Gorey Sarah, McCabe John J, Collins Sean, McAuley Karl, Inzitari Rosanna, Harbison Joe, Marnane Michael, Williams David J, Kelly Peter J
Stroke Clinical Trials Network Ireland (SCTNI), Dublin, Ireland.
School of Medicine, University College Dublin, Dublin, Ireland.
Cerebrovasc Dis Extra. 2025;15(1):19-29. doi: 10.1159/000540773. Epub 2024 Dec 11.
Acute and late inflammatory markers including high-sensitivity C-reactive protein (hsCRP) and interleukin-6 (IL-6) are associated with future vascular events after stroke. However, few longitudinal studies exist examining the intra-individual reproducibility of inflammatory biomarker measures at different timepoints after atherosclerotic stroke. We sought to examine the reproducibility of hsCRP and IL-6 in a cohort of patients with minor stroke or transient ischaemic attack (TIA) caused by ipsilateral carotid atherosclerosis.
Two observational cohort studies (DUCASS and BIOVASC) were pooled. Included patients had non-severe ischaemic stroke and ipsilateral internal carotid artery stenosis (≥50%). Patients had bloods drawn within 2 weeks of their index stroke/TIA event which was stored for later analysis. All patients included were followed up at 5 years, and repeat phlebotomy was performed. Bloods were analysed for hsCRP and IL-6 using high-throughput immunochemiluminescence. Difference between baseline and follow-up blood levels and intraclass correlation (ICC) was calculated.
Ninety-five participants were included, median age 69 (IQR: 63-77), and 51 (53.7%) had TIA as their presenting event. When biomarkers were dichotomised (for hsCRP <2 mg/L or ≥2 mg/L, and for IL-6 <7.5 pg/mL [median] or ≥7.5 pg/mL), 68.4% (IL-6) and 65.2% (hsCRP) of participants remained in the same risk category (high or low) over time. However, when analysed as a continuous variable, ICC coefficients were low: ICC for IL-6 0.14 (95% CI: -0.06 to 0.33), ICC for hsCRP 0.05 (95% CI: -0.14 to 0.25). ICC increased after removing outliers. Clinical characteristics and treatment were not associated with observed variability.
Our results suggest that concordance between early- and late-phase inflammatory marker risk categories is modest, and absolute levels are not highly correlated at early and late timepoints, despite associations at both times with future vascular risk. Investigators should standardise timing of phlebotomy and analysis protocols in future studies of inflammatory biomarkers.
包括高敏C反应蛋白（hsCRP）和白细胞介素-6（IL-6）在内的急性和晚期炎症标志物与卒中后未来的血管事件相关。然而，很少有纵向研究探讨动脉粥样硬化性卒中后不同时间点炎症生物标志物测量的个体内可重复性。我们试图在一组由同侧颈动脉粥样硬化引起的轻度卒中和短暂性脑缺血发作（TIA）患者中研究hsCRP和IL-6的可重复性。
汇总两项观察性队列研究（DUCASS和BIOVASC）。纳入的患者患有非严重缺血性卒中和同侧颈内动脉狭窄（≥50%）。患者在首次卒中/TIA事件发生后2周内采血并储存以备后续分析。所有纳入患者均随访5年，并进行重复静脉穿刺采血。使用高通量免疫化学发光法分析血液中的hsCRP和IL-6。计算基线和随访血液水平之间的差异以及组内相关系数（ICC）。
纳入95名参与者，中位年龄69岁（四分位间距：63 - 77岁），51名（53.7%）以TIA为首发事件。当将生物标志物进行二分法分类（hsCRP <2 mg/L或≥2 mg/L，IL-6 <7.5 pg/mL[中位数]或≥7.5 pg/mL）时，随着时间推移，68.4%（IL-6）和65.2%（hsCRP）的参与者仍处于相同风险类别（高或低）。然而，当作为连续变量分析时，ICC系数较低：IL-6的ICC为0.14（95%置信区间：-0.06至0.33），hsCRP的ICC为0.05（95%置信区间：-0.14至0.25）。去除异常值后ICC增加。临床特征和治疗与观察到的变异性无关。
我们的结果表明，早期和晚期炎症标志物风险类别之间的一致性一般，尽管早期和晚期炎症标志物水平均与未来血管风险相关，但早期和晚期的绝对水平相关性不高。在未来炎症生物标志物的研究中，研究者应规范静脉穿刺采血时间和分析方案。
