NHLBI Working Group
Cardiovascular Consequences of Chronic Stress
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
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:
- 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
- Foster vascular wall biology studies to understand the vascular responses
to stress, including alterations in blood pressure and the development
- 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
- 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
Last updated: August 9, 2004