Robert Soufer, MD

Data show that psychological factors play an important role in acute coronary syndromes. We and others, have found mentally demanding tasks such as mental arithmetic to provoke ischemia in approximately 50% of patients with ischemic heart disease. We have also found a specific psychological profile, characterized by emotional reactivity, and easily aroused anger and hostility, to be associated with this “mental stress ischemia”; conversely, we have not found an association between this profile and exercise ischemia. Follow up of these mental stress positive patients reveal a significantly poorer 1-2 year prognosis. Hence, mental stress ischemia may be a distinct phenomenon with unique risk factors and prognosis. The mechanisms of mental stress ischemia are, however, not well understood. Critical questions remain regarding the ways by which mental and psychological factors contribute to coronary syndromes. We believe that psychological, neurobiological and coronary vasomotor processes are key factors, expanding upon our pilot work, conducted in the context of our current funding. We are examining the functional CNS correlates of mental stress ischemia; these CNS correlates will be defined by positron emission tomography (PET) conducted while patients perform an arithmetic task that we have found to reliably provoke ischemia in half of those we have studied. This approach will illuminate CNS processes that may be serving to transduce mental stress susceptibility into risk for acute coronary events. Specific issues concerning gender interaction and relationship to psychological profiles/coping styles are currently being explored.

The overarching research theme of our research is the elucidation of those mechanisms, which transduce cognitive stress as a provocation of myocardial ischemia. Specifically, we are interested in the neurobiology and coronary flow dynamics that results from mentally stressful tasks. Our work utilizes simultaneous measurements of brain activation and myocardial function/coronary flow with PET imaging, echocardiography and pulse arterial tonometry during laboratory mental stress. We are developing conceptual constructs based upon our previous work, which support a model that suggests certain regional and global brain activation maps are associated with coronary flow responses specific to psychosocial stress.

Our goal for the next academic year is to describe the pathophysiologic mechanisms of mental stress induced myocardial ischemia that differs from those that are a result of exercise. We have the largest series of subjects to date (n=138) undergoing simultaneous imaging with PET during Mental Stress and then again with dobutamine as a surrogate for exercise in a population of CAD subjects. Our results thus far support our hypothesis of regional activation in the brain that promote parasympathetic withdrawal, increase in sympathetic tone and decrease LV flow/ function that is not observed in the dobutamine group (exercise surrogate) is thus far confirmed. A manuscript based on these results is in preparation. We have studies that show a gender interaction that has just been analyzed and these data will be prepared and submitted afterwards.

An individual’s biological substrate interacts within this neurobehavioral context thru genetic, endocrine, immune and neural processes. Many of these processes are shape by inflammatory responses. Our previous published reports reinforced the principle that inflammatory processes may also be associated with other dimensions of CAD expression. In this past year we have expanded our constructs regarding the role of other vascular factors, which may be operative during Mental Stress Ischemia. Specifically our recent data suggests an up regulation of ET-1 among CAD patients who are subjected to a standardized Anger recall paradigm. We have also described these findings in the context of the parasympathetic inflammatory response, which predicts such increases in response to w withdrawal of parasympathetic tone, a cardinal feature of Mental Stress Induced Myocardial Ischemia. We have observed an inverse relationship of TNF-alpha and parasympathetic withdrawal in subjects who become ischemic and have specific regional brain activation coincident with this process. Finally, we have developed and published a noninvasive stress test to index those most vulnerable to Mental Stress Ischemia.

Title: Depression and Coronary Disease: Prognosis and Mechanisms.The objectives of this project are to explore prognosis in subjects with CAD and depression after percutaneous intervention.

Title: Neurobehavioral Correlates of Mental Stress Ischemia. The objectives of this project are to examine CNS involvement in mental stress ischemia, using a combination of modalities, including positron emission tomography and echocardiography.

Title: Neurobehavioral Correlates of Mental Stress Ischemia: Supplement for Serological Core Lab.
The objectives of this project are to examine the inflammatory underpinnings of MSI.