Cardiovascular risk associated with binge drinking in young adults

年轻人酗酒与心血管风险相关

• 批准号: 9173125
• 负责人: MARIANN R PIANO
• 金额: $ 22.99万
• 依托单位: UNIVERSITY OF ILLINOIS AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-03-01 至 2019-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9173125
• 关键词: Acetylcholine; Address; Adrenergic Agents; Adult; Affect; Age; Alcohol abuse; Alcohol consumption; Alcohols; American; Area; Arteries; Atherosclerosis; Biological Models; Biopsy; Blood; Blood Circulation; Blood Pressure; Blood Vessels; Cardiovascular Diseases; Cardiovascular system; Centers for Disease Control and Prevention (U.S.); Central Artery; Clinical; Consumption; Cross-Sectional Studies; Data; Endothelium; Ethanol; Event; Exercise; Female; Funding Opportunities; Future; Generations; Goals; Grant; Health; Healthcare; Hour; Human; Hypertension; Impairment; Inflammation; Injury; Intervention; Measures; Mediating; Microcirculation; Microvascular Dysfunction; Molecular; National Institute on Alcohol Abuse and Alcoholism; Nitric Oxide; Nitroglycerin; Norepinephrine; Oxidative Stress; Pathogenesis; Physiologic pulse; Population; Predisposition; Public Health; Recording of previous events; Reporting; Research; Resistance; Rest; Risk; Risk Marker; Stroke; Structure; Students; Tissues; Vascular Diseases; Vasodilation; Woman; Youth; aged; alcohol measurement; arterial stiffness; arteriole; binge drinker; binge drinking; body system; cardiovascular risk factor; cerebrovascular; college; design; drinking; injury and repair; insight; longitudinal design; male; men; premature; pressure; programs; response; screening; university student; young adult

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.

暴饮暴食或大量情节饮酒是美国面临的严重公共卫生问题 大学。更令人震惊的是暴饮暴食情节的普遍性和规律性：五分之一 学生报告在前两周内报告三个或更多的bbinge饮酒剧集。国家研究所 酒精滥用和酒精中毒将暴饮暴食定义为在两个小时内消耗4-5杯饮料。 该建议旨在解决资金机会中突出显示的几个主题领域 宣布（PA-14-124）的标题为“酒精诱导的对组织损伤和修复的影响”，并将揭示 临床，分子和其他与与有害酒精相关的组织损伤有关的机制 人类。我们集成研究计划的长期目标是开发模型系统和 进行机械研究以检查暴饮暴食的倡议和发病机理（CV） 年轻人的后果。除我们的数据外，与反复饮酒有关的简历障碍 在大学生中，情节是意外的。暴饮暴食可能会损害血管功能，增加 交感神经活动和氧化压力产生倾向或环境，突显注射和 有助于动脉粥样硬化，高血压和CV疾病。这项R21赠款的总体目的是 在有暴饮暴食史的年轻人中，确定饮酒史加速了亚临床的发作 简历疾病，改变微血管功能，增加交感神经活性并导致夸张的血液 对运动的压力反应。我们有2个主要假设。 假设1：将有证据表明CV风险标志物，以降低的动脉功能为例 导管和电阻动脉。中央动脉的动脉刚度将增加（使用 脉搏波速度）和中央血压升高 - 暴饮暴食者中的所有脉冲速度都会更大（n = 50） 与戒酒者（n = 50）和中等饮酒者（n = 50）相比。我们假设没有区别 在中度饮酒者和临床之间的简历标记中。 假设2：与戒酒者和中度饮酒者相比，饮料者会增加 肾上腺驱动和微血管功能障碍，以静止和静止肾上腺素水平升高为例 夸大对最大运动的血压反应。此外，我们假设该升高 血管内压将增加氧化应激的产生，并降低内皮依赖性 与中度饮酒者和临床药物相比，暴饮暴食者的孤立动脉膨胀。确定 后者，我们将暴露“孤立的血管”（从臀部活检）到高腔内压力​​，以此作为一种手段 发现高压后循环对血管功能障碍的敏感性。此外，我们将 研究了分离的耐药血管中对乙酰胆碱的血管舒张反应性。