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.
Regular heavy episodic or binge drinking is one of the most serious public health problems confronting American colleges. The cardiovascular impairments associated with repeated binge drinking episodes are unexplored in college-aged students. This study is designed to examine changes in the function and structure of the vasculature (ie. arteries) and mechanisms (oxidative stress) in young adult binge drinkers compared to those who do not drink or drink at moderate levels. Our study will provide clinically important data on how binge drinking contributes to premature cardiovascular and cerebrovascular risk in youth.
| Piano, Mariann R; Mazzuco, Adriana; Kang, Minkyung et al. (2017) Binge Drinking Episodes in Young Adults: How Should We Measure Them in a Research Setting? J Stud Alcohol Drugs 78:502-511 |
