Vascular Reactivity to Compounding Stressors across the Blood Alcohol Curve: Interactions with Chronic Drinking and Polysubstance Use

PROJECT SUMMARY/ABSTRACT Despite national health guidelines and the prevalence of alcohol-related cardiovascular disease, alcohol remains among the most popular recreational substances misused across the lifespan. Drinking behaviors are often initiated in early adulthood and, in the absence of overt illness or diagnosis of an alcohol use disorder (AUD), may be maintained for decades. Such drinking often occurs on a backdrop of chronic stress, even in ostensibly healthy young adults. Further, recent societal shifts in perspectives and laws surrounding recreational cannabis use have encouraged open positivity around alcohol co-use behaviors, even in otherwise health-conscious individuals. A critical public health problem in fighting cardiovascular disease is that alcohol- related physical health deterioration is insidious, evolving slowly as the result of chronic allostatic pressure placed on organ systems by alcohol in combination with other lifestyle factors. Alcohol acutely elicits both vasodilation and vasoconstriction that undoubtedly amplifies tension on the vasculature; yet, symptoms of vascular injury (e.g., coronary artery disease) are often hidden until >90% vessel occlusion. This makes it difficult for most people to ‘connect’ health behaviors, like alcohol consumption, to vascular degeneration. This application proposes that identification of early biomarkers of alcohol’s effects on the vasculature are critically needed to lower the prevalence of alcohol-related cardiovascular disease. The NIAAA F31 application proposes a novel study design and analytical approach to unravel individualized vascular dynamics across the blood alcohol concentration (BAC) curve in relation to chronic alcohol use behaviors (Research Aim 1), a concurrent acute stressor (Research Aim 2), and alcohol/cannabis co-use behaviors (Research Aim 3). The single-session alcohol administration study of chronic binge versus non-binge drinkers incorporates a periodic isometric handgrip task, an acute vascular challenge that can magnify vascular responses, during peak intoxication and recovery to evaluate adaptive potential. Recent cannabis use, measured from urinary THC metabolite concentration, on vascular responsivity will be also explored. A multilevel mixed modeling approach will capture changes in continuous blood pressure during the alcohol challenge alone and during the grip tasks. This research study will be supported by extensive training in alcohol studies, with a focus on pharmacological effects of alcohol (Training Goal 1), alcohol/cannabis interactions (Training Goal 2), cardiovascular physiology (Training Goal 3), and advanced statistical design (Training Goal 4). Together, the research and training plans will lay the foundation for the applicant’s future line of research to examine physiological factors that ultimately contribute to the development of alcohol-related disease across the lifespan. Receiving the NRSA F31 fellowship will relieve the applicant from a time-intensive teaching assistant position to effectively double his time available to conduct research and establish a strong professional network (Training Goal 5) within the field of alcohol studies.