Atrial Fibrillation Incidence, Risk Factors and Genetics

描述（由申请人提供）：本研究的目的是评估与房颤（AF）风险相关的常用药物的安全性，并评估几种遗传多态性与AF发作后卒中风险的相关性。多项证据表明，β受体阻滞剂和ACE抑制剂均可预防或抑制心房电重构，而心房电重构可使房颤得以建立和维持。停用这些药物可能与高危人群房颤风险增加有关。促进血栓形成的基因多态性与静脉血栓形成风险增加相关，在一些研究中，与动脉血栓形成（包括中风或心肌梗死）相关。尽管最近发表的几项试验表明，华法林或阿司匹林治疗AF患者可降低卒中风险，但对作为AF并发症的卒中风险与影响凝血的遗传变异的关系知之甚少。 拟议的项目将建立在一个大型非营利健康维护组织团体健康合作组织（GHC）成功的基于人群的心肌梗死和中风研究的基础上。来自GHC计算机化药房数据库的关于约1500例新发AF病例和1750例经药物治疗的高血压对照者的用药时间的详细信息将允许我们评估与使用或近期停用β受体阻滞剂或ACE抑制剂相关的新发AF风险。该项目将收集约855名AF患者的基于人群的初始队列的DNA样本，并将检查与已知影响凝血的遗传变异相关的卒中风险。 拟议项目的主要任务是：1）识别新发房颤病例和对照病例; 2）审查门诊和住院病历，以评估合格性，并收集风险因素和病史信息; 3）随时间推移对药物使用进行分类; 4）对于房颤患者，电话访谈和采集血样; 5）血样处理，DNA提取和基因分型;（6）药物使用和基因型与房颤发作和卒中并发症相关性的数据分析。该项目将提供有关药物安全性的重要信息，并将结合分子生物学的进展来研究AF及其并发症，这些问题对老年人的公共卫生具有重要意义。

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.