Arenillas Juan F, Alvarez-Sabín José, Molina Carlos A, Chacón Pilar, Fernández-Cadenas Israel, Ribó Marc, Delgado Pilar, Rubiera Marta, Penalba Anna, Rovira Alex, Montaner Joan
Neurovascular Unit, Vall d'Hebron Universitary Hospital, Barcelona, Spain.
Stroke. 2008 May;39(5):1456-63. doi: 10.1161/STROKEAHA.107.498600. Epub 2008 Mar 6.
The molecular pathways involved in the progression of intracranial large artery atherosclerosis (ILA) are largely unknown. Our objective was to prospectively study the relationship between circulating levels of inflammatory markers and fibrinolysis inhibitors, and the risk of progression of symptomatic ILA.
Seventy-five consecutive patients with first-ever symptomatic intracranial atherostenosis were studied. Blood levels of C-reactive protein (CRP), E-selectin, monocyte chemoattractant protein-1, intercellular adhesion molecule-1, matrix metalloproteinases 1, 2, 3, 8, 9, 10, and 13, plasminogen activator inhibitor-1 (PAI-1), and lipoprotein(a) were measured 3 months after the qualifying stroke or transient ischemic attack. Thereafter, patients underwent long-term transcranial Doppler follow-up to detect progression of ILA.
During a median follow-up time of 23 months, 25 (33%) patients showed ILA progression. Multivariable adjusted Cox regression models and Kaplan-Meier curves showed that high baseline level of CRP, E-selectin, intercellular adhesion molecule-1, matrix metalloproteinase 9, PAI-1, and lipoprotein(a) predicted ILA progression independently of vascular risk factors. Of them, only CRP (CRP>5.5 mg/L; HR, 5.4 [2.3 to 12.7]; P=0.0001) and PAI-1 (PAI-1>23.1 ng/mL; HR, 2.4 [1.0 to 5.8]; P=0.05) predicted ILA progression also independently of the other studied molecules.
Progression of symptomatic ILA is associated with a proinflammatory state, as reflected by high levels of inflammatory markers, and with defective fibrinolysis, as indicated by raised concentrations of endogenous fibrinolysis inhibitors.
颅内大动脉粥样硬化（ILA）进展所涉及的分子途径在很大程度上尚不清楚。我们的目的是前瞻性研究炎症标志物和纤溶抑制剂的循环水平与有症状ILA进展风险之间的关系。
对75例首次发生有症状颅内动脉狭窄的连续患者进行研究。在符合条件的卒中或短暂性脑缺血发作后3个月，测量血液中C反应蛋白（CRP）、E选择素、单核细胞趋化蛋白-1、细胞间黏附分子-1、基质金属蛋白酶1、2、3、8、9、10和13、纤溶酶原激活物抑制剂-1（PAI-1）和脂蛋白（a）的水平。此后，对患者进行长期经颅多普勒随访以检测ILA的进展。
在中位随访时间23个月期间，25例（33%）患者出现ILA进展。多变量调整的Cox回归模型和Kaplan-Meier曲线显示，CRP、E选择素、细胞间黏附分子-1、基质金属蛋白酶9、PAI-1和脂蛋白（a）的高基线水平独立于血管危险因素预测ILA进展。其中，只有CRP（CRP>5.5 mg/L；HR，5.4[2.3至12.7]；P=0.0001）和PAI-1（PAI-1>23.1 ng/mL；HR，2.4[1.0至5.8]；P=0.05）也独立于其他研究分子预测ILA进展。
有症状ILA的进展与炎症标志物水平升高所反映的促炎状态以及内源性纤溶抑制剂浓度升高所表明的纤溶功能缺陷有关。
