95% CI, 1.00-1.11]). Comparing the top with the bottom quarters (Q4 versus Q1), IL-6 (RR, 1.35 [95% CI, 1.09-1.67]) and hsCRP (RR, 1.31 [95% CI, 1.07-1.61]) were associated with MACE after adjustment. Similar results were observed for recurrent stroke for IL-6 (RR, 1.33 [95% CI, 1.08-1.65]) but not hsCRP (RR, 1.16 [95% CI, 0.93-1.43]).
Blood markers of inflammation were independently associated with vascular recurrence after stroke, strengthening the rationale for randomized trials of anti-inflammatory therapies for secondary prevention after ischemic stroke/TIA.
抗炎疗法可降低冠心病患者的复发性血管事件。现有研究报告称，血液炎症标志物与中风后血管复发之间的关联存在高度冲突的结果，导致对中风后抗炎治疗的潜在作用存在不确定性，且目前的指南中也没有关于炎症标志物测量的效用的共识。
我们从 10 项前瞻性研究中，对 8420 例缺血性中风/短暂性脑缺血发作患者的个体参与者数据，调查了 hsCRP（高敏 C 反应蛋白）、IL-6（白细胞介素-6）与主要不良心血管事件（MACE）和中风的复发之间的关联。我们进行了研究内多变量回归分析，然后通过随机效应荟萃分析合并调整后的风险比（RR）。
在 18920 人年的随访期间，1407 例（16.7% [95%CI，15.9-17.5%]）患者发生 MACE，1191 例（14.1% [95%CI，13.4-14.9%]）患者发生中风复发。在二元分析中，基线 IL-6 与 MACE（RR，1.26 [95%CI，1.10-1.43]）和中风复发（RR，1.18 [95%CI，1.05-1.32]）呈正相关，每单位 logIL-6 增加。hsCRP 也观察到类似的关联（MACE RR，1.19 [95%CI，1.09-1.29]；中风复发 RR，1.12 [95%CI，1.04-1.21]，每单位 loghsCRP 增加）。在调整血管危险因素和治疗后，与 MACE（IL-6，RR，1.12 [95%CI，1.04-1.21]；hsCRP，RR，1.09 [95%CI，1.04-1.15]）和中风复发（IL-6，RR，1.09 [95%CI，1.00-1.19]；hsCRP，RR，1.05 [95%CI，1.00-1.11]）仍存在独立关联。与 Q4 与 Q1 相比（最高四分位数与最低四分位数相比），IL-6（RR，1.35 [95%CI，1.09-1.67]）和 hsCRP（RR，1.31 [95%CI，1.07-1.61]）在调整后与 MACE 相关。IL-6（RR，1.33 [95%CI，1.08-1.65]）与中风复发相关，但 hsCRP（RR，1.16 [95%CI，0.93-1.43]）无相关性。
炎症血液标志物与中风后血管复发独立相关，为缺血性中风/TIA 后二级预防的抗炎治疗随机试验提供了更强的理论依据。
