Predisposing Factors for the Development of Atrial Fibrillation Among Women

描述(申请人提供)：房颤(AF)是最常见的持续性心律失常。目前，美国估计有230万人被诊断为房颤，预计到2020年，这一数字将上升到330万。房颤患病率的快速增长并不能完全用人口老龄化来解释。与男性相比，患有房颤的女性死亡率和中风发生率更高；房颤是老年女性中风的最常见原因。房颤还会对女性的生活质量造成更大的损害。因此，有必要针对女性房颤的预防进行研究。这份R21申请是为了响应PA-06-181，NIH探索-发展研究资助计划而重新提交的，建议利用一个持续的、具有良好特征的39,876名女性健康专业人员的前瞻性队列，她们在过去14年中因各种相互关联的疾病而接受跟踪，以有效地解决关于预测和预防女性房颤的重要假设。在整个队列中收集了关于流行病学暴露的广泛最新数据，以及在基线水平捐献血液样本的28,345人中测量的生物标记物的广泛清单。选定的炎症和氧化应激的标志物和调节物、代谢综合征的成分、特定的营养物质和继发房颤的风险之间的关系将被检查。需要检测的生物标志物包括hsCRP、纤维蛋白原、ICAM-1、Lp(A)、HgbA1C和血脂水平。传统的流行病学暴露包括测量肥胖、糖尿病和运动，以及营养暴露，包括膳食脂肪和类黄酮摄入量。还将评估随机维生素E治疗和非随机他汀类药物治疗与房颤的关系。对于许多暴露，还将探索房颤模式和亚型的具体关系。估计有1296例房颤确诊病例，其中估计有1001例将储存血液样本，这将构成女性中最多的房颤病例，并将成为这些和其他未来流行病学、生物标记物和基因分析的独特资源。这些研究的结果可能会确定潜在的可改变的代谢和饮食因素，这些因素可能会潜在地预防房颤，也可能为深入了解女性房颤的潜在机制提供依据。这一知识最终可能导致房颤的发生率和患病率降低，房颤是一种导致中风、心力衰竭和死亡的疾病。公共卫生相关性：这项研究的目标是确定潜在的可改变因素，使女性易患上最常见的持续性心律失常--心房颤动。在女性中，心房颤动约占中风的15%，并可显著损害身体功能和生活质量。房颤一旦确诊，就很难治疗；因此，针对预防房颤的研究对女性来说是必不可少的。这些研究的结果可能确定生活方式的改变和可能的药物，这些药物可能会预防女性的心房颤动。

DESCRIPTION (provided by applicant): Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia. At present, an estimated 2.3 million people are diagnosed with AF in the United States, and this number is expected to rise to 3.3 million by 2020. This rapid increase in AF prevalence is not entirely explained by the aging of the population. Women with AF have higher mortality and stroke rates compared to their male counterparts; and AF is the most common cause of stroke among elderly women. AF also leads to a greater impairment of quality of life among women. Therefore, research directed at the prevention of AF in women is needed. This R21 application resubmitted in response to PA-06-181, NIH Exploratory-Developmental Research Grant program, proposes to utilize an ongoing, well-characterized prospective cohort of 39,876 female health professionals who have been followed for a variety of interrelated medical conditions over 14 years to effectively address important hypotheses with respect to prediction and prevention of AF among women. Extensive updated data on epidemiologic exposures have been collected in the entire cohort along with an extensive list of measured biomarkers in the 28,345 who donated blood samples at baseline. The relationship between selected markers and modulators of inflammation and oxidative stress, components of the metabolic syndrome, and specific nutrients and risk of subsequent AF will be examined. Biomarkers to be examined include hsCRP, Fibrinogen, ICAM-1, Lp (a), HgbA1C, and lipid levels. Traditional epidemiologic exposures include measures of adiposity, diabetes, and exercise, as well as nutritional exposures including dietary fat and flavonoid intake. The relationship between randomized vitamin E treatment and non-randomized statin therapy and AF will also be assessed. For many of the exposures, specific relations for patterns and subtypes of AF will also be explored. The estimated 1296 confirmed AF cases, of which an estimated 1001 will have stored blood samples, will comprise the largest number of AF cases among women and will serve as a unique resource for these and other future epidemiologic, biomarker, and genetic analyses. The results from these studies may identify potentially modifiable metabolic and dietary factors that could potentially protect against atrial fibrillation, and may also provide insights into underlying mechanisms of atrial fibrillation among women. This knowledge may ultimately lead to a reduction in AF incidence and prevalence, a disease leading to strokes, heart failure and death. PUBLIC HEALTH RELEVANCE: The goal of this research is to identify potentially modifiable factors that predispose women to develop the most common sustained heart rhythm disturbance, atrial fibrillation. Among women, atrial fibrillation accounts for approximately 15% of strokes and can significantly impair physical functioning and quality of life. Once established, atrial fibrillation is difficult to treat; and therefore, research directed at prevention of atrial fibrillation is essential for women. The results from these studies may identify lifestyle changes and possible medications that could potentially prevent atrial fibrillation among women.