基于血清生物标志物的对低卒中风险房颤病人预测模型的研究

卒中是房颤病人最主要的并发症，新型口服抗凝药的出现，使识别出低卒中风险人群成为卒中预测模型的发展方向，但现有的CHA2DS2-VASC风险评分对低风险人群的预测能力有限。本项目组前期开展了一项Meta分析，发现在房颤病人众多的生物标志物中，高水平的纤溶酶原激活物抑制剂和凝血酶-抗凝血酶复合物能增加卒中的风险。在我们开展的一项2709名房颤病人的病例对照研究中，合并脑卒中的房颤病人外周血C反应蛋白、纤维蛋白原、中性粒细胞/淋巴细胞比值都显著高于未合并脑卒中的房颤病人。提示将炎症、止血、心功能相关生物标志物纳入风险预测模型，将有助于识别低卒中风险的病人。本项目组前期已在房颤病人中建立起了前瞻性队列，收集到房颤病人965例，基线资料已全部收集完成。本研究拟基于此队列，建立适合中国人群的、能识别出低卒中风险的房颤病人的预测模型，并在外部人群中对模型进行验证。本研究将对卒中的干预有重要的临床意义。

Stroke is the main complication of atrial fibrillation (AF). With the advent of novel anticoagulant, guidelines have recommended that there should be a clinical practice shift so that the first step is to identify ‘low risk’ patients who do not need any antithrombotic therapy. However, the CHA2DS2-VASc score which is now widely used in the clinical practice has only modest predictive value for predicting “low risk” subjects. A novel stroke risk stratification model for refining true low risk patients with AF is urgently needed. We have conducted a comprehensive meta-analysis and found that elevated circulating plasminogen activator inhibitor-1 and thrombin-antithrombin were significantly associated with increased risk of stroke in patients with AF. In addition, we have carried out a case-control study on 2709 AF patients. We compared the levels of serum biomarkers between AF patients complicated with stroke and those without stroke, and found that the levels of C-reactive protein, fibrinogen and neutrophils/ lymphocytes ratio were significantly higher in AF patients with stroke than those without. These evidences indicate that adding inflammatory, hemostatic and cardiac markers to the stroke risk prediction model will improve the predictive accuracy for refining “true low risk” patients. We have already set up a prospective cohort among 965 eligible AF patients, and all of the baseline information has been collected. We plan to develop a novel stroke risk stratification model for refining true low risk patients with AF which is suitable for Chinese population, and then validate this model externally in another cohort. This study will have great significance on clinical intervention of stroke in AF patients.