Atrial Fibrillation Incidence, Risk Factors and Genetics

心房颤动的发病率、危险因素和遗传学

• 批准号: 6542416
• 负责人: SUSAN R HECKBERT
• 金额: $ 57.04万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-07-01 至 2006-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6542416
• 关键词: ACE inhibitors; atrial fibrillation; beta antiadrenergic agent; blood chemistry; cardiovascular disorder chemotherapy; cardiovascular disorder epidemiology; cardiovascular disorder risk; cerebral ischemia /hypoxia; clinical research; comorbidity; disease /disorder onset; drug administration rate /duration; drug screening /evaluation; genetic polymorphism; genetic screening; genetic susceptibility; genotype; human genetic material tag; human subject; hypertension; interview; nucleic acid purification; polymerase chain reaction; restriction fragment length polymorphism; statistics /biometry; stroke

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.

描述（由申请人提供）：本研究的目的是评估与房颤（AF）发生风险相关的常用药物的安全性，并评估房颤发作后几种遗传多态性与卒中风险的关系。一些证据表明-受体阻滞剂和ACE抑制剂都可以预防或抑制心房电重构，从而使房颤得以建立和维持。这些药物的停药可能与高危人群发生房颤的风险增加有关。促进血栓形成的遗传多态性与静脉血栓形成的风险增加有关，在一些研究中，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，使用华法林或阿司匹林治疗房颤患者可降低卒中风险，但对于房颤并发症卒中风险与影响凝血的基因变异之间的关系知之甚少。