Cardiovascular risk associated with binge drinking in young adults

酗酒或间歇性大量饮酒是美国人面临的一个严重的公共卫生问题 院校更令人担忧的是酗酒事件的普遍性和规律性：五分之一 学生报告在前两周内有三次或三次以上的酗酒事件。国家研究所 酒精滥用和酒精中毒将酗酒定义为在两小时内饮用超过4-5杯饮料。 本提案旨在解决融资机会中强调的几个主题领域 公告（PA-14-124）标题为“酒精对组织损伤和修复的影响”，并将揭示 与有害酒精使用相关的组织损伤的临床、分子和其他机制 人类我们的综合研究计划的长期目标是开发模型系统， 进行机制研究，以检查暴饮暴食引起的心血管（CV）的起始和发病机制 对年轻人的影响。除了我们的数据，与反复酗酒相关的CV损伤 在大学年龄段的学生中还没有发现。酗酒可能会损害血管功能， 交感神经活动和氧化应激，产生加重炎症的倾向或环境， 导致动脉粥样硬化、高血压和CV疾病。R21赠款的总体目标是 在有酗酒史的年轻人中，确定酗酒是否加速了亚临床的发病， 心血管疾病，改变微血管功能，增加交感神经活动，并导致过度的血液 压力对锻炼的反应。我们有两个主要的假设，以实现这一目标。 假设1：将有CV风险标志物的证据，例如动脉功能降低， 导管和阻力动脉。在中央动脉中将存在增加的动脉硬度（使用 脉搏波速度）和中心血压升高-所有这些都将在酗酒者中更大（n=50） 与戒酒者（n=50）和适度饮酒者（n=50）相比。我们假设， 中度饮酒者和戒酒者之间的CV标志物。 假设2：与戒酒者和适度饮酒者相比，暴饮暴食者将增加 肾上腺素能驱动和微血管功能障碍，例如静息时去甲肾上腺素水平升高， 对最大运动量的过度血压反应。此外，我们假设， 血管内压力会增加氧化应激的产生，降低内皮依赖性 与适度饮酒者和戒酒者相比，酗酒者的孤立小动脉扩张。以确定 对于后者，我们将使“孤立血管”（来自臀肌活检）暴露于高腔内压力， 揭示高压后循环对血管功能障碍的易感性。此外，我们将 研究离体阻力血管对乙酰胆碱舒张反应性。

Binge drinking or heavy episodic alcohol use is a serious public health problem confronting American colleges. More alarming are the pervasiveness and regularity of binge drinking episodes: one in five students reports three or more binge drinking episodes in the prior two weeks. The National Institute on Alcohol Abuse and Alcoholism defines binge drinking as consuming more than 4-5 drinks in a two-hour period. This proposal is designed to address several of the topic areas highlighted in the Funding Opportunity Announcement (PA-14-124) titled, "Alcohol-Induced Effects on Tissue Injury and Repair” and will reveal clinical, molecular and other mechanisms related to tissue injury associated with harmful alcohol use in humans. The long-term objective of our integrated research program is to develop model systems and conduct mechanistic studies to examine the initiation and pathogenesis of binge-induced cardiovascular (CV) consequences in young adults. Except for our data, CV impairments associated with repeated binge drinking episodes are unexplored in college-aged students. Binge drinking may impair vascular function, increase sympathetic activity, and oxidative stress creating a proclivity or milieu that accentuates inflammation and contributes to atherosclerosis, hypertension, and CV disease. The overall aim of this R21 grant is to determine in young adults with a history of binge drinking, if binge drinking accelerates the onset of subclinical CV disease, alters microvascular function, increases sympathetic activity and leads to exaggerated blood pressure responses to exercise. We have 2 primary hypotheses to this aim. Hypothesis 1: There will be evidence of CV risk markers, exemplified by reduced arterial function in conduit and resistance arteries. There will be an increased arterial stiffness in central arteries (measured using pulse wave velocity) and increased central blood pressure--all of which will be greater in binge drinkers (n=50) compared to abstainers (n=50) and moderate drinkers (n=50). We hypothesize that there will be no difference in CV markers between moderate drinkers and abstainers. Hypothesis 2: Compared to abstainers and moderate drinkers, binge drinkers will have increased adrenergic drive and microvascular dysfunction, exemplified by increased norepinephrine levels at rest and exaggerated blood pressure response to maximal exercise. In addition, we hypothesize that elevated intravascular pressure will increase the generation of oxidative stress and reduce endothelium-dependent dilation in isolated arterioles of binge drinkers compared to moderate drinkers and abstainers. To determine the latter, we will expose ‘isolated vessels’ (from gluteal biopsies) to high intraluminal pressure as a means to uncover the susceptibility of the circulation to vascular dysfunction following high pressure. In addition, we will investigate vasodilatory reactivity to acetylcholine in isolated resistance vessels.