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文献速递TIA

血液炎症生物标志物对卒中/TIA后长期复发风险的预测价值

Persistence of Association of Blood Biomarkers With Risk of Recurrent Stroke on Long-Term Follow-Up: Population-Based Study
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本研究基于牛津血管研究（OXVASC）2002–2011年连续纳入的1292例TIA或卒中患者，随访至2025年，评估12种血液生物标志物对长期卒中复发的预测作用。结果显示炎症相关生物标志物对10年复发风险有持续预测价值，且不随随访时间延长而减弱。

要点

  • 炎症生物标志物升高可预测TIA/卒中后10年卒中复发风险
  • 多个炎症标志物同时升高时复发负担更高，风险不随时间减弱
  • 神经元损伤和血栓相关标志物对卒中复发的预测价值普遍较低

核心结论

  • 炎症生物标志物对TIA/卒中后长期卒中复发的预测价值高于神经元损伤或血栓相关生物标志物
  • 多个炎症标志物升高时预测价值更强，且独立于其他血管危险因素
  • 预测价值在5–10年随访期内未随时间减弱，支持长期抗炎二级预防策略的试验

研究设计与样本

  • 基于人群的前瞻性队列研究（OXVASC），纳入2002–2011年连续的TIA或卒中患者1292例
  • 采用Cox回归和负二项回归分析，调整年龄、性别和基线血管危险因素

主要发现

  • 1292例患者平均年龄73.1岁（SD 13.2），男性占47.8%，280例患者发生365次卒中复发
  • IL-6调整后发病率比为1.21（95%CI 1.04–1.42），CRP为1.29（95%CI 1.11–1.49），TNFR-1为1.24（95%CI 1.05–1.46）
  • NGAL调整后发病率比为1.15（95%CI 0.99–1.33），炎症标志物中相对较弱
  • 炎症标志物升高个数（最高四分位数）与复发负担相关，发病率比为1.31（95%CI 1.15–1.50），P<0.001
  • TIA和轻型卒中亚组的关联与整体结果相似

关键数值与推荐

  • 按随访时间段分组，90天内心血管事件HR为1.24（95%CI 0.98–1.57），90天至1年HR为1.24（95%CI 0.95–1.62）
  • 1至5年HR为1.22（95%CI 1.01–1.47），5至10年HR为1.34（95%CI 1.06–1.68）

临床怎么用

  • TIA或卒中患者急性期后检测炎症标志物有助于识别长期复发高危人群
  • 多个炎症标志物同时处于最高四分位数的患者可考虑更积极的长期二级预防管理
  • 炎症通路可能成为TIA/卒中后长期二级预防的抗炎治疗靶点

局限性

  • 仅纳入单一中心的基于人群队列，结果的普遍性需在其他人群中验证
  • NGAL的效应估计置信区间跨1，关联证据相对不充分
  • 生物标志物仅测量TIA或卒中后单次时间点，无法反映动态变化

以上解读依据论文摘要（全文未开放获取或许可不允许翻译转载）。

原文

Stroke, Volume 57, Issue 10, Page 3035-3045, October 1, 2026. BACKGROUND:Raised inflammatory biomarkers predict an increased short-term risk of recurrent vascular events after stroke or transient ischemic attack, but it is uncertain whether the hazard is maintained thereafter. In the absence of previous population-based studies, we aimed to determine the predictive value of biomarkers for the long-term risk of recurrent stroke in intensively treated patients following transient ischemic attack or stroke.METHODS:We studied 12 blood biomarkers related to inflammation, neuronal cell damage, and thrombosis soon after transient ischemic attack or stroke in a population-based study (OXVASC [Oxford Vascular Study]; 2002–2011) with follow-up to 2025. We used Cox and negative binomial regressions to assess associations between each log-transformed biomarker (per SD increase) and recurrent stroke (first event and total number), adjusted for age, sex, and baseline vascular risk factors.RESULTS:Of 1292 consecutive patients (mean/SD age, 73.1/13.2 years; 47.8% male), 365 recurrent strokes occurred in 280 patients during 11 336 patient-years. All inflammatory biomarkers were associated with 10-year risk of recurrence, with little impact of adjustment for other risk factors (adjusted incidence rate ratio: IL-6 [interleukin-6], 1.21 [95% CI, 1.04–1.42]; CRP [C-reactive protein], 1.29 [95% CI, 1.11–1.49]; TNFR-1 [tumor necrosis factor receptor-1], 1.24 [95% CI, 1.05–1.46]; and NGAL [neutrophil gelatinase–associated lipocalin], 1.15 [95% CI, 0.99–1.33]). Moreover, number of elevated (top quartile) inflammatory markers was associated with higher burden of recurrence (incidence rate ratio, 1.31 [95% CI, 1.15–1.50];P<0.001), with no diminution over time (90 days: hazard ratio, 1.24 [95% CI, 0.98–1.57]; 90 days–1 year: 1.24 [95% CI, 0.95–1.62]; 1–5 years: 1.22 [95% CI, 1.01–1.47]; and 5–10 years: 1.34 [95% CI, 1.06–1.68]), and similar associations for transient ischemic attack and minor stroke. Biomarkers related to neuronal cell damage or thrombosis were generally less predictive of recurrent stroke.CONCLUSIONS:Inflammatory biomarkers were more predictive of long-term recurrent stroke than neuronal or thrombotic biomarkers, particularly when several inflammatory markers were raised. Predictive value was independent of other vascular risk factors and did not diminish with duration of follow-up, supporting trials of anti-inflammatory strategies for long-term secondary prevention

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引用

  1. Stroke：Persistence of Association of Blood Biomarkers With Risk of Recurrent Stroke on Long-Term Follow-Up: Population-Based Study
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