房颤增加缺血性卒中、血栓栓塞和死亡的风险。房颤和心衰共存时预后更差，心衰前期虽无心衰症状但已出现心脏结构或功能异常，其是否能增加房颤不良预后风险尚不清楚。本研究旨在探索房颤发生缺血性卒中、血栓栓塞和死亡的危险因素以及房颤合并心衰前期和心衰不同类型与终点事件的关系。本研究共纳入2137例非瓣膜性房颤患者，平均随访32.4月，通过回顾性分析发现：房颤致缺血性卒中、血栓栓塞和全因死亡的发生率分别为4.86、6.6和1.7/100人年。单变量和多变量Cox回归分析显示，高脂血症、陈旧性脑梗死、高同型半胱氨酸血症、左心房直径、收缩压≥140mmHg是缺血性卒中和血栓栓塞的共同独立危险因素；而年龄＞60岁仅是缺血性卒中的独立危险因素; hs-cTnT和NT-proBNP仅是血栓栓塞的独立危险因素, 提示房颤两种不良预后的危险因素不完全一致。房颤抗凝组和未抗凝组的亚组分析显示两组预后的危险因素也不同：未抗凝组左心房直径与缺血性卒中和血栓栓塞独立相关；抗凝组高脂血症、hs-TnT和NT-proBNP与缺血性卒中和血栓栓塞独立相关。房颤发生全因死亡的独立危险因素包括：年龄＞75岁、心力衰竭、NT-proBNP, 其与是否抗凝治疗无显著相关。我们首次探讨房颤合并心衰前期和心衰不同类型与终点事件的关系，结果显示：心衰前期组缺血性卒中、血栓栓塞和全因死亡的累积发病率和风险均高于心衰风险期组，并且缺血性卒中和血栓栓塞的累积发病率与HFpEF组、HFmrEF组和HFrEF组均无显著差异，而全因死亡的累积发病率低于HFpEF、HFmrEF组。HFpEF组、HFmrEF组缺血性卒中、血栓栓塞和全因死亡的累积发病率和风险均高于心衰风险期组，HFrEF组仅血栓栓塞的累积发病率和风险高于心衰风险期组。通过对房颤合并缺血性卒中和无缺血性卒中患者的外周血进行转录组学分析，共筛选出7个差异表达基因，且对炎症和心肌纤维化相关基因SOCS3和S1PR1进一步PCR验证发现，房颤患者中S1PR1高表达与缺血性卒中发生相关。综上，我们通过回顾性研究发现高脂血症、高同型半胱氨酸血症、hsTnT、NT-proBNP、左心房直径、收缩压≥140mmHg是房颤发生缺血性卒中或血栓栓塞的独立危险因素、但未被CHA2DS2-VASc评分纳入。房颤合并心衰前期可能增加缺血性卒中、血栓栓塞和全因死亡的风险，房颤合并心衰风险期、心衰前期和心衰不同类型中,HFpEF组的卒中、血栓栓塞和全因死亡风险最高。

Atrial fibrillation（AF） increases the risk of stroke, thromboembolism, and death. AF and heart failure（HF） are closely intertwined, with each disease predisposing to the other. When present in combination, AF and HF portend a worse prognosis than either. Patients with pre-HF has asymptomatic but there have been demonstrate cardiac structure and/or impaired function. It is not clear wether it can increase the risk of poor prognosis of AF. The aim of this study is to explore the risk factor for ischemic stroke, thromboembolism, and death in atrial fibrillation, as well as the relationship between endpoints and pre-HF and different types of HF in patients with AF.In this study, we included 2137 patients with nonvalvular AF, with an average follow-up of 32.4 months. Through retrospective analysis, it was found that the incidence of ischemic stroke, thromboembolism, and all-cause death in AF was 4.86, 6.6 and 1.7per 100 person years, respectively. Univariate and multivariate Cox regression analysis shows that hyperlipidemia, history of stroke, left atrial diameter, systolic blood pressure ≥140 mmHg and hyperhomocysteinemia were common independent risk factors for ischemic stroke and thromboembolism; while age＞60 years was independent risk factors for stroke, hs-cTnT and NT-proBNP are both independent risk factors for thromboembolism. These results suggested that the risk factors for the two outcomes were not entirely consistent. We further conducted a subgroup analysis of the anticoagulant and non anticoagulant groups of AF, indicating that the risk factors were different between the two groups representing that the left atrial diameter in the non anticoagulant group was independently associated with ischemic stroke and thromboembolism; Hyperlipidemia, hs-TnT and NT-proBNP were independently associated with ischemic stroke and thromboembolism in the anticoagulant group. The independent risk factors for all cause death from atrial fibrillation include: age＞75 years old, heart failure and NT-proBNP, which are not significantly related to whether anticoagulation therapy is used. In this study we investigated the relationship between endpoints and pre-HF in patients with AF for the first time. Furthermore,we analyze the ralationship between endpoints and different types of HF in patients with AF. The results showed that cumulative incidence rate and risk of ischemic stroke, thromboembolism and all-cause death were higher in the pre-heart failure group than in the at risk for heart failure group. There was no significant difference in the cumulative incidence rate of stroke and thromboembolism between the pre-HF group and three type of HF group （HFpEF、HFmrEF、HFrEF）, while the all-cause mortality cumulative incidence rate was lower than the HFpEF and HFmrEF groups. The cumulative incidence rate and risk of ischemic stroke, thromboembolism and all-cause death were remarkably higher in HFpEF group and HFmrEF group than in pre-HF group, the cumulative incidence rate and risk of thromboembolism were significantly higher in HFrEF group than in at risk for heart failure group. In this study, peripheral blood from AF with and without stroke patients were subjected to transcriptome analysis. Among identified 7 differential expressed genes two genes （SOCS3 and S1PR1） that were related to inflammation and myocardial fibrosis were selected to verify by PCR. The result showed that high expression of S1PR1 in patients with AF was associated with stroke.In summary, through retrospective studies, we found that hyperlipidemia, hyperhomocysteinemia, hsTnT, NT-proBNP, left atrial diameter, and systolic blood pressure ≥ 140mmHg were independent risk factors for ischemic stroke or thromboembolism in patients with atrial fibrillation, but were not included in the CHA2DS2-VASc score. pre-heart failure in peitents with atrial fibrillation may increase the risk of ischemic stroke, thromboembolism, and all-cause death. Among at risk for heart failure、pre-heart failure and different types of heart failure group in peitents with atrial fibrillation, the HFpEF group has the highest risk of stroke, thromboembolism, and all-cause death.