The National Heart, Lung, and Blood Institute convened a working group of investigators on June 14-15, 2004, in Bethesda, Maryland to identify areas for future research on the detrimental physiological effects of chronic stress on the heart and vasculature. Stimulation of research interest in this area may enable preventive or ameliorative interventions for promoting cardiovascular health. The Working Group members included experts in physiology, neuroendocrinology, behavioral stress, and heart and vascular biology.
The detrimental effects of stress on the cardiovascular system have been documented through research in animal models and humans. Primarily two systems mediate the stress response, by exerting an acute influence on cardiovascular function: the hypothalamic-pituitary-adrenocortical (HPA) axis and the sympatho-adrenomedullary system (SAS). Individuals with confirmed cardiovascular disease or its risk factors respond differently to these two systems. Although humans are physiologically equipped to respond to acute stressors, chronic (longtime) stress disrupts the HPA axis and the SAS, resulting in harmful effects on human health. Moreover, cross-sectional (and, to a lesser extent, longitudinal) epidemiological data show that chronic job stress and cardiovascular reactivity in response to stress are associated with hypertension, coronary heart disease, and stroke. However, the specific physiological and behavioral mechanisms, as well as the degree of cardiovascular risk attributable to chronic stress, remain poorly understood.
In recent years, new discoveries in basic science and evidence from longitudinal studies have underscored the importance of stress in cardiovascular disease. For example, animal studies have shown that ACTH-glucocorticoid-induced hypertension is not prevented by drugs that block the classical glucocorticoid or mineralocorticoid receptors, suggesting the existence of alternative mechanisms and/or abnormalities in glucocorticoid metabolism. The existence of newly identified ACTH receptors in aortic endothelial cells suggests that ACTH is involved in the action of glucocorticoids on the vasculature. Furthermore, evidence of new links among energy consumption, stress, and obesity has been described.
Preliminary human data are consistent with data from animal models. Longitudinal studies of cumulative exposure to job strain provide support for a possible association between stress and blood pressure. Studies in people with preexisting coronary disease or essential hypertension consistently show a positive relationship between stress reactivity and subsequent clinical outcomes, including stroke. Nonetheless, links between chronic stress and disease have not been conclusively established. Measuring chronic stress exposure in longitudinal observational studies remains an important objective in this area.
The working group underscored the biological differences between acute and chronic stress on the cardiovascular system. Chronic stress sets the stage for, or increases susceptibility to, acute events of coronary artery disease. In spite of its importance, however, this area has been understudied and further investigations are needed, since the public health consequences are considerable. The working group recommended research support for mechanistic studies as well as small clinical studies with intermediate physiological end points, and confirmed that continued observational research on the effects of stress on cardiovascular disease and its risk factors is warranted.
Specific recommendations include:
Chair: Mary F. Dallman, Ph.D., Department of Physiology,University of California-San Francisco