Stress factors and the risk of myocardial infarction

.lournal

of

Psychosomatic

Research,Vol. 17,pp. 43 to 57. PergamonPress,1973.Printedin Great Britain

STRESS FACTORS AND THE RISK OF MYOCARDIAL INFARCTrON* HANS G. THIEL, DONALD (Received

PARKER

and

THOMAS A. BRUCE

2 June 1972)

IN THE

absence of knowledge of the pathogenesis of coronary heart disease, efforts to extend our understanding may be furthered by simultaneous analysis of multiple factors potentially operative. This investigation was undertaken to determine whether psychosocial factors in patients with myocardial infarction might differ from those in healthy individuals and, consequently, might be playing a significant role in pathogenesis, previously underemphasized. Thus, longstanding stress patterns in men suffering their first myocardial infarction were characterized. Life style and habits of fifty patients, age 40-60, who had recently experienced a myocardial infarction were compared to those in hfty age-matched, healthy control subjects. The results indicate that apart from metabolic disorders the clustering of multiple psychosocial stresses and excessive habits, demonstrated in the majority of our patient study group, may contribute significantly to the early development of coronary heart disease in men. METHODS

Fifty patients, age 40-60, admitted consecutively to the hospital following a recent myocardial infarction (MI) were compared to fifty age-matched, healthy control subjects. Each group consisted of twenty-five men age 40-50, and X-60. In addition, ten patients below age 40 with recent MI were studied but no attempt was made to match the small number of these patients with a control population. The myocardial infarction group was selected according to the following criteria: 1. Diagnosis of MI based on typical changes of the electrocardiogram (ECG), history, or enzyme elevation. 2. No history of previous myocardial infarction. 3. No history of diabetes prior to the onset of the myocardial infarction. 4. General good health before the occurrence of MI (one individual, however, had chronic asthma). In the MI group, interviews and laboratory tests were conducted about two weeks after the onset of the myocardial infarction and only after discharge from the coronary care unit. In order to study patients with myocardial infarction from different socioeconomic backgrounds, patients were chosen from the University Hospital, Veterans Administration Hospital, and several major community hospitals. There being no strictly comparable control population available for study, the healthy control subjects were selected from volunteer patients seen for routine physical examination. Many of the subjects had responded to public education campaigns on the value of periodic health evaluation, and were aware of screening tests available at no cost in the Medical Center. These subjects were accepted if they were in good health, without known diabetes or cardiovascular disease. Men with pathologic Q waves and ST or T wave changes on the ECG were excluded. Men from all socioeconomic groups participated. Both the patients and the healthy control subjects were fully cooperative with the detailed evaluation. Only one of all the candidates with recent myocardial infarction declined to participate in the study. Interview

techniques

Each of the 110 individuals was interviewed by the principal investigator using a standardized questionnaire. All questions had been designed in simple, direct language. For certain questions, * From the Cardiovascular Section, Department Medicine, Oklahoma City, Oklahoma. 43

of Medicine, University of Oklahoma School of

44

HANS G. THIEL, DONALDPARKERand THOMASA. BRUCE

brief explanations were necessary to assure accurate comprehension. Each subject was instructed to answer the questions based on his average habits, feelings, or behavior over the past 12-24 months, rather than at the time of the interview. The following groups of questions were asked. 1. Marital status; personal loneliness; interpersonal relationships with parents, friends and colleagues; attitudes to environment; feelings of hate; and decreased sense of enjoyment. 2. Average working hours per week, Sunday work, and duration of work habits; physical activity at work. 3. Type of occupation, occupational responsibility, annual income and spouses’ occupational activity. 4. Total daily fluid intake, daily milk and coffee consumption, food intake (qualitative) and night eating. 5. Vegetative signs such as quality of appetite, sleep and digestion; history of palpitations and dyspnea. 6. Frequency of feeling nervous; change in degree of nervousness; ability to cope with unexpected stressful situations. 7. Anxiety and depression questions. These twenty-five questions were modifications of the Bendig Anxiety and Welsh Depression subscales of the Minnesota Multiphasic Personal Inventory. The usefulness of the modified questions had been demonstrated by Rodda [I]. The following statements referring to anxiety and depression were arranged in random order and each subject was asked to indicate his answers in writing (yes or no). A. Anxiety Questions (Past 12-24 months, YESor NO) 1. I get upset easily. 2. I feel restless and tense. 3. I do become impatient easily. 4. I am always in a hurry. 5. I am a high strung person. 6. I get nervous if I sit still a lot. 7. I am usually worrying about something. 8. I am feeling I am not getting ahead fast enough. 9. I feel I am always trying to meet deadlines. 10. I feel like I am pushing myself all the time to get things done in a hurry. B. Depression Questions (Past 12-24 months, YESor NO) 1. I feel useless. 2. I get tired for no reason. 3. I have a good appetite (“no” is significant). 4. I am hopeful about the future (“no” is significant). 5. I feel that others would be better off if I were dead. 6. I have trouble sleeping at night. 7. I think about myself a lot. 8. Every day seems exactly the same. 9. Life seems dull to me. 10. I am usually bored. 11. In thinking of my life, I often wonder why I exist. 12. I feel down in the dumps. 13. I awake in the morning feeling tired. 14. I prefer to be by myself most of the time. 15. I just don’t seem to have the energy to do things. s. In addition to the variables above, we also asked questions in respect to behavior pattern previously reported to be related to myocardial infarction by Friedman and Rosenman [2]. Each subject was asked to rank himself in regard to competitive behavior, excessive drive, enhanced sense of time urgency, excessively rapid body movements (fast walking), and impatience. A “passive” and “active” classification was made for each subject, using a point system where Never = 1, Sometimes = 2, Often = 3, and Always = 4, in the five categories above. Individuals with twelve or less ooints were considered “Dassive”; those with 13-16 points, “active”; and those with seventeen or more points, “extremely aciive”. The term “always” was accepted only if the individual could extend his behavior to his total pattern of living; otherwise, the term “often” was used. 9. Detailed smoking habits such as the type and quantity of smoking, present and past, and cessation of smoking habits. 10. Average time for various sporting activities (walking was considered sport only if not occupationally connected); extent of involvement in indoor and outdoor hobbies and average time for it weekly. 11. Personal and family history. Clinical data and laboratory tests The clinical variables examined included electrocardiogram, relative body weight, blood pressure, complete serum lipids, and blood glucose two hours after a 75 g oral glucose* load. The blood tests usually followed the personal interview by one or two days and with the patients having fasted twelve hours. The serum lipid studies included measurement of cholesterol, triglycerides, and phospholipids by well established methods in the Lipid Research Laboratories of the Oklahoma Medical Research Foundation?. The blood sugar test determinations were performed in the clinical laboratories of each of the hospitals involved. * Courtesy of Ames Company, Division Miles Laboratories, Inc., Elkhart, Indiana 46514. Glucola was extraordinarily well tolerated with no side effects of nausea or vomiting. t All lipid determinations were performed through the courtesy of Dr. Regan Bradford and Mr. Gerald Hillerman at the Oklahoma Medical Research Foundation.

Stress factors and the risk of myocardial infarction

45

Data analysis and statistical procedures

Each ten-year age group of control and myocardial infarction subjects was examined for differences in the various tests which occurred within that age group. The age groups were combined to compare the overall infarction and control groups. In order to meet the assumption of the statistical method (chi square test), it was necessary to combine some of the categorical answers, e.g. “never” and “occasionally” were summed for certain questions. Where meaningful combinations could not be made, Fisher’s exact test was used. In the test on anxiety and depression scores, the Mann Whitney U test was employed. Since the same subjects are used in each test performed, the results are not independent in the sense of probability. In view of the fact that the summation results might obscure the tendency for one group to have more extreme answers such as “always” and “never”, a subset of the questions were selected to compare the frequencies of these extreme answers in the two groups. As a further consideration, information on the clustering of extreme answers within individuals was obtained. A similar tabulation was made using those questions for which statistical significance (p< 0.05) was demonstrated. RESULTS The results of this study suggest that a variety of previously unknown or often underemphasized habits, life style, personal behavior, patterns of life stress, and their duration are closely connected with the onset of myocardial infarction in men, and consequently, may be of etiological significance. Emotional and environmental factors (Table 1). All the variables tested in this table indicate a tendency for more instability in the infarction patients. This was particularly true in the 40-50 yr age group. Divorce was significantly more frequent TABLE 1.-EMOTIONALAND

ENVIRONMENTALFACTORS

50 Healthy control 40-50 51-60 Total 1. Marital status: (p < 0.01) Married 22 22 Divorced 3 3 2. Feeling of loneliness: (p -C 0,005) Never (almost never) 17 23 Sometimes 7 2 Often 1 3. Decreased sense of enjoyment : (p < 0.05) Yes 5 4. Rating of parents’ marriage : Happy 13 23 Medium 8 1 I Not happy 4 5. Rating of own boyhood: Happy 19 21 Medium 5 3 Not happy 1 1 6. Loss of friends (within past 3 yr): Yes 3 1 7. Did you hate anyone in the past? Yes 5 3 Item 1 was compared: Item 2 was compared: Item 3 was compared:

50 Myocardial infarction 40-50 51-60 Total

887; 12%

10 15

22 3

64% 36%

80% 18% 2%

6 12 I

19 4 2

50% 32% 18%

10%

10

6

32%

72% 18% 10%

15 4 6

18 3 4

66% 14% 20%

80% 16% 4%

21 2 2

18 5 2

78% 14% 8%

8%

7

3

20%

16%

8

7

30%

Married vs. divorced. Never vs. sometimes, often. Yes vs. No.

in the MI group (p i 0.01). Four patients were divorced and/or remarried even two or three times. A feeling of loneliness also occurred more frequently in the patients with myocardial infarction (p < 0.01). More infarction patients rated their parents’ marriage and their own boyhood as “not happy” but this difference was not statistically significant. Disturbed relations with colleagues and loss of friends were more often recorded in the infarction patients. Feelings of hate were more frequently expressed and the sense of enjoyment was significantly decreased. About half of the patients who gave a positive response to “feelings of loneliness” had significant depression scores (5 or more positive answers.)

46

HANS G. THIEL, DONALDPARKERand THOMASA. BRUCE

Working hours (Table 2) As a part of everyday stress these revealed extreme readings again in the infarction patients (p < 0.05); of thirteen patients who worked over seventy hr per week, two had been working in the TABLE2.-ACTIVITIES 50 Healthy control 40-50 51-60 Total Average working hours per week: Cp < 0.05) 50 and below 12 12 48% 51-60 6 7 26% 61-70 5 5 20% Over 70 2 1 6% Average working hours Sundays if working 6 days a week : Not working 19 19 76% l-4 5 6 22% 5-8 1 2% Over 8 0% Physical activity at work : Mostly sedentary 21 20 82% 50 % Physical activity 3 2 10% Mostly physical work 1 3 8% Item 1 was compared: 60 and below vs. 61 and above.

50 Myocardial infarction 40-50 51-60 Total 10

4 6 5

7 6 4 8

15 5 4

18 2 3 3

66%

12 6 6

15 7 3

54% 26% 18%

34%

20% 20% 26% 14% 6% 14%

same manner for five years, six for ten years, two for more than fifteen years, and three for more than twenty-five years. Furthermore, six of those men worked over eight hours on Sundays, raising the average total working hours as high as eighty to ninety hours per week. Twenty-two patients were not sedentary in that they spend 50-100 per cent of their job time in physical work, considerably more than the healthy control subjects. Occupation (Table 3) This table reflects some differences in the composition of the two study groups. Healthy blue-collar workers were more difficult to obtain for study and the control group, as a result, contains more high salary, executive individuals than does the patient study group. TABLE3.--OCCUPATION 50 Healthy control 40-50 51-60 Total Type of occupation : 14 Supervisory Sales and Publicity Self-employed and 10 professional 1 Blue collar workers Level of occupational responsibility: 4 Minor responsibility 5 Medium level Top level 16 Annual income : 6 Below 10,000 14 10,000-25,000 5 Over 25,000 Spouses’ occupational activity: 16 Not working 3 Part-time working Full-time working 6

50 Myocardial infarction 40-50 51-60 Total

13 4

54% 8%

4 1

8 5

24% 12%

7 1

34% 4%

11 9

8 4

38% 26%

7 18

8% 24% 68%

6 14 5

5 10 10

22% 48% 30%

11 10

20% 50% 30%

16 7 2

12 7 6

56% 28% 16%

16 2 7

64% 10% 26%

15

17

64% 0

-9

81

3:$

-

4

Liquid and food intake (Table 4) Infarction patients had a significantly higher fluid intake than the control subjects (p < 0.05). Ten per cent of the myocardial infarction patients consumed over four quarts fluids daily, primarily

47

Stress factors and the risk of myocardial infarction TABLET.---FOOD

AND LIQUID INTAKE

50 Healthy control 40-50 51-60 Total

50 Myocardial infarction 40-50 51-60 Total

Average daily fluid intake in quarts: (1 quart = 8 cups) (p < 0.05) About 1 6 11 34% About 2 15 12 54% About 4 4 2 12% Over 4 0% Daily intake of at least 1 quart of whole milk: Yes 1 2% Average daily coffee intake in cups : O-4 8 16 48% 5-8 7 5 24% 9-12 I 2 18% Over 12 3 2 10% Additional snack after dinner: (Night eating) (p i 0.05) Yes 8 6 28% Item 1 was compared: Item 4 was compared:

2 15 5 3

5 15 3 2

14% 60% 16% 10%

5

1

12%

7 8 4 6

10 7 5 3

34% 30% 18% 18%

14

11

50%

2 and below vs. 4 and above. Yes vs. No.

water; none of the healthy subjects consumed that amount. As surprising was the daily milk intake of six men in the infarction group, age 40-60, who drank at least one quart of whole milk daily for over fifteen-twenty years. Of the ten subjects below age forty with myocardial infarction, fifty per cent drank one to two quarts of milk daily for at least ten years. Coffee was also consumed in excess. Of those nine men who drank over twelve cups daily, three drank between fifteen and thirty cups for many years. Heavy fluid intake correlated only in part with excessive coffee and/or milk consumption but by no means accounted for the total amount of fluids. Significant anxiety scores were present in 50 per cent of all men with high fluid intake. Alcohol consumption did not differ significantly in the two groups; however, heavy alcohol intake was always accompanied by high anxiety scores. The evaluation of average daily food intake is extremely difficult by history if a complex food classification form is used. The problem was approached, therefore, in a simple, qualitative fashion. The men were asked whether they ate significant amounts of sweets or of fatty food on a daily, weekly, or monthly basis. No difference in sweet food was found, although several men of the infarction group did admit an unusually heavy intake of candy, cake, etc. for a longer period. A more clear difference was found in daily fatty food consumption. Seventy per cent of the men in the infarction group had a “considerable” daily fat intake compared to only 48 per cent of the control group. Nearly twice as many patients responded affirmatively to the question: “Do you take an additional snack after dinner?’ (night eating). There was a positive correlation of night eating with anxiety and overweight in the MI group and no correlation with sleep disturbances. The indices of appetite, sleep, digestion, dyspnea, and palpitations revealed normal responses in about 95 per cent of the control subjects, in contrast to only 58-84 per cent of the infarction patients. SIeep disturbances

and nervous stress (Table 5)

In particular, sleep disturbances and dyspnea (shortness of breath at rest or with minor exertion, daily or weekly) were significantly different (p < @05) in both groups. Most of the men with insomnia had a history of this problem for five to ten years. Feelings of nervous stress (Table 5)

These were evaluated by asking how often there was a “feeling” of nervousness in the past 12-24 months prior to myocardial infarction in the patient group. The majority of the control subjects either felt no nervousness at all or “sometimes” only (i.e. once or twice a week). Twenty of the infarction patients felt “frequently” nervous; four of those patients expressed a feeling of nervous tension “all of the time” or “all their lives”, a highly significant finding (p < 0.001). Increasing nervousness (p -C 001) over the past twelve months was stated by every other MI patient and unexpected stress situations created nervousness much more often in the MI men. Seventy-five per cent of both patients and control subjects with marked nervousness had significant anxiety scores. Anxiety

scores (Table 6)

These differed significantly in both groups (p < 0031). Half of the healthy control subjects gave no more than two positive answers, in contrast to only 20 per cent of the MI patients. The number of extreme scores (seven or more positive answers) were considerably higher in the infarction patients. Depression

(Table 7)

Similar findings to the above were obtained

in the deprelsion

scores (p c 0,001). Most of the

48

HANS G. THIEL, DONALDPARKERand THOMASA. BRUCE TABLES.--SLEEP DISTURBANCES, NERVOUSSTRESS 50 Healthy control 4C50 51-60 Total

1. Sleep: (p < 0.05) Good Fair Poor 2. Dyspnea: (p c 0.05) Never Monthly Weekly Daily 3. Nervousness (p -C 0.001) None Sometimes Often/daily

50 Myocardial infarction 40-50 51-60 _~Total

24 1

24

96% 4% 0%

18 4 3

18 6 1

72% 20% 8%

24

24 -

96% 0% 2%

1

2%

14 2 4 5

15 3 3 4

58% 10% 14% 18%

5 7 24% 2 17 18 70% 11 3 0 9 Tense all the time/life :$ 3 4. Increase of nervousness: (p < 0.01) Yes 4 4 16% 16 5. Ability to compete with sudden unexpected stress situations: 8 You like it 16 11 54% 11 You get easily nervous 2 7 18% You dislike it 7 7 6 28% Item 1 was compared: Good vs. fair; poor. Item 2 was compared: Never; monthly vs. weekly; daily. Item 3 was compared: None; sometimes vs. often, daily; all the time/life. Item 4 was compared: Yes vs. No. TABLE6.-ANXIETY (10 positive answers possible)

4 13 7 1

12% 48% 32% 8%

12

56%

11 10 4

38% 42% 20%

I

1

50 Healthy control 40-50 51-60 Total

50 Myocardial infarction 40-50 51-60 Total

Positive answers: (p c 0.001) None 1 2 3 4

45 3 3 1

5 5 3 2 4

18% 20% 12% 10% 10%

-1 1 2 2

31 4 5 2

102 14% 8%

5

4

1

(Z) 0

5

2

(Z) 0

67 8 9 10

21 2

2

:G0 4% 0% 2%

61 3 3 1

23 2 1

1:: 10%

-

-

1

-

;$

;;

TABLE7.-DEPRESSION (15 positive answers possible) 50 Healthy control 40-50 51-60 Total Positive answers: (p < 0031) None

50 Myocardial infarction 40-50 51-60 Total

2

12 7 3

17 6 1

58% 26% 8%

2 4 2

8 3 4

20% 14% 12%

3 4

I

1

-

(97 02 (96 ;$$ F)

5 1

4 3

(Z) $

2 1

(Z) 102 2%

1

5 6 7 8 10 II 12

1 1

-

02 ;zj

5 3 -

-

I -

-

1 1

-

;g

Stress factors and the risk of myocardial infarction

49

control subjects had no positive answers, compared to 20 per cent of the infarction patients. High scores were much more frequently found in the infarction patients. It should be emphasized that all subjects were strongly urged not to answer the twenty-five anxiety and depression questions according to their present feelings, but to their average feelings during the previous twelve months. Many infarction patients stated very clearly that they had been anxious and depressed for a considerable time prior to their present hospitalization. Behavior patterns (Table 8)

Important differences were noted in gauging the five behavioral categories. The infarction patients consistently gave a higher number of ALWAYS answers in each of the five areas. Moreover, numerous subjects gave an ALWAYS response in two or more categories. Excessive drive (p < 0.05) and exTAKE 8.-BEHAVIOR PATTERN 50 Wealthy control 40-50 51-64 Total

50 Myocardial infarction 51-60 40-50 Total

1. Excessive Drive: (p < 0.05)

2.

3.

5.

6.

7.

2 Never 0% 10 7 Sometimes 16 9 50% 12 5 Often 7 14 42% 11 3 Always 2 2 8% Excessively rapid body movement: (Fast walking) (p < 0.01) 1 Never 1 2% 7 11 Sometimes 11 15 52% 4 7 Often 10 7 34% 10 10 Always 3 3 12% Competitiveness: 1 Never 0% 11 13 Sometimes 12 12 48% 7 Often 10 9 38% 2 5 Always 3 4 14% Enhanced sense of time urgency: 2 Never 0% 9 11 Is 11 Sometimes 52% 12 9 Often 12 9 42% 1 6 Always 2 1 6% Air of impatience: Never 0% 13 16 Sometimes 16 17 66% 8 9 Often 9 7 32% 3 1 Always 1 2% Group distribution of combined personality pattern: 10 7 Passive 13 15 56% 9 16 Active 10 9 38% Extremely active 2 1 6% 2 6 In item 1 and 2 “always response” between healthy subjects and patients was compared.

4% 34% 34% 28% 2% 36% 22% 40% 2% 48% 28% 22% 4;$ 42: 14% 0% 58% 34% 8% 34% 50% 16%

cessively rapid body movements (p < 0.01) showed the most marked differences. Forty-four per cent of the control subjects fell in the “active” classification, whereas two-thirds of the infarction patients fell either into the “active” or “extremely active” groups. In both groups the extremely active individuals had significant anxiety scores (5 or more positive answers). Smoking habits (Table 9)

Smoking habits differed significantly (p < 0.05) in both groups; sixteen healthy control men had stopped smoking five to ten years before. The total amount of previous cigarette consumption was lower in the control group. The data show clearly that the healthy men as a group are moderate smokers, while the infarction patients show many individuals with extreme habits. Of the nine infarction patients who smoked over forty cigarettes per day, three smoked seventy to eighty cigarettes per day! Seventy five per cent of all heavy smokers in both groups had significant anxiety scores. Sports and hobbies (Table 10)

Engagement in various sports similarly differed significantly (p < 0.005). Thirty-eight of the infarction patients had not participated in sports for years, compared to thirteen of the control subjects. Conversely, eight men of the infarction group were active in sports five or more hours per week (one patient spent about fifteen hours per week in various sports in addition to more than sixty

50

HANS

PARKERand THOMASA. BRUCE

G. THIEL, DONALD

TABLE9.-SMOKING HABITS 50 Healthy control 40-50 51-60 Total Do you smoke? (p < 0.01) Yes 19 9 What do you smoke? Pipe 2 1 Cigars 5 1 Cigarettes 12 7 How much do you smoke? (p < 0.05) Below 10 6 4 I I-20 3 2 21-30 6 1 31-40 3 1 Over 40 1 1 When did you stop smoking? Recently 3 2 l-3 years ago 1 5 years ago 8 10 years ago 2 6 Item 1 was compared: Yes vs. No. Item 3 was compared: Below 21 vs. 21 and above.

56%

22

19

82%

6%

1 2 19

-

2% 6% 74%

12% 38%

20%

1

10% 14% 8% 4%

4 9 5 3

16%

TABLEIO.-SPORTS AND HOBBIES 50 Healthv Control 40-50 51-60 Total Average (hr) for various sport activities per week: 5 or more I 12 34 5 3 l-2 5 5 Inactive 8 5 Average time for hobby weekly: 5 or more 6 6 34 3 9 l-2 4 3 Occasional, none 12 7 Item 1 was compared : One or more vs. inactive.

50 Myocardial infarction 40-50 51-60 Total

(p < O+lOS) 38% 16% 20 % 26% 24% 24% 14% 38%

1 18 3 7 3 6

8% 8% 32% 16% 18%

2

4%

-

-

50 Mvocardial infarction 4c5051-60 Total 3 2 20

5 1 1 18

16% 2% 6% 76%

4 5 2 14

5 3 2 15

18% 16% 8% 58%

-

TABLE11.-PERSONAL ANDFAMILYHISTORY 50 Myocardial infarction 50 Healthy control 40-50 51-60 Total Total 40-50 51-60

1.

Personal history of: 4 Hypertension Peptic Ulcer 2. History of parents’ disease: 3 Heart Disease-Father -Mother 3 Diabetes-Father -Mother 3. Parents cause of death : 5 Heart Disease-Father -Mother 2 Cancer-Father 1 -Mother 4. Non-accident death: (Between 21-60 yr) 3 Father 3 Mother Brother 3 Sister 1

6

20%

7

-

3

1 2 1

8% 4% 8% 0%

7 5 2 2

3 1 2 2

16% 2% 8% 6%

5 3 2 4

2 3 1 1

10%

6 3 3 2

-

12% 8% 4%

5 1

24 % 10%

3 -

6 I 6 3 7 6 2

22% 6% 18% 20%

18% 20% 18% 8%

51

Stress factors and the risk of myocardial infarction

working hours per week). The tendency to extremes should again be noted in the infarction patients: either they had no sports activity at all or they seemed committed to gross overactivity. Inactivity, however was much more common. Involvement in an indoor or outdoor hobby was less frequent in the infarction patients. The data suggest an additional trend of limited interests away from occupational duties; this did not always correlate with lack of spare time. and family history (Table 11) A history of hypertension was similar in both groups. Five infarction patients had a history of peptic ulcer disease, one with perforation. The comparison of parental diabetes, hypertension, stroke, and overweight did not reveal significant difference between the groups. History of heart disease, however, was 2.5 times higher in the infarction parents than in the control parents. It was surprising that the parents of the infarction patients died 2.5 times more frequently from cancer as well. Non-accidental death in parents and siblings between ages 21-60 yr was almost twice as frequent in the infarction patients as in the control subjects. The personal

Clinical and laboratory data (Table 12) A. Blood Pressure. Five individuals from each group had elevated blood pressure.

that blood pressure may fall in a number TABLE

of hypertensive

12.-CLINICAL AND

LABORATORYDATA

50 Healthy control Total 40-50 51-60 1. Blood Pressure: Above 140/90 2. Relative weight : Normal ll-20% Over 20% 3. Serum cholesterol : Below 200 mg % 20&250 mg % 251-350 mg % Over 350 mg % Not obtained 4. Serum triglycerides : Below 100 mg % IO&150 mg % Over 150 mg % Not obtained 5. Oral gtt: 2 hr pp: (p< 0.01) Serum glucose level of: 110 mg % and below 111-150 mg % Over 150 mg % Item 5 was compared: 110 mg %

It is known after acute myocardial

patients

50 Myocardial infarction Total 40-50 51-60

1

4

10%

2

3

10%

9 8 8

8 12 5

34% 40% 26%

3 12 10

9 6 10

24% 36% 40%

4 8 12 1 -

2 10 13 -

12% 36% 50% 2% 0%

4 8 11

9 8 8

26% 32% 38%

11 5 9

11 8 6 -

44% 26% 30% 0%

1

3 6 8 8 3

12 82% 9 18% 4 0% and below vs 111 mg % and above. 22 3

19 6 -

xg 9 7 9

-

30% 30% 34% 6%

9 11 5

42% 40% 18%

infarction and a positive correlation may, therefore, be hidden in the results. B. Relative weight. Although statistical significance could not be demonstrated, a trend seemed to be present in the greater than twenty per cent overweight category. Five MI patients had seriously excessive weight (220-250 lb); none of the healthy subjects had such extreme readings. C. Serum cholesterol. The healthy group showed slightly higher serum cholesterol levels than the infarction group. A real comparison between the groups is not possible since serum cholesterol levels may decrease somewhat in acute myocardial infarction. Since the tests were taken about two weeks after the onset of illness, many of the patients had lost three to tifteen pounds weight in the hospital. It is interesting to note, nonetheless, that serum cholesterol levels less than 200 mg% were found in thirteen men in the myocardial infarction group. Of those thirteen patients only four had abnormal serum triglyceride levels (151-200 mg%). Furthermore five patients had serum cholesterol levels between 2OCL230mg %. Their serum triglyceride values were also in the normal range (74-139 mg%). In those subjects normal or only moderately increased body weight correlated well with their relatively low serum lipid levels. The data indicate that about 30 per cent of the MI patients probably had normal serum lipids prior to their myocardial infarction.

HANSG. THIEL, DONALDPARKERand THOMASA. BRUCE

52

D. Serum triglycerides. The same reservations have to be made as in the serum cholesterol findings. Again it is of interest that fifteen infarction patients had serum levels below 100 mg%, none of them had serum cholesterol levels above 250 1119%. E. Oralglucose tolerance test (GTT). Serum glucose abnormalities two hours after a 75 g glucose load were frequently found in the infarction patients (p i 0.01). Patients with a history of overt diabetes were, of course, excluded from the study by plan. It is important to note that the same number of parents had known history of diabetes in both groups (four each), confirming that the groups were properly matched in this important hereditary defect. TABLE13.-EXTREME ANSWERS 50 Healthy controls (40-60)

2% 4% 6% n0/

” /cl

12% 10% 0% 0%

10 Myocard. infarct (Below 40)

18% 8% 26%

0% 10% 50%

14% 34% 18% 14%

30% 60% 40% 10% 20% 30% 0% 50% 50% 50% 10% 10% 60% 40%

,$

14% 2%

8;

28%

8% 12%

40% 22% 14% 8% 18% 40%

14% 12% 2% 4% 26% Myocardial

50 Myocard. infarct (40-60)

infarction patients

Loneliness-often Childhood-not happy Working hours weekly-over 70 Working hours Sunday-over 8 Daily fluid intake4 quarts or more Daily coffee intake-more than 12 cups Sleep-poor Nervousness-all the time/all the life Anxiety scores-7 or more Depression scores-7 or more Excessive drive-always Rapid body movements-always Competitiveness-always Time urgency-always Air of impatience-always Cigarette smoking daily--40 or over Relative weight-over 20 %

below age forty years

The data reveal a similar pattern to men of the infarction group between age forty and sixty, except that the younger patients scored 1.5 times higher on the combination of all extreme factors (Table 13). Four of these patients had an abnormal GTT, two had hypertension (one of these had both disorders). Statistical

unalysis

All categories in which there were differences in the extreme findings between the study groups were combined for further analysis (Table 13). The ten patients with recent infarction below age forty were added for additional comparison. The Table shows clearly the tendency of the patients in the infarction group to give more extreme answers than the control subjects. This tendency is even more noticeable in the ten patients below age 40. The distribution of extreme answers in the healthy control subjects and in the fifty infarction patients is seen in Fig. 1. Note that only i.e. 2 per cent of the control group gave three or more extreme answers, compared with 60 per cent of the infarction patients. Individuals in the infarction group seem to give clusters of many extreme answers where the control individuals do not. Figure 2 also reflects the clustering of multiple answers in the infarction patients but with respect to those questions where statistically significant differences were demonstrated. In the control group, only 26 per cent of the individuals had four or more positive answers, compared to 90 per cent of the infarction patients. The “hazardous” factors (statistically significant variables plus obesity, hypertension, hypercholesterolemia, and hypertriglyceridemia) are seen in Fig. 3. A rightward shift was demonstrated for control and MI subjects but no change in the relative group distribution was seen. Note that only 8 per cent of the healthy men had 6 or more of these combined factors compared to 80 per cent of the infarction patients. Three men with myocardial infarction showed l-3 combined factors only. The first man, age 58, had bronchial asthma for more than fifty years, took regular bronchodilators which caused tachycardias and extrasystoles; his serum cholesterol was 275 mg%, smoked fifty cigarettes daily and got no exercise. The second man, 57, was extremely competitive, smoked 20-30 cigarettes daily and had lived with his mother-in-law in silent protest for ten years. The third patient, 59, had a history of recurrent peptic ulcers, elevated two-hour pp., 117 mg%, sleep disturbances

Stress factors and the risk of myocardial infarction

(50)

healthy

(50)

myocardial

controls

53

m

infarct

m

5

6

5

0

2

I

3

Number FIG.

1 .-Number

of

7

answers

of men giving positive response to exactly 0, 1, 2, . . . extreme answers to selected questions,

(50) (50)

Number

FIG. 2.-Number

4 extreme

of

healthy controls myocardlal infarct

signif

icont

m m

answers

of men giving positive response to questions was shown.

for which significant

difference

for fifteen years, daily consumption of one quart of whole milk, smoked sixty cigarettes per day and showed four positive answers on anxiety and two on depression. It is worth mentioning here that a definite difference was observed between the age groups 40-50 and 51-60. Most of the extreme life stress patterns were found in the younger patient group. DISCUSSION

There is still controversy about the extent to which cause myocardial infarction rather than merely follow cently reviewed the evidence for anxiety long before disease. Our findings provide strong supportive data

anxiety and depression may its onset. Jenkins [3] has rethe onset of overt coronary for this hypothesis. Patients

HANS G. THIEL, DONALD PARKER and THOMAS A. BRUCE

54 25

(50) (50)

t

healthy controls m myocardial infarct m

5

O-I

2-3

4-5

Number

6-7 of

8-9

hazardous

IO-11 12-13 I4 factors

FIG 3.-Hazardous factors: positive responses for which significant difference was shown, plus findings of obesity, hypertension, hypercholesterolemia and hypertriglyceridemia.

emphasized clearly that they had been anxious, with or without depression, for at least one to two years prior to their first myocardial infarction. Moreover, the higher incidence of divorce, the long period of heavy smoking, the excessive fluid intake, the years of extreme overwork, the hyperactive behavior pattern, the chronic insomnia, and the recurrent feelings of nervousness indicate longstanding elements of anxiety. In addition, the anxiety and depression tests of the modified MMPI [l] intentionally covered the emotional state during the twelve to twenty-four months prior to hospitalization. Certain limitations are inherent in any retrospective analysis. It is likely that some kinds of recall will be altered by an event of life-threatening illness, such as myocardial infarction. This study was designed to avoid the period of potential maximum anxiety and depression by studying the patients only after the acute phase of their illness when recovery seemed assured. Nearly all patients then indicated during the questioning period that they were optimistic about their future. Moreover, certain of the questions such as marital status, number of working hours, etc. would be extremely unlikely to be affected by variations in mood. To test the meaningfulness of the data, anxiety scores were compared with various of the stress parameters. There was strong correlation in both study groups between anxiety and three variables-excessive behavior pattern, smoking and nervousness. The role of depression is more difficult to evaluate. Of the 14 patients with high depression scores, 13 had high anxiety scores as well. There was a very high prevalence of divorce in combination with feelings of loneliness on the patients with high depression scores. In addition, frequent interpersonal communication problems were manifested (Table 1) long before the myocardial infarction, suggesting again the potentially causal relationship of this emotional disturbance. Nevertheless, it appears too simple to relate all stressful life patterns with anxiety or depression. Twenty-five per cent of the patients with myocardial infarction gave negative or low scores on both these i terns.

Stress factors and the risk of myocardial infarction

55

The choice of a control group of healthy, non-hospitalized subjects was a deliberate attempt to avoid the confusion of a reference group with other acute or chronic illnesses and their own causative factors. The focus thus remains on the factors at risk in myocardial infarction, rather than on the more complex problem of precipitating events of illness per se. There is some risk, it must be acknowledged, that some of the differences observed may be due to one group being sick and the other well, or to one group being hospitalized and the other not. Since the patient group in this study had been asymptomatic and vigorously active prior to their first myocardial infarction, it would appear that the selection of an analogous healthy group would best serve as the ideal control population. Investigations in regard to working hours have been generally neglected by the longitudinal studies [4-71. In this group one of every four of the patients with myocardial infarction worked more than 70 hours weekly. The prototype of those men was the truckdriver who worked 12 to 16 hours for six to seven days a week. Other subjects were even engaged in two different full time occupations. Certain of the differences between patients and control subjects may be due to the imbalance in the socio-economic levels of the two groups. This would include such variables as sedentary occupation and hobbies. These have not, in fact, turned out to be of much importance in differentiating the two groups. If anything, it might be guessed that the risks would be higher in executive subjects who comprise more of the control population, and that the differences may be underestimated. The variable of total fluid intake has been previously overlooked. Excessive milk and coffee consumption, apart from the total fluid intake, fall into the same pattern of risk. Whether this relates to concealed anxiety or is an acquired habit from childhood is speculative. Patients treated with a high milk diet (Sippy diet) for peptic ulcer disease were noted by Briggs et al. [8] to have a higher frequency of myocardial infarction. A recent article by Davies [9] contemplates an immunologic mechanism against milk protein which may accelerate coronary atherosclerosis in heavy milk drinkers. Paul et al. [6] noted coffee to be one of the variables to be associated with coronary heart disease. Friedman and Rosenman [2] were the first investigators who approached the problem of coronary artery disease by studying the behavior pattern of their coronary patients. Their Type A patient, felt to be coronary prone, was described as a competitive and driving individual with an enhanced sense of time urgency. They also defined Type B behavior pattern as non-coronary prone and to be the converse of pattern A and Type C behavior pattern, which is a combination of Type B with chronic anxiety and insecurity. We have classified our patients as passive, active, and extremely active. Our results mirror the findings of Rosenman et al. [7], in that twothirds of the infarction patients had an active or extremely active behavior pattern. On the other hand, 34 per cent of our subjects with myocardial infarction and 29 per cent of their patients did not fit the pattern of the highly competitive and driving individual. It is our impression, therefore, that the concept of Type B behavior as “non-coronary prone” is too optimistic. Most of our “passive” patients with myocardial infarction had six or more statistically significant responses. For longitudinal studies, the extremely active man presenting personality traits such as impatience,

56

HANS G. THIEL,DONALD

PARKER and THOMAS A. BRUCE

rapid body movements, and time urgency appear prone to drop out.

in combination

with high anxiety,

would

Turning to the acknowledged risk factors, smoking was in our group, in concert with other reports [IO-131, related to myocardial infarction. Exercise is a controversial factor in the cause and prevention of myocardial infarction. Our findings correlate with Mulcahy et al. [14], that even heavy exercise apparently did not protect from coronary artery disease if a patient was exposed to other high risk factors. With regard to history of heart disease in the parents of the total study group, our results are similar to Suri et al. [15], who found that heart disease was 2.6 times more common in relatives of coronary patients than in relatives of non-coronary control subjects. Epstein [16] demonstrates the evidence of a definite but not striking tendency for coronary disease to cluster in certain families, probably due to genetic or environmental factors, or both. The simultaneous assay of a variety of factors has revealed surprising discrepancies from previously recorded concepts. Obesity, hypertension, hypercholesterolemia, hypertriglyceridemia, and genetic aspects, though of relevance on the individual level, were not statistically important in separating patient and control populations in this study. Very strong differences, on the other hand, were noted again and again in the various life stress patterns. Wolf [17, 181 emphasized the direct relationship of life stresses with disease. His classic description of the coronary patient correlates best with the results of this study. The patient is likened to Sysiphus continually carrying a burden and never quite getting it to the top of the hill or finding a resting place. This is not to say that myocardial infarction patients fall into a homogenous group. Theoretically, every man is coronary prone to the extent that he is exposed to recurrent situational stresses. Whether or not he falls victim to the disease may be determined by his patterns of reaction, measured by such variables as have been examined in this report. This investigation clearly was not initiated to be an epidemiological study. On the contrary; the purpose was to analyze in detail the psychosocial aspects of a number of patients to determine if previously unexplored additional mechanisms may exist. The statistical validity of the data was clearly established by appropriate methods. The results may be applied to larger sample populations in future studies. SUMMARY

Retrospective analysis of longstanding stress patterns in fifty men, age 40-60, with recent myocardial infarction was performed by evaluation of life style, habits, behavior pattern and incidence of anxiety and depression. An attempt was made to compare the patients with fifty clinically healthy, age-matched control subjects who were analyzed by the same methods. Statistically significant differences pt0.05 were noted with regard to factors such as higher incidence of divorce, loneliness, excessive working hours, fluid consumption, night eating, sleep disturbances, nervousness, anxiety and depression. Well known risk factors such as glucose metabolism disorders, cigarette smoking, lack of exercise and personal behavior pattern were also significant. In this study obesity, hypertension, hyperlipidemia and family history-undoubtedly of significance on the individual level-were not important in separating the two groups. Clustering of the multiple

Stress factors and the risk of myocardial

infarction

57

statistically significant variables in the myocardial infarction patients was striking in contrast to the healthy subjects, suggesting the possible importance of utilizing a multifactorial approach to the pathogenesis of coronary heart disease. are indebted to Dr. Stewart Wolf for his advice and encouragement of the study and the preparation of the manuscript.

Acknowledgment-We

conduction

in the

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