Background: Inflammatory markers, such as C-reactive Protein (CRP), Interleukin-6 (IL-6), tumor necrosis factor (TNF)-alpha and fibrinogen, are upregulated following acute stroke. Studies have shown associations of these biomarkers with increased mortality, recurrent vascular risk, and poor functional outcome. It is suggested that physical fitness training may play a role in decreasing long-term inflammatory activity and supports tissue recovery. Aim: We investigated the dynamics of selected inflammatory markers in the subacute phase following stroke and determined if fluctuations are associated with functional recovery up to 6 months. Further, we examined whether exposure to aerobic physical fitness training in the subacute phase influenced serum inflammatory markers over time. Methods: This is an exploratory analysis of patients enrolled in the multicenter randomized-controlled PHYS-STROKE trial. Patients within 45 days of stroke onset were randomized to receive either four weeks of aerobic physical fitness training or relaxation sessions. Generalized estimating equation models were used to investigate the dynamics of inflammatory markers and the associations of exposure to fitness training with serum inflammatory markers over time. Multiple logistic regression models were used to explore associations between inflammatory marker levels at baseline and three months after stroke and outcome at 3- or 6-months. Results: Irrespective of the intervention group, high sensitive CRP (hs-CRP), IL-6, and fibrinogen (but not TNF-alpha) were significantly lower at follow-up visits when compared to baseline (p all ≤ 0.01). In our cohort, exposure to aerobic physical fitness training did not influence levels of inflammatory markers over time. In multivariate logistic regression analyses, increased baseline IL-6 and fibrinogen levels were inversely associated with worse outcome at 3 and 6 months. Increased levels of hs-CRP at 3 months after stroke were associated with impaired outcome at 6 months. We found no independent associations of TNF-alpha levels with investigated outcome parameters. Conclusion: Serum markers of inflammation were elevated after stroke and decreased within 6 months. In our cohort, exposure to aerobic physical fitness training did not modify the dynamics of inflammatory markers over time. Elevated IL-6 and fibrinogen levels in early subacute stroke were associated with worse outcome up to 6-months after stroke. Clinical Trial Registration:ClinicalTrials.gov, NCT01953549.

中文翻译：

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亚急性中风中升高的血清炎症标志物与临床结果相关，但不受有氧健身训练的影响：随机对照 PHYS-STROKE 试验的结果。

背景：炎症标志物，如 C 反应蛋白 (CRP)、白细胞介素-6 (IL-6)、肿瘤坏死因子 (TNF)-α 和纤维蛋白原，在急性中风后上调。研究表明，这些生物标志物与死亡率增加、血管复发风险和功能预后不良有关。有人提出，体能训练可能在减少长期炎症活动和支持组织恢复方面发挥作用。目的：我们研究了中风后亚急性期所选炎症标志物的动态，并确定波动是否与长达 6 个月的功能恢复有关。此外，我们检查了在亚急性期进行有氧体能训练是否会随着时间的推移影响血清炎症标志物。方法：这是对参加多中心随机对照 PHYS-STROKE 试验的患者的探索性分析。中风发病 45 天内的患者随机接受 4 周的有氧体能训练或放松课程。使用广义估计方程模型来研究炎症标志物的动态变化以及随着时间的推移进行体能训练与血清炎症标志物的关联。使用多元逻辑回归模型来探索基线和卒中后 3 个月的炎症标志物水平与 3 个月或 6 个月的结果之间的关联。结果：无论干预组如何，与基线相比，高敏 CRP (hs-CRP)、IL-6 和纤维蛋白原（但不是 TNF-α）在随访时显着降低（p 均 ≤ 0.01）。在我们的队列中，随着时间的推移，接受有氧体能训练不会影响炎症标志物的水平。在多变量逻辑回归分析中，基线 IL-6 和纤维蛋白原水平升高与 3 个月和 6 个月时的较差结果呈负相关。中风后 3 个月 hs-CRP 水平升高与 6 个月时的结果受损有关。我们没有发现 TNF-α 水平与研究的结果参数之间存在独立关联。结论：中风后血清炎症标志物升高，6个月内下降。在我们的队列中，暴露于有氧体能训练并没有随着时间的推移改变炎症标志物的动态。早期亚急性卒中中 IL-6 和纤维蛋白原水平升高与卒中后长达 6 个月的更差结果相关。临床试验注册：ClinicalTrials.gov，