Associations of proinflammatory cytokines with the risk of recurrent stroke
Associations of proinflammatory cytokines with the risk of recurrent stroke
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DOI：
10.1161/strokeaha.107.504498
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发表时间：
2008-08-01
期刊：
影响因子：
8.3
通讯作者：
Woodward, Mark
中科院分区：
文献类型：
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作者：
Welsh, Paul;Lowe, Gordon D. O.;Woodward, Mark
背景和目的 - 关于促炎细胞因子和原发性或复发性中风风险的报道很少。我们在源自培哚普利预防复发性中风研究 (PROGRESS) 的巢式病例对照研究中研究了白细胞介素 (IL)-6、IL-18 和肿瘤坏死因子-α (TNF-α) 与复发性中风的关联。 方法 - 我们对随机、安慰剂对照期间发生的 591 例中风（472 例缺血性中风、83 例出血性中风、36 种未知亚型）进行了巢式病例对照研究。对 6105 名有中风或短暂性脑缺血发作病史的患者进行基于培哚普利的治疗的多中心试验。对照组在年龄、治疗组、性别、地区和进入母试验时最近的合格事件方面进行匹配。结果 - IL-6 和 TNF-α（而非 IL-18）与复发性缺血性中风风险相关，独立于常规风险标记。比较最高和最低三分之一分布的调整后比值比，IL-6 为 1.33（95% CI，1.00 至 1.78），TNF-α 为 1.46（1.02 至 2.10）。没有炎症标记物与出血性中风风险相关。在多变量模型中，IL-6 和 TNF-α 充分解释了观察到的 C 反应蛋白和纤维蛋白原与缺血性中风风险之间的关联，但 TNF-α 在全面调整后保留了临界意义。结论 - 与急性期反应相关的炎症标志物（IL-6、TNF-α、C 反应蛋白和纤维蛋白原，但不是 IL-18）与复发性中风风险相关。这些标志物在多变量模型中相互依赖，一旦全部纳入，只有 TNF-α 保留了边界关联。急性期反应的全身炎症标志物与复发性中风相关，而不是特别与 IL-6、C 反应蛋白或纤维蛋白原相关。
Background and Purpose - There are few reports on proinflammatory cytokines and risk of primary or recurrent stroke. We studied the association of interleukin (IL)-6, IL-18, and tumor necrosis factor-alpha (TNF-alpha) with recurrent stroke in a nested case-control study derived from the Perindopril Protection Against Recurrent Stroke Study (PROGRESS).Methods - We performed a nested case-control study of 591 strokes (472 ischemic, 83 hemorrhagic, 36 unknown subtype) occurring during a randomized, placebo-controlled multicenter trial of perindopril-based therapy in 6105 patients with a history of stroke or transient ischemic attack. Controls were matched for age, treatment group, sex, region, and most recent qualifying event at entry to the parent trial.Results - IL-6 and TNF-alpha, but not IL-18, were associated with risk of recurrent ischemic stroke independently of conventional risk markers. Adjusted odds ratios comparing the highest to lowest third of their distributions were 1.33 (95% CI, 1.00 to 1.78) for IL-6 and 1.46 (1.02 to 2.10) for TNF-alpha. No inflammatory marker was associated with hemorrhagic stroke risk. In multivariable models, IL-6 and TNF-alpha fully explained observed associations of C-reactive protein and fibrinogen with risk of ischemic stroke, but TNF-alpha retained borderline significance after full adjustment.Conclusions - Inflammatory markers associated with the acute-phase response (IL-6, TNF-alpha, C-reactive protein, and fibrinogen, but not IL-18) are associated with risk of recurrent stroke. These markers are dependent on each other in multivariable models, and once all were included, only TNF-alpha retained a borderline association. Markers of generalized inflammation of the acute-phase response are associated with recurrent stroke, rather than IL-6, C-reactive protein, or fibrinogen in particular.