Pedersen Annie, Redfors Petra, Lundberg Linnea, Gils Ann, Declerck Paul J, Nilsson Staffan, Jood Katarina, Jern Christina
Annie Pedersen, MD, Institute of Biomedicine, Sahlgrenska Academy at the University of Gothenburg, Box 440, SE-405 30 Gothenburg, Sweden, Tel.: +46 31 343 48 11, Fax: +46 31 842 160, E-mail:
Thromb Haemost. 2016 Aug 30;116(3):537-43. doi: 10.1160/TH15-12-0938. Epub 2016 Jun 30.
Ischaemic stroke patients continue to be at risk for recurrent vascular events for many years. Predictors of long-term prognosis are needed. It was the objective of this study to investigate levels of four haemostatic proteins as long-term predictors of recurrent vascular events after ischaemic stroke. We prospectively followed 548 ischaemic stroke patients, 18-69 years, and registered recurrent vascular events. Plasma levels of tissue-type plasminogen activator (t-PA), von Willebrand factor (VWF), fibrinogen and thrombin activatable fibrinolysis inhibitor activation peptide (TAFI-AP) were measured three months after index stroke. Cox regression models were used to assess associations to outcomes for single biomarkers and for a combined biomarker measure. For single biomarkers significantly associated with any of the outcomes, we performed subanalyses stratified for age, sex, diabetes and atherosclerosis. During 5,637 person-years of follow-up, we registered 74 vascular deaths, 90 recurrent strokes and 62 coronary events. Levels of t-PA, VWF and fibrinogen were significantly associated with vascular death and coronary events. After adjustment, the association between t-PA and vascular death remained (HR per 1 SD increase in plasma level 1.27, 95 % CI 1.00-1.61, p=0.047). The combined effect of t-PA, VWF and fibrinogen was associated with coronary events (adjusted HR 1.35, 1.02-1.80, p=0.04). In non-diabetic patients, an association with coronary events was seen for VWF levels (adjusted HR 2.23, 1.45-3.43, p<0.01). In conclusion, plasma levels of haemostatic factors were associated with vascular death and coronary events, but not with recurrent stroke. Our results suggest that the predictive value of biomarkers differ by specific outcome measure and subgroup of patients.
缺血性中风患者多年来一直面临复发性血管事件的风险。因此需要了解长期预后的预测因素。本研究的目的是调查四种止血蛋白水平,作为缺血性中风后复发性血管事件的长期预测指标。我们前瞻性地随访了548例年龄在18至69岁之间的缺血性中风患者,并记录复发性血管事件。在首次中风后三个月测量血浆组织型纤溶酶原激活剂(t-PA)、血管性血友病因子(VWF)、纤维蛋白原和凝血酶激活的纤溶抑制物激活肽(TAFI-AP)水平。使用Cox回归模型评估单一生物标志物以及联合生物标志物测量与预后的关联。对于与任何预后显著相关的单一生物标志物,我们按年龄、性别、糖尿病和动脉粥样硬化进行亚组分析。在5637人年的随访期间,我们记录了74例血管性死亡、90例复发性中风和62例冠状动脉事件。t-PA、VWF和纤维蛋白原水平与血管性死亡和冠状动脉事件显著相关。调整后,t-PA与血管性死亡之间的关联仍然存在(血浆水平每增加1个标准差,风险比为1.27,95%置信区间为1.00-1.61,p=0.047)。t-PA、VWF和纤维蛋白原的联合作用与冠状动脉事件相关(调整后风险比为1.35,1.02-1.80,p=0.04)。在非糖尿病患者中,VWF水平与冠状动脉事件相关(调整后风险比为2.23,1.45-3.43,p<0.01)。总之,止血因子的血浆水平与血管性死亡和冠状动脉事件相关,但与复发性中风无关。我们的结果表明,生物标志物的预测价值因具体的预后指标和患者亚组而异。