Atrial Fibrillation Incidence, Risk Factors and Genetics

描述(申请人提供)：这项研究的目标是评估常用药物与房颤发病风险的安全性，并评估几种基因多态与房颤发病后中风风险的关系。多项证据表明，β-受体阻滞剂和血管紧张素转换酶抑制剂均可预防或抑制房颤发生和维持的房电重构。停用这些药物可能与高危个体房颤风险增加有关。促进血栓形成的基因多态与静脉血栓形成的风险增加有关，在一些研究中，还与包括中风或心肌梗死在内的动脉血栓形成有关。尽管最近发表的几项试验表明，华法林或阿司匹林治疗房颤患者可降低中风风险，但人们对中风作为房颤并发症与影响凝血的基因变异有关的风险知之甚少。 拟议的项目将建立在大型非营利性健康维护组织团体健康合作社(GHC)对心肌梗死和中风的成功人群研究的基础上。来自GHC计算机化药房数据库的关于大约1500例房颤事件患者和1750名接受药物治疗的高血压对照的用药时间的详细信息，将使我们能够评估与使用或最近停止使用β-受体阻滞剂或血管紧张素转换酶抑制剂相关的房颤事件的风险。该项目将在大约855名房颤患者中收集以人群为基础的初始队列中的DNA样本，并将检查与已知影响凝血的基因变异有关的中风风险。 拟议项目的主要任务是：1)确定发生房颤的病例和对照；2)审查门诊和住院患者的病历，以评估是否符合条件，并收集有关危险因素和病史的信息；3)随着时间的推移对用药情况进行分类；4)对房颤患者进行电话访谈和采集血液样本；5)血样处理、DNA提取和基因分型；以及6)药物使用和基因与房颤发病和中风并发症的关系的数据分析。该项目将提供有关药物安全的重要信息，并将结合分子生物学的进展来研究房颤及其并发症，这些问题对老年人的公共卫生具有相当重要的意义。

DESCRIPTION (provided by applicant): The goal of this research is to assess the safety of commonly used medications in relation to the risk of incident atrial fibrillation (AF), and to assess the association of several genetic polymorphisms with stroke risk after AF onset. Several lines of evidence suggest that both beta-blockers and ACE inhibitors may prevent or inhibit the atrial electrical remodeling that allows AF to become established and maintained. Withdrawal of these medications may be associated with increased risk of AF in individuals at risk. Genetic polymorphisms that promote thrombosis are associated with an increased risk of venous thrombosis, and in some studies, with arterial thrombosis including stroke or myocardial infarction. Although several recently published trials indicate that warfarin or aspirin treatment of patients with AF decreases the risk of stroke, little is known about the risk of stroke as a complication of AF in relation to genetic variants that affect clotting. The proposed project will build on successful population-based studies of myocardial infarction and stroke at Group Health Cooperative (GHC), a large non-profit health maintenance organization. Detailed information from the GHC computerized pharmacy database on the timing of medication use among approximately 1500 incident AF cases and 1750 controls with medically treated hypertension will permit us to assess the risk of incident AF associated with the use or recent stopping of beta-blockers or ACE inhibitors. This project will collect DNA samples on a population-based inception cohort of approximately 855 AF patients, and will examine the risk of stroke in relation to genetic variants known to affect coagulation. The main tasks of the proposed project are: 1) identification of cases with incident AF and controls; 2) review of outpatient and inpatient medical records to assess eligibility and collect information on risk factors and medical history; 3) classification of medication use over time; 4) for AF patients, telephone interview and collection of blood samples; 5) blood specimen processing, DNA extraction, and genotyping; and 6) data analysis of the associations of medication use and genotype with AF onset and stroke complications. This project will contribute important information about drug safety and will incorporate advances in molecular biology to study AF and its complications, problems of considerable public health importance in the elderly.