Epidemiology of HIV-Related Atrial Fibrillation

项目摘要/摘要 在人类免疫缺陷病毒(HIV)感染者中，有效的抗逆转录病毒治疗(ART) 导致存活率显著增加，因此美国约有一半的艾滋病毒携带者(PLWH)是 现在50岁或更大了。心血管疾病在老年PLWH中很常见，通常要高得多 这一比例高于普通人群。这可能是由于艾滋病毒感染和结果的复杂相互作用 炎症、抗逆转录病毒药物及其毒性、病毒合并感染、其他共病情况、传统危险因素以及 其他行为，如滥用药物。房颤是一种常见的心律失常。 随着年龄的增长，中风的风险大大增加，认知能力下降更快， 痴呆症，以及普通人群中的心力衰竭。房颤的发病机制涉及炎症、纤维化、 和心房重塑。与HIV感染相关的慢性炎症可能导致早期发病 PLWH中的心律失常。减少慢性炎症的治疗进展，如有效的抗逆转录病毒疗法，可能 减少房颤。然而，人们对PLWH中的房颤知之甚少。拟议的项目将决定房颤的发生率， 严格评估其危险因素，确定PLWH发生房颤并发症的风险。了解 房颤风险增加的多种因素对制定改善房颤的策略至关重要 PLWH的预防、诊断和治疗此应用程序利用来自 艾滋病研究中心综合临床系统网络(CNICs)，一个成熟的动力 超过32,000名PLWH接受临床护理的队列。未感染的房颤患者的数据将来自 动脉粥样硬化(MESA)的多种族研究，其中房颤已经使用经过验证的方法在 一种持续的时尚。大型、多样化的CNICs队列捕获纵向临床数据和患者报告 结果，促进采用详细的方法来处理PLWH中的风险。此外，CNICS基础设施还允许 房颤结果将通过审查原始医疗记录进行识别和仔细验证，从而允许我们 找出易发生房颤的急症。这个项目的多学科研究团队是独一无二的 准备解决在理解疾病的病理生理、诊断、治疗和影响方面的重要差距 房颤与HIV感染的关系通过追求四个目标。目标1是确定特定于年龄、性别和种族的 PLWH中房颤的发生率。目标2是确定PLWH中与房颤相关的患者特征，包括 脓毒症、药物中毒和胸腔内疾病等沉淀物。目标3是评估现有的AF 风险模型，并开发和测试用于预测PLWH房颤的新风险模型。最后，目标4是检查 临床识别房颤后发生PLWH的结果。从这些调查中获得的新知识将 为临床决策提供信息，并将提高对房颤机制的理解，这将增强 开发合理和有针对性的治疗方法，以改善结果。

PROJECT SUMMARY / ABSTRACT Among individuals with human immunodeficiency virus (HIV) infection, effective antiretroviral therapy (ART) has resulted in a marked increase in survival, so that about half of people living with HIV (PLWH) in the US are now 50 years of age or older. Cardiovascular diseases are common among aging PLWH, often at much higher rates than in the general population. This is likely due to a complex interplay of HIV infection and resulting inflammation, ART and its toxicities, viral co-infections, other co-morbid conditions, traditional risk factors, and other behaviors such as substance abuse. Atrial fibrillation (AF) is a common cardiac arrhythmia, strongly associated with aging, that confers substantially elevated risks of stroke, more rapid cognitive decline, dementia, and heart failure in the general population. The pathogenesis of AF involves inflammation, fibrosis, and atrial remodeling. The chronic inflammation associated with HIV infection may contribute to early onset of the arrhythmia in PLWH. Therapeutic advances that reduce chronic inflammation, such as effective ART, may reduce AF. Yet little is known about AF in PLWH. The proposed project will determine the incidence of AF, rigorously assess its risk factors, and determine the risk of AF complications in PLWH. Understanding the contribution of multiple factors to the increased risk of AF is crucial to developing strategies to improve AF prevention, diagnosis, and treatment in PLWH. This application leverages comprehensive clinical data from the Centers for AIDS Research Network of Integrated Clinical Systems (CNICS), a well-established dynamic cohort of over 32,000 PLWH receiving clinical care. Data on AF in uninfected individuals will come from the Multi-Ethnic Study of Atherosclerosis (MESA), in which AF is already ascertained using validated methods in an ongoing fashion. The large, diverse CNICS cohort captures longitudinal clinical data and patient-reported outcomes, facilitating a detailed approach to addressing risk in PLWH. In addition, CNICS infrastructure allows AF outcomes to be identified and carefully validated by review of original medical records, permitting us to identify acute conditions that predispose to AF. The multidisciplinary research team for this project is uniquely poised to address important gaps in understanding the pathophysiology, diagnosis, treatment, and impact of AF in relation to HIV infection by pursuing four aims. Aim 1 is to determine the age, sex-, and race-specific incidence of AF in PLWH. Aim 2 is to identify patient characteristics associated with AF in PLWH, including precipitants such as sepsis, drug intoxication, and intrathoracic disease. Aim 3 is to evaluate an existing AF risk model and to develop and test new risk models for AF prediction in PLWH. Finally, Aim 4 is to examine outcomes in PLWH following clinical recognition of AF. New knowledge gained from these investigations will inform clinical decision-making and will improve understanding of the mechanisms of AF, which will enhance the development of rational and targeted therapeutic approaches to improve outcomes.