Predisposing Factors for the Development of Atrial Fibrillation Among Women

描述（由申请人提供）：房颤（AF）是最常见的持续性心律失常。目前，美国估计有230万人被诊断患有AF，预计到2020年这一数字将上升到330万。AF患病率的快速增加并不能完全由人口老龄化来解释。女性房颤患者的死亡率和中风率高于男性;房颤是老年女性中风的最常见原因。AF还导致女性生活质量的更大损害。因此，需要针对预防女性AF的研究。该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，该申请建议利用一个由39，876名女性卫生专业人员组成的正在进行的、特征良好的前瞻性队列，这些女性卫生专业人员在14年内接受了各种相关医疗状况的随访，以有效地解决关于预测和预防女性AF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更新数据，沿着收集了28，345名在基线时捐献血液样本的测量生物标志物的广泛列表。将检查选定的炎症和氧化应激的标志物和调节剂、代谢综合征的组分、特定营养素和随后的AF风险之间的关系。待检查的生物标志物包括hsCRP、纤维蛋白原、ICAM-1、Lp（a）、HgbA 1C和脂质水平。传统的流行病学暴露包括肥胖、糖尿病和运动的测量，以及营养暴露，包括膳食脂肪和类黄酮的摄入。还将评估随机维生素E治疗和非随机他汀类药物治疗与AF之间的关系。对于许多暴露，还将探索AF模式和亚型的特定关系。估计有1296例确诊的AF病例，其中估计有1001例将储存血液样本，将构成女性中最大数量的AF病例，并将作为这些和其他未来流行病学、生物标志物和遗传分析的独特资源。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，这些因素可能会预防房颤，也可能会为女性房颤的潜在机制提供见解。这些知识可能最终导致AF发病率和患病率的降低，AF是一种导致中风、心力衰竭和死亡的疾病。公共卫生相关性：这项研究的目的是确定潜在的可改变的因素，使妇女更容易发展为最常见的持续性心律失常，心房颤动。在女性中，房颤约占中风的15%，可显著损害身体功能和生活质量。一旦确诊，房颤就很难治疗;因此，针对预防房颤的研究对女性至关重要。这些研究的结果可以确定生活方式的改变和可能预防女性房颤的药物。

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.