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.

PROJECT NARRATIVE The proposed research aims to contribute a better understanding of how environmental and social factors influence cardiovascular disease, given this is the leading cause of death in the U.S. and worldwide for over a century. This research is aligned with the National Institutes of Health’s commitment to supporting research to reduce the impact of disease by identifying and improving understanding of risk factors and protective factors. Moreover, the proposed training will enhance women-led efforts in the biomedical, behavioral, and clinical research workforce in the United States.