Chronic psychosocial stress exposure is a potent but largely under-recognized risk factor for cardiovascular disease (CVD); however, the underlying mechanism remains uncertain. Chronic stress triggers a neurohormo- nal response, but the upstream brain centers initiating this cascade are incompletely defined. Several recent studies have shown that higher stress is associated with increased inflammation that drives CVD. Furthermore, a growing body of research shows a benefit for stress reduction in individuals with CVD via modification of brain activity and reduction of systemic inflammation and CVD symptoms. Advanced imaging with positron emission tomography and magnetic resonance imaging (PET/MRI) provides an opportunity to reproducibly evaluate the neurobiological activity of stress-associated neural centers (e.g., the amygdala) that participate in the initiation of this pathway while concurrently evaluating the activities of several other tissues that may partic- ipate in this mechanism, such as the bone marrow and arterial wall, to derive novel mechanistic insights. Within this paradigm, our group has shown that heightened activity of the amygdala associates with increased bone marrow activity and increased inflammation of the arterial wall. The current proposal addresses these knowledge gaps by assessing the impact of mindfulness-based stress reduction on arterial inflammation (Aim 1) as well as amygdalar activity and systemic inflammation (Aim 2) in individuals with known coronary artery disease using PET/MRI. This randomized controlled trial will enroll 36 subjects randomized to stress reduction or usual care who will undergo baseline and follow-up imaging and inflammatory biomarkers. Subjects with confounding conditions (i.e., psychiatric or neurologic disease, etc.) will be excluded. Dr. Michael Osborne is an Instructor of Medicine at Harvard Medical School and Massachusetts General Hospital (MGH) who is highly qualified and invested in leading this study. He has a unique background in engineering and advanced imaging and a track record of successful research, including publications and awards, using several imaging modalities. Via this proposal, he will develop expertise in multi-system PET/MRI and improve his foundation in the imple- mentation of clinical trials, biostatistics, inflammation biology, stress, and mind-body medicine while generating the data and profile needed to transition to R-level independent NIH-supported research. His long-term goal is to apply multi-parametric PET/MRI to better understand the relationship between stress and physical disease and identify effective treatments. He is supported by a well-qualified mentorship team that is led by Dr. Ahmed Tawakol, a cardiologist with expertise in PET, and includes other NIH-funded investigators in radiology, psychi- atry, epidemiology, and cardiology. His institutional environment is robust and has a long history of supporting the development of early investigators via myriad resources including didactics, facilities, and mentorship. The MGH Division of Cardiology has made a strong commitment to Dr. Osborne with assurance of 75% of pro- tected time for this proposal to foster his career as an autonomous investigator.
Chronic psychosocial stress exposure is a potent but largely under-recognized risk factor for cardiovascular disease (CVD), and research shows that stress reduction techniques may have a benefit in individuals with CVD; however, the underlying mechanism linking stress to CVD remains uncertain. Cutting-edge brain imaging techniques have demonstrated changes in brain center activity in the setting of chronic stress. This multi- parametric hybrid PET/MRI study tests the hypothesis that stress reduction reduces stress-associated neurobiological activity as well as systemic and arterial inflammation and seeks to yield insights into mechanisms that translate stress into physical disease with the goal of improving our ability to prevent and treat CVD.
