Our first Cyberounds^® conference provided a broad introduction to the relationship between stress and its effects on disease processes and it introduced the terms, allostasis and allostatic load. This Cyberounds^® looks at data that suggest there are some very basic everyday situations -- such as economic hardship or a humdrum, yet demanding job -- that affect allostatic load and increase the stress on the cardiovascular system.

Allostasis refers to the body's mounting an active response, for example, increasing heart rate and blood pressure or putting out stress hormones, in order to re-establish homeostasis in the face of a challenge. The challenge can be as simple as getting out of bed in the morning or as complex as giving a lecture or dealing with a grueling day of keeping appointments. When blood pressure and stress hormones are elevated they then need to be turned off when the challenge is over and, yet, this is not always the case. We are only too aware of situations in which we continue to experience feelings of stress in the evenings and on weekends when something is really bothering us.

Allostatic load is the concept that the body's own attempts to adapt to stress contribute to pathophysiological changes and lead to disease and it refers to the wear and tear produced by repeated elevations of blood pressure and stress hormones as well as their continued elevation even when not needed. We noted, in our first conference, that our definition of stress includes daily hassles on the job and at home and that allostatic load is often a very gradual process that can be counteracted, to some degree, by health-promoting behaviors (e.g., following a prudent diet, engaging in regular exercise) or it can be exacerbated by unhealthy behaviors (e.g., poor diet, lack of exercise, smoking, drinking and substance abuse). Indeed, my co-moderator, Dean Krahn, has embarked on a discussion of impulsivity and control of behaviors that can be beneficial or harmful.

We also noted that allostatic load is the product of brain function and is influenced by behavior and, yet, it has long-term effects upon key systems of the body such as the cardiovascular and metabolic systems, the brain and the immune system. As we will discuss shortly, job stress, for example, has subtle but powerful effects that accelerate cardiovascular disease. Like homeostasis, a concept such as allostatic load only takes on meaning when it is illustrated by concrete examples. The next several conferences develop the concept of allostatic load further by discussing specific systems of the body that are involved and provide real meaning to the notion of wear and tear on the body and brain.

Allostatic Load in the Cardiovascular System

The cardiovascular system and its links to obesity and hypertension provide some of the best examples of allostatic load. When cynomologus monkeys are put together into groups, they form a social hierarchy and all of the subordinate females show accelerated deposition of atherosclerotic plaques in the coronary arteries, whereas only the dominant males in unstable social hierarchies show increased coronary plaque formation(12),(25) or the females, subordination reduces estrogen secretion and renders the female cynomologus monkeys as vulnerable to atherosclerotic plaque formation as if they were ovarectomized.(25)

Apparently, for the males, having to prove themselves in maintaining their position is very stressful(12) and beta blockers are able to retard the atherosclerosis, indicating that blood pressure surges play a role.(11) Moreover, diet and exercise contribute as well in this animal model to the risk for cardiovascular disease.(7) An atherogenic diet containing 188 mg of cholesterol per day with 43% of calories as saturated fat, accelerated abdominal fat deposition in cynomologus monkeys and psychosocial stress from an unstable social hierarchy accelerated this process. Unfortunately for these animals, exercise did not counteract either the stress or diet effects on the abdominal fat under this rather extreme dietary condition.

In humans, the lack of control on the job-- a sign of subordination in many, if not most, companies -- increases the risk of coronary heart disease(4) and job strain (defined as high psychological demands and lack of control). The lack of control leads to elevated ambulatory blood pressure even in evenings and weekends at home and also produces increased left ventricular mass index, (22) as well as increased progression of atherosclerosis (6). Chronic feelings of hostility and also of stress (specifically, feelings of fatigue, lack of energy, irritability, and demoralization) are linked to increased reactivity of the fibrinogen system and platelet reactivity, both of which increase the risk for myocardial infarction.(13),(20)

How Can One Measure Allostatic Load?

The first successful attempt was made using eight measures of metabolic and cardiovascular pathophysiology(24) collected in the MacArthur Successful Aging study between 1988 and 1991. An allostatic load score was assessed for an individual by determining the number of these eight measures for which that individual was in the most extreme quartile: that is, highest in systolic blood pressure, overnight urinary cortisol, catecholamines, waist/hip ratio, glycosylated hemoglobin, the ratio of HDL to total cholesterol; or in the lowest quartile in DHEA-sulfate or HDL cholesterol. Thus an allostatic load score of three meant that a person was in the most extreme quartile in three of eight measures.

The analysis yielded three main findings. First, in cross-sectional analyses of baseline data, the individuals who had higher levels of physical and mental functioning had lower allostatic load scores. Moreover, these people also had less prevalent cardiovascular disease, hypertension and diabetes.

Second, looking at the higher functioning group, during the three year interval between 1988 and 1991, individuals with higher baseline allostatic load scores were more likely to experience incident cardiovascular disease and were significantly more likely to show declines in cognitive and physical functioning.

Third, in women in this group, increased cortisol excretion between 1988 and 1991 predicted memory decline.(23)

Allostatic Load, Socioeconomic Status and Social Unrest

It is a remarkable fact that there are gradients of health when people are grouped according to education and income (referred to as socioeconomic status) in western societies.(1) Cardiovascular disease is one of the most sensitive and consistent markers of these gradients --people with higher levels of education and income are healthier and live longer, on average. Such gradients of health and disease relate to a complex array of risk factors that are differentially distributed in human society,(10),(26)

including the living and working environment, economic security and health behaviors.

The Whitehall studies of the British Civil Service have been the most influential sources of data linking cardiovascular disease to job stress and emotional states such as hostility and depression. In these studies, gradients of mortality and morbidity were found across all six grades of the British Civil Service. These gradients were stepwise and did not simply reflect the extreme ends of the scale.(14) For instance, plasma fibrinogen, which predicts increased risk of death from coronary heart disease, is elevated in men and women in lower British Civil Service grades; expressed as odds ratios, the difference between lowest and highest civil service grades was almost two-fold for men and 1.8-fold for women, with the middle grades lying almost exactly in between.(13) Similar to this is mortality related to cardiovascular disease. Moreover, hypertension is a sensitive index of job stress,(18) particularly in factory workers, in other workers with repetitive jobs and time pressures.(15) orkers whose jobs were unstable, due to departmental privatization, also showed a tendency to hypertension (Professor Michael Marmot, University College, London, personal communication).

Social conflict and social instability have been found to accelerate pathophysiological processes and increase morbidity and mortality. In Russia, since the fall of communism, there was an almost 40% increase in mortality among males and cardiovascular disease was a major contributor to the drastically shortened life span.(3) Hostility and anger are among the consequences of the social collapse, along with loss of hope. Hostility and anger lead to blood pressure surges and sustained or repeated elevations of blood pressure are linked to accelerated atherosclerosis(8) as well as increased risk for myocardial infarction.(17)

Another aspect of allostatic load that impacts upon cardiovascular function concerns metabolism. Chronic stress, defined as feelings of fatigue, lack of energy, irritability, demoralization, as well as hostility, has been linked to development of insulin resistance,(19) which is a risk factor for non-insulin resistant (Type II) diabetes. Moreover, the deposition of abdominal fat, a risk factor for coronary heart disease and diabetes,(2) is increased by the psychosocial stress of colony reorganization in primates(7) nd may also be enhanced by stress in humans.(16) Abdominal obesity is most often assessed in people as increased waist/hip ratio, and there is a reported connection between this measure and socioeconomic status. (See Cyberounds' Endocrinology Conference, Fat Distribution in Obesity.) Waist/hip ratio is increased at the lower end of the socioeconomic status gradient in Swedish males,(9) and also increases with decreasing civil service grade in the Whitehall studies.(5)

The effects of allostatic load may be quite subtle, as is the case for gradients of cardiovascular health found in the British Civil Service study. Similar subtle effects on the cardiovascular system are also seen as the result of decades spent in a repetitive (as in boring) time-pressured job. Or, they may be quite dramatic, as in Russia where the increased mortality was detected beween 1989 and 1993. Yet, both situations make it clear that a consideration of allostatic load is increasingly important for undestanding the origins of cardiovascular disease and related metabolic conditions like abdominal obesity. Allostatic load is undoubtedly important in understanding the relationships between disease and job loss or the long-term effects of dangerous living environments. It is also worth noting that medical illness itself is a potential source of chronic stress, including anxieties related to prognosis, experiencing treatment, the effects of disability, as well as disruptions of social roles and relationships.

What Can Be Done?

There are catastrophic situations involving social chaos, as in Russia or Bosnia or Algeria, that seem to be beyond human control, at least for the time being. The same is unfortunately true for dangerous living environments in our cities, although new information from studies of Chicago neighborhoods raises the hope that an increasing sense of collective efficacy, i.e., social ties and sense of community, can reduce the amount of violence in impoverished neighborhoods.(1) For the more fortunate, the main hope to reduce stress and allostatic load lies in good personal counselling by physicians and health professionals that will induce stressed-out patients to adopt healthier life styles and reduce chronic sources of personal aggravation.

Variety and Control, Keys to Reducing Stress

Aside from personal counselling, there is at least one larger scale intervention that has proven effective in the workplace and provides hope for reducing stress on the job. In Sweden, at the Volvo assembly plants, workers in the old production line system experienced great tedium and time pressures and expressed the effects of this chronic stress in terms of absenteeism and job dissatisfaction. Reorganization of the production line into worker teams, with interchangeable jobs and less time pressure, resulted in increased productivity, reduced absenteeism and greater job satisfaction.(15) One would hope that reorganization of jobs in other industries might achieve similar benefits of increased productivity and improved health, considering that a $300 billion price tag is attached to losses of productivity and health costs related to stress.

Thus, health can benefit by intervening to decrease stress and allostatic load at both a personal level and through changes in social and work organization. The cardiovascular and metabolic systems are not the only ones that can benefit from such interventions. In the next conference we consider another system of the body that is affected by stress, namely, the immune system and consider how stress can both benefit and impair immune function.