The aims of our ongoing program are to better understand the biologic and clinical importance of stress on lipid concentrations and metabolism. Building on the findings of our previous studies, the projects described in this application are designed to advance our knowledge of the relationships between behavioral stress, gender, hostility, coping, and lipid and lipoprotein concentrations, and to specifically identify the direct mechanisms driving these relationships. In our currently funded projects, we have demonstrated that both chronic and acute stress result in significant increases in total cholesterol, low density lipoprotein- cholesterol (LDL-c) and triglyceride concentrations in healthy, middle- aged individuals. Our work has also identified several individual difference variables that are sensitive to lipid changes during stress. The studies described in this renewal build on these findings by seeking to understand the mechanisms driving these alterations, and to refine our understanding of how individual difference variables result in distinct lipid patterns of response to stress. The first proposed study will specifically test the hypothesis that behavioral stress alters lipid and lipoprotein concentrations by altering lipoprotein lipase and hepatic triglyceride lipase activity. The second proposed study will specifically test the hypothesis that behavioral stress alters triglyceride fat clearance after administration of an intravenous fat load. Both studies will test the hypothesis that alterations in lipid metabolism during behavioral stress are moderated by individual differences in constitutional (gender, age/menopausal status) and psychosocial (hostility, coping, anxiety) characteristics. Statistical analyses are hypothesis-driven, and are designed to test several pathways of the proposed model. Coronary heart disease is a major public health concern and the well- documented gender differences in disease are poorly understood. Psychosocial characteristics such as hostility are also associated with coronary heart disease. To the extent that lipid metabolism and lipid reactivity are relevant to the initiation and progression of coronary heart disease, these studies will advance our understanding of the manner in which behavioral stress, reproductive hormones, and psychosocial characteristics impact on lipid metabolism to alter risk for coronary heart disease.
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