PROJECT SUMMARY/ABSTRACT
Despite cardiovascular disease (CVD) being the leading cause of death in the U.S. and worldwide for over a
century, traditional risk factors (e.g., diabetes, blood pressure, cholesterol) account for only 50% of the
variance in CVD outcomes. Over four decades of research provide robust, replicated, consistent evidence that
psychological stress is linked to CVD outcomes and hypothesized behavioral and biological paths of risk. Thus,
there is a critical need for understanding how stress gets “under the skin” to cause CVD. This work begins with
an ecologically valid understanding of how stress is experienced and connotes risk. One major contemporary
theory, the Generalized Unsafety Theory of Stress (GUTS), conceptualizes stress as a “default state” of
emotion with concomitant physiological sequelae. Robust data supports GUTS framework by demonstrating
associations between structural indicators of contextual safety, acute stress reactivity profiles, and risk of heart
disease. Another major contemporary model, Social Safety Theory (SST), also points to the importance of
perceived indicators of security. SST emphasizes the human propensity for social engagement, positing
exposure to perceived social threat drives physiological stress reactivity and perception of available social
safety cues moderates such stress responses. Extensive work supports perception of social safety and
exposure to social threat as contributors to inflammatory stress response patterns associated with CVD
progression. Both theories suggest humans are in a constant state of environmental safety evaluation or
“vigilance” influencing a constellation of behavioral, physiological, and psychological reactions. The
overarching goal of this proposal is to investigate, for the first time, a harmonized model detailing stress as an
ecologically valid risk determinant of CVD. I will use existing longitudinal data from an NHLBI-funded R01 to
address this goal through three aims. Under aim 1, I investigate the relationship between environmental safety,
social safety, daily social vigilance, and 2-year change in carotid intima-media thickness (cIMT) as a preclinical
marker of CVD. With aim 2, I examine the extent to which social vigilance mediates associations between
environmental safety, social safety, and 2-year change in cIMT. Finally through exploratory aim 3, I
characterize how blood pressure and inflammatory markers account for relationships among environmental
safety, social safety, daily social vigilance, and 2-year change in cIMT. A highly experienced mentorship team
of investigators will support my research and training to become a leading psychosocial mechanism scientist
contributing to understanding nontraditional determinants of CVD. Through the proposed training opportunities,
I will: 1) deepen conceptual understanding of contemporary stress models related to cardiovascular health; 2)
develop methodological understanding of key pathways from stress to disease; 3) gain advanced knowledge in
CVD etiology; 4) enhance my professional development and research dissemination; and 4) improve my
grantsmanship skills and apply for future grant support.
