Recent studies provide clear and convincing evidence that psychosocial factors contribute significantly to the pathogenesis and expression of coronary artery disease (CAD). This evidence is composed largely of data relating CAD risk to 5 specific psychosocial domains: (1) depression, (2) anxiety, (3) personality factors and character traits, (4) social isolation, and (5) chronic life stress. Pathophysiological mechanisms underlying the relationship between these entities and CAD can be divided into behavioral mechanisms, whereby psychosocial conditions contribute to a higher frequency of adverse health behaviors, such as poor diet and smoking, and direct pathophysiological mechanisms, such as neuroendocrine and platelet activation. An extensive body of evidence from animal models (especially the cynomolgus monkey, Macaca fascicularis) reveals that chronic psychosocial stress can lead, probably via a mechanism involving excessive sympathetic nervous system activation, to exacerbation of coronary artery atherosclerosis as well as to transient endothelial dysfunction and even necrosis. Evidence from monkeys also indicates that psychosocial stress reliably induces ovarian dysfunction, hypercortisolemia, and excessive adrenergic activation in premenopausal females, leading to accelerated atherosclerosis. Also reviewed are data relating CAD to acute stress and individual differences in sympathetic nervous system responsivity. New technologies and research from animal models demonstrate that acute stress triggers myocardial ischemia, promotes arrhythmogenesis, stimulates platelet function, and increases blood viscosity through hemoconcentration. In the presence of underlying atherosclerosis (eg, in CAD patients), acute stress also causes coronary vasoconstriction. Recent data indicate that the foregoing effects result, at least in part, from the endothelial dysfunction and injury induced by acute stress. Hyperresponsivity of the sympathetic nervous system, manifested by exaggerated heart rate and blood pressure responses to psychological stimuli, is an intrinsic characteristic among some individuals. Current data link sympathetic nervous system hyperresponsivity to accelerated development of carotid atherosclerosis in human subjects and to exacerbated coronary and carotid atherosclerosis in monkeys. Thus far, intervention trials designed to reduce psychosocial stress have been limited in size and number. Specific suggestions to improve the assessment of behavioral interventions include more complete delineation of the physiological mechanisms by which such interventions might work; increased use of new, more convenient "alternative" end points for behavioral intervention trials; development of specifically targeted behavioral interventions (based on profiling of patient factors); and evaluation of previously developed models of predicting behavioral change. The importance of maximizing the efficacy of behavioral interventions is underscored by the recognition that psychosocial stresses tend to cluster together. When they do so, the resultant risk for cardiac events is often substantially elevated, equaling that associated with previously established risk factors for CAD, such as hypertension and hypercholesterolemia.

Impact of psychological factors on the pathogenesis of cardiovascular disease and implications for therapy.

In this review, the authors examine the evidence linking social support to physiological processes and characterize the potential mechanisms responsible for these covariations. A review of 81 studies revealed that social support was reliably related to beneficial effects on aspects of the cardiovascular, endocrine, and immune systems. An analysis of potential mechanisms underlying these associations revealed that (a) potential health-related behaviors do not appear to be responsible for these associations; (b) stress-buffering effects operate in some studies; (c) familial sources of support may be important; and (d) emotional support appears to be at least 1 important dimension of social support. Recommendations and directions for future research include the importance of conceptualizing social support as a multidimensional construct, examination of potential mechanisms across levels of analyses, and attention to the physiological process of interest.

The relationship between social support and physiological processes: a review with emphasis on underlying mechanisms and implications for health.

Social support has been reliably related to lower rates of morbidity and mortality. An important issue concerns the physiological mechanisms by which support influences such health endpoints. In this review, I examine evidence linking social support to changes in cardiovascular, neuroendocrine, and immune function. Consistent with epidemiological evidence, social support appears to be related to more positive “biological profiles” across these disease-relevant systems. Recent research on immune-mediated inflammatory processes is also starting to provide data on more integrative physiological mechanisms potentially linking social support to health. The implications of these links, along with future research directions are discussed.

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Social Support and Health: A Review of Physiological Processes Potentially Underlying Links to Disease Outcomes

Information obtained during the past decade suggests the need to reexamine the possibility that the onset of myocardial infarction and sudden cardiac death is frequently triggered by daily activities. The importance of physical or mental stress in triggering onset of coronary thrombosis is supported by the findings that 1) the frequencies of onset of myocardial infarction, sudden cardiac death, and stroke show marked circadian variations with parallel increases in the period from 6:00 AM to noon, 2) transient myocardial ischemia shows a similar morning increase, and episodes are often preceded by mental or physical triggers, 3) a ruptured atherosclerotic plaque, often nonobstructive by itself, lies at the base of most coronary thrombi, 4) a number of physiologic processes that could lead to plaque rupture, a hypercoagulable state or coronary vasoconstriction, are accentuated in the morning, and 5) aspirin and beta-adrenergic blocking agents, which block certain of these processes, have been shown to prevent disease onset. The hypothesis is presented that occlusive coronary thrombosis occurs when 1) an atherosclerotic plaque becomes vulnerable to rupture, 2) mental or physical stress causes the plaque to rupture, and 3) increases in coagulability or vasoconstriction, triggered by daily activities, contribute to complete occlusion of the coronary artery lumen. Recognition of the circadian variation--and the possibility of frequent triggering--of onset of acute disease suggests the need for pharmacologic protection of patients during vulnerable periods, and provides clues to mechanism, the investigations of which may lead to improved methods of prevention.

Circadian variation and triggers of onset of acute cardiovascular disease.

Background: Major damage to gray and white matter in the prefrontal cortex and autonomic deficits have been found to result in pseudopsychopathic personality in patients with neurological disorders, but it is not known whether people with antisocial personality disorder (APD) in the community who do not have discernable brain trauma also have subtle prefrontal deficits. Methods: Prefrontal gray and white matter volumes were assessed using structural magnetic resonance imaging in 21 community volunteers with APD (APD group) and in 2 control groups, comprising 34 healthy subjects (control group), 26 subjects with substance dependence (substancedependent group), and 21 psychiatric controls. Autonomic activity (skin conductance and heart rate) was also assessed during a social stressor in which participants gave a videotaped speech on their faults. Results: TheAPD group showed an 11.0% reduction in prefrontal gray matter volume in the absence of ostensible brain lesions and reduced autonomic activity during the stressor. These deficits predicted group membership independent of psychosocial risk factors. Conclusions: To our knowledge, these findings provide the first evidence for a structural brain deficit in APD. This prefrontal structural deficit may underlie the low arousal, poor fear conditioning, lack of conscience, and decision-making deficits that have been found to characterize antisocial, psychopathic behavior. Arch Gen Psychiatry. 2000;57:119-127

https://jamanetwork.com/journals/jamapsychiatry/articlepdf/481571/yoa9157.pdf

Reduced prefrontal gray matter volume and reduced autonomic activity in antisocial personality disorder.

To assess the causal relation between acute mental stress and myocardial ischemia, we evaluated cardiac function in selected patients during a series of mental tasks (arithmetic, the Stroop color--word task, simulated public speaking, and reading) and compared the responses with those induced by exercise. Thirty-nine patients with coronary artery disease and 12 controls were studied by radionuclide ventriculography. Of the patients with coronary artery disease, 23 (59 percent) had wall-motion abnormalities during periods of mental stress and 14 (36 percent) had a fall in ejection fraction of more than 5 percentage points. Ischemia induced by mental stress was symptomatically "silent" in 19 of the 23 patients with wall-motion abnormalities (83 percent) and occurred at lower heart rates than exercise-induced ischemia (P less than 0.05). In contrast, we observed comparable elevations in arterial pressure during ischemia induced by mental stress and ischemia induced by exercise. A personally relevant, emotionally arousing speaking task induced more frequent and greater regional wall-motion abnormalities than did less specific cognitive tasks causing mental stress (P less than 0.05). The magnitude of cardiac dysfunction induced by the speaking task was similar to that induced by exercise. Personally relevant mental stress may be an important precipitant of myocardial ischemia--often silent--in patients with coronary artery disease. Further examination of the pathophysiologic mechanisms responsible for myocardial ischemia induced by mental stress could have important implications for the treatment of transient myocardial ischemia.

S Hilton-Chalfen

Papers

Mental stress and the induction of silent myocardial ischemia in patients with coronary artery disease.