A cardiovascular "accident" is no accident; there is nothing fortuitous about the concatenation of events leading, to it. Enough is now known about its sociobiologie genesis to establish a definite series of cause-and-effect relationships both necessary and sufficient. Very little in nature is truly capricious, deserving of the designation "accident." For the most part, our use of the term actually means that the antecedents of the event have not been analyzed in sufficient detail to establish the logical, scientific basis required for a suitably parsimonious explanation of its pathogenesis.
This caveat leads to a second one: The concept of what is meant by "disease" has been expanding. Claude Bernard's concept of homeostasis was complemented by Haeckel's recognition of the state of environmental interdependence that he called ecology. Progressively, as knowledge of such relationships was delineated, they expanded to include attitudes, beliefs, mores, habits, social institutions - in fact, all sociopsychologic stimuli. They came to be seen as compelling forces for health and illness despite their physical intangibility. The influence of these forces is a variation of the old concept of action at a distance. In essence, the theory postulates that powerful forces are at work, the operations of which are not readily apparent. They are hidden from casual observation either by a prolonged latency between psychologic stimulus and physiologic response or by the cryptic manner in which the operations of cause and effect are concealed by intermediate factors. Logicians have formulated two interlocked conditions required for an event to be manifest: necessity and sufficiency.
Recent developments in social biology have used these expanded insights to account for a number of human conditions that would otherwise have remained inexplicable. Researchers have, for example, linked the increased prevalence of hemachromatosis among male Bantu to their consumption of beer brewed in iron pots, and the increased resistance against falciparum malaria among certain African tribes to their predisposition to the red cell sickling trait. They have also illuminated the heretofore cryptic sociopsychologic predisposition to myocardial infarction.
Our ideas about etiology have been greatly expanded by our awareness of the role of outside influences. We now have far more understanding of such factors as the adverse effects of cigarette smoking on cardiovascular and respiratory tract function, and the carcinogenic risks of exposure to vinyl chloride.
Folk wisdom recognizes the connection between heart disease and emotions. Bereaved persons have been termed "heart-sick"; angry persons are said to have their gorge rise. The increase in heart rate as a consequence of fright, consciously appreciated as palpitation, has been recognized from time immemorial. Poets and dramatists wrote what we have now substantiated empirically. John Hunter linked environmentally induced stressful emotion and cardiac pain when he observed, "My life is in the hands of the rascal who chooses to take it."
LEARNING AND BEHAVIOR
Learning theorists distinguish between two types of learning: classical or Pavlovian conditioning, which is involuntary, and operant learning, which is clearly subjective, under voluntary control, and subject to reinforcement that strengthens any immediately preceding response. Neal Miller1 has held that these are in fact two manifestations of the same phenomenon under different conditions. Yogis were known to have the ability to alter their cardiac rate long before Datey and his co-workers2 reported on the effects of training in the Yoga exercise Sharasan, and transcendental meditation has been shown by physiologic monitoring to exert control of cardiac acceleration and deceleration and blood pressure. Careful animal studies have shown uncontested evidence that training and habituation can markedly influence blood flow, which is mediated by catecholamines. Norepinephrine serves as a nerveimpulse transmitter in the central nervous system. Alterations in the heart rate are produced by an increase in sympathetic- nerve activity and are accompanied by changes in the synthesis, uptake, and utilization of catecholamines in the heart, suggesting that it is possible to influence cardiac catecholamine metabolism through instrumental learning of heart rate response.3
Among the various pandemics currently ravaging the people of the world, according to the World Health Organization,4 is cardiovascular disease. An extensive epidemiologic study by Jenkins5 in 1971 provided evidence that although the so-called standard factors of age, sex, blood lipid levels, blood pressure, cigarette smoking, obesity, and sedentary occupation are associated with high risk, they predict only a small minority of cases. Although the psychiatric literature had postulated a positive relationship between cardiovascular disease and personality since the early 1930s, this was based on small samples, anecdotes, and hypotheses. Until 1965 the sociopsychologic factors were given little weight in large-scale surveys.
It appears that certain psychologic, social, and behavioral conditions do put persons at higher risk of clinically manifest coronary disease. These suggestions have been gleaned from a proliferation of epidemiologic studies, mostly retrospective but now sometimes prospective and multinational, premised on largescale inquiries conducted by sophisticated epidemiologists. Enormous difficulty exists in controlling the many variables that have been identified as influential; moreover, their interaction adds to the difficulty of assigning proportionate enologie weight to any individual factor.
All this considered, it would appear that there is a syndrome of coronary-prone behavior. It is a pattern composed of different kinds of elements and is a statistical characterization of a model group; thus the individuals who properly belong in this category need not present all aspects of this pattern. The salient features are competitiveness and its social manifestation, striving for achievement. This tendency includes interpersonal attitudes of aggressiveness, but these need not be overtly expressed. In fact, control is a significant feature. It is seen in the state of hyperalertness, restlessness, and impatience, attributes that are recognized by family and close associates in the stridency of speech, physical tension, inability to relax on vacations or weekends, compulsive punctuality, and dedication to the job. The term "workaholic" gives the connotation of addiction. These persons are less sensitive than the average to their environment. They are reluctant to accommodate to the demands of everyday life or compromise their stand once they have taken it. This intolerance is an external manifestation of their obsessive-compulsive perfectionism.
Rosenman,6 who has done much to popularize what he and Friedman call type A behavior, has contended that higher rates of coronary artery disease are a function of the interaction among individual behavior patterns, environmental demands, and dietary factors. The suggestion is that our typically American hectic, go-getter pace carries with it a high burden of tension-anxiety that infers a degree of latent insecurity as a result of culturally encouraged competitiveness. The reason stated for this interlocked situation is that if a person is driven and his life is governed by the clock, he necessarily has learned to march to drumbeats that do not match his regular pace. To be sure, when he has done this goose-stepping long enough, the new pace inevitably becomes internalized.
ECG findings indicate the surprising frequency of "silent infarction." In one study/ 21 per cent of the myocardial infarctions observed during a seven-year period were unrecognized clinically, and in more than half of these instances the patient had no symptoms. When persons who had experienced this insult were studied, most were found to be suffering from diabetes or hypertension, and had habitually ingested a diet rich in cholesterol and animal fats. They were chronically inactive, smoked cigarettes, and had a parental history of coronary disease. They were also in a higher income bracket and fitted the type A behavior pattern. A greater positive correlation exists in the cases of silent myocardial infarction with the type A pattern than with blood pressure, serum lipid levels, cigarette smoking, parental history, or any of the other factors studied. So it is clear that the paramount influence is exerted by personal emotional attributes.
Significantly, many studies report a façade of well-being as an aspect of the coronary-prone personality. This is attributed to repression, denial, and control in the service of presenting a conscious picture of health. It is a derivative of the person's perfectionistic insistence on an unflawed attitude and appearance.
As far as metabolic mechanisms are concerned, there is evidence that catecholamine output increases in situations that are novel to the subject; hence an increase may be expected in response to every change. It has also been shown that diet affects catecholamine excretion, serum triglycerides, cholesterol, and uric acid levels.
An enormous amount of valuable data has been derived from the Framingham study,8 which was undertaken by the National Heart and Lung Institute and reported in the monograph series by Dr. William B. Kannel and associates. The study, begun in 1948, has followed 5,209 adults for the development of cardiovascular disease by means of a biennial examination and surveillance of death certificates, hospital admissions, and interim illness. Over this period, fewer than 2 per cent have been completely lost to follow-up, and 85 per cent have taken every possible examination. Consequently, these epidemiologic indices are of considerable significance.
It has been found that there are weight changes mirrored in atherogenic traits and that body weight correlates with each of the variables of serum cholesterol, systolic blood pressure, blood glucose, and uric acid. As long ago as 1923, it was shown9 that blood pressure increases with weight. Other studies10 have shown that a weight loss of 12 pounds, for example, was accompanied by a drop in systolic blood pressure of 26 mm. Weight reduction is also accompanied by improvement in serum cholesterol and fasting blood glucose levels. Representative data indicate that a loss of 18 pounds in body weight corresponds to a reduction in serum cholesterol of 26 mg. per 100 ml.; an increase of 18 pounds in weight results in an increase in serum cholesterol of 57 mg. per 100 ml. Another study, done on prison volunteers who increased their body weights by 25 per cent within a few months, found that the serum cholesterol levels increased about 50 mg. per 100 ml.
For each 10-unit change in relative weight for men, there is a change of 11.3 mg. /100 ml. in cholesterol, 6.6 mm. in systolic blood pressure, 2.5 mg./100 ml. in glucose, and 0.33 mg./lOO ml. in uric acid. In women, the changes are more modest: 6.3 mg./100 ml. for cholesterol, 4.5 mm. for systolic blood pressure, 1.3 mg./100 ml. for glucose, and 0.17 mg./100 ml. for uric acid.
Weight gain is accompanied by atherogenic alterations in blood lipids, blood pressure, uric acid, and carbohydrate tolerance. It is uncertain whether the nutritional composition of the excess calories, derived largely from saturated fats and simple carbohydrates, or the positive energy balance per se is more important. Whatever the cause, development of ordinary exogenous obesity is associated with excess development of coronary artery disease. Data from the Framingham study show that for each 10 per cent increase in weight for men, about a 30 per cent increase in coronary disease can be anticipated.
The data also show that for each 10 per cent reduction in weight for men, about a 20 per cent reduction in coronary incidents can be expected. It would seem reasonable to suppose that correction of overweight will improve the coronary risk problem, and may also improve exercise tolerance in persons with a compromised coronary circulation. Whether this will actually reduce propensity to lethal coronary attacks has not been demonstrated. It does seem reasonable, however, to advocate correcting overweight in vulnerable persons, and to promote avoidance of overweight as a desirable goal in the general population, if the appalling annual toll from atherosclerotic disease is to be substantially reduced.
THE EFFECTS OF ACCULTURATION
Although the occurrence of atherosclerotic vascular disease is world wide in its distribution, a number of primitive societies have been studied in which the manifestations of atherosclerosis appear to be strikingly absent. These appear to shed light on the influence of lifestyle. Where comparisons have been made between people who maintain the traditional, primitive life and town dwellers of similar origin who have been at least partly assimilated into the life of Western civilization, the town dwellers frequently exhibit familiar risk factors for atherosclerotic disease, such as elevated arterial pressure and blood lipids. This is attributable to the process of acculturation, which includes changes in diet, different social and moral values, crowding, anxiety engendered by entry into a differently oriented society, economic stress, racial and ethnic tensions, noise, pollution, and pace of life. In most studies, the multiplicity of simultaneous forces acting on acculturation makes it difficult to assess the importance of any individual influence. Data assembled by the Harvard Solomon Islands Project,12 however, have examined interrelationships among culture, environment, human biology, and disease patterns in a variety of populations that differ in habitat, way of life, and exposure to Western civilization.
In all, 2,586 persons in six tribal societies were examined. Three of the societies lived on the island of Bougainville, Territory of Papua and New Guinea, and three on the island of Malaita, British Solomon Islands Protectorate. Malaita was not occupied during World War II, and few Europeans have visited the interior of the island. All the tribes are Melanesian, and ethnographers have appraised their status as an early acculturated one.
For the Solomon Islanders, who are all at fairly low levels of acculturation, several factors that are commonly present in changing societies can be excluded. For example, all lacked motor vehicles and developed roads; thus patterns of locomotion and physical activity remained unchanged. Telephones, electricity, industrial and household equipment, noise, pollution, and smog were all absent. Some changes in tribal custom had occurred where Christianity had replaced traditional belief, but social and family roles had remained essentially unchanged. Entry into the cash economy and wage earning as a consequence of employment may have introduced stresses that are difficult to assess, but these activities were confined to males, who showed less change - at least in blood pressure - than did females. In one community there was crowded living, but this was a traditional mode of life among these persons.
The most constant difference between the more and less acculturated populations was the adoption of Western dietary items, especially salt, rice, and canned meat. Salt intake was substantially greater in all of the more acculturated groups. One group, whose custom it was to cook vegetables in sea water, had by far the highest salt intake of all of those studied, and they exhibited the highest systolic and diastolic pressure in both sexes and at nearly all ages. This confirms the contention of Dahl13 that blood pressure levels may be related to sodium intake.
These subjects showed an almost total lack of coronary artery disease, however. Even among the more acculturated groups, who are beginning to exhibit biologic changes that may lead to the development of risk factors for cardiovascular diseases, these changes have not yet been translated into clinical evidence. But the signs that they are now manifesting may represent the earliest antecedents of cardiovascular disease.
Thus the biobehavioral effects of habitat range from the ecologie relationships among hosts, parasites, and environment to the effects of crowding, social stress, and ways of life on a group's adaptation to its surroundings. The interplay between human biology and the socially relevant components of the ecosystem is coming to be understood as playing an important role in man's adaptations. The relationship between poor nutrition and infection is well known. The presence or absence of certain dietary components can influence health; low or absent iodine in volcanic soils leads to goiter, hypothyroidism, and cretinism. Salt intake increases with Westernization. Intake of saturated fats, when combined with sedentary habits, is associated with elevated serum cholesterol levels and coronary heart disease. Customs that are characteristic of Westernization set in motion a train of physiologic and behavioral responses of the kinds that have been noted as developing among the Solomon Islanders.
STRESS AND THE DEFENSE-ALARM SYSTEM
Let me digress for a moment to talk about rats.
From the middle of the 19th century on, Norway rats were used extensively in European laboratories, and shortly after 1890 H. H. Donaldson brought the first domesticated Norway rats to the United States. His classic book The RatH gives a full account of his valuable and interesting studies. As a consequence, we have a great fund of knowledge about the domesticated form of the Norway rat.
However, there is another strain - the wild Norway rat, which lives chiefly in burrows and cellars, yards, alleys, and fields, where it has to search for its food and water, provide its own shelter, fight for its mates, and protect itself from many natural enemies. In short, it lives under constant stress. But the domestic strain lives in a protected environment in laboratory cages under conditions in which food and water are always available, relatively luxurious shelter from heat and cold is provided, mates are readily accessible, and no natural enemies threaten existence. As a consequence, this different way of life has resulted in marked anatomic and physiologic changes.
Richter15 studied and reported on the striking differences that he found between the strains. The wild Norway is fierce, aggressive, suspicious, and constantly on the alert for attack. In captivity, it tries to escape; it breeds very poorly and often eats any young that are born. On the other hand, the domesticated Norways are tame, gentle, and apparently entirely contented with captivity, rarely trying to escape even when being transported in open-top cages. They breed readily and seldom eat their young. When two wild rats are placed in a Richter fighting chamber and given a shock, they tum on each other and begin fighting; when two domestic rats are placed in the same situation, they merely jump into the air, and apparently do not in any way indicate that they hold each other responsible. When subjected to repeated shocks, they often huddle together, and they learn better than the wild rats how to place their feet so as to avoid the shock.
In 1957, Richter16 reported on the capacity of these rats to stay afloat when placed in a large water-filled jug from which there was no escape. The domesticated rats swam for as long as 60 hours, but the tough, fierce, wild rats succumbed within a few minutes. If, however, the wild rats were persuaded that their situation was not hopeless (a state achieved by removing them from the water on several occasions), they would swim for as long as the domesticated rats or longer. Richter compared the responses of the wild rats with the "voodoo death response" in man that was described in a remarkable essay by Walter Cannon:17
"In records of anthropologists and others who have lived with primitive people in widely scattered parts of the world, it is the testimony that when subjected to spells or sorcery or the use of black magic, men may be brought to death. Among the natives of South America, Africa, Australia, New Zealand, and the Islands of the Pacific, as well as among the Negroes of nearby Haiti, voodoo death has been reported by apparently competent observers.
"The phenomenon is so extraordinary and so foreign to the experience of civilized people that it seems incredible; certainly if it is authentic it deserves careful consideration."
Cannon goes on to quote from Dr. Basedow's anthropologic observations on the Australian aborigine who is a victim of bone pointing:
"... The man who discovers that he is being boned by an enemy is, indeed, a pitiable sight He stands aghast with his eyes staring at the treacherous pointer and with his hands lifted as though to ward off the lethal medium, which he imagines is pouring into his body. His cheeks blanch and his eyes become glassy and the expression of his face becomes horribly distorted. ... He attempts to shriek but usually the sound chokes in his throat, and all that one might see is froth at his mouth. His body begins to tremble and the muscles twist involuntarily, he sways backwards and falls to the ground and after a short time appears to be in a swoon; but soon afterwards he rises as if in mortal agony, and covering his face with his hands, begins to moan.
"After awhile he becomes very composed and crawls to his wurley. From this time onwards, he sickens and frets, refuses to eat and keeps aloof from the daily affairs of the tribe. Unless help is forthcoming, in the shape of a countercharm administered by the hands oí a medicine man, his death is only a matter of a comparatively short time. If the coming of the medicine man is opportune, he might be saved."
Cannon observes that inasmuch as these primitive people's life is bound up in communal activities, "they are able to develop a sufficient esprit de corps to resist the mysterious and malicious influences that they feel can vitiate their lives." Also, they have
"a fixed assurance that under certain conditions, such as being subjected to bone pointing or failing to observe sacred tribal regulations, death is sure to supervene. This belief is so firmly held that the individual not only has that conviction himself, but is obsessed by the knowledge that all of his fellows likewise hold it. Thereby he becomes a pariah, in which condition he is wholly deprived of the confidence and social support of his tribe. In his isolation. the malicious spirits can exert supremely their evil power. He then succumbs to what has been called 'the gravest known extremity of fear,' the immediate threat of death, and as a consequence lies down and dies."
It is obvious that the symptoms that bring the patient to the physician are only the last phase in a complex chain of events whose start lies buried in the patient's early experience and his culturally determined response to an environment that is becoming increasingly dissonant. Our discussion of human and animal data has illustrated certain basic concepts. The stimuli that lead to activation of the defense-alarm reaction are not necessarily associated with conscious fight-or-flight responses. Visceral motor and hormonal responses may take place without emotional disturbance or awareness on the part of the organism. Within any social group, individuals exhibit differences in the level of stimulation (and hence neuroendocrine arousal) depending on their genetically determined responsibility and their individual positions in the social field of force. Group life tends to promote a similar response, with those in subordinate positions tending to respond in a more extreme fashion to similar stimuli. Finally, the effect of a given stimulus is determined by the organism's perception, which in turn depends on the past history of stimulation and particularly on early experience.
1. Miller. N. E. Learning of visceral and glandular responses. Science 163 (1969). 434-445.
2. Datey, K. K., et al. "Shavasan": A yogic exercise in the management of hypertension. Angioiogy 20 (1969), 325-333.
3. Blanchard, E. D., and Young, L. D. Self-control of cardiac functioning: A promise as yet unfulfilled. Psychol. Bull. 79 (1973), 1 45-1 63.
4. World Health Statistics Report 29: 10 (1974), 683-685.
5. Jenkins, C. D. Psychologic and social precursors of coronary disease. New Engl. J. Med. 284 (1971). 244-255; New Engl. J. Med. 284(1971), 307-317.
6. a. Rosenman, R. H., and Friedman, M. Association of specific overt behavior pattern with blood and cardiovascular findings. J.A.M.A. 169 (1959), 1286-1296.
b. Rosenman, R. H., and Friedman, H. Behavior patterns, blood lipids and coronary heart disease. J.A.M.A. 184 (1963), 934-938.
c. Friedman, M., and Rosenman, R. H. Type A behavior pattern: Its association with coronary heart disease. Ann. Clin. Res. 3 (1971). 300-312.
7. Rosenman, R. H.. et al. Clinically unrecognized myocardial infarction in the Western Collaborative Group study. Amer. J. Cardiol. 19 (1967), 776-782.
8. Kannel, W. B., and Gordon, T. (eds.). The Framingham Study: An Epidemiological Investigation of Cardiovascular Disease. Bethesda, Md.: National Heart and Lung Institute. Monograph Sec. 26, 27, 1971.
9. Ashley, F. W., Jr.. and Kannel, W. B. Relation of weight change to changes in atherogenic traits: The Framingham study. J. Criran. Dis. 27(1974), 103-114.
10. Symonds, B. The blood pressure of healthy men and women. J.A.M.A. 80 (1923). 232-236.
11. Sims, E. A. H., et al. Experimental obesity in man. Trans. Assoc. Am. Physicians 81 (1968), 153-170.
12. Page, L. B., Damon. A., and Moellerina, R. C1 Jr. Antecedents of cardiovascular disease in six Solomon Island societies. Circulation 49(1974), 1132-1146.
13. Dahl. L. K. Salt intake and salt need. New Engl. J. Med. 258 (1958), 1152-1205.
14. Donaldson, H. H. The Rat: Mémoires ofWistar Institute, Second Edition. 1924.
15. Richter. C. P. Domestication of the Norway rat and its implications for the problem of stress. In Wolff, H. G.. Wolf, S. G., and Hare, C. C. (eds.). Ufe Stress and Bodily Disease. Res. Pubi. Assoc. Res. Nerv. Ment. Dis., Volume XXIX. Baltimore: The Williams & Wilkins Company, 1950, pp. 19-48.
16. Richter, C. P. On the phenomenon of sudden death in animals and man. Psychosom. Med. 19 (1957), 191-198.
17. Cannon. W. B. "Voodoo" death. Amer. Anthropol. 44 (1942). 169-181.