ABSTRACT
Adverse childhood experiences (ACEs), including abuse, neglect, household and community dysfunction,
represent potentially traumatic psychosocial stressors that occur during critical development periods and
represent a latent risk factor for future cardiovascular disease (CVD). ACE exposure promotes cardiovascular
disease risk in adulthood in a dose-dependent manner, such that adults exposed to 4 or more ACEs have a
more than two-fold increased risk of ischemic heart disease and stroke compared to individuals with no ACEs.
ACEs are also widespread, with 1 in 6 US adults reporting exposure to four or more ACEs. Identification of
modifiable, bio-behavioral mechanisms by which ACEs promote early onset CVD risk is critical to establish
effective interventions to improve cardiovascular health in the millions of individuals affected by ACEs. Our recent
evidence indicates that young adults exposed to ACEs demonstrate impaired vascular endothelial function that
is manifest prior to overt elevations in blood pressure or other CVD risk factors, and that is related to systemic
oxidative stress. These vascular impairments were also observed alongside poor sleep, and our strong
preliminary data suggests that poor sleep quality, or low sleep efficiency, may mediate the association of ACE
exposure with vascular dysfunction. Therefore, we propose that disturbed sleep is a critical, modifiable bio-
behavioral pathway by which ACEs promote vascular dysfunction in early life. Here, we propose the critical
studies necessary to understand the causal, mechanistic role of disturbed sleep in ACEs-related endothelial
dysfunction in young adults. To do so, we propose to 1) objectively quantify the degree to which lower sleep
quality contribute to ACEs-related endothelial dysfunction, inflammation, and oxidative stress in young adults,
and 2) manipulate sleep quality using an established behavioral sleep intervention, Cognitive Behavioral Therapy
for Insomnia (CBT-I), in a cohort of young adults with moderate-to-severe ACE exposure in order to establish
the causal, mechanistic role of disturbed sleep in ACEs-related vascular endothelial dysfunction. To accomplish
these aims, we will use an innovative translational human approach that includes rigorous at home sleep
monitoring using actigraphy and polysomnography, in vivo assessment of endothelial function via flow-mediated
dilation testing, and in vitro determination of endothelial cell inflammation and oxidative stress from biopsied
endothelial cells. Notably, while vascular endothelial dysfunction contributes to and is prognostic of future CVD,
it is also reversable. Thus, outcomes of this study are expected to be of high impact by identifying and
understanding how disturbed sleep, a key, targetable bio-behavioral mechanism, contributes to vascular
endothelial dysfunction in young adults with exposure to ACEs.
