针对人类急性中风血液生物标志物的鉴定：全面的系统综述。
Towards the identification of blood biomarkers for acute stroke in humans: a comprehensive systematic review.
机构信息
Imperial College Cerebrovascular Research Unit-ICCRU, Division of Experimental Medicine, Imperial College, London, UK.
出版信息
Br J Clin Pharmacol. 2012 Aug;74(2):230-40. doi: 10.1111/j.1365-2125.2012.04212.x.
AIMS
Identification of biomarkers for stroke will aid our understanding of its aetiology, provide diagnostic and prognostic indicators for patient selection and stratification, and play a significant role in developing personalized medicine. We undertook the largest systematic review conducted to date in an attempt to characterize diagnostic and prognostic biomarkers in acute ischaemic and haemorrhagic stroke and those likely to predict complications following thrombolysis.
METHODS
A comprehensive literature search was carried out to identify diagnostic and prognostic stroke blood biomarkers. Mean differences (MDs) and 95% confidence intervals (CIs) were calculated for each biomarker.
RESULTS
We identified a total of 141 relevant studies, interrogating 136 different biomarkers. Three biomarkers (C-reactive protein, P-selectin and homocysteine) significantly differentiated between ischaemic stroke and healthy control subjects. Furthermore, glial fibrillary acidic protein levels were significantly different between haemorrhagic stroke and ischaemic stroke patients (MD 224.58 ng l⁻¹; 95% CI 25.84, 423.32; P= 0.03), high levels of admission glucose were a strong predictor of poor prognosis after ischaemic stroke and symptomatic intracerebral haemorrhage post-thrombolysis, glutamate was found to be an indicator of progressive (unstable) stroke (MD 172.65 µmol l⁻¹, 95% CI 130.54, 214.75; P= 0.00001), D-dimer predicted in-hospital death (MD 0.67 µg ml⁻¹, 95% CI 0.35, 1.00; P= 0.0001), and high fibrinogen levels were associated with poor outcome at 3 months (MD 47.90 mg l⁻¹, 95% CI 14.88, 80.93; P= 0.004) following ischaemic stroke.
CONCLUSIONS
Few biomarkers currently investigated have meaningful clinical value. Admission glucose may be a strong marker of poor prognosis following acute thrombolytic treatment. However, molecules released in the bloodstream before, during or after stroke may have potential to be translated into sensitive blood-based tests.
目的
识别中风的生物标志物将有助于我们了解其病因，为患者选择和分层提供诊断和预后指标，并在开发个性化医学方面发挥重要作用。我们进行了迄今为止最大规模的系统评价，试图描述急性缺血性和出血性中风以及可能预测溶栓后并发症的诊断和预后生物标志物。
方法
进行了全面的文献检索，以确定中风的诊断和预后血液生物标志物。为每个生物标志物计算了平均值差异（MDs）和 95%置信区间（CIs）。
结果
我们共确定了 141 项相关研究，检测了 136 种不同的生物标志物。三种生物标志物（C 反应蛋白、P 选择素和同型半胱氨酸）可显著区分缺血性中风和健康对照组。此外，胶质纤维酸性蛋白水平在出血性中风和缺血性中风患者之间存在显著差异（MD 224.58ng/ml；95%CI 25.84，423.32；P=0.03），入院时血糖水平升高是缺血性中风和溶栓后症状性颅内出血预后不良的强预测指标，谷氨酸被发现是进展性（不稳定）中风的指标（MD 172.65µmol/l，95%CI 130.54，214.75；P=0.00001），D-二聚体预测住院期间死亡（MD 0.67µg/ml，95%CI 0.35，1.00；P=0.0001），高纤维蛋白原水平与缺血性中风后 3 个月的不良结局相关（MD 47.90mg/l，95%CI 14.88，80.93；P=0.004）。
结论
目前研究的生物标志物很少具有有意义的临床价值。入院时血糖可能是急性溶栓治疗后预后不良的有力标志物。然而，在中风发生之前、期间或之后释放到血液中的分子可能具有转化为敏感的基于血液的测试的潜力。
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