Key 2010 publications in behavioral medicine

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Previous research has demonstrated an association between depression and incident coronary heart disease (CHD); in 2010, well-controlled studies and meta-analyses went beyond depression to include anxiety, anger expression, and negative affect as predictors of incident CHD. Emerging research suggests that positive emotions and resilience (including the ability to self-regulate) offer protection against CHD. New research is elucidating the pathophysiology to explain the effects of emotion and resilience on disease risk; for example, recent work has begun to consider how the relaxation response promotes resilience and found that it induces genomic changes that counter oxidative stress and associated cellular damage.



The effect of emotion on the heart is not confined to depression, but extends to a variety of mental states; as William Harvey described in 1628, “A mental disturbance provoking pain, excessive joy, hope or anxiety extends to the heart, where it affects its temper and rate, impairing general nutrition and vigor.”

In going beyond the well-established role of depression as a risk factor for heart disease, 2010 delivered several important publications recognizing anxiety, anger, and other forms of distress as key factors in the etiology of coronary heart disease (CHD). Other papers of merit elucidated new and overlooked insights into the pathways linking psychosocial stress and cardiovascular risk, and also considered psychologic states that appear to promote healthy functioning.


In a meta-analysis of 20 prospective studies that included 249,846 persons with a mean follow-up of 11.2 years, Roest et al1 examined the impact of anxiety characterized by the presence of anxiety symptoms or a diagnosis of anxiety disorder on incident CHD. Most of the studies adjusted for a broad array of relevant potential confounders. Findings suggest the presence of anxiety increases the risk of incident CHD by 26% (P P = .003).

In a meta-analysis of 25 prospective studies of 7,160 persons with a mean follow-up exceeding 10 years, Chida and Steptoe2 found that anger increased the risk of incident CHD by 19%, after adjustment for standard coronary risk factors. The effect was less stable than that associated with anxiety and depression, and when stratified by gender, the harmful effects of anger were more evident in men than in women. The effect of anger was attenuated when controlling for behavioral covariates. The association between anger and CHD did not hold for all ways of measuring anger, which suggests that the type of anger or the ability to regulate anger may be relevant to the relationship.

A study that did account for the type of anger expression on the risk of incident CHD was conducted by Davidson and Mostofsky.3 The independent effect of three distinct types of anger expression (constructive anger, destructive anger justification, and destructive anger rumination) on 10-year incident CHD was examined, controlling for other psychosocial factors. In men, higher scores for constructive anger were associated with a lower rate of CHD; in both men and women, higher scores for destructive anger justification were associated with an increased risk of CHD.

Insights gained from these studies are as follows:

  • The impact of anxiety appears to be comparable to depression, and the effects of anxiety and depression are largely independent.
  • If anxiety and depression co-occur, the effect on CHD is synergistic.
  • The effects of anger are less clear; its impact may be independent of or dependent on other forms of psychologic distress.
  • Distress in general appears to serve as a signal that something is wrong and needs to be addressed. If ignored, it may become chronic and unremitting; because symptoms of distress may lead to systemic dysregulation and increased CHD risk, they may indicate the need for increased surveillance and intervention.


A clear biologic explanation for the influence of emotional factors on physical health would serve to assuage skeptics who doubt that such a link exists or who attribute a common underlying genetic trait to both negative affect and heart disease. Further, focusing on the biology may help answer key questions with respect to emotions and disease processes: What is the damage incurred by negative emotional states and is it reversible? Can compensatory pathways be activated to bypass the mechanisms causing damage or slow the progression of disease?

Cardiac response to worry and stress

In one study attempting to shed light on relevant emotion-related biologic process, the prolonged physiologic effects of worry were examined. Worry episodes and stressful events were recorded hourly along with ambulatory heart rate and heart rate variability in 73 teachers for 4 days.4 Autonomic activity, as reflected by a concurrent elevation in heart rate and a decrease in heart rate variability, was increased up to 2 hours after a worry episode. The findings also suggested that the prolonged cardiac effects of separate worry episodes were independent.

Another study sought to determine whether heightened reactivity or delayed recovery to acute stress increases risk of cardiovascular disease.5 This meta-analysis included 36 studies to assess whether acute cardiovascular response to various laboratory stressors (ie, cognitive tasks, stress interviews, public speaking). Findings indicated that heightened cardiovascular reactivity was associated with worse cardiovascular outcomes, such as incident hypertension, coronary calcification, carotid intima-media thickness, and cardiovascular events over time.

Role of aldosterone overlooked

Reprinted from Neuroscience and Biobehavioral Reviews (Kubzansky LD, et al. Aldosterone: a forgotten mediator of the relationship between psychological stress and heart disease. Neurosci Biobehav Rev 2010; 34:80–86), © 2010, with permission from Elsevier.

Figure 1. A model of aldosterone as a mediator of the relationship between distress and heart disease. ACTH = adrenocorticotropic hormone; HPA = hypothalamic-pituitary-adrenal; MR = mineralocorticoid receptor; SNS = sympathetic-adrenomedullary system

Although identified by Selye as a stress-related hormone that may be relevant when considering health, few studies have considered aldosterone as a potential pathway linking emotional distress and heart disease. Aldosterone is an adrenocorticosteroid hormone that is released by activation of the hypothalamic-pituitaryadrenal (HPA) axis and the renin-angiotensin system in response to stress. Aldosterone, which activates the mineralocorticoid receptors, has widespread cardiovascular and metabolic effects beyond its effects on fluid and electrolyte balance. Clinical trials have shown that blocking activation of mineralocorticoid receptors in patients with heart failure reduces the incidence of cardiovascular mortality. Pharmacologic blockade of the renin-angiotensin system is also known to improve mood, leading to speculation that by activating the HPA axis and sympathetic nervous system, psychosocial distress may trigger the release of angiotensin II and aldosterone and activate mineralocorticoid receptors, thereby promoting pathophysiologic processes that can lead to heart disease (Figure 1).

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