Åberg N David, Stanne Tara M, Jood Katarina, Schiöler Linus, Blomstrand Christian, Andreasson Ulf, Blennow Kaj, Zetterberg Henrik, Isgaard Jörgen, Jern Christina, Svensson Johan
Department of Internal Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden Center of Brain Repair and Rehabilitation, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
Department of Medical and Clinical Genetics, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
BMJ Open. 2016 Feb 25;6(2):e009827. doi: 10.1136/bmjopen-2015-009827.
Erythropoietin (EPO), which is inversely associated with blood haemoglobin (Hb), exerts neuroprotective effects in experimental ischaemic stroke (IS). However, clinical treatment trials have so far been negative. Here, in patients with IS, we analysed whether serum EPO is associated with (1) initial stroke severity, (2) recovery and (3) functional outcome.
Prospective. Controls available at baseline.
A Swedish hospital-initiated study with outpatient follow-up after 3 months.
Patients (n=600; 64% males, mean age 56 years, controls n=600) were included from the Sahlgrenska Academy Study on IS (SAHLSIS).
In addition to EPO and Hb, initial stroke severity was assessed by the Scandinavian Stroke Scale (SSS) and compared with SSS after 3 months (follow-up) as a measure of recovery. Functional outcome was evaluated using the modified Rankin Scale (mRS) at follow-up. Serum EPO and SSS were divided into quintiles in the multivariate regression analyses.
Serum EPO was 21% and 31% higher than in controls at the acute phase of IS and follow-up, respectively. In patients, acute serum EPO was 19.5% higher in severe versus mild IS. The highest acute EPO quintile adjusted for sex, age and Hb was associated with worse stroke severity quintile (OR 1.70, 95% CI 1.00 to 2.87), better stroke recovery quintile (OR 1.93, CI 1.09 to 3.41) and unfavourable mRS 3-6 (OR 2.59, CI 1.15 to 5.80). However, the fourth quintile of EPO increase (from acute to follow-up) was associated with favourable mRS 0-2 (OR 3.42, CI 1.46 to 8.03). Only the last association withstood full adjustment.
The crude associations between EPO and worse stroke severity and outcome lost significance after multivariate modelling. However, in patients in whom EPO increased, the association with favourable outcome remained after adjustment for multiple covariates.
促红细胞生成素（EPO）与血液血红蛋白（Hb）呈负相关，在实验性缺血性中风（IS）中发挥神经保护作用。然而，迄今为止的临床治疗试验结果均为阴性。在此，我们对IS患者进行分析，以确定血清EPO是否与以下因素相关：（1）初始中风严重程度；（2）恢复情况；（3）功能结局。
前瞻性研究。有基线对照。
一项由瑞典医院发起的研究，门诊随访3个月。
纳入了来自萨尔格伦斯卡学院缺血性中风研究（SAHLSIS）的患者（n = 600；64%为男性，平均年龄56岁，对照组n = 600）。
除EPO和Hb外，初始中风严重程度通过斯堪的纳维亚中风量表（SSS）进行评估，并与3个月后（随访）的SSS进行比较，作为恢复情况的衡量指标。随访时使用改良Rankin量表（mRS）评估功能结局。在多变量回归分析中，将血清EPO和SSS分为五分位数。
在IS急性期和随访时，患者的血清EPO分别比对照组高21%和31%。在患者中，重度IS患者的急性血清EPO比轻度IS患者高19.5%。在对性别、年龄和Hb进行校正后，急性EPO最高五分位数与更差的中风严重程度五分位数相关（比值比[OR] 1.70，95%置信区间[CI] 1.00至2.87），与更好的中风恢复五分位数相关（OR 1.93，CI 1.09至3.41），与不良的mRS 3 - 6相关（OR 2.59，CI 1.15至5.80）。然而，EPO增加的第四个五分位数（从急性期到随访）与良好的mRS 0 - 2相关（OR 3.42，CI 1.46至8.03）。只有最后一种关联在完全校正后仍然成立。
在多变量建模后，EPO与更差的中风严重程度和结局之间的粗略关联失去了显著性。然而，在EPO增加的患者中，在对多个协变量进行校正后，与良好结局的关联仍然存在。
