Neurovascular Research Laboratory, Universitat Autònoma de Barcelona, Vall d'Hebron Hospital, Barcelona, Spain.
J Intern Med. 2011 Aug;270(2):166-74. doi: 10.1111/j.1365-2796.2010.02329.x. Epub 2010 Dec 27.
At present, a rapid and widely available diagnostic test for stroke remains elusive. The aim of this study was to examine the predictive value of a panel of blood-borne biochemical markers for stroke diagnosis.
Consecutive patients with strokes or stroke-mimicking conditions (mimics) were evaluated within 24 h from symptom onset (915 strokes and 90 mimics). Blood samples were analysed by enzyme-linked immunosorbent assay for C-reactive protein, d-dimer, soluble receptor for advanced glycation end products (sRAGE), metalloproteinase 9 (MMP-9), S100B, brain natriuretic peptide, caspase-3, neurotrophin-3, chimerin and secretagogin.
The main independent predictors of stroke versus mimics were caspase-3 >1.96 ng mL(-1) [odds ratio (OR) = 3.32; 95% confidence interval (CI) 1.88-5.88, P < 0.0001], d-dimer >0.27 μg mL(-1) (OR = 2.97; 95% CI 1.72-5.16, P = 0.0001), sRAGE >0.91 ng mL(-1) (OR = 2.19; 95% CI 1.26-3.83, P = 0.006), chimerin <1.11 ng mL(-1) (OR = 0.4; 95% CI 0.19-0.81, P = 0.011), secretagogin <0.24 ng mL(-1) (OR = 0.51; 95% CI 0.27-0.97, P = 0.041) and MMP-9 > 199 ng mL(-1) (OR = 1.66; 95% CI 1.01-2.73, P = 0.046). The model's predictive probability of stroke when the six biomarkers are above/below these cut-off levels was 99.01%. The best combination of biomarkers in the model was caspase-3 and d-dimer. Moreover, a model developed for samples obtained within the first 3 h showed high sensitivity (Se) and specificity (Sp) (threshold at 25th percentile: Se 0.87, Sp 0.55; threshold at 75th percentile: Se 0.28, Sp 0.99).
A combination of biomarkers including caspase-3 and d-dimer appears to be the most promising to achieve a rapid biochemical diagnosis of stroke. If replicated, this approach could be used as a tool for urgent referral of stroke patients to hospitals in which acute treatments are available.
目前，仍缺乏一种快速且广泛可用的脑卒中诊断检测手段。本研究旨在探讨一组血液生化标志物对脑卒中诊断的预测价值。
连续纳入发病 24 h 内的脑卒中或类似脑卒中的患者（脑卒中患者 915 例，脑卒中模拟患者 90 例）。采用酶联免疫吸附法检测患者的 C 反应蛋白、D-二聚体、晚期糖基化终产物可溶性受体（sRAGE）、金属蛋白酶 9（MMP-9）、S100B 蛋白、脑利钠肽、半胱氨酸天冬氨酸蛋白酶-3（caspase-3）、神经营养因子-3、拟肽和分泌颗粒蛋白。
脑卒中与脑卒中模拟患者的主要独立预测因子为 caspase-3 >1.96 ng/mL（比值比（OR）=3.32；95%置信区间（CI）1.88-5.88，P<0.0001）、D-二聚体>0.27 μg/mL（OR=2.97；95%CI 1.72-5.16，P=0.0001）、sRAGE>0.91 ng/mL（OR=2.19；95%CI 1.26-3.83，P=0.006）、拟肽<1.11 ng/mL（OR=0.4；95%CI 0.19-0.81，P=0.011）、分泌颗粒蛋白<0.24 ng/mL（OR=0.51；95%CI 0.27-0.97，P=0.041）和 MMP-9>199 ng/mL（OR=1.66；95%CI 1.01-2.73，P=0.046）。当六个生物标志物的水平高于/低于这些截点时，模型对脑卒中的预测概率为 99.01%。模型中标志物的最佳组合是 caspase-3 和 D-二聚体。此外，对发病 3 h 内采集的样本建立的模型具有较高的敏感性（Se）和特异性（Sp）（第 25 百分位数的阈值：Se 0.87，Sp 0.55；第 75 百分位数的阈值：Se 0.28，Sp 0.99）。
包括 caspase-3 和 D-二聚体在内的生物标志物联合检测似乎最有希望实现脑卒中的快速生化诊断。如果得到验证，该方法可用于将脑卒中患者快速转诊至可进行急性治疗的医院。
