PROJECT SUMMARY/ABSTRACTDespite cardiovascular disease (CVD) being the leading cause of death in the U.S. and worldwide for over acentury traditional risk factors (e.g. diabetes blood pressure cholesterol) account for only 50% of thevariance in CVD outcomes. Over four decades of research provide robust replicated consistent evidence thatpsychological stress is linked to CVD outcomes and hypothesized behavioral and biological paths of risk. Thusthere is a critical need for understanding how stress gets under the skin to cause CVD. This work begins withan ecologically valid understanding of how stress is experienced and connotes risk. One major contemporarytheory the Generalized Unsafety Theory of Stress (GUTS) conceptualizes stress as a default state ofemotion with concomitant physiological sequelae. Robust data supports GUTS framework by demonstratingassociations between structural indicators of contextual safety acute stress reactivity profiles and risk of heartdisease. Another major contemporary model Social Safety Theory (SST) also points to the importance ofperceived indicators of security. SST emphasizes the human propensity for social engagement positingexposure to perceived social threat drives physiological stress reactivity and perception of available socialsafety cues moderates such stress responses. Extensive work supports perception of social safety andexposure to social threat as contributors to inflammatory stress response patterns associated with CVDprogression. Both theories suggest humans are in a constant state of environmental safety evaluation orvigilance influencing a constellation of behavioral physiological and psychological reactions. Theoverarching goal of this proposal is to investigate for the first time a harmonized model detailing stress as anecologically valid risk determinant of CVD. I will use existing longitudinal data from an NHLBI-funded R01 toaddress this goal through three aims. Under aim 1 I investigate the relationship between environmental safetysocial safety daily social vigilance and 2-year change in carotid intima-media thickness (cIMT) as a preclinicalmarker of CVD. With aim 2 I examine the extent to which social vigilance mediates associations betweenenvironmental safety social safety and 2-year change in cIMT. Finally through exploratory aim 3 Icharacterize how blood pressure and inflammatory markers account for relationships among environmentalsafety social safety daily social vigilance and 2-year change in cIMT. A highly experienced mentorship teamof investigators will support my research and training to become a leading psychosocial mechanism scientistcontributing to understanding nontraditional determinants of CVD. Through the proposed training opportunitiesI 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 inCVD etiology; 4) enhance my professional development and research dissemination; and 4) improve mygrantsmanship skills and apply for future grant support.