This is an application for an Independent Scientist Award (K02) to study cardiovascular autonomic control in stress and anxiety. It is based on a research program whose focus is to explore the relationships among psychological/behavioral characteristics such as anxiety, hostility, depression, and physical conditioning, the central and autonomic nervous system, and the cardiovascular and respiratory systems. The application proposes a series of experiments deriving from a model which identifies blood pressure variability (BPV) as a potential mechanism by which psychological/psychiatric factors and health behaviors confer increased risk of coronary artery disease (CAD) and catastrophic cardiac events. While evidence suggests that psychological factors such as anxiety, depression, and hostility are associated with increased risk of CAD, the mechanisms by which these factors exert their pathogenic effects are only poorly understood. Our model holds that autonomic control of the heart serves a buffering or inhibitory function over oscillations in blood pressure, which recent research in vascular biology and dynamics suggests may have pathogenic effects on the endothelium, in the case of atherogenesis, and on plaque stability, in the case of catastrophic cardiac events. We recently have shown that under conditions of psychological stress, the magnitude of these blood pressure oscillations is inversely related to the degree of autonomic control of the heart, as measured by heart period variability (HPV). Thus, in subjects with high levels of cardiac autonomic control, blood pressure oscillations are minimal whereas in subjects with low levels of control, they are increased considerably. Since psychological/behavioral characteristics such as anxiety, depression, and hostility have been shown to be associated with lower levels of HPV, these characteristics may be associated with disinhibition of blood pressure oscillations, either at rest, or more likely, in response to psychological stress. Together, these findings suggest that the mechanism by which psychological characteristics such as hostility have their pathogenic effect is through reduced inhibition of BPV responses to challenge, which in turn promotes atherogenesis and plaque rupture. In this application, 5 experimental tests of this model are proposed.
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