Stress and the aching heart
Reference: New England Journal of Medicine 1984; 311: 594-95, http://content.nejm.org
Author: TB Graboys
The following article was written by Dr. Thomas Graboys of the Lown Cardiovascular Research Foundation.
Full text: "Every affection of the mind that is attended with either pain or pleasure, hope or fear, is the cause of an agitation whose influence extends to the heart." William Harvey, 1628 
Written more than 350 years ago, Harvey's allusion to an intimate association between neural factors and the heart received some attention in anecdote and fable, yet it was not subjected to systematic direct scientific inquiry until the 1960s. Over the past 20 years we have greatly refined our approach to identifying persons at risk of cardiac death.
When it was found that in most cases persons experiencing sudden cardiac death had no evidence of acute damage to the heart muscle, there began a period of intense investigation in an attempt to define other elements that might make up the "equation of vulnerability" contributing to the phenomenon of the aching heart. For example, we came to appreciate that the presence of certain forms of ventricular premature beats exerted an independent prognostic effect on survival in patients with ischemic heart disease. [2,3] Yet, because of the ubiquity of ventricular ectopy in the general population, the presence of complex forms of ventricular premature beats was meaningful primarily when they were found in conjunction with, and as an expression of, a jeopardized substrate-i.e., the ischemic myocardium. Furthermore, this coupling of factors became particularly crucial when it was associated with left ventricular dysfunction.
A troublesome fact, however, was that some patients who for many years had evidence of the triad of ischemic heart disease, ventricular arrhythmias, and left ventricular dysfunction remained virtually asymptomatic, whereas others with a similar constellation of findings succumbed suddenly, without prodrome. Lown postulated that one or more so-called transient risk factors might trigger the sudden demise of the vulnerable heart.  Platelet aggregation-disaggregation, coronary-artery vasospasm, electrolyte disorders, antiarrhythmic drugs, and perhaps most important, neural factors have all been suggested as transient catalysts in the development of ventricular fibrillation.
Although a wealth of evidence has linked central and peripheral sympathetic mechanisms to changes in cardiac electrophysiology, an independent relation between psychosocial stress and cardiac mortality h as yet to be defined, owing to the difficulty inherent in the quantification of higher neural activity.
Sudden changes in sympathetic adrenergic tone and in levels of catecholamines and neurotransmitters may acutely alter cellular automaticity and excitability. A causal link between acute psychologic stress and a cardiac event may thus be easier to define. Hence, the inference that an immediate and easily recognizable antecedent event can provoke sporadic arrhythmias, angina pectoris, or even sudden cardiac death has perhaps been more credible than extrapolation of the role of diffuse or chronic biobehavioral inducers of stress as independent mediators of mortality.
At present, the medical profession emphasizes that modification of the traditionally accepted risk factors should receive a high priority in preventive cardiology. Understandably, cigarette smoking, hyperlipidemia, and hypertension are reasonable and perceptible targets for therapeutic intervention. Yet such risk factors are found in less than half of those who succumb to ischemic heart disease. Psychological stress, on the other hand, has been viewed as a vague, subjective entity that cannot be quantified and has therefore not been accorded much attention in terms of prophylaxis.
Emergence of the concept of a specific personality type deemed "coronary prone" (i.e., Type A behavior) afforded us a distinct profile of the vigilant male beset with internal fury and living in a state of relentless, joyless striving.  As an extension of this construct, which focuses on endogenous personal factors, a number of studies have addressed the role of our daily environment, examining psychosocial and occupational influences that may have some bearing on the high prevalence of coronary-artery disease in the population today. Jenkins  found excess mortality in geographically impoverished areas where men had low educational and socioeconomic status. In an extensive survey of civil servants in the United Kingdom, Rose and Marmot  observed an inverse relation between social class and coronary-artery disease. In addition to perceived job dissatisfaction, so-called loss of autonomy appeared to create a "high stress-no exit" scenario. Karasek et al.  noted significantly higher rates of cardiac death among workers frustrated by the occupational paradox of considerable demands but little or no latitude in decision making. Such studies not only complemented the concert of the Type A personality but formulated an Orwellian recipe in which the estranged worker, besieged from above and below, mixes internal rage and incessant frustration into a fatal brew.
Other factors proposed to have a potentially adverse effect on the ailing heart include depression, chronic anxiety, role ambiguity, lack of adaptability and personal resources, situational stress, and marital discord. Helsung et al.  drew attention to an association between bereavement and increased subsequent mortality among spouses or next of kin. Similarly, Rees and Lutkins  noted that within a year of loss, the mortality rate among widowers was 12.2 percent, as compared with 1.2 percent among matched control subjects.
These and similar studies have been criticized because of their retrospective design or other methodologic problems. Thus, although epidemiologic and anecdotal evidence has indicated some association between psychosocial stress and cardiac mortality, a priori evidence of causality has not been compelling. The study by Ruberman and co-workers reported in this issue of the Journal  provides data to substantiate the notion of a causal role for biobehavioral stress in cardiac death. The observation that high indexes of life stress and social isolation, independent of other variables (including educational level and the presence of ventricular arrhythmias), were significantly associated with a high risk for cardiac death has profound and far-reaching implications. It emphasizes the need for us to elicit a social history from our patients with ischemic heart disease before we proceed to the technologic forms of diagnostic evaluation that characterize the contemporary practice of cardiology. We should explore the psychosocial causes of stress that may be impairing a patient's ability to resist the adversity of heart disease and may ultimately lead to a chronic and debilitating sense of despair and futility. Methods for dealing with these psychological elements must be incorporated into the fabric of management in conjunction with medical or surgical therapy. This critical interplay between the emotions and the health of the heart was articulated by Dr. Viktor Frankl in his memoirs of the holocaust:
Those who know how close the connection is between the state of mind of a man-and his courage and hope, or lack of them-and the state of immunity of his body will understand that the sudden loss of hope and courage can have a deadly effect. 
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