Cardiovascular Consequences of Chronic Stress

Introduction:

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.

Recommendations:

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:

• Stimulate integrated multidisciplinary research on chronic stress and cardiovascular function through collaborations among scientists in neuroscience, behavior, molecular genetics, and endocrinology.
• Support mechanistic studies to elucidate how neuroplastic modifications resulting from chronic stress produce long-term changes in the control of autonomic nervous system functions that affect cardiovascular and metabolic parameters.
• Foster vascular wall biology studies to understand the vascular responses to stress, including alterations in blood pressure and the development of atherosclerosis.
• Promote the application and development of genomics, proteomics, and imaging tools to study brain-cardiovascular system interactions under conditions of stress.
• Encourage studies on the influence of social stress on energy metabolism, eating behavior, and obesity.
• Develop randomized trials of stress management in primary and secondary prevention of cardiovascular diseases.

Working Group Members

Chair: Mary F. Dallman, Ph.D., Department of Physiology,University of California-San Francisco

Members:

• Philip W. Gold, M.D., NIMH, NIH
• Stafford L. Lightman, M.B., Ph.D., University of Bristol, U.K.
• Murray A. Mittleman, M.D., Dr.P.H., Harvard Medical School
• Dominique Musselman, M.D., M.S., Emory University School of Medicine
• David M. Pollock, Ph.D., Medical College of Georgia
• Lynda Powell, Ph.D., Rush Medical University
• Morton P. Printz, Ph.D., University of California-San Diego
• Alan Rozanski, M.D., Saint Luke's Roosevelt Hospital
• Deborah Scheuer, Ph.D.,University of Missouri-Kansas City
• Carol A. Shively, Ph.D., Wake Forest University
• Robert Soufer, M.D., Yale School of Medicine
• Frank Treiber, Ph.D.,Medical College of Georgia