Arterial Structure and Function and Atrial Fibrillation

描述（由申请人提供）：房颤（AF）是最常见的持续性心律失常，在老龄化人群中达到流行比例，并造成相当大的发病率、死亡率和社会经济负担。AF主要是老年人的疾病-84%的患者年龄超过65岁。此外，房颤后遗症（如中风）的发生率随着年龄的增长而增加。最近，动脉结构和功能的指标，如颈动脉内膜中层厚度（cIMT）和脉压（动脉硬度的替代品）已被证明与AF相关。这种关联有一个潜在的机制：血管系统的结构和功能变化导致高血压，左心室肥大，最后，心房的结构重塑。然而，仍然存在一些知识差距。目前尚不清楚cIMT测量是否可以改善AF的风险预测，超过AF的既定风险因素。此外，在前瞻性队列研究中，尚未研究其他动脉僵硬度指标（如颈动脉扩张性）与AF的关系。此外，关于cIMT、颈动脉扩张性或脉搏波传导速度（PWV）是否可预测AF的重要临床后遗症（如缺血性卒中和死亡），我们知之甚少。识别动脉结构和功能的其他指标，改善AF及其后遗症的预测，将使我们能够识别将从预防性干预中受益的个体， 从而减少老年人群的AF负担。此外，如果发现cIMT、颈动脉扩张性、PWV测量可改善AF的风险预测，则这些发现将加强AF病理生理学的新兴概念观点，特别是AF不纯粹是一种电生理疾病，但可能是血管疾病的结果。在本项目中，我们将评估cIMT、颈动脉扩张性和PWV与AF发生率的相关程度。我们还将评估这些新的风险因素的区分能力，这些风险因素提高预测风险模型的准确性和校准的程度，以及这些风险因素改善风险分类的能力。我们的总体假设是，动脉结构和功能的指标可以提高AF及其后遗症的风险预测。我们将在NIH赞助的前瞻性birthday队列研究-社区动脉粥样硬化风险（ARIC）中检验我们对cIMT和颈动脉扩张性的假设，并在心血管健康研究（CHS）和鹿特丹研究（RS）中复制我们的发现。我们将评估PWV在RS中的作用。我们将利用广泛的表型数据、3个队列中AF受试者的3，900多例新发AF病例、2，500多例死亡和500例新发缺血性卒中事件，以实现以下特定目标：1）识别改善AF风险预测的动脉指数，2）识别改善AF中缺血性卒中风险预测的动脉指数，和3）确定哪些动脉指数可增强AF全因和心血管死亡率的风险预测。

DESCRIPTION (provided by applicant): Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia, reaching epidemic proportions in the aging population and causing considerable morbidity, mortality, and socioeconomic burden. AF is primarily a disease of older people-84% are older than 65 years. Moreover, the incidence of AF sequelae such as stroke increases with advancing age. Recently, indices of arterial structure and function, such as carotid intima-media thickness (cIMT) and pulse pressure (a surrogate of arterial stiffness) have been shown to be associated with AF. There is a potential mechanism for this association: structural and functional changes in the vasculature lead to hypertension, left ventricular hypertrophy, and finally, structural remodeling in the atria. However, several knowledge gaps remain. It is unknown whether cIMT measurement improves risk prediction of AF, over and above established risk factors for AF. In addition, other indices of arterial stiffness such as carotid distensibility have not been studied in relation to AF in prospective cohort studies. Furthermore, very little is known about whether cIMT, carotid distensibility, or pulse wave velocity (PWV) predicts important clinical sequelae of AF, such as ischemic stroke and death. Identification of other indices of arterial structure and function that improve prediction of AF an its sequelae will enable us to identify individuals who will benefit from preventive interventions, thus reducing AF burden in the elderly population. In addition, if cIMT, carotid distensibility, an PWV measurements are found to improve risk prediction of AF, these findings will reinforce an emerging conceptual viewpoint on the pathophysiology of AF, specifically, that AF is not purely an electrophysiological disorder, but may be a consequence of vascular disease. In this project, we will evaluate the extent to which cIMT, carotid distensibility, and PWV are associated with AF incidence. We will also evaluate the discriminatory power of these novel risk factors, the extent to which these risk factors improve accuracy and calibration of predictive risk models, and the ability of these risk factors to improve risk classification. Our overall hypothesis is that indice of arterial structure and function improve risk prediction of AF and its sequelae. We will test our hypothesis for cIMT and carotid distensibility in an NIH- sponsored prospective biracial cohort study-Atherosclerosis Risk in Communities (ARIC) and replicate our findings in the Cardiovascular Health Study (CHS) and the Rotterdam Study (RS). We will evaluate the role of PWV in the RS. We will leverage the extensive phenotypic data, more than 3,900 incident AF cases, more than 2,500 deaths and 500 incident ischemic stroke events in participants with AF in the 3 cohorts to achieve the following specific aims: 1) Identify arterial indices that improve risk prediction of AF, 2) Identify arterial indices that improve risk prediction of ischemic strokein AF, and 3) Establish which arterial indices enhance risk prediction of all-cause and cardiovascular mortality in AF.