Despite significant gains in diagnosis and treatment, coronary artery disease remains the primary cause of death and disability in the United States. The search for causes other than standard risk factors has led to the study of mental stress and psychological factors. This search has revealed a phenomenon which the investigators call mental stress ischemia. Mental stress ischemia occurs in 50 percent of patients with coronary artery disease (CAD), is associated with poor prognosis, and is predicted by the presence of specific psychological profiles; the mechanisms of this ischemic syndrome remains unknown. Research to date has identified hemodynamic and neuroendocrine processes as important physiologic correlates of mental stress ischemia. A model for the transduction of environmental stimulation (such as stressful mental demand) into clinically significant endpoints (such as mental stress ischemia) for patients identified as at risk due to psychological traits (such as anger and hostility) of necessity, requires the elucidation of the role played by the central nervous system (CNS). The investigators believe that the psychological traits of anger and hostility serve as markers for a susceptibility to heightened activation of cognition and emotion related CNS pathways, under the conditions of environmental demand represented by laboratory mental stress tasks. Thus, specific aim #1 will identify, using PET imaging, regional CNS activation during mental stress ischemia (as detected with simultaneous echocardiography). The investigators hypothesize that mental stress ischemia is associated with heightened activation of cognition and emotion related CNS pathways during laboratory mental stress. Their second specific aim will examine the relationship between these CNS processes and the psychological traits of anger and hostility. They hypothesize that the susceptibility represented by anger and hostility can be observed directly in the CNS through dynamic imaging of cognition and emotion related pathways during mental stress ischemia, using PET imaging. Such studies would provide important insight into how mental stress and psychologically related emotional experiences provoke ischemia, and provide an independent physiologic marker (CNS) for individuals with trait anger and hostility who are at risk for this mental stress ischemia. The investigators believe that this work will contribute towards an integrative model of psychological and neurobiologic factors of mental stress ischemia and provide the basis of mental stress testing for diagnosis, prognosis, and the development of new behavioral and pharmacologic therapies.
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