emotional stress, physical activity and ischemic heart disease

Emotional Stress, Physical Activity and

Ischemzc Heart D,,lsease JOHN NAUGHTON

JOHN BRUHN

T A B L E O F C O N T E N T S

PSYCHOSOCIAL FACTORS AND ]SCHEMIC HEART DISEASE . 4

B e h a v i o r P a t t e r n s . . . . . . . . . . . . 4

L i fe A d j u s t m e n t . . . . . . . . . . . . . 7

E m o t i o n a l D r a i n . . . . . . . . . . . . . 10

R e s p o n s e s to E m o t i o n a l S t r e s s . . . . . . . . 10

EMOTIONAL STRESS IN THE HOSPITAL ENVIRONIMENT. . 13

PItYSICAL ACTIVITY AND ISCHEMIC HEART DISEASE . . 14

E p i d e m i o l o g i c S t u d i e s . . . . . . . . . . . 14

T h e M e a s u r e m e n t of P h y s i c a l W o r k i n g C a p a c i t y . 16

R e s p o n s e s A s s o c i a t e d w i t h A c u t e P h y s i c a l E x e r c i s e . . 18

T h e Ef fec t s o f P h y s i c a l C o n d i t i o n i n g . .~ . . . . 2 0

INTERVENTION IN ISCttEMIC HEART DISEASE . ,,'. . . . 2 3

D i e t a r y R e g i m e n s . . . . . . . . . . . . 2 4

E x e r c i s e P r o g r a m s . . . . . . . . . . . . . 25

SUMMARY . . . . . . . . . . . . . . . . 2 7

%- is Associate Professor of Medicine and Director of the Rehabilitation Center, University of Illinois College of Medicine. He received his M.D. from the University of Oklahoma School of Medicine, served his in- ternship at George Washington University ttospital and took his res- idency training at the University of Oklahoma Medical Center. Doctor Naughton is an authority in the field of exercise and health and is cur- rently President of the American College of Sports Medicine.

is Professor and Chairman of the Department of Human Ecology in the School of ttealth at the University of Oklahoma Medical Center. He also holds joint appointments in the Departments of Medicine and Preventive Medicine and Public ttealth. With academic preparation in medical so- ciology, Doctor Bruhn's interests are broadly concerned v, ith the social factors in medicine. He has special interests in the psychosocial aspects of coronary heart disease and has conducted research in such other areas of medicine as hemophilia, diabetes, suicide and social psychiatry.

SINCE WORLD WAR II, epidemiologists, cardiologists, basic scientists and other health-related personnel hav e engaged in the search for the cause or causes of ischemie heart disease. Despite their efforts, the principal manifestations of this disease process--namely, angina pectoris, myocardial infarction and sudden death--continue to occur in the prosperous, industrial- ized Western societies at an alarmingly high rate. The results of various epidemiologic studies conducted in the United States have indicated that individuals characterized either singly or in combination by excessive obesity, hypertension, hypercholcs- terolemia, hyperlipidemia, diabetes mellitus, a family history of ischemic heart disease, excessive coffee drinking or heavy cigarette smoking are statistically more likely to succumb to

some manifestation of isehemic heart disease at a premature age than those individuals without such characteristics (1-6) . These factors are often referred to as "risk factors," and the individuals so endowed are considered "coronary prone." In addition to the factors enumerated above, the importance of psychosocial adjustment and of lifelong habits of activity also have been implicated as possible "risk factors" for the "coronary prone" individual. It seems probable that, with the exception of genetic contributions, most of the manifestations of ischemic heart disease are preventable if the etiologic factor or factors are altered by appropriate technics of intervention. Since ischemic heart disease apparently results from multiple interacting factors rather than a single etiologic agent, any approach to treatment requires an extensive and comprehensive program of dietary discretion, personality adjustment and the modification of habits of activity. The apparent relationship between personality adjustment and lifelong habits of activity to the manifestations of isehemie heart disease received less emphasis than did dietary factors (7-9) in earlier years. The former relationships, together with possible approaches to interventive therapy, will form the subject matter of this report.

Psychosocial Factors and Ischemic Heart Disease

BEHAVIOR PATTERNS

Life stress has long been attributed an etiologic role in some of the manifestations of ischemic heart disease. Usually, this role was assigned as a result of the circumstances that surrounded the onset of the cardiac event. If a.myocardial infarction occurred in relation to "an acutely stressful situation," the physician usually credited the emotional state a causative role for the consequences, but was cautious about relating the underlying atheroselerotic process to any states of chronic stress that may have existed previously.

The existence of an apparent relationship between stress and the development of isehemie heart disease was emphasized by such investigators as Raab (10), Wolf (11) and Groover (12). However, it remained for Friedman and Rosenman (13) to organize an approach with which to explore the mechanisms

that might be operative in such a relationship. These investigators became disenchanted with the concept that ischemic heart disease was the sole result of dietary indiscretion when they surveyed the eating patterns of 46 healthy American women and their husbands. The women ingested approximately the same amount of calorics and a near-identical proportion of fat in their diets as did their husbands. Since ischemic heart disease occurred at a much lower frequency in American Caucasian women than in men, these findings suggested that dietary fat ingestion alone did not account for the development of coronary artery disease.

During the subsequent dccade, these t~vo investigators, together with their co-workers, sought to define the relationship between behavior patterns and the manifestations of ischemic heart disease. The results of an early study indicated that serum cholesterol concentrations and the blood clotting time varied in accordance with the occupational responsibilities experienced by tax and corporate accountants (14) . The highest serum cholesterol concentrations and the shortest clotting times were measured when men from either group were under maximal pressure to meet a deadline, and the lowest cholesterol levels and longest clotting times were measured during periods devoid of specific deadlines. Therefore, deadlines were characterized as stressful, and it was concluded that these variables reflected the physiologic response to adverse or pressing life situations.

Subsequently, three basic personality types characterized as Pattern A, Pattern B and Pattern C were described (15) . An individual with personality Pattern A characteristically pos- sessed (1) a tense, sustained drive to achieve self-selected'but usually poorly defined goals, (2) a profound "inclination and eagerness to compete, (3) persistent drive for recognition and advancement, (4) continuous involvement in multiple and diverse functions constantly subject to time restrictions (deadlines), (5) a habitual propensity to accelerate the rate of ex- ecution of many physical and mental ftinctions and (6) an extra- ordinary mental and physical alertness. Pattern B represented essentially the converse of Pattern A, and was described by a relative absence of drive, ambition, sense of urgency, drive to compete and involvement with deadlines. Originally, those sub-

jects with Pattern C were 46 blind men who often exhibited a chronic state of anxiety or insecurity. Of the three groups, Pattern A subjects had significantly higher serum cholesterol concentrations, more rapid clotting times, more arcus senilis and a higher incidence of ischemic heart disease than did the subjects with either Pattern B or C.

The classification of subjects was eventually refined by ad- ministering a standardized interview in which each subject's response to a particular question was characterized as that of either Type A or B, depending on the quality of the response. Since some subjccts could possess traits consistent with both personality types, the classifications were further subdivided into Types A1, A2, Ba and B4.

In the ensuing years, Rosenman, Friedman and their staff conducted a prospective study to identify whether or not a specific overt behavior pattern was indeed a potential "risk factor." Subjects with both types of behavior patterns exhibited essentially the same average daily heart rates during comparable life activity (16) . However, the prevalence of myocardial infarction differed in the two groups. One hundrcd and thirteen of the 3411 subjects studied eventually succumbed to myocardial infarctions. Eighty of the 113 victims were characterized prior to entering the study as possessing Type A personality traits (17) . Since most subjects with either one or more "risk factors," including the Type A behavior pattern, did not manifest overt evidence of ischemic heart disease, the concept of immunity to myocardial infarction also was investigated (18) . During a period of 4 � 8 9 years, the normotensive middle-aged man with a fully developed Type B behavior pattern and a serum cholesterol concentration of less than 226 mg./dl.*, a serum triglyceride concentration of less than 126 mg./dl, or a beta/alpha lipoprotein ratio of less than 2.01, either singly or in combination, did not develbp clinically manifest ischemic heart disease. These data supported the concept that some individuals probably were immune to the manifestations of ischemie heart disease, and that the incidence of the disease might be effectively reduced by appropriate lifelong interventive technics.

*One-tenth of a liter, eclual to 6.1028 cubic inches.

Necropsy studies were performed on 25 subjects who died as a result of ischemic heart disease (19). Twenty-two of these 25 patients were characterized prior to entering the study as possessing personality pattern Type A, and the other 3 as Type B. Not only did the group with personality pattern Type A succumb to ischemic heart disease five to six times more frequently than did those with Type B but, in addition, the extent of their coronary atherosclerosis was six times more severe.

Brozek, Keys and Blackburn (20) administered the Min- nesota Multiphasic Personality Inventory (MMPI) and the Thurstone Temperament Schedule (TTS) to 258 business and professional men whose ages ranged from 45 to 55. Thirty-one in the group eventually developed manifest ischemic heart disease. This group scored significantly higher on the "Hypo- chondriasis" scale of the MMPI and on the "Activity Drive" scale of the TTS at the outset of the study than did those subjects whose cardiovascular health was unchanged throughout the next 14 years. In fact, those changes were somewhat better predictors of risk than were some of the other parameters previously reported by these investigators.

Although a causal relationship between behavior pattern and coronary atherosclerosis was not established, the fact was emphasized that the predisposition to the potential consequences was apparently aggravated by the manner in which a "coronary prone" individual adapts to the life situation. Whether appropriate modification of the Type A personality pattern would.lead to a significant reduction in either the incidence of ischemic heart disease or the severity of the atherosclerotic process awaits further documentation.

LIFE ADJUSTMENT

Cathey et al. (21) investigated the relationship of life adjustment to the level of serum cholesterol concentration in 14 patients with healed myocardial infarctions. Their serum cholesterol concentrations were higher during periods of emotional unrest than during quiescent periods. The patients were characterized as having lived life "the hard way" prior to the onset of their disease states, and they had a deep desire to attain goals

they could not define in clear terms and which they could not reach on their own. The patients' personality pattern was likened to that of the mythologic character Sisyphus* (22) . These findings stimulated a long-term study of 65 patients with myocardial infarctions and 62 age-matched, presumably healthy control subjects in which the psychosocial patterns were measured at periodic intervals for 6 years (23) . Each subject com- pleted a battery of psychologic tests, including the MMPI and the Rmenzweig Picture-Frustration Test. Each subject was in- terviewed on entering the study, and thereafter at periodic intervals by a medical sociologist and a psychiatrist, both of whom graded the subject's life situation as either stable, more stressful or less stressful than that which existed at the preceding clinic visit.

The sociologie findings indicated that the cardiac patients were less successful than the controls in achieving higher levels in education and occupation than their fathers. The upwardly socially mobile patients usually held occupational positions that were superior to their level of education and /o r ability. The occupational histories revealed that the patients viewed their jobs as demanding, and that they changed employers more frequently than did the control subjects. More of the patients married women who had achieved a higher level of education, whereas the educational levels of the controls generally exceeded those of their wives. More cardiac patients, especially the smokers, acknowledged being tense persons, and as a group they scored higher on the Cornell Medical Index than did the con- trois. Although the problems and conflicts documented in the lives of the cardiac patients were not necessarily more excessive than those reported by the control subjects, their conflicts were of a more longstanding and cumulative nature. The conflicts differed from those of the controls in that they usually were centered around the patient's self-conception, high ideals and underestimation of personal self-worth. These symptoms were translated into a feeling of chronic self-deprecation. Morally, the patients played the game of life straight, and they were

*A character in Greek mythology who was required to roll a huge stone up a hill. only to have it roll down again every time it reached the top.

chronically frustrated because their efforts often appeared un- rewarded by others. The patients were chronically angry with those individuals who, despite the fact that they deviated from the rules, were nonetheless successful in achieving life goals.

Many of the items recorded in the MMPI and the Rosenzweig Picture-Frustration Test differentiated the cardiac patients and the controls. The findings of significantly higher scores on the F, Hs, D, Hy and Sc scales and significantly lower scores on the K and Es scales indicated that the patients were more defensive against psychologic weakness, more depressed, more concerned with bodily symptoms, more hysterical, more socially introverted and had a lower ego strength than the controls. During the 6-year period, some patients maintained a consistently elevated depression score, whereas the scores of others tended to vary from visit to.visit or to return to a "normal" score. This pattern indicated that while depression was un- doubtedly an expected reaction to a life-threatening cardiac event, more patients than controls reacted to subsequent life events with depression. Therefore, depression may be the result of chronic, unresolved and cumulative conflicts in life as well �9 as of the more acute, life-threatening episode of myocardial infarction.

The patients made more impunitive and more obstacle-ira- punitive responses than the controls with the Rosenzweig Picture-Frustration Test. The results indicated that the cardiac patients usually glossed over situations in which aggression was prominent, and that they tended to deny the existence of frus- trating situations.

Two psychiatrists independently recorded over-all impres- sions of the subjects' life styles, retrospective and current, and classified each subject as personality pattern Type A or Type B, according to the criteria of Rosenman and Friedman. As a group, the patients had less-satisfying situations at home and at work, and they did not take time for, or enjoy, leisure time activities. Although the lives of the controls certainly were not totally free of conflict or stress, the controls apparently had established realistic goals for themselves, had experienced less difficulty in expressing their feelings and had found satisfactions in life in addition to success through work.

In general, patients with ischemic heart disease were ex- tremely sensitive reactors to their environment and interpersonal situations and were more introverted and had lower self-esteem than did the controls. As a group, the cardiac patients were reluctant to express their feelings, especially anger, and they maintained an ingratiating, socially acceptable faqade in the face of conflict.

EMOTIONAL DRAIN

Bruhn, McCrady and du Plessis (24) reported that 25 cardiac patients who were studied prior to death exhibited evidence of "emotional drain." This premorbid state was characterized by (1) conflict beginning early in life that accumulated in intensity if no mitigating influences intervened, (2) a nearly constant state of mental preparedness on the part of the individual to cope with conflict and (3) a lack of supportive and meaningful relationships with others. In summary, emotional drain cut deeply into the patient's self-esteem, threatened his security and deprived him of the appropriate recognition usually derived from achievement.

RESPONSES TO EMOTIONAL STRESS

Although the stress-response studies conducted in recent years did not resolve the problem of causality of ischemic heart disease, they confirmed that external stimuli that either provoked a state of acute arousal or set the subject on guard produced significant physiologic and biochemical alterations. While most of the reported studies were concerned with relatively acute situations, it might be hypothesized that chronic unresolved stress is associated with prolonged physiologic and biochemical alterations which, if not allowed to recover adequatcly, could aggravate those predisposing conditions necessary to the clinical manifestation of ischemic heart disease.

Von Euler and his co-workers (25) investigated the role of cortical and medullary adrenal activity in states of emotional stress, and reportcd that urinary volumes, as well as urinary excretion of the 17-ketosteroids, corticosteroids, pregnanediol,

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epinephrine and norepinephrine increased significantly after a group of 10 subjects watched a relatively stimulating movie. The urinary excretion of epinephrine increased 70% and that of norcpinephrine increased 35% over those values recorded during the 2-hour control period. The urinary excretion of catecholamines (principally epinephrine) was also increased significantly in subjects during airplane flights.

The effect of life stress on serum lipids was studied under a variety of circumstances (26-28) . The serum cholesterol concentration was invariably elevated in medical students studied at the time of meaningful examinations. For instance, Grundy and Griffin (29) studied two groups of medical students; the serum cholesterol concentrations were measured in one group during the winter and in the other during the spring session prior to and during the period of examinations. In each study, the serum cholesterol concentrations were significantly elevated over the control values by 16.5 and 11%, respectively. Similarly, Bog- donoff and co-workers (30) measured metabolic responses in a group of 20 medicalstudents subjected to a state of acute arousal. Each student's overt response was characterized as minimal, moderate or marked. Each subject group experienced significant elevations of the nonesterified fatty acids ( N E F A ) , blood glucose, urinary excretion of epinephrine and heart rate. However, those 7 students whose psychologic response was judged to be most severe failed to increase the level of norepinephrine excreted in the urine. The elevation of NEFA (31) was pre- vented if the ganglionic blocker Arfonad was administered prior to provoking the acute arousal, even though the students still exhibited specific overt behavioral manifestations indicative of psychologic stress.

In addition to the earlier observations of Friedman and Rosenman, which related occupational stress and the magnitude of the serum cholesterol concentrations, Wolf et al. (32) measured the concentrations of cholesterol and triglyceride in a group of cardiac patients at rest and following two types of interview situations. The content of one interview was considered neutral and the other stressful. The patients responded to the neutral interview with little or no change in serum lipid levels, but following an interview that dealt with their specific

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life conflicts, elevation of serum cholesterol concentrations in the range of 70 mg./dl, or higher were recorded.

Thirty-nine episodes of chest pain occurred during 12 full nights of observed sleep in 4 patients with a history of angina pectoris (33). Significant electrocardiographic changes were measured in each subject studied. Thirty-two of the episodes of chest pain occurred in association with REM (rapid eye movements) or dream activity, a relationship that was statistically significant. These results emphasized the importance of considering sleep patterns in the appraisal of a patient's life situation, and certainly confirmed that not all sleep is restful.

Simonson et al. (34) reviewed the available evidence detail- ing known electrocardiographic changes associated with automobile driving, and reported that heart rate was a more re- sponsive parameter than was blood pressure. Significant ST-T wave changes were documented during driving in both healthy and cardiac subjects, with the latter having a higher frequency of changes. Heart rates as high as 200 per minute were recorded in some situations, and in many instances changes of comparable magnitude were documented in passenger and driver alike during moments that were associated with alarm. Bellet et al. (35) also reported an increased frequency of electrocardiographic changes in cardiac patients during automobile driving. Subsequently, significant elevations of the urinary excretion of 11-hydroxycorticosteroids and total catecholamines were measured in 36 normal subjects and cardiac patients alike during automobile driving (36).

Hickam, Cargill and Golden (37) measured the cardiovascular responses to anxiety in a group of 23 medical students and in 12 patients with various disease states. The medical students characteristically reacted to anxiety with significant increases of blood pressure ( 10%) , heart rate (27%) , stroke volume (16%) and cardiac index (48%) , and with a decrease in peripheral resistance (23%) . These changes were similar in magnitude to those that usually accompany the administration of small doses of epinephrine or those that occur during mild exercise. Some of the patients responded to anxiety with the same pattern as the healthy medical students, whereas others demonstrated two vastly different types of responses--

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namely, either a lack of significant change in cardiac output, a decreased heart rate and a large decrease in peripheral resistance; or an increased vascular tone, a decreased cardiac output, a slight increase in blood pressure and essentially no change of heart rate. Physiologically, the former group of patients were potential candidates for total vascular collapse because of the concomitant peripheral vasodilatation that occurred simultaneously with a decreased cardiac output.

Emotional Stress in the Hospital Environment

A common experience for many survivors of a myocardial infarction is that of transfer from the coronary care unit to another ward or to an intermediate care facility. Although this change usually is considered a routine part of the evolution in a patient's recovery, recent observations have suggested that the transfer was indeed "stressful." The urinary excretion of catecholamines in cardiac patients was invariably elevated following the transfer of patients from a coronary care unit to the ward (38) . These findings indicated that the move from a protective environment to the more routine hospital situation was an emotionally significant event.

There is also evidence which indicates that factors such as the nature of the equipment used in a coronary care unit, the witnessing of cardiac arrest and resuscitation and the observation of the clinical progress and decline of other patients pro- duce certain psychologic stresses for the cardiac patient (39) . Bruhn and his co-workers (40) reported that patients in a coronary care unit who witnessed the death of an adjacent patient showed significant increases in systolic blood pressure, heart rate and anxiety, whereas these c h a n t s were not apparent among patients in the unit who did not witness the event.

The above studies documented the ability of the human organism to react to events usually characterized as "stressful." However, whether cardiac patients had a different pattern of life stress than healthy subjects or than patients with other disease conditions was not known until Pearson (41) paired 24 patients with ischemic heart disease with fully matched patients with gastrointestinal disease. He reported that both the fre-

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quehcy and severity of stresses were greater in 16 of the 24 cardiac patients, with equal values recorded in 4 pairs. The home life of the two matched groups was comparable, but the cardiac group had a greater frequency of difficult interpersonal conflicts while on the job. These conflicts usually occurred between the patient and his supervisor, and were considered un- avoidable.

Physical Activity and lschemic Heart Disease

EPIDEMIOLOGIC STUDIES

Although Hedley (42) reported a significantly reduced incidence of myocardial infarction in men engaged in physically active occupations in 1939, it remained for Morris and his co- workers (43-45) to stimulate renewed interest in the relationship between lifelong physical activity and ischemic heart disease. The latter investigators reported that bus conductors and mail carriers in London had approximately one-half the incidence of myocardial infarcts experienced by bus drivers and mail clerks. The hearts of men classified as active (based on their last recorded occupational status) had areas of "small multiple scars" in the myocardium with minor degrees of focal narrowing in the main coronary arteries. These findings con- trasted with "the large, discrete p a t c h . . , over 1.5 cm. in one dimension and often solitary . . . commonly transmural . . . and presumably the result of myocardial infarction" often seen in the hearts of sedentary men. Regardless of the population groups studied, the incidence of myocardial infarction was significantly less in men whose level o f occupational activity was mild to moderately severe; but "those stonemasons and boilermakers engaged in very strenuous work had incidence rates that approached those observed in men of sedentary occupational status.

Several additional studies (46-51) relating occupational activity to protection from myocardial infarction were reported and, in general, their results agreed with those reported by Hedley and by Morris and his colleagues. Of these, the findings reported by Zukel et al. (52) most closely resembled those of Morris and his co-workers. North Dakota farmers had approxi-

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mately one-half the number of myocardial infarcts observed in men of other occupational groups employed in the same geo- graphic area. When the actual hours of physical activity worked by each subject were tabulated, these investigators found that those men whose jobs required from 1 to 7 hours of physical activity per day had an incidence rate for myocardial infarction that was approximately one-fifth of that observed in men who were physically active for less than 1 hour per day. However, the rate of myocardial infarction increased significantly in those men whose work demanded 8 or more hours of physical activity per day.

Chapman and his co-workers (53) were unable to establish a significant difference in the incidence of myocardial infarction in men of varying occupational activity when they reported similar rates among civil servants in Los Angeles. Since the total daily level of energy expenditure may not differ significantly among various urban occupations, these results indicated a need for measuring performance capacity in preference to the usually employed arbitrary historical classification.

Although the occupational data supported the concept that rcgular, lifelong physical activity might exert a protective effect on the myocardium, it did not render solace in regard to the pathogenesis of coronary atherosclerosis. The incidence ratio of angina pectoris in men engaged in physically active and sedentary occupations varied from 1.98 in Morris' study of London bus men (44) to 1.42 in Shapiro's observations of New York businessmen (49). It was not determined whether angina pectoris occurred more frequently in the active men because their higher daily level of energy expenditure permitted its precipitation.

In the Framingham study (54), men with resting heart rates of 67 beats or below per minute or whose body weight approached the ideal norm had significantly lower mortality ratios from myocardial infarction than did those men with resting heart rates in excess of 85 beats per minute or a body weight 20% or more above the ideal.

Twenty-five episodes of myocardial infarction were documented in 317 former Harvard football players who resorted to a life pattern characterized by a reduced level of physical

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activity, \veight gain and cigarette smoking during a period ranging from 25 to 50 years after graduation from college (55). However, no cardiac events were recorded in the38 cx-athletes who maintained regimens of regular, lifelong physical activity. At necropsy, the heart of the famous marathon runner, Clar- ence De Mar, was free of myocardial infarction, even though mild degrees of sclerosis were present in the coronary arteries and the aorta (56). Tile lumen of the coronary arteries were two to three times the dimensions usually seen in men of comparable age. Unfortunately, the study did not resolve whether the vessels were congenitally enlarged or were the result of his running.

Frank et al. (57) reported that patients' habits of activity prior to the onset of myocardial infarction exerted a significant influence on the initial 28-day survival rate. Those patients who performed light to moderate levels of physical activity regularly had significantly higher survival rates than those whose life patterns were essentially sedentary. The survival rate of the most active group was slightly, but insignificantly, higher than that of the moderately active group of patients.

TtIE MEASUREMENT OF PHYSICAL WORKING CAPACITY

The aforementioned epidemiologic studies stimulated several investigators to evaluate the physical working capacity of sedentary and physically active subjects and to determine the effects of regular physical activity on perform~ince capacity. The investigations were accomplished by applying technics and principles developed by work physiologists during the first half of the twentieth century. Although the instruments employed in various studies differed, i.e., motor-driven treadmills (58), bicycle ergometers (59) and steps (60), the principles of test- ing were similar. Subjects usually began walking, pedaling or stepping at a low level of energy expenditure relative to the resting metabolic state and the workload was increased gradually at periodic intervals of 1-6 minutes. Any particular exercise test was terminated either at a predetermined heart rate, when the subject became symptomatic, or if significant electrocardiographic alterations were recorded. The types of tests

]6

varied from those that employed intermittent periods of exercise interspersed with rest to those in which the work was continuous.

Physical working capacity is defined in terms of the peak quantity of oxygen that an individual is capable of consuming, and i t is determined either directly With a maximal exercise stress test or indirectly from the results of a submaximal test.

FIG. l .--Relationship of aerobic capacity to age. Man's aerobic capacity decreases with age regardless of his activity status. However, the regularly physically active individual maintains a higher peak oxygen consumption throughout life than does his sedentary colleague. In the subjects studied by Naughton, the decrease with age was less marked than in the studies by Robinson and by Hermansen and Andersen. This difference probably was due, in part at least, to the source of the subjects studied, but the observation indicates that many young people never achieve a significantly high level of "physical fitness."

7O

60 LI.I "v"

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z .=- 5O z E m

X - - o E 40 - ~

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o" ~ - - ~ " - o - - - - - - - - . - ~ S e d e n t a r v ~ - ILl

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I I I I I I

20 3 0 4-0 50 6 0 70

AGE iN YEARS

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The value is expressed as the oxygen consumed per kilogram body weight per minute (ml. 02/kg: min.). The physical working capacity is affected by many variables, including age, health status, daily physical habits Of activity and fatigue. The performance capacity of-healthy men in the third decade of life ranges from 32.1 in the sedentary to 71 ml. 02/kg. min. in the vigorously active (Fig. 1). These measurements decrease with age, so that during the first half of the sixth decade the range for healthy subjects is nearer 24.2-44 ml. 02/kg. min. (61-66). Of course, the physical working capacity of a patient population may be far below that recorded in a healthy sedentary population.

Standardized exercise tests are now administered by work physiologists, internists and cardiologists as a means of deter- mining a person's limitations and potentials for work and exercise; of diagnosing suspected, but l~reviously undetected, cardiac disease; and of evaluating the patient's response to either a prophylactic or therapeutic program of exercise therapy. The ability to define a patient's physiologic limitations has pro- vided the physician an added tool with which to counsel his patient.

RESPONSES ASSOCIATED WITH ACUTE

PHYSICAL EXERCISE

The onset of physical exertion stimulates a complex assort- ment of physiologic and biochemical reactions, many of which are similar to those that accompany emotional stress. In contrast to emotional stimuli, which are difficult to measure, the external oxygen cost of physical work can be measured rather accurately and, therefore, the physiologic stress induced by exercise can be standardized.

The demand for increased oxygen by the working tissues stimulates the cardiovascular system to increase its blood flow. During mild upright exercise, the heart rate, systolic blood pressure, stroke volume, arteriovenous oxygen difference and cardiac output increase, whereas the diastolic blood pressure and peripheral vascular resistance decrease (67-69). The magnitude of the changes varies in proportion to the level and

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severity of the energy expenditure. At peak levels of performance, blood flow to the liver, spleen and kidneys is minimal, whereas that to the heart, brain, muscles and skin is near maximal. It is the ultimate limitation imposed by the organism's inability to increase cardiac output further that actually deter- mines an individual's performance capacity for work. At peak workloads, the heart rate may be two to three times that recorded at rest, whereas the A-V oxygen difference may increase three- to fourfold, the stroke volume one arid one-half- to twofold and cardiac output four- to sixfold.

A portion of the cardiac output response during exercise results'from the secretion of norepinephrine and epinephrine. While their absolute contribution to cardiac output and to myocardial contractility is unknown, Epstein et al. (70) demonstrated significant reductions in heart rate (21%) and cardiac output (16%) during submaximal work after the administration of the fl-adrenergic blocker propranolol. Neal et al. (71) reported that each ml. increase in oxygen requirement above the resting metabolic state was associated with an increase in urinary excretion of 3-methoxy-4-hydroxymandelic acid (VMA) of 5.5 units. These studies indicated that the autonomic nervous system made a substantial and relatively proportional contribution to cardiovascular performance at all levels of energy requirement varying from rest to maximal physical exertion.

Free fatty acids, glycerol and ct~olesterol are mobilized during exercise (72). In the nonathlete, blood lactate and pyruvate increase at a greater rate than in the athlete. Increased factor VIII activity stimulates a.shortening of the whole blood clotting time, but any potentially detrimental effects from this change are counteracted by a simultaneous increase in fibrinolytic activity (73, 74).

Raab (75) reported that greater elevations of plasma cortisol occurred during emotional stress than during physical exercise. He hypothesized that the myocardial cells were vulnerable to necrosis during periods of prolonged emotional stress because the increased plasma cortisol concentrations potentiated the "cardiotoxic" effects of the catecholamines at a time when tile etIlux of potassium and magnesium was maximal and myocardial sodium content was increasing. He emphasized that this mech-

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anism might explain the occurrence of myocardial infarction in the absence of significant coronary atherosclerosis in patients during bouts of acute arousal.

THE EFFECTS OF PHYSICAL CONDITIONING

The data suggesting that lifelong occupational physical activity was associated with a reduced attack rate of myocardial infarcts stimulated several investigations of the effects of regular physical activity on "risk factors" and basic physiologic mechanisms. Although it is not clearly established that regular physical activity ensures long-term health maintenance (76), the results were nevertheless promising.

Naughton and Nagle (77) tested 18 middle-aged healthy men prior to and after 7 months of regular physical activity. The participants in the program met 3 days a week for sessions of 30 minutes each; the activities included calisthenics, walking and jogging. The results demonstrated statistically significant increases in aerobic working capacity from 31.3 to 36.1 ml . / kg. rain., together with significant reductions of systolic and diastolic blood pressures, heart rates and minute ventilation at rest and during comparable levels of energy expenditure. Simi- larly, the mean oxygen intake increased 5.6 ml./kg, min. in 62 healthy men between the ages of 25 and 60 after 6 months of regular physical activity in a program conducted by Mann and his co-workers (78). Nineteen of the healthy men originally studied by Naughton and Nagle remained regularly active for 6 years. At their last evaluation, the men had a mean peak oxygen intake of 42.1 ml./kg, min., a value approximately 30% higher than that measured originally. These results suggested that healthy middle-aged men had the capacity for developing greater levels of physical endurance and that at least such risk factors as blood pressure and pulse rate were affected positively. Since a reduction of myocardial oxygen consumption at comparable levels of energy demand accompanies the training response, physically active subjects probably are more effective in meeting the challenge of day-to-day physical stress.

Although little is known about the effects of physical activity on myocardial contractility, Crews and Aldinger (79) reported

20

that this function was enhanced following chronic exercise in rats. Whitsett and Naughton (80) measured the rate of left ventricular ejection in man with the modifications previously reported by Weissler et al. (81) and reported that the left ventricular ejection time (corrected for heart rate) remained essentially unchanged following acute exercise in sedentary men, whereas its duration decreased significantly (p<0.05) in physically active subjects. These findings indicated that the rate of myocardial fiber shortening was enhanced by regular, chronic exercise.

Several significant metabolic alterations accompany the process of physical conditioning. Krebs (82) reported that the gluconeogenic capacity of the kidney was increased substantially in chronically exercised rats (Fig. 2). The rate of gluconeogenesis was limited by an inhibition of fructose-l, 6-diphos-

FtG. 2.--Effect of physical activity on the gluconeogenic capacity of rat kidney slices. Chronic exercise increased the gluconeogenic capacity for such substrates as lactate, fumurate and pyruvate (Krebs et al. [82]).

4 0 0 - �9 Exercised Rots �9

0 Control Rots T = 3 0 0 - 7 �9

o

-o 200 o

a )

o 0 E I00 :=L

o 1 | I I

None Lactate Fumurote Pyruvote

SUBSTRATE

21

phatase activity due to an accumulation of either AMP and/or the substrate fructose diphosphate in excess of 0.5 mM. The gluconeogenic reaction was enhanced by the addition of a precursor such as lactate. Of the commonly associated metabolic changes observed during exercise, Johnson et al. (72) reported that lactate and pyruvate increased less markedly in athletes than in nonathletes, and that the nonathletes experienced significant postexercise ketosis, together with marked elevations of free fatty acids. The free fatty acid concentrations of the athletes changed little during exercise and, therefore, their level of postexercise ketosis was minimal. Mann (78) did not detect any appreciable effect of physical training on glucose tolerance. Although Naughton and Wulff (83) found no significant difference in the characteristics of the glucose tolerance curves between athletic and nonathletic middle-aged men following the intravenous administration of glucose, the levels of plasma insulin secretion were significantly lower in the active subjects. This response indicated that less insulin was required for glucose metabolism, and suggested that physical training exerted specific effects on cellular and membrane processes.

The effects of chronic, regular physical activity on resting serum lipid concentrations are controversial. Earlier work indicated that the serum concentration of cholesterol was reduced independent of such factors as weight reduction and dietary modifications. However, Holloszy et al. (84) ,were unable to demonstrate that chronic exercise significantly affected the serum cholesterol concentration. Naughtofl and McCoy (85) reported that the resting serum cholesterol concentrations decreased significantly in cardiac and healthy subject groups who either trained for 8 months or maintained their sedentary life habits. These changes apparently were related to factors other than increased physical activity, dietary changes or seasonal variation. Holloszy's data indicated that regular physical activity exerted an effect on the fasting triglyceride concentrations-- a potentially important effect bccause of the association of hyperlipidemia with accelerated blood clotting, increased vis- cosity, platelet adhesiveness and the aggregation of red blood cells.

22

Many changes occurred in the psychosocial characteristics of middle-aged healthy and cardiac subjects engaged in prolonged programs of regularly supervised physical activity (86). The principal effects included significant reductions in cigarette smoking, alcoholic intake, eating habits, emotional conflicts at home and on the job and increased duration of sound sleep without the aid of sedation. In general, all participants, regardless of whether they demonstrated objective physiologic or metabolic alterations following training, reported an improved state of well-being. The over-all psychosocial changes associated with regular physical activity suggest that participation stimulates the healthy individual or the cardiac patient to determine the relative importance of his various functions in life, an evaluation that may provide a method with which to modify his behavior pattern.

Intervention in Ischemic Heart Disease

When viewed in total perspective, it is readily apparent that the atherosclerotic process is ubiquitous in Western society, and begins at least as early as the adolescent years (87). The so-called "risk" factors probably are "accelerating" factors rather than causative in nature. Since the cost in lives, man- hours lost from the job and financial loss to the economy is enormous, most investigators agree that it is appropriate, if not mandatory, that interventive programs designed to reduce the manifestations of ischemie heart disease be established. The recommended interventive programs are of two types; primary and secondary. Primary interventive programs are designed to prevent the clinical manifestations of a disease process and, therefore, are applied to the healthy population at risk. Such programs will require lifelong application to be totally effective. Secondary interventive programs care for the survivors of myocardial infarction and for patients with angina pectoris. By necessity, they include rehabilitative as well as preventive technics. At present, modification of dietary patterns, programs of regular physical exercise and personality adjustment may provide the greatest hope for altering the disease process. Thus far, only a few attempts at interventive programs have been

23

established. In general, the particular programs employed dealt with one major variable such as dietary manipulation or exercise programs rather than attempting to alter dietary customs, exercise habits and personality traits simultaneously.

DIETARY REGIMENS

Several long-term dietary studies were conducted during the past decade. The approach included controlling the total fat intake in the diet as well as substituting polyunsaturates for saturated fats. In the New York Anti-Coronary Club study (88), the ratio of polyunsaturated to saturated fats varied from 1.25 to 1.5 and the total calories derived from fat approached 33%. The mean serum cholesterol concentrations decreased 12% in the 814 free-living men between the ages of 41 and 59 who participated in the study. These men were controlled with a group of 463 men of comparable age. Although the incidence of ischemic heart disease was significantly less in the experimental than in the control group, this difference may have occurred because the experimental subjects altered other life habits as well as the quality of their diets. Turpeinen et al. (89) studied two institutionalized population groups in which the serum cholesterol concentration of the experimental group was consistently 51 mg./dl, lower than that of the control groups during a period covering 6 years. The incidence rate for myocardial infarction was significantly different between the experimental and control groups (14.4 and 33/1,000 respectively). Leren's (90) study in Sweden indicated that the recurrence rate of myocardial infarction was affected positively by dietary intervention, whereas sudden death was not. Middle- aged and elderly men in a veterans' domicile (9) treated with an experimental diet low in saturated fats had fewer episodes of myocardial infarction, sudden death and cerebral infarctions than did control subjects. When considered individually, the results did not differ significantly; however, when the total number of coronary and cerebral events were combined, the experimental groups had significantly fewer episodes (48 fatal- ities in the experimental group vs. 70 in the control). Brown (91) stressed that although the concentration of serum lipids

2,*

was definitely affected by a program of fat control and the substitution of polyunsaturated for saturated fats, the available evidence suggested that the changes could be attributed to weight reduction rather than to the quality of the diet. It may be that the "prudent diet" is one that provides caloric balance and that drastically altering its quality may not be necessary.

EXERCISE PROGRAMS

The concept that programs of regular lifelong physical activity are appropriate for primary and secondary intervention was received enthusiastically in recent years. Part of this appre- ciation was related to the potentially beneficial biochemical and physiologic changes known to accompany chronic exercise and part was related to the fact that exercise programs provide a positive rather than a negative approach to intervention in ischemic heart disease. Unfortunately, a sufficiently large primary prevention program utilizing exercise has not been com- pleted. However, secondary intervention studies conducted by Hellerstein (92) and Gottheiner (93) resulted in an annual decrease in mortality from recurrent myocardial infarction of approximately 30%.

Every middle-aged subject, regardless of his or her state of health, should have an appropriate history and physical examination prior to entering a vigorous physical activity regimen. All subjects over 35 years of age should have either a Master two-step test or, if available, a standardized multistage exercise test. Any activity regimen should begin with a minimum of strenuous exercise, and the level of energy expenditure should be increased gradually over an extended period. In recent years, jogging was recommended as the exercise of choice by some investigators. In reality, just as a child must crawl before he can walk, so a man must walk before he can jog. For the average sedentary American man with a peak oxygen consumption of 32.1 ml. 02/kg. min., walking at a pace of 3 . 5 -4 mph requires approximately 40% of his aerobic working capacity. If performed for an extended period, this type of exercise is sufficient to stimulate an initial training response. Obviously, more vigorous exercise is required before an individual's performance

25

capacity can be increased significantly, but its recommended level should be maintained within each patient's capacity for work and state of health.

Most work physiologists and physicians advocated programs that included calisthenics, games and intermittent jogging. Once a subject is adequately conditioned, he can utilize 200-300 cal. during an average workout in a period of 30-45 minutes. Since men who participated regularly for several years eventually developed a mean aerobic capacity of 42.1 ml. 02/kg. min., a practical program probably is one in which the healthy middle- aged man maintains his physical working capacity by jogging a total distance of 2 miles in a period of 19-20 minutes. Faster speeds that require greater levels of anaerobic work might be detrimental rather than beneficial to the preservation of health. Once an optimal level of capacity was achieved, Naughton and Nagle (77) reported that it was maintained by exercising three times a week. Mann et al. (78) suggested that one exercise session a week might be sufficient for maintaining an individual's level of performance capacity once it was achieved through a more regular program that lasted 6 months.

Just as was the case with the New York Anti-Coronary Club, many participants in the reported exercise programs changed other aspects of their life situations by discontinuing cigarettes, eating regularly, sleeping more regularly and by handling conflicts at home and on the job more reasonably. Therefore, any appreciable change in the incidence or the recurrence rate of myocardial infarct must take these changes into account as well. The apparent importance of exercise programs is that they offer a positive approach in which the institution of a single new life pattern or habit provides a keystone from which other favorable health habits are developed and, therefore, an indirect method with which to modify the Type A personality pattern and other risk factors, such as the serum triglyceridc concentrations. Although placebo exercise programs have not been conducted, the available evidence suggests that it is un- likely that significant increases in performance capacity would occur independent of active participation by the healthy individual.

26

PSYCttOTHERAPY

The services of the psychiatrist form an integral part of the rehabilitative regimen for coronary patients, especially for those who appear to have greater difficulty in adjusting to their illness. Their services may be as important in preventive programs as well. Adsett and Bruhn (94) involved the wives of patients as well as the patients in the group technic. Although adequate controls were lacking, they reported that both the patients and their wives achieved an improved psychosocial adapta- tion as a result of the group sessions. The short-term and long- term effects resulting from either individual or group psychotherapy for coronary patients need further investigation.

While intensive efforts have been directed toward influencing changes in attitudes and living habits among the general public through literature and the mass media, little is known about the effects of this type of intervention on the preservation of health. As evidenced by the questionable success of recent public a p - peals with respect to cigarette smoking and the use of seat belts, the precipitant of change in life habits lies with the individual's weighing the balance between the immediacy of the threat to his life and the degree of satisfaction he obtains from his present habits.

Summary Ischemic heart disease occurs at near-epidemic proportions

in Western civilization. Although all persons, especially Cau- casian males, are "at risk," there is a constellation of factors that apparently characterizes those individuals whose lives may be jeopardized prematurely. Available epidemiologic evidence indicates that the presence of hypertension, hypercholesterole- mia and heavy cigarette smoking, either singly or in combination, are definite risk factors in the over-all population. Fpctors such as excessive obesity, heavy coffee drinking, diabetes mellitus and a positive family history of isehemie heart disease are also important, even though additional clarification of their over- all importance is still needed. In more recent years, two other areas of the life pattern have been strongly implicated as risk factors; namely, behavioral characteristics and habits of physi-

27

cal activity, either occupational or leisure-time. Unfortunately, these two areas were not well explored in some of the earliest large-scale epidemiologic studies, and further documentation of their influence on the natural history of ischemic heart disease is still required.

The evidence available at present strongly suggests that individuals can be classified prospectively according to their behavioral traits and habits of activity. In general, the individuals with overzealous, poorly directed drive, increased Hypochon- driasis (MMPI) and increased Activity Drive (TTS) have a higher incidence of myocardial infarction than do those subjects who lack these characteristics. Rosenman and Friedman labeled such individuals as possessing personality pattern Type A, whereas Wolf et al. suggested that their life style was pat- terned after that of the Greek mythologie character Sisyphus. The rate of myocardial infarction appears to be approximately one-half that of the sedentary population in men who are either regularly physically active throughout life or who enjoy an occupation that demands regular physical activity; i.e:, bus conductors, mailmen, etc. In general, lifelong physically active men are characterized by a paucity of risk factors, whereas the sedentary population and Type A individuals often possess one or more.

These findings suggest that the clinical manifestations of ischemic heart disease should be preventable if a suitable program were instituted in early life, preferably in the" adolescent years. Such a program should be multifaceted and should include appropriate dietary" manipulation, psychotherapy or improved education regarding behavioral traits, and supervised programs of regular physical activity. Of the three approaches, physical activity might be considered the keystone, since it offers a positive approach to health maintenance and can serve as the source around which an individual modifies the remainder of his life style. Coordination of the educational system and family structure with the efforts of the physician will be required to make such a preventive program feasible and successful.

28

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32

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33

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emotional stress, physical activity and ischemic heart disease

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