Changes in Cardiovascular Control Mechanisms Related to Binge Drinking during College

摘要 有强有力的证据表明，长期大量饮酒是心血管疾病的主要危险因素。 发生在中年，但导致心脏病和中风的动脉粥样硬化过程通常 由于潜在的可改变的、不健康的生活方式行为，在生命更早的时候就开始了。酗酒， 或大量饮酒导致血液酒精浓度飙升，是一种高风险的生活方式行为，即 流行于新兴的成人和大学人群。几十年的动物和人类研究已经建立了 个别饮酒事件会引起动态的生理、神经和行为反应，但如何以及 当这些对个体饮酒事件的生物行为适应转变为慢性功能障碍和 疾病尚不为人所知。此R01应用程序旨在了解与饮酒相关的心血管损伤是如何 以及它是如何进行的。它源于我们最近完成的NIAAA资助的R21项目 提出了研究人类临床前心血管功能障碍的新方法，确定了潜在的 将行为与心血管活动联系起来的生理机制，以及区分心血管 在大学年龄的酗酒者与适度饮酒者/不饮酒者之间的功能。此应用程序构建在我们的 基础工作，建议对表面上健康的大学生(n=300)进行每周一次的纵向研究 饮酒行为追踪两年及饮酒前后的心血管评估 评估期。其目标是更好地捕捉酗酒对特定人群的影响 关于心血管控制系统以及这些系统之间的协调。该提案通过以下方式进行创新 量化饮酒“剂量”和临床前心血管疾病的概念和方法 “回应”。具体地说，它建议每周对饮酒行为进行纵向评估，以捕捉细节 个别饮酒事件，包括严重程度(估计每次饮酒)、频率(每次饮酒次数 周)，以及这些插曲的起搏(两次狂欢之间的间隔)。它进一步提出了非侵入性测量 不同负荷模式下饮酒对心血管和心脏控制系统的损伤 (副交感、交感和认知挑战任务)，并利用更敏感的措施 改善对心血管细微变化的检测。AIM 1旨在识别早期心血管生物标志物 酗酒。AIM 2将在两年内前瞻性地监测详细的酒精使用数据，并将饮酒与 对这些生物标志物变化的行为。目标3将探索酗酒是否能缓解 心血管功能与认知能力的关系。使用系统生物学框架来 识别高风险饮酒的早期心血管生物标记物具有深远的公共健康意义，因为它 可能提供了一种新的工具，在酒精相关的心血管损害出现之前很久就能识别出来 临床疾病或疾病状态。

Abstract There is strong evidence that chronic heavy alcohol use is a major risk factor for adverse cardiovascular events in middle age, but the atherosclerotic processes that underlie heart disease and stroke are often initiated much earlier in life as the result of potentially modifiable, unhealthy lifestyle behaviors. Binge drinking, or high quantity drinking episodes that spike blood alcohol concentration, is a high-risk lifestyle behavior that is prevalent in emerging adult and college populations. Decades of animal and human research have established that individual drinking episodes evoke dynamic physiological, neural, and behavioral responses, but how and when these biobehavioral adaptations to individual drinking episodes transition into chronic dysfunction and disease is not known. This R01 application seeks to understand how drinking-related cardiovascular injury is instigated and how it progresses. It derives from our recently completed NIAAA-funded R21 project that produced new methodologies for studying human, preclinical cardiovascular dysfunction, identified underlying physiological mechanisms that link behavior to cardiovascular activity, and differentiated cardiovascular functioning in college-aged binge drinkers versus moderate/non-drinkers. This application builds on our foundational work by proposing a longitudinal study of ostensibly healthy college students (n=300) with weekly tracking of drinking behaviors for two years and cardiovascular assessments prior to and following this drinking assessment period. The goal is to better capture the progression of binge drinking effects on specific cardiovascular control systems and on the coordination across these systems. This proposal innovates through its conceptual and methodological approach to quantifying drinking “dose” and preclinical cardiovascular “response”. Specifically, it proposes a weekly longitudinal assessment of drinking behaviors to capture details of individual drinking episodes, including the severity (estimated drinks per occasion), frequency (times per week), and pacing (intervals between binges) of these episodes. It further proposes to non-invasively measure drinking-related injury to vascular and cardiac control systems under different loading paradigms (parasympathetic, sympathetic, and cognitive challenge tasks) and utilizes more sensitive measures to improve detection of subtle cardiovascular change. Aim 1 seeks to identify early cardiovascular biomarkers of binge drinking. Aim 2 will prospectively monitor detailed alcohol use data over two years and link drinking behaviors to changes in these biomarkers. Aim 3 will explore whether binge drinking moderates the relationship of cardiovascular functioning to cognitive performance. The use of a systems biology framework to identify early cardiovascular biomarkers of high-risk drinking has far-reaching public health implications, as it may provide a new tool for identifying alcohol-related cardiovascular harm long before the emergence of clinical illness or disease state.