Epidemiologic Study of Risk Factors and Biomarkers of Atrial Fibrillation

描述（由申请人提供）：本申请涉及广泛的挑战领域（04）：临床研究，以及特定的挑战主题04- HL-104：对现有数据进行二次分析，以回答重要的临床和预防医学研究问题。心房颤动（AF）是临床上最常见的心律失常。流行病学研究为房颤的危险因素提供了有价值的信息。然而，这些结果来自于美国和西欧主要为白色人群的有限队列。我们对房颤流行病学的了解存在重要的知识缺口。首先，AF在非白人族群中的流行病学尚不明确。其次，关于房颤危险因素的变化如何影响未来房颤风险的信息很少。第三，炎症、纤维化、心房牵张、心肌损伤和止血在房颤发病率中的作用尚未得到适当的理解。我们建议在两个种族人群中评估AF的危险因素，并在社区动脉粥样硬化风险（ARIC）队列的背景下探索AF的新危险因素和生物标志物。ARIC队列包括来自1987-89年检查的4个美国社区的15，792名男性和女性（27%为非洲裔美国人）的代表性样本，并从那时起进行随访。具体而言，我们将评估以下目的：（1）评估先前描述的白人AF风险因素是否与ARIC非洲裔美国人人群的AF发病率相关，并描述先前描述的风险因素的变化是否影响未来的AF风险;（2）研究新的心血管危险因素在AF发病中的作用。具体而言，我们将评估炎症，心房牵张，心肌损伤、心房纤维化和重构以及止血。在基线和随后的3次访问中，参与者进行了体检，广泛的风险因素确定，并收集血液样本。我们将通过住院出院、随访中进行的ECG和来自医疗保险索赔的数据来识别AF的事件病例，并测量研究人群样本中的纤维化生物标志物。一个队列或病例队列的方法，根据具体的目的，将被用来评估风险因素和生物标志物和AF的风险之间的关联。这一建议将提供新的信息AF的风险因素，特别是在非洲裔美国人，将决定性地有助于我们了解的ethiopathogenic过程的基础AF，并将有助于告知潜在的预防措施，在高危人群。这一建议将为房颤的病因提供新的见解。特别是，我们将试图解开解释非洲裔美国人房颤发病率较低的机制，并确定新的房颤生物标志物。该提案的结果将为房颤的新治疗和预防措施的开发提供信息。

DESCRIPTION (provided by applicant): This application addresses broad Challenge Area (04): Clinical Research, and specific Challenge Topic, 04- HL-104: Perform secondary analyses of existing data to answer important clinical and preventive medicine research questions. Atrial fibrillation (AF) is the most frequent cardiac arrhythmia in clinical practice. Epidemiologic studies have provided valuable information on risk factors for AF. These results, however, come from a limited set of cohorts of mostly white populations in the United States and Western Europe. Important knowledge gaps exist in our knowledge of AF epidemiology. First, the epidemiology of AF in non-white ethnic groups is not well defined. Second, little information exists on how changes in AF risk factors could affect the future risk of AF. Third, the role of inflammation, fibrosis, atrial stretch, myocardial injury and hemostasis in the incidence of AF is not appropriately understood. We propose to assess risk factors for AF in a bi-racial population, and explore novel risk factors and biomarkers of AF in the context of the Atherosclerosis Risk in Communities (ARIC) cohort. The ARIC cohort comprises a representative sample of 15,792 men and women (27% African-Americans) from 4 US communities examined in 1987-89, and followed up since then. Specifically, we will assess the following aims: (1) to evaluate whether previously described risk factors for AF in whites are associated with AF incidence in the ARIC African-American population and to describe whether changes in previously described risk factors affect the future risk of AF; (2) to study the role of novel cardiovascular risk factors in the incidence of AF. Specifically, we will evaluate biomarkers of inflammation, atrial stretch, myocardial injury, atrial fibrosis and remodeling, and hemostasis. At baseline and in 3 subsequent visits, participants underwent a physical exam, extensive risk factor ascertainment, and collection of blood samples. We will identify incident cases of AF through hospitalization discharges, ECGs conducted in the follow-up and data from Medicare claims, and measure biomarkers for fibrosis in a sample of the study population. A cohort or case-cohort approach, depending on the specific aim, will be used to evaluate the association between risk factors and biomarkers and the risk of AF. This proposal will provide novel information on risk factors for AF, particularly among African-Americans, will contribute decisively to our understanding of the ethiopathogenic processes underlying AF, and will help to inform potential preventive measures in high-risk populations. This proposal will provide new insights into the causes of atrial fibrillation. Particularly, we will try to disentangle the mechanisms explaining the lower incidence of atrial fibrillation in African-Americans, and identify new biomarkers for atrial fibrillation. Results of this proposal will inform development of new treatments and preventive measures for atrial fibrillation.