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Acute Myocardial Infarction in Patients Thirty-Five Years of Age and Under
Acute Myocardial Infarction in Patients Thirty-Five Years of Age and Under* ARTHUR
s.
KAPLAN, M.D.
Norfolk, Virginia
I
T WILL BE THE PURPOSE OF THIS PAPER
to review the medical literature on the subject of myocardial infarction in patients below 40 years of age and to present a series of 59 cases of clinically proved myocardial infarction in patients 35 years of age or younger taken from an unselected urban population in a community of approximately 500,000 people comprising 26 1 per cent Negroes during the period 19511963. These cases were selected from the records of the Norfolk General, De Paul, Leigh Memorial, and Community Hospitals, and the Office of the State Medical Examiner, Norfolk, Virginia. This study, unbiased by such selection as restricted studies of servicemen only, offers certain new facts heretofore not emphasized. Smith and Bartels' in 1932 reported two cases of myocardial infarction in patients 35 and 36 years of age and stated that a review of the literature up to that time revealed only 20 confirmed cases of myocardial infarction in patients under 40 years of age. Prior to World War II coronary artery disease in men under 30 years of age was regarded as rare, and in men between 30 and 40 years of age, as uncommon. Yater and associates' in 1948 reviewed the previous literature and found 744 cases of coronary artery disease in patients under 40. The youngest was a I 0-year-old boy reported by Jokl and 11 Greenstein in 1944. Baker and Schillhammer4 in 1951 still felt that myocardial infarction in young adults was seldom seen by the practicing physician and they felt that myocardial infarctions in young persons was most frequently non-fatal because of the excellent recuperating poten•Presented at the Virginia Regional Meeting, American College of Physicians, Williamsburg, Virginia, February 20, 1965.
tialities of the youthful myocardium. Friedbert states that probably 5 per cent of first attacks of acute coronary thrombosis occur before the age of 40 and rarely proved cases have even been observed in childhood. Yater,• in his extensive review of the experience of the Armed Forces during World War II, reported 866 cases of coronary disease in men 18 to 39 years of age with 450 necropsies. He concluded that coronary artery sclerosis in this series is a specific disease of the coronary arteries confmed to the heart and not a part of generalized atherosclerosis, as in older groups. This is what makes the young or middle-aged man's thrombosis a separate and interesting disease. Other authors have stated that ischemic heart disease in younger age groups under 40 is different and is a more localized arterial disease, and the factor of importance is therefore not the nature but the distribution of the lesions.'·' Crawford' and co-workers, however, in a review of 75 necropsies, concluded that the so-called more localized lesions found in the younger groups can be similarly found in patients in their 50's, and that there is nothing to support the contention that under the age of 40 fatal coronary disease differs in any essential way from the disease in other subjects. Other authors have concurred in this latter opinion.' In the current series, henceforth to be referred to as the Norfolk series, 59 patients are presented, ranging in age from 21 to 35 years (Table 1 ) . Analysis reveals 46 white men and four white women comprise 85 per cent of the total group while five Negro men and five Negro women comprise 15 per cent (Table 2). In a population made up of 26 per cent Negroes, this is a rate among Negroes 60 per cent 137
w
00
1-Frnv-NrNB PATIENTs 35 YEARs OF Aoa OR YouNOER WITH PROVED MYOCARDIAL INFARCTIONs ECG Infarct. Diabetes Serum CholesOverRace HyperFollow-Up Status Pattern weight terol mg/100 ml tenJion
TABLE
Cue No.
Age
Sex
1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13.
21 22 22 26 27 29 29 30 30 30 30 31 31 32 32 32 32 32 32 32 32 32 33 33 33 33 33 33 34 34 34 34
M M M F M M M M M M M F F M M M F M M M F F M M M M M M M M M M
14.
15. 16. 17. 18. 19. 20. 21. 22. 23. 24. 25. 26. 27. 28. 29. 30. 31. 32.
w w
N N
w w
N
w w w w w N
w w w N
w w
N N
w w w w w w N
w w w w
No No No
--
No No Yes No Yes Yes No No
-Yes No No
No
265 285
----
---
---
---
Yes No No No No No
--No No
450 310
-217 265
--
-365
-289
--
--
--
--
--
---
No No Yes
No No No
No No Yes
--No
--
--
--
--
No No
No Yea No No
No No
No No No No
346 339
t
240
--197 251
--
---375
Yes Yes
-Yes No No Yes No Yea Yes No No No No No No No No No No No No
--
No No No No No No Yea No No
Antt"rior Posterior Anteroseptal
--
Anteroseptal Posterolateral --
Anterior Posterior Posterior Posterior Anterior
--
Anteroseptal Posterolateral Anterior
--
Anteroseptal Posterior Anterior ---
Posterior Posterior Posterior Posterolateral Anteroseptal
--
Anteroseptal Posterior Anterior Posterior
Alive - 3 years *Dead - I 0 years 2 mos. 3 mos. *Dead In minutes *Dead *Dead - 3 days Dead - 3 yean I 0 mos. *Dead - In minutes *Dead - 3 I /2 houn Alive - 2 yean 11 mos. Alive - I year I 0 mo. Alive- II months Alive - 8 yean 1 mo. *Dead - 12 hours Alive - 12 yean Dead - 6 years 8 mos. Alive - 8 yean 1 mo. *Dead - In minutes 2 yean 8 mos. Alive Alive - 5 years 6 mos. Alive - 3 yean 4 mos. *Dead - In minutes *Dead - 4 hours Dead - 72 hours Alive - 6 years 7 mos. *Dead - 10 minutes Alive - 2 years 8 mo. Alive -1 year 5 mos. *Dead - In minutes Not available Alive - 8 years l mos. Dead- 4 yean Alive - 8 year 2 mos.
> ~
c::: =
"~ ,.:
> ~
~
.. !;' if~
95
ae.
~s:
"'C
s~
--
. "' ~-
-~~
33. 34. 35. 36. 37. 38. 39. 40. 41. 42. 43. 44. 45. 46. 47. 48. 49. 50. 51. 52. 53. 54. 55. 56. 57. 58. 59.
34 34 34 34 34 34 34 34 34 35 35 35 35 35 35 35 35 35 35 35 35 35 35 35 35 35 35
M M M M M M M M M F M M M M M M M M
F
M M M M M M M M
w w w w w w w
N
w w w w w w w w w w w w w w w w w w w
No No No
-Yes -No Yes Yes No No No No Yes Yes No
-Yea Yes No No Yea No Yes Yes Yes No
-No No
-Yes -No
-No No No
-Yes No No Yes
-No Yes No No
-No No No Yes No
--265
-460 -191
-265 268 284
--284 310 245
-270 320 274
-316 410 267
-315 260
No Yes No Yes Yes No No No No Yes Yes No No No No
-No Yes No Yes No No No No. No No No
Lateral Anteroseptal Posterior
--
Posterolateral
--
Posterior
--
Posterolateral Anteroseptal Posterior Anterior Anteroseptal Posterolateral Posterior Posterior
--
Posterior Posterior Posterior Posterolateral Posterolateral Anteroseptal Anterolateral Anteroseptal Anterolateral Anterolateral
*Dead - 48 hours Alive - 3 yean Alive - 5 years 3 mos. *Dead - In minutes Alive - 4 yean I mo. *Dead - In minutes Alive - 2years 6 mos. *Dead - In minutes Alive - 1 month Alive - 10 years 8 mos. Alive - 8 years 11 mos. Not available Alive - 6 months Alive - 6 years 9 mos. Alive - 6 years 6 mos. Alive - 6 years 6 mos. *Dead - In minutes Alive - 4 1/2 years Dead - 6 months Alive - 3 yean 8' mos. Alive - 3 yean 4 mos. Alive - 6 monthi Alive - 1 year 1 mo. Alive - 1 year 1 mo. Alive - 1 year 1 mo. Alive - 1 year 7 mos. Alive - 2 mos.
'
> n c ~
til
rc
I s:
t""
~
t
~
z
*Necropsied tXanthaleama clinically
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of the Chest
ARTHUR S. KAPLAN
Di~a.scs
TABLE 2-FIFTY-NINE PATIENTS 35 YEARs OF AoE OR You:-;oF.R WITH PRovEn MYOCAllDIAL INFARCTION
White Women
Men Number
Total White
Negro Women
Men
Total Negro
Casea
46
4
50
5
5
9
Cases
78
7
85
8
7
15
12
2
4
4
26
50
80
100
Per cent Number Deaths Per cent Sex Dead
lower than the occurrence among whites. In Yater's first series1 which did not include women, the Negro incidence in the younger age group was approximately two-thirds that among Caucasians. In Yater's later report 11 of 950 men dying of coronary disease in the files of the Anned Forces Institute of Pathology, although Negroes constituted only 4 per cent of the World War II soldiers of the series, they constituted approximately 10 per cent of the Army during that period. Zion and Crosby, 11 in a study of 679 cases of necropsy proved infarction, noted that the Negro race showed a distincdy lower incidence, the significance of which he could not evaluate. ( It is to be noted that there were only four cases 34 years of age and under in this last series) . The nine women in the Norfolk series constitute 14 per cent of the total, or a 7: 1 ratio of men to women. This ratio has variouslv been reported as high as 20: 1,• and as l~w as 3: 1.• However, in the current series, the men to women ratio is 11 : 1 among the whites and almost 1 : 1 among the Negroes. Clinical data (Table 3) in those cases where history was available revealed an incidence of overweight (not further defined as to degree) of 27 per cent, hyper-
tension 34 per cent, and diabetes mellitus 18 per cent. Serum cholesterol was elevated to above 250 mg/ 100 ml in 84 per cent of cases. Further analysis of the serum cholesterols revealed a range of 191 to 460 mg/ 100 ml, or an average cholesterol of 297 mg/ 100 ml with a standard deviation of ±63 mg/ 100 ml. Only one patient had hypertension, diabetes, and was overweight. Three had combinations of hypertension and diabetes, and five had hypertension and overweight. Electrocardiograms were available in 48 of the 59 cases and revealed anterior infarction pattern in 25 cases, posterior in 26 cases, and lateral extension in 14 cases. Follow-up study has been made in 57 of the 59 cases in this series. Twenty-two of the patients have died. Of these, 15 died instantaneously or in less than 24 hours after the first acute myocardial infarction. Two survived less than one week, two cases died in three to six months, and two in four years. One case each lived seven years and ten years respectively prior to death. Further analysis reveals that of the nine Negroes, eight died, and of these, seven died instantaneously or lived less than 24 hours. The eighth lived only three months. Of the seven patients under age
TABLE 3-CLINICAL DATA
Number Cases with Data Available Overweight Hypertension Diabetes mellitus Hypertension (Above 250 mg/100 ml) • Including 2 juvenile diabetics
Number Cases with Abnormality Found
Percentage
52 50
14 17
27
50
17
34
39
7•
34
18
Volume 51, No.2 February, 1967
ACUTE MYOCARDIAL INFARCTION
30, six have died. Necropsies were performed in 17 ( 77 per cent) of the 22 deaths. Data revealed predominant involvement with thrombosis or extensive atherosclerotic narrowing and almost complete occlusion in the left anterior descending coronary artery in 15 cases, left circumflex artery in nine cases, and right coronary artery in eight cases. This compares favorably with other large series in these age groups3 ' 1 (Table 4). Three of the 17 necropsy cases not included in the foregoing figures revealed changes worthy of individual mention. The right coronary artery in the first case ( patient 49) was described as small and rudimentary; the left coronary patent to the bifurcation. Just distal to the origin of the anterior descending there was a hard, yellowish-green elevation from the intimal surface compromising approximately 85 per cent of the lumen. The second case ( patient 33 ) , revealed a normal right coronary artery, atheromatosis with narrowing of the left coronary, and hypoplasia and atheromatosis of the left circumflex. In the last case (patient 3 ) , there was a common origin of the right and left coronary artery from the coronary sinus. H ypoplasia of the horizontal branch of the left coronary artery and a small descending branch and markedly dilated right branch with vein-like thinning of the coronary artery wall was present. Specific comment concerning the women seems indicated and will be further discussed later in this paper. Of the eight women (four white and four Negro), six
died and were necropsied. Three of those who were necropsied had normal tubes and ovaries and history revealed normal menstrual activity, and it is to be noted that of the two women who survived there was also a normal menstrual history. One who was necropsied had a well-healed suprapubic scar suggesting previous pelvic surgery. The left ovary was surgically absent in the second necropsied patient, and in the third, the patient was diabetic but had active menses. DiscussiON
Many problems and relationships which predispose to coronary artery disease in the young group have been noted and bear further discussion. These include family history, obesity, hypertension, diabetes mellitus, hypercholesterolemia, smoking, work habits and occupation, other non-specific relationship, prognosis, and differential diagnosis. Family History Family history was not available in enough of the Norfolk series cases to warrant discussion. Family history of heart diseases has been said to be more likely to be positive in the young coronary than in a controlled group.• Obesity Obesity was noted in 27 per cent of the Norfolk series. Yater• did not fmd obesity or alterations in height-weight of the group d)ing from coronary disease different from the group who died of accident. He later•• felt that there was an apparent tendency toward overweight with advancing age, but the etiologic importance of the factor
TABLE 4--PATROLOGIC DATA
Left Anterior Descending
Right Coronary
Right Circumflex
Almost Complete Sclerotic Occlusion
192
59
60
Thrombotic Occlusion Thrombotic Occlusion
174 27
49 15
29
Non-Occlusive Mural Thrombi Combined Lesions
9
2
2
15
8
9
Status of Coronary Arteries At Necropsy Yater Series' ( 450 Necropsies, Men Ages 18-29) Crawford Series' ( 75 Necropsies, includes 25 men ages 20-39) Norfolk Series ( 17 Necropsies, ages 35 and under)
6
ARTHUR S. KAPLAN
could not definitely be established in any age group. Adiposity has been called of lesser importance.• In an analysis of myocardial infarction in 14 hospital patients 35 years of age and under, overweight was the common finding, and in no instance was underweight encountered. Of these cases, 75 per cent were below average adult male height. 11 In another series of 50 cases collected from British servicemen under the age of 35, body build appeared an important factor, as most of these subjects were powerfully built, robust, and often adipose. Hypertension Hypertension was noted in 34 per cent of the Norfolk series. Presumably many of these cases are not related to hypertension. There appears to be some relationship between coronary artery disease and hypertension which increases with age. It may be said that there is an hereditary predisposition to the two diseases, or that there is a common etiologic factor. Another possibility has been suggested that reduction in the coronary blood flow resulting from disease of the coronary arteries may cause hypertension as a compensatory mechanism to increase the head of pressure in the coronary arterial tree. Yater found 27 per cent of the series with systolic pressures above 139 mm Hg, and 19.1 per cent with diastolic pressures above 89 mm Hg.• Diabetes Mellitus Diabetes mellitus was noted in seven ( 18 per cent) of the cases in the Norfolk series where history was available, including two cases 'of so-called juvenile diabetes. Duncan" states that in "diabetic atherosclerosis" deposits of lipids occur not only in the larger arteries, as is usually seen in the non-diabetic atherosclerotic subject, but in the small arteries and arterioles as well. The coronary arteries are involved in both men and women to about the same degree. Hence, it is not surprising to find coronary occlusive disease as common in the woman as in the man diabetic. Occlusion of the coronary arteries has far outstripped other causes of death in diabetic patients at the Pennsylvania Hospital and this serious
Diseases of the Chest
complication has been more frequent in the woman than the man diabetic patient. Cholesterol Cholesterol levels in the Norfolk series ranged from 191-460 mgjlOO ml with an average of 297 mgj100 m1 with a standard deviation of ±63.2 per cent. It is of interest that this series of figures fairly well satisfied a normal frequency distribution curve when plotted as such. Cholesterol was found above 250 mgj 100 m1 in 84 per cent of the 31 cases where the determination was available. Yater,' in his extensive series, recorded 66 patients with cholesterol determined. Forty-three of these ranged in the 150-250 mgjlOO ml normal and 23 patients showed elevations ranging between 264 and 505 mgj 100 mi. In a studyu of serum cholesterol data from 95 normal men compared to 88 patients with coronary heart disease for the purpose of evaluating differences in relationship to age, it was observed that the greatest difference between mean cholesterols from these two groups was in the youngest (fourth) decade. Not infrequently the serum cholesterol determination is included in routine or screening examinations of older men. The data suggested that the interpretation of elevated values with respect to the prediction of coronary heart disease may be more meaningful in subjects under the age of 40. In the fourth decade, normals of 222 mgf 100 m1 compared with 271 mg/100 m1 in the group with coronary heart disease. Smoking Smoking was not evaluated in the Norfolk series, but is certainly a factor in coronary disease in the younger age group. Yater' found 68 per cent of the patients in his coronary group smoked over ten cigarettes per day compared to 19 per cent in the control group. Physical Activity and Occupation Exertion is said to play a greater role in the cause of myocardial infarction in the younger than in the older age groups, and in one series a rnajority of the cases were manual workers. • Another author' felt that
Volume H, No.2 February, 1967
ACUTE MYOCARDIAL INFARCTION
there appears to be a slightly greater tendency for those affected to have been gaged in less physically arduous occupations such as clerical, service, professional, and supervisory. Analysis of the relationship between the ages of the men and their activity when stricken gave no indication that age was correlated with this factor within the age limits of the same. The onset of the "coronary attack" has occurred in a higher percentage of the younger men w bile they were engaged in strenuous activity, and in a higher percentage of the older men while they were in bed. 10
Differential Diagnosis
The problem of acute myocardial infarction in the very young group has been reviewed by Bristow and colleagues1• in presenting a case of a 15-year-old boy who survived an acute myocardial infarction due to coronary atherosclerosis proved by coronary arteriograms. In excluding causes of coronary disease in children, they felt that idiopathic coronary artery calcification with fibroblastic intimal proliferation, a reported cause of myocardial necrosis in small children17•11 was quite unlikely in view of this patient's age. Anomalous origin of the left coronary artery from the pulmonary artery rarely permits survival to the age of 15.10 Coronary arteritis can produce arterial occlusion through aneurysm formation and thrombosis. Polyarteritis nodosa will produce this sequence and according to Strykee' can be limited to the coronary arteries. Since this patient had survived for over a year since his acute attack, remaining entirely free of symptoms of inflammatory disease, polyarteritis was unlikely. Rheumatic fever has been described as the cause of coronary arteritis although rarely, if ever, myocardial infarction• as have other causes of inflammatory arterial disease such as bacterial endocarditis and tuberculosis. Likoff'1 and ~iates presented six cases of white men 16-24 years of age with electrocardiographic evidence of myocardial infarction, but with no other stigmata of coronary disease. Each had low intensity
143
ejection-type systolic murmur best heard in the thir.d_left_ iJltercostal space at the sternal border. in three patients the murmur was of equal intensity at the apex. He felt that they represented an obscure congenital defect that has not previously been recorded. All had normal arteriograms. The possibility remained that non coronary myocardial disease was present with each of these patients. The conclusion was not supported by past or present evidence of infections, collagen disease, amyloidosis, hemochromatosis, sarcoidosis, muscular dystrophy, or metabolic abnormality. It was a simple matter to reason that electrocardiographic changes stemmed from healed myocarditis. Confmnation of this diagnosis and that of fibroelastosis or endomyocardial fibrosis actually is unwarranted without tissue studies. They concluded that for the present the primary obligations of their communication was to acknowledge that the electrocardiographic pattern of myocardial ischemia, injury, or necrosis may appear in asymptomatic young adult men who have low intensity systolic murmurs, to record that any implication that these electrical deviations resulted from obstructive coronary disease cannot be substantiated by coronary arteriography, and to suggest that individuals possessing these diagnostic features may represent a distinct, recognizable clinical entity, the etiology of which remains obscure. THE YouNG WoMAN
The problem of the young woman with coronary disease bears some specific discussion as noted earlier in this communication. In the Norfolk series, eight women, four white and four Negro, were presented. There was a 50 per cent mortality in the white and 100 per cent (instant) mortality in the Negro group. This appears to be one of the largest series of myocardial infarction in this young age group among women noted in the medical literature at this time. In a recent review of the literature, Thomas and Cohen11 found it generally accepted that myocardial infarction may
ARTHUR S. KAPLAN
occur in a few young men under the age of 40, but is extremely rare among young 11 women of this age. Zinn and Crosby, in his series of 679 cases of necropsy proved infarction, recorded only two cases in women under 34 years of age. In another series of 345 casesu of acute infarction in women studied over ten years, only 9 per cent of the entire group ( 36 patients) were in the fifth decade, including ten patients under the age of 46, but not a single case under the age of 41. Of these 36 patients, 32 had a negative diabetic history; history was not available in four; 19 had hypertension (51 per cent) ; six had hypertension and obesity; 14 had a negative hypertensive history; 13 still had regular menses ( 36 per cent) ; menopause had occurred in eight; hysterectomies had been performed in six; and there was no menstrual history in 15 cases. Cochran and Gwinup," writing on coronary artery disease in the young woman, stated that young women without attendant diabetes, hypertension, or hyperlipemia a remarkable freeinducing states po~ess dom from the disease until the menopausal age, at which time the incidence of the disorder becomes nearly equal to that of men of comparable age. He presented 29 cases with medical history of surgical castration in 45 per cent of these. This history was present in more of these than was either hypertension ( 41 per cent) or diabetes ( 39 per cent). Accordingly he suggested that if sacrifice of ovaries is necessary, the administration of estrogens until age 50, or thereabouts, would appear indicated on the basis of present evidence. Cochran and Gwinup's series had only four cases under the age of 35. The first patient was age 33, a white woman, without hypertension or diabetes, with cholesterol 265 mg/ 100 ml, and was premenopausal; the second, age 33, a white woman, was hypertensive, non diabetic, and had a cholesterol of 240 mg/100 ml, with a previous unilateral oophorectomy eight years before, but was premenopausal; the third, a 32-year-old white woman, had hypertension and
Drscascs of th~
Ch~st
diabetes, cholesterol 280 mg/ 100 ml, and was premenopausal; the last, a 26-yearold white woman, was premenopausal, but has disseminated lupus erythematosus with coronary arteritis. In a specific study of myocardial infarction in women, Weinreb and collaborators" reviewed the rna jor clinical features in 231 women with proved myocardial infarction. The group as a whole showed increased frequency of diastolic hypertension ( 51.5 per cent), diabetes mellitus ( 52.6 per cent), and elevated serum cholesterol ( 44.8 per cent). A positive family history of diabetes, hypertension, or coronary artery disease was present in more than twothirds of the patients. A strikingly poor prognosis was noted among the women with diabetes compared to the non diabetics. Of 156 patients about whom information was available, 13.5 per cent had neither diabetes nor hypertension; of the 23 women in this group under the age of 50, 26.1 per cent had neither disease. Only two women, both under 50 years of age at the time of the fli'St myocardial infarction, did not have diabetes, hypertension, hypercholesterolemia, or a positive family history. Coronary artery disease must be seriously considered in women presenting a suggested clinical picture, particularly in the younger age group, despite the absence of hypertension or diabetes mellitus. They note that almost all report~ on coronary disease in women emphasize a history of diabetes or hypertension as important predisposing factors. Of his group of 231 cases, five ( 2.3 per cent) were ages 3039. Menstrual history revealed that 9 per cent of the cases with available history were still menstruating at the time of the first infarct; 72.6 per cent had had natural menopause; 6.5 per cent had had bilateral oophorectomy; and 10.7 per cent had had hysterectomy. Wuest and co-workers11 in a study of 160 necropsies of oophorectomized women at the Mayo Clinic noted more severe atherosclerosis in the hearts of 61 per cent of 49 bilaterally oophorectomized women
VniUOlC H. No.2 Frilruuy. 1967
145
ACUTE MYOCARDIAL INFARCTION
than in the hearts of normal women of the same ages. There was no significant increa~ in intimal change until five years had elapsed after operation. Within the first five years, apparently, the findings were very little different from control women. After five years, however, the degree of coronary atherosclerosis in oophorectomized women approached very nearly that found in men of the same age range. Only 6 per cent of such women, however, had clinical evidence of coronary artery disease. The Negro Women In view of the 100 per cent instant mortality in the four cases of myocardial infarction in young Negro women in the Norfolk series, the problem in this group certainly deserves special consideration. Keil and and Me Vay" stated that no previous investigation into the etiology of coroand its occurrence in nary artery di~iease women had considered the Negro race separately. In reviewing 519 cases of proved myocardial infarction in all ages in a hospital where 70 per cent of the hospital admissions were Negro and 30 per cent white, they concluded that the classic sex predominance of myocardial infarction in men was not present in Negroes where they found a ratio of approximately 1 : 1, (comparing almost exactly to the Norfolk series), as compared to a 3: 1 ratio in whites. In general, infarction in their group occurred more than ten years earlier on the average in Negro women than in white women. They found only four white women with infarction prior to the 50th year of life, whereas 43 Negro women had been afflicted by the end of the fifth decade. It is of note that their series contained no white patients in the third decade and only one Negro man and one Negro woman. In the fourth decade, they noted five white men, no women, eight Negro men, and seven women of age not further broken down within the fourth decade. They felt that it was apparent that the Negro woman wali striken at a significantly earlier age than any of the other groups,
white man or woman, or Negro man. The mortality rate was a startling deviation from the classic description of myocardial infarction in women and they concluded that it would appear that coronary atherosclerosis is a different disease in the Negro woman as compared with that described in the literature, and this would certainly be borne out by the Norfolk series study. SUMMARY
A series of 59 cases of clinically proved myocardial infarction in patients 35 years of age and under has been presented and the literature on the subject of myocardial infarction in patients under the age of 40 reviewed. The group consisted of 46 white men of whom 12 (26 per cent) died; four white women of whom two (50 per cent) died; five Negro men of whom four (80 per cent) died; and four Negro women of whom four ( 100 per cent) died. Hypertension was noted in 34 per cent of the cases. Diabetes mellitus was noted in 18 per cent, and obesity was a factor in 27 per cent of the cases. Elevated serum cholesterol (above 250 mg/ 100 m1) was noted in 84 per cent of the cases with a range of 191 to 460 mg/ 100 ml, or an average of 297 mg/1 00 ml. Necropsy in 17 ( 77 per cent) of the 22 deaths revealed a predominant involvement in the left anterior descending coronary artery. Electrocardiographic infarction pattern was found to be as frequently anterior as posterior in distribution with lateral extention about half as frequent. There is no question that myocardial infarction is a more severe and devastating disease in the overall younger age groups than in the older age groups, the current study having shown a 24 per cent instant mortality. The mortality in white women is higher than that of white men, although the incidence of the disease is less. The incidence of the disease in the Negro is almost equal in men and women, but the mortality rate in the Negro, particularly women, approaches 100 per cent.
Disuses of
ARTHUR S. KAPLAN RESUMEN
Este trabajo consiste en Ia presentaci6n de 50 casos de infano cardiaco cllnicamente probados en sujetos menores de 35 anos y revision de Ia literatura sobre infarto del miocardia en individuos menores de 40 anos. El grupo consiste en 46 hombres de Ia raza blanca, de los que 12 ( 26 por ciento) fallecieron, cuatro mujeres blancas, de las que 2 (50 por ciento) murieron, 5 hombres de raza negra de los que 4 (80 por ciento) sucumbieron y 4 mujeres negras; de las que ( 4 por ciento) fallecieron. En 34% de los casos se comprob6 hipertensi6n, diabetes mellitus en 18% y obesidad como factor en 27%. La elevaci6n del colesterol sangufneo (sobre 250 mgm por den mi.) fut> comprobada en el 84%, con niveles variables entre 191 a 460 mgm por cien mililitros. La autopsia, practicada en 17 ( 77 por ciento) de las 22 muenes, revel6 una panicipaci6n predominante de Ia A. coronaria descendente anterior. Los trazados ECG indicativos de infano fueron de distribuci6n anterior o posterior con igual frecuencia, con extension lateral aproximadamente en Ia mitad de los casos. No cabe duda que el infano del miocardia es mas grave y devastador entre el grupo joven que entre los de mayor edad, observ.indose en el presente estudio una mortalidad inmediata de un 50%. La monalidad entre las mujeres blancas es mayor que entre los hombres blancos, si bien Ia jncidencia de Ia afecci6n es menor. La incidencia entre los de raza negra es igual en ambos sexos, aunque Ia mortalidad en esta raza particulannente entre las mujeres se aproxima al 100%. REsuME
d'une serie de 59 cas d'infarctus myocardiques cliniquement trouves chez des rnalades ayant 35 ans et au-dessous; et revue de Ia litterature sur le sujet de l'infarctus du myocarde chez les sujets au-dessous de 40 ans. Le groupe consistait en 46 hommes blancs dont 12 ( 26 pour cent ont succomb); 4 femmes blanches. dont 2 (50 pour cent) sont mones; 5 hommes noirs dont 4 (80 pour cente son mons; et 4 femmes noires, doot 4 ( 100 pour cent) ont succombee. L'hypertension a ete notee dans 34 pour cent des cas. Le diabete sucre dans 18 pour cent, et l'obesite jouait un role dans 27 pour cent des cas. Une elevation du cholesterol dans le serum ( au-dessus de 250 mg/ 100 mi.) a ete note dans 84 pour cent des cas, avec des chiffres extremes de 191 a 460 mg/ 100 ml, ou une moyenne de 297 mg. P~ntation
th~
Ch~st
L'autopsie ches 17 (77 pour cent} des 22 cas monals a montre une atteinte predominante de l'anere interventriculaire anterieure. Le type electrocardiographique d'infarctus etait aussi souvent anterieur que posterieur dans sa distribution, avec une extension laterale environ dans Ia moitie des cas. II n'y a pas de doute que l'infarctus du myocarde est une maladie plus severe et mutilante dans le groupe d'age jeune que dans les groupes d'age plus age, l'etude presente ayant montre une monalite precoce de 24 pour cent. La mortalite chez les femmes blanches est plus fone que ceUe des hommes blancs, quoique Ia frequence de Ia maladie soit moindre. La frequence de Ia maladie chez les noirs est a penu pres equivalente chez les hommes et les femmes, mais le taux de mortalite chez le noir, particulierement dans le sexe feminin, approche 100 pour cent. ZusAMMENFASSUNG
Bericht tiber eine Reihe von 59 Fallen klinisch bestiitigten Herzinfarktes bei Patienten im Alter von 35 Jahren und weniger mit Literaturiibersicht iiber die Berichte einer solchen Erkrankung bei Patienten von weniger als 40 Jahren. Die Gruppe hestand als 46 WeiPen mannlichen Geschlechtes, von denen 12 ( 26%) starben, 4 weiPen Frauen, von denen 2 (50%) starben 5 mannlichen Negern, von denen 4 (80%) starben und 4 weiblichen Negem, von denen 4 ( 100%) starben. Eine Hypertension wurde bei 34% der Faile festgestelh. Ein Diabetes mellitus wurde bei 18% beobachtet, und Fettsucht war ein begleitender Faktor bei 27% der Faile. Erhohtes Serum Cholesterin (mehr als 200 mg/100 ml) wurde bei 84% der Faile beobachtet mit einer Schwankungsbreite von 191-460 mg/ I00 mi. bei einem Durchschnittswen von 297 mg/100 mi. Die Sektion von 17 ( 77%) der 22 Todesfalle ergab einen iiberwiegenden Befall der linken vorderen absteigenden Coronar-arterie. Elektrokardiographische Infarktzeichen wurden ebenso haufig im vorderen wie im riickwanigen Anteil gefunden, bei einer lateralen Beteiligung in ungefahr der halben Haufigkeit. Es ist keine Frage, daP der Myocardinfarkt eine schwerere und verheerendere Erkrankung bei der insgesamt jiingeren Ahersgruppe ist als bei der aheren Ahersgruppe, wobei die vorliegende Untersuchung eine Mortalitatsziffer zeigt von 24%. Die Sterblichkeit bei weiPen Frauen ist hoher als bei weiPen Mannern, obwohl deren Kranheitshaufigkeit niedriger liegt. Das Vorkommen des Herzinfarktes bei den Negem ist ungefahr gleich haufig bei Mannem wie bei den Frauen, jedoch erreicht die Mortalitat bei dieser Rasse-insbesondere beim weiblichen Geschlecht -100%.
Volu~ 51, No.2 February, 1967
2
3
4 5 6 7 8
9
10
11
12 13 14 15
ACUTE MYOCARDIAL INFARCTION
REFERENCES NoRFOLK ( V a.) Chamber of Commerce Sta.tistical Digest, 1963. SMITH, H. L. AND BARTLES, E. C.: "Coronary thrombosis with myocardial infarction and hypertrophy in young persons," ]AMA, 98: 1072, 1932. YATER, w. M., TRAUM, A. H., BROWN, w. G., FITZGERALD, R. P., GEISLER, M. A., WILCOS, B. B. : "Coronary artery disease in men 18 to 39 yean of age," A mer. Heart ]., 36:334, 481, 683, 1948. BAKER, M. R. AND ScHILLHAMMER, w. R., jR.: "Myocardial infarction in young adults," U. S. Armed Forces Medical ]., 11:75, 1951. FRIEDBERG, C. K.: Diseases of the Heart, 2nd Ed., W. B. Saunden Co., Philadelphia, 1956. WRIGHT, H. B.: "Atherosclerosis and coronary heart disease," Lancet, II: 980, 1960. AcHESON, R. M.: "Atherosclerosis and coronary heart disease," lAncet II. 706, 1960. CRAWFORD, T., DEXTER, D. AND TEARE, R. D.: "Coronary artery pathology in sudden death from myocardial ischaemia. A comparison by age groups," Lancet I: 181, 1961. MoLL, A. AND HAMACHER, F.: Der herzinfarkt in juengeren lebensalter, beitraege zur praktischen medizin, No. 44, F. Enke Verlag, Stuttgart, 1962. YATER, w. M., WELSH, P. P., STAPLETON, J. F. AND CLARK, M. L.: "Comparison of clinical and pathologic aspects of coronary artery disease in men of various age groups," a study of 950 autopsied cases from the Armed Forces Institute of Pathology. Ann. Intern. M ed. 34: 352, 1951. ZINN, W. J., AND CROSBY, R. S.: "Myocardial infarction, statistical analysis of 679 autopsy-proven cases," Amer. ]. Med., 8:169, 1950. CouNTRY, J. C.: '"Myocardial infarction in young men," U.S. Armed Forces Med. J. 5: 688, 1954. NEWMAN, M.: "Coronary occlusion in young adults," Lancet II: 409, 1946. DuNCAN, G. G.: Diseases of Metabolism, 5th Ed., W. B. Saunden Co., Philadelphia, 1964, p. 949, 1030. ORVIS, H. H., TsoHAs, R. E., FAWAL, I. A. AND EVANS, J. M.: "Serum cholesterol in normal males versus males with coronary heart
16
17 18 19
20 21
22
23
24 25
26 27
28
147
disease, difference with respect to age," Am. ]. M. Sc. 241: 167, 1961. BRisTow, J. D., Don-n, C. T., GRiswoLD, H. E. AND KAssEBAUM, D. G.: "Myocardial infarction in a fifteen year old boy," Am. J. Med., 30:961, 1961. STRYKER, W. A.: "Coronary occlusive disease in infants and in children," J. Dis. Child. 71: 280, 1946. COCHRAI'Ii"E, w. A. AND BoWDEN, D. H.: "Calcification of the arteries in infancy and childhood," Pediatrics 14: 222, 1954. TRAISMAN, H. s., LIHPERIS, N. M. TRAISJUN, A. S.: "Myocardial infarction due to calcification of the arteries in an infant," J. Dis. Child. 91:34, 1956. CoHEN, H. AND SIEw, S.: "Aberrant left coronary artery, report of a case and review of the literature," Circulation 20:918, 1959. LJKOFF, W., SEGAL, B. AND DREIFUS, L.: "Myocardial infarction patterns in young subjects with normal coronary arteriograms," Circulation 26:373, 1962. THOMAS, C. B. AND CoHEN, B. H.: "The familial occurrence of hypertension and coronary artery disease with observations concering obesity and diabetes," Ann. Int. Med. 42: 90, 1955. BLACKMAN, N. S. AND KoLOOLU, Y.: "Acute myocardial infarction in women under fifty yean of age," New York J. M ed. 61 : 3079. 1961. CocHRAN, R. AND GWINUP G.: "Coronary artery disease in young females,'' Arch. Int. Med., 110:162, 1962. WuEsT, J. H., DaY, T. J. AND EDWARDS, J. E.: "The degree of coronary atherosclerosis in bilaterally oophorectomized women," Circulation 7:801, 1953. WEINREB, H. L., GERMAN, E., AND RosENBERG, B.: "A study of myocardial infarction in women," Ann. Intern. Med. 46:285, 1957. KEIL, P. G., AND McVAY, L. V., Ja.: "A comparative study of myocardial infarction in the white and negro races," Circulation 13: 712, 1956. Jo~.:L, E. AND GREENSTEIN, M. D.: "Total coronary sclerosis in a boy of ten yean," Lancet, II :659, 1944.
For reprints, please write: Dr. Kaplan, 803 Medical Tower, Norfolk.
MISSILES IN HEART The after-histories of 40 soldiers of World War II with missiles In the heart were recorded. The record Is complete In every case, and all the veterans have survived. Pericarditis was a common accompaniment of the Injury, and an etruslon of considerable degree (sometimes delayed) OttUrred In 25 per cent. Electrocardiograms were helpful In the acute phase and often called attention for the flrst time to the cardiac Injury. In all but 2 cases the tracIngs have returned to a normal pattern. The size of the heart on x-ray examination ls now normal In all except the soldier with aorticvalve InJury. Elective removal of the missile was later attempted In 8 patients. It was successful In 3 but was abandoned In 5. 2 of whom the foreign body could not now be found.
A delayed complication of major importance occurred In a soldier In whom the shell fragment lodged ftrst In the left pulmonary artery, subsequently shifted to the right and 15 years later eroded Into and obstructed a bronchus. necessitatIng pneumonectomy (Burford's case). The subsequent course of the remainder of these veterans has been benign except for the formidable psychologic strain of living with a mlsslle In the heart. All are genuinely concerned about the missile, and 5 are totally Incapacitated by an anxiety neurosis. Subsequent migration. erosion or Infection occurs Infrequently once the foreign body Is flxed ln the myocardium. These complications have not appeared In the 20 years covered by this study.
E. F. AND BE.EBI!, G. W.: "Missiles in the heart" Ntw Engl. }. M,J., 274: 1046, 1966.
BLAND,
s.
KAPLAN, M.D.
Norfolk, Virginia
I
T WILL BE THE PURPOSE OF THIS PAPER
to review the medical literature on the subject of myocardial infarction in patients below 40 years of age and to present a series of 59 cases of clinically proved myocardial infarction in patients 35 years of age or younger taken from an unselected urban population in a community of approximately 500,000 people comprising 26 1 per cent Negroes during the period 19511963. These cases were selected from the records of the Norfolk General, De Paul, Leigh Memorial, and Community Hospitals, and the Office of the State Medical Examiner, Norfolk, Virginia. This study, unbiased by such selection as restricted studies of servicemen only, offers certain new facts heretofore not emphasized. Smith and Bartels' in 1932 reported two cases of myocardial infarction in patients 35 and 36 years of age and stated that a review of the literature up to that time revealed only 20 confirmed cases of myocardial infarction in patients under 40 years of age. Prior to World War II coronary artery disease in men under 30 years of age was regarded as rare, and in men between 30 and 40 years of age, as uncommon. Yater and associates' in 1948 reviewed the previous literature and found 744 cases of coronary artery disease in patients under 40. The youngest was a I 0-year-old boy reported by Jokl and 11 Greenstein in 1944. Baker and Schillhammer4 in 1951 still felt that myocardial infarction in young adults was seldom seen by the practicing physician and they felt that myocardial infarctions in young persons was most frequently non-fatal because of the excellent recuperating poten•Presented at the Virginia Regional Meeting, American College of Physicians, Williamsburg, Virginia, February 20, 1965.
tialities of the youthful myocardium. Friedbert states that probably 5 per cent of first attacks of acute coronary thrombosis occur before the age of 40 and rarely proved cases have even been observed in childhood. Yater,• in his extensive review of the experience of the Armed Forces during World War II, reported 866 cases of coronary disease in men 18 to 39 years of age with 450 necropsies. He concluded that coronary artery sclerosis in this series is a specific disease of the coronary arteries confmed to the heart and not a part of generalized atherosclerosis, as in older groups. This is what makes the young or middle-aged man's thrombosis a separate and interesting disease. Other authors have stated that ischemic heart disease in younger age groups under 40 is different and is a more localized arterial disease, and the factor of importance is therefore not the nature but the distribution of the lesions.'·' Crawford' and co-workers, however, in a review of 75 necropsies, concluded that the so-called more localized lesions found in the younger groups can be similarly found in patients in their 50's, and that there is nothing to support the contention that under the age of 40 fatal coronary disease differs in any essential way from the disease in other subjects. Other authors have concurred in this latter opinion.' In the current series, henceforth to be referred to as the Norfolk series, 59 patients are presented, ranging in age from 21 to 35 years (Table 1 ) . Analysis reveals 46 white men and four white women comprise 85 per cent of the total group while five Negro men and five Negro women comprise 15 per cent (Table 2). In a population made up of 26 per cent Negroes, this is a rate among Negroes 60 per cent 137
w
00
1-Frnv-NrNB PATIENTs 35 YEARs OF Aoa OR YouNOER WITH PROVED MYOCARDIAL INFARCTIONs ECG Infarct. Diabetes Serum CholesOverRace HyperFollow-Up Status Pattern weight terol mg/100 ml tenJion
TABLE
Cue No.
Age
Sex
1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13.
21 22 22 26 27 29 29 30 30 30 30 31 31 32 32 32 32 32 32 32 32 32 33 33 33 33 33 33 34 34 34 34
M M M F M M M M M M M F F M M M F M M M F F M M M M M M M M M M
14.
15. 16. 17. 18. 19. 20. 21. 22. 23. 24. 25. 26. 27. 28. 29. 30. 31. 32.
w w
N N
w w
N
w w w w w N
w w w N
w w
N N
w w w w w w N
w w w w
No No No
--
No No Yes No Yes Yes No No
-Yes No No
No
265 285
----
---
---
---
Yes No No No No No
--No No
450 310
-217 265
--
-365
-289
--
--
--
--
--
---
No No Yes
No No No
No No Yes
--No
--
--
--
--
No No
No Yea No No
No No
No No No No
346 339
t
240
--197 251
--
---375
Yes Yes
-Yes No No Yes No Yea Yes No No No No No No No No No No No No
--
No No No No No No Yea No No
Antt"rior Posterior Anteroseptal
--
Anteroseptal Posterolateral --
Anterior Posterior Posterior Posterior Anterior
--
Anteroseptal Posterolateral Anterior
--
Anteroseptal Posterior Anterior ---
Posterior Posterior Posterior Posterolateral Anteroseptal
--
Anteroseptal Posterior Anterior Posterior
Alive - 3 years *Dead - I 0 years 2 mos. 3 mos. *Dead In minutes *Dead *Dead - 3 days Dead - 3 yean I 0 mos. *Dead - In minutes *Dead - 3 I /2 houn Alive - 2 yean 11 mos. Alive - I year I 0 mo. Alive- II months Alive - 8 yean 1 mo. *Dead - 12 hours Alive - 12 yean Dead - 6 years 8 mos. Alive - 8 yean 1 mo. *Dead - In minutes 2 yean 8 mos. Alive Alive - 5 years 6 mos. Alive - 3 yean 4 mos. *Dead - In minutes *Dead - 4 hours Dead - 72 hours Alive - 6 years 7 mos. *Dead - 10 minutes Alive - 2 years 8 mo. Alive -1 year 5 mos. *Dead - In minutes Not available Alive - 8 years l mos. Dead- 4 yean Alive - 8 year 2 mos.
> ~
c::: =
"~ ,.:
> ~
~
.. !;' if~
95
ae.
~s:
"'C
s~
--
. "' ~-
-~~
33. 34. 35. 36. 37. 38. 39. 40. 41. 42. 43. 44. 45. 46. 47. 48. 49. 50. 51. 52. 53. 54. 55. 56. 57. 58. 59.
34 34 34 34 34 34 34 34 34 35 35 35 35 35 35 35 35 35 35 35 35 35 35 35 35 35 35
M M M M M M M M M F M M M M M M M M
F
M M M M M M M M
w w w w w w w
N
w w w w w w w w w w w w w w w w w w w
No No No
-Yes -No Yes Yes No No No No Yes Yes No
-Yea Yes No No Yea No Yes Yes Yes No
-No No
-Yes -No
-No No No
-Yes No No Yes
-No Yes No No
-No No No Yes No
--265
-460 -191
-265 268 284
--284 310 245
-270 320 274
-316 410 267
-315 260
No Yes No Yes Yes No No No No Yes Yes No No No No
-No Yes No Yes No No No No. No No No
Lateral Anteroseptal Posterior
--
Posterolateral
--
Posterior
--
Posterolateral Anteroseptal Posterior Anterior Anteroseptal Posterolateral Posterior Posterior
--
Posterior Posterior Posterior Posterolateral Posterolateral Anteroseptal Anterolateral Anteroseptal Anterolateral Anterolateral
*Dead - 48 hours Alive - 3 yean Alive - 5 years 3 mos. *Dead - In minutes Alive - 4 yean I mo. *Dead - In minutes Alive - 2years 6 mos. *Dead - In minutes Alive - 1 month Alive - 10 years 8 mos. Alive - 8 years 11 mos. Not available Alive - 6 months Alive - 6 years 9 mos. Alive - 6 years 6 mos. Alive - 6 years 6 mos. *Dead - In minutes Alive - 4 1/2 years Dead - 6 months Alive - 3 yean 8' mos. Alive - 3 yean 4 mos. Alive - 6 monthi Alive - 1 year 1 mo. Alive - 1 year 1 mo. Alive - 1 year 1 mo. Alive - 1 year 7 mos. Alive - 2 mos.
'
> n c ~
til
rc
I s:
t""
~
t
~
z
*Necropsied tXanthaleama clinically
~
c.o
~
of the Chest
ARTHUR S. KAPLAN
Di~a.scs
TABLE 2-FIFTY-NINE PATIENTS 35 YEARs OF AoE OR You:-;oF.R WITH PRovEn MYOCAllDIAL INFARCTION
White Women
Men Number
Total White
Negro Women
Men
Total Negro
Casea
46
4
50
5
5
9
Cases
78
7
85
8
7
15
12
2
4
4
26
50
80
100
Per cent Number Deaths Per cent Sex Dead
lower than the occurrence among whites. In Yater's first series1 which did not include women, the Negro incidence in the younger age group was approximately two-thirds that among Caucasians. In Yater's later report 11 of 950 men dying of coronary disease in the files of the Anned Forces Institute of Pathology, although Negroes constituted only 4 per cent of the World War II soldiers of the series, they constituted approximately 10 per cent of the Army during that period. Zion and Crosby, 11 in a study of 679 cases of necropsy proved infarction, noted that the Negro race showed a distincdy lower incidence, the significance of which he could not evaluate. ( It is to be noted that there were only four cases 34 years of age and under in this last series) . The nine women in the Norfolk series constitute 14 per cent of the total, or a 7: 1 ratio of men to women. This ratio has variouslv been reported as high as 20: 1,• and as l~w as 3: 1.• However, in the current series, the men to women ratio is 11 : 1 among the whites and almost 1 : 1 among the Negroes. Clinical data (Table 3) in those cases where history was available revealed an incidence of overweight (not further defined as to degree) of 27 per cent, hyper-
tension 34 per cent, and diabetes mellitus 18 per cent. Serum cholesterol was elevated to above 250 mg/ 100 ml in 84 per cent of cases. Further analysis of the serum cholesterols revealed a range of 191 to 460 mg/ 100 ml, or an average cholesterol of 297 mg/ 100 ml with a standard deviation of ±63 mg/ 100 ml. Only one patient had hypertension, diabetes, and was overweight. Three had combinations of hypertension and diabetes, and five had hypertension and overweight. Electrocardiograms were available in 48 of the 59 cases and revealed anterior infarction pattern in 25 cases, posterior in 26 cases, and lateral extension in 14 cases. Follow-up study has been made in 57 of the 59 cases in this series. Twenty-two of the patients have died. Of these, 15 died instantaneously or in less than 24 hours after the first acute myocardial infarction. Two survived less than one week, two cases died in three to six months, and two in four years. One case each lived seven years and ten years respectively prior to death. Further analysis reveals that of the nine Negroes, eight died, and of these, seven died instantaneously or lived less than 24 hours. The eighth lived only three months. Of the seven patients under age
TABLE 3-CLINICAL DATA
Number Cases with Data Available Overweight Hypertension Diabetes mellitus Hypertension (Above 250 mg/100 ml) • Including 2 juvenile diabetics
Number Cases with Abnormality Found
Percentage
52 50
14 17
27
50
17
34
39
7•
34
18
Volume 51, No.2 February, 1967
ACUTE MYOCARDIAL INFARCTION
30, six have died. Necropsies were performed in 17 ( 77 per cent) of the 22 deaths. Data revealed predominant involvement with thrombosis or extensive atherosclerotic narrowing and almost complete occlusion in the left anterior descending coronary artery in 15 cases, left circumflex artery in nine cases, and right coronary artery in eight cases. This compares favorably with other large series in these age groups3 ' 1 (Table 4). Three of the 17 necropsy cases not included in the foregoing figures revealed changes worthy of individual mention. The right coronary artery in the first case ( patient 49) was described as small and rudimentary; the left coronary patent to the bifurcation. Just distal to the origin of the anterior descending there was a hard, yellowish-green elevation from the intimal surface compromising approximately 85 per cent of the lumen. The second case ( patient 33 ) , revealed a normal right coronary artery, atheromatosis with narrowing of the left coronary, and hypoplasia and atheromatosis of the left circumflex. In the last case (patient 3 ) , there was a common origin of the right and left coronary artery from the coronary sinus. H ypoplasia of the horizontal branch of the left coronary artery and a small descending branch and markedly dilated right branch with vein-like thinning of the coronary artery wall was present. Specific comment concerning the women seems indicated and will be further discussed later in this paper. Of the eight women (four white and four Negro), six
died and were necropsied. Three of those who were necropsied had normal tubes and ovaries and history revealed normal menstrual activity, and it is to be noted that of the two women who survived there was also a normal menstrual history. One who was necropsied had a well-healed suprapubic scar suggesting previous pelvic surgery. The left ovary was surgically absent in the second necropsied patient, and in the third, the patient was diabetic but had active menses. DiscussiON
Many problems and relationships which predispose to coronary artery disease in the young group have been noted and bear further discussion. These include family history, obesity, hypertension, diabetes mellitus, hypercholesterolemia, smoking, work habits and occupation, other non-specific relationship, prognosis, and differential diagnosis. Family History Family history was not available in enough of the Norfolk series cases to warrant discussion. Family history of heart diseases has been said to be more likely to be positive in the young coronary than in a controlled group.• Obesity Obesity was noted in 27 per cent of the Norfolk series. Yater• did not fmd obesity or alterations in height-weight of the group d)ing from coronary disease different from the group who died of accident. He later•• felt that there was an apparent tendency toward overweight with advancing age, but the etiologic importance of the factor
TABLE 4--PATROLOGIC DATA
Left Anterior Descending
Right Coronary
Right Circumflex
Almost Complete Sclerotic Occlusion
192
59
60
Thrombotic Occlusion Thrombotic Occlusion
174 27
49 15
29
Non-Occlusive Mural Thrombi Combined Lesions
9
2
2
15
8
9
Status of Coronary Arteries At Necropsy Yater Series' ( 450 Necropsies, Men Ages 18-29) Crawford Series' ( 75 Necropsies, includes 25 men ages 20-39) Norfolk Series ( 17 Necropsies, ages 35 and under)
6
ARTHUR S. KAPLAN
could not definitely be established in any age group. Adiposity has been called of lesser importance.• In an analysis of myocardial infarction in 14 hospital patients 35 years of age and under, overweight was the common finding, and in no instance was underweight encountered. Of these cases, 75 per cent were below average adult male height. 11 In another series of 50 cases collected from British servicemen under the age of 35, body build appeared an important factor, as most of these subjects were powerfully built, robust, and often adipose. Hypertension Hypertension was noted in 34 per cent of the Norfolk series. Presumably many of these cases are not related to hypertension. There appears to be some relationship between coronary artery disease and hypertension which increases with age. It may be said that there is an hereditary predisposition to the two diseases, or that there is a common etiologic factor. Another possibility has been suggested that reduction in the coronary blood flow resulting from disease of the coronary arteries may cause hypertension as a compensatory mechanism to increase the head of pressure in the coronary arterial tree. Yater found 27 per cent of the series with systolic pressures above 139 mm Hg, and 19.1 per cent with diastolic pressures above 89 mm Hg.• Diabetes Mellitus Diabetes mellitus was noted in seven ( 18 per cent) of the cases in the Norfolk series where history was available, including two cases 'of so-called juvenile diabetes. Duncan" states that in "diabetic atherosclerosis" deposits of lipids occur not only in the larger arteries, as is usually seen in the non-diabetic atherosclerotic subject, but in the small arteries and arterioles as well. The coronary arteries are involved in both men and women to about the same degree. Hence, it is not surprising to find coronary occlusive disease as common in the woman as in the man diabetic. Occlusion of the coronary arteries has far outstripped other causes of death in diabetic patients at the Pennsylvania Hospital and this serious
Diseases of the Chest
complication has been more frequent in the woman than the man diabetic patient. Cholesterol Cholesterol levels in the Norfolk series ranged from 191-460 mgjlOO ml with an average of 297 mgj100 m1 with a standard deviation of ±63.2 per cent. It is of interest that this series of figures fairly well satisfied a normal frequency distribution curve when plotted as such. Cholesterol was found above 250 mgj 100 m1 in 84 per cent of the 31 cases where the determination was available. Yater,' in his extensive series, recorded 66 patients with cholesterol determined. Forty-three of these ranged in the 150-250 mgjlOO ml normal and 23 patients showed elevations ranging between 264 and 505 mgj 100 mi. In a studyu of serum cholesterol data from 95 normal men compared to 88 patients with coronary heart disease for the purpose of evaluating differences in relationship to age, it was observed that the greatest difference between mean cholesterols from these two groups was in the youngest (fourth) decade. Not infrequently the serum cholesterol determination is included in routine or screening examinations of older men. The data suggested that the interpretation of elevated values with respect to the prediction of coronary heart disease may be more meaningful in subjects under the age of 40. In the fourth decade, normals of 222 mgf 100 m1 compared with 271 mg/100 m1 in the group with coronary heart disease. Smoking Smoking was not evaluated in the Norfolk series, but is certainly a factor in coronary disease in the younger age group. Yater' found 68 per cent of the patients in his coronary group smoked over ten cigarettes per day compared to 19 per cent in the control group. Physical Activity and Occupation Exertion is said to play a greater role in the cause of myocardial infarction in the younger than in the older age groups, and in one series a rnajority of the cases were manual workers. • Another author' felt that
Volume H, No.2 February, 1967
ACUTE MYOCARDIAL INFARCTION
there appears to be a slightly greater tendency for those affected to have been gaged in less physically arduous occupations such as clerical, service, professional, and supervisory. Analysis of the relationship between the ages of the men and their activity when stricken gave no indication that age was correlated with this factor within the age limits of the same. The onset of the "coronary attack" has occurred in a higher percentage of the younger men w bile they were engaged in strenuous activity, and in a higher percentage of the older men while they were in bed. 10
Differential Diagnosis
The problem of acute myocardial infarction in the very young group has been reviewed by Bristow and colleagues1• in presenting a case of a 15-year-old boy who survived an acute myocardial infarction due to coronary atherosclerosis proved by coronary arteriograms. In excluding causes of coronary disease in children, they felt that idiopathic coronary artery calcification with fibroblastic intimal proliferation, a reported cause of myocardial necrosis in small children17•11 was quite unlikely in view of this patient's age. Anomalous origin of the left coronary artery from the pulmonary artery rarely permits survival to the age of 15.10 Coronary arteritis can produce arterial occlusion through aneurysm formation and thrombosis. Polyarteritis nodosa will produce this sequence and according to Strykee' can be limited to the coronary arteries. Since this patient had survived for over a year since his acute attack, remaining entirely free of symptoms of inflammatory disease, polyarteritis was unlikely. Rheumatic fever has been described as the cause of coronary arteritis although rarely, if ever, myocardial infarction• as have other causes of inflammatory arterial disease such as bacterial endocarditis and tuberculosis. Likoff'1 and ~iates presented six cases of white men 16-24 years of age with electrocardiographic evidence of myocardial infarction, but with no other stigmata of coronary disease. Each had low intensity
143
ejection-type systolic murmur best heard in the thir.d_left_ iJltercostal space at the sternal border. in three patients the murmur was of equal intensity at the apex. He felt that they represented an obscure congenital defect that has not previously been recorded. All had normal arteriograms. The possibility remained that non coronary myocardial disease was present with each of these patients. The conclusion was not supported by past or present evidence of infections, collagen disease, amyloidosis, hemochromatosis, sarcoidosis, muscular dystrophy, or metabolic abnormality. It was a simple matter to reason that electrocardiographic changes stemmed from healed myocarditis. Confmnation of this diagnosis and that of fibroelastosis or endomyocardial fibrosis actually is unwarranted without tissue studies. They concluded that for the present the primary obligations of their communication was to acknowledge that the electrocardiographic pattern of myocardial ischemia, injury, or necrosis may appear in asymptomatic young adult men who have low intensity systolic murmurs, to record that any implication that these electrical deviations resulted from obstructive coronary disease cannot be substantiated by coronary arteriography, and to suggest that individuals possessing these diagnostic features may represent a distinct, recognizable clinical entity, the etiology of which remains obscure. THE YouNG WoMAN
The problem of the young woman with coronary disease bears some specific discussion as noted earlier in this communication. In the Norfolk series, eight women, four white and four Negro, were presented. There was a 50 per cent mortality in the white and 100 per cent (instant) mortality in the Negro group. This appears to be one of the largest series of myocardial infarction in this young age group among women noted in the medical literature at this time. In a recent review of the literature, Thomas and Cohen11 found it generally accepted that myocardial infarction may
ARTHUR S. KAPLAN
occur in a few young men under the age of 40, but is extremely rare among young 11 women of this age. Zinn and Crosby, in his series of 679 cases of necropsy proved infarction, recorded only two cases in women under 34 years of age. In another series of 345 casesu of acute infarction in women studied over ten years, only 9 per cent of the entire group ( 36 patients) were in the fifth decade, including ten patients under the age of 46, but not a single case under the age of 41. Of these 36 patients, 32 had a negative diabetic history; history was not available in four; 19 had hypertension (51 per cent) ; six had hypertension and obesity; 14 had a negative hypertensive history; 13 still had regular menses ( 36 per cent) ; menopause had occurred in eight; hysterectomies had been performed in six; and there was no menstrual history in 15 cases. Cochran and Gwinup," writing on coronary artery disease in the young woman, stated that young women without attendant diabetes, hypertension, or hyperlipemia a remarkable freeinducing states po~ess dom from the disease until the menopausal age, at which time the incidence of the disorder becomes nearly equal to that of men of comparable age. He presented 29 cases with medical history of surgical castration in 45 per cent of these. This history was present in more of these than was either hypertension ( 41 per cent) or diabetes ( 39 per cent). Accordingly he suggested that if sacrifice of ovaries is necessary, the administration of estrogens until age 50, or thereabouts, would appear indicated on the basis of present evidence. Cochran and Gwinup's series had only four cases under the age of 35. The first patient was age 33, a white woman, without hypertension or diabetes, with cholesterol 265 mg/ 100 ml, and was premenopausal; the second, age 33, a white woman, was hypertensive, non diabetic, and had a cholesterol of 240 mg/100 ml, with a previous unilateral oophorectomy eight years before, but was premenopausal; the third, a 32-year-old white woman, had hypertension and
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diabetes, cholesterol 280 mg/ 100 ml, and was premenopausal; the last, a 26-yearold white woman, was premenopausal, but has disseminated lupus erythematosus with coronary arteritis. In a specific study of myocardial infarction in women, Weinreb and collaborators" reviewed the rna jor clinical features in 231 women with proved myocardial infarction. The group as a whole showed increased frequency of diastolic hypertension ( 51.5 per cent), diabetes mellitus ( 52.6 per cent), and elevated serum cholesterol ( 44.8 per cent). A positive family history of diabetes, hypertension, or coronary artery disease was present in more than twothirds of the patients. A strikingly poor prognosis was noted among the women with diabetes compared to the non diabetics. Of 156 patients about whom information was available, 13.5 per cent had neither diabetes nor hypertension; of the 23 women in this group under the age of 50, 26.1 per cent had neither disease. Only two women, both under 50 years of age at the time of the fli'St myocardial infarction, did not have diabetes, hypertension, hypercholesterolemia, or a positive family history. Coronary artery disease must be seriously considered in women presenting a suggested clinical picture, particularly in the younger age group, despite the absence of hypertension or diabetes mellitus. They note that almost all report~ on coronary disease in women emphasize a history of diabetes or hypertension as important predisposing factors. Of his group of 231 cases, five ( 2.3 per cent) were ages 3039. Menstrual history revealed that 9 per cent of the cases with available history were still menstruating at the time of the first infarct; 72.6 per cent had had natural menopause; 6.5 per cent had had bilateral oophorectomy; and 10.7 per cent had had hysterectomy. Wuest and co-workers11 in a study of 160 necropsies of oophorectomized women at the Mayo Clinic noted more severe atherosclerosis in the hearts of 61 per cent of 49 bilaterally oophorectomized women
VniUOlC H. No.2 Frilruuy. 1967
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than in the hearts of normal women of the same ages. There was no significant increa~ in intimal change until five years had elapsed after operation. Within the first five years, apparently, the findings were very little different from control women. After five years, however, the degree of coronary atherosclerosis in oophorectomized women approached very nearly that found in men of the same age range. Only 6 per cent of such women, however, had clinical evidence of coronary artery disease. The Negro Women In view of the 100 per cent instant mortality in the four cases of myocardial infarction in young Negro women in the Norfolk series, the problem in this group certainly deserves special consideration. Keil and and Me Vay" stated that no previous investigation into the etiology of coroand its occurrence in nary artery di~iease women had considered the Negro race separately. In reviewing 519 cases of proved myocardial infarction in all ages in a hospital where 70 per cent of the hospital admissions were Negro and 30 per cent white, they concluded that the classic sex predominance of myocardial infarction in men was not present in Negroes where they found a ratio of approximately 1 : 1, (comparing almost exactly to the Norfolk series), as compared to a 3: 1 ratio in whites. In general, infarction in their group occurred more than ten years earlier on the average in Negro women than in white women. They found only four white women with infarction prior to the 50th year of life, whereas 43 Negro women had been afflicted by the end of the fifth decade. It is of note that their series contained no white patients in the third decade and only one Negro man and one Negro woman. In the fourth decade, they noted five white men, no women, eight Negro men, and seven women of age not further broken down within the fourth decade. They felt that it was apparent that the Negro woman wali striken at a significantly earlier age than any of the other groups,
white man or woman, or Negro man. The mortality rate was a startling deviation from the classic description of myocardial infarction in women and they concluded that it would appear that coronary atherosclerosis is a different disease in the Negro woman as compared with that described in the literature, and this would certainly be borne out by the Norfolk series study. SUMMARY
A series of 59 cases of clinically proved myocardial infarction in patients 35 years of age and under has been presented and the literature on the subject of myocardial infarction in patients under the age of 40 reviewed. The group consisted of 46 white men of whom 12 (26 per cent) died; four white women of whom two (50 per cent) died; five Negro men of whom four (80 per cent) died; and four Negro women of whom four ( 100 per cent) died. Hypertension was noted in 34 per cent of the cases. Diabetes mellitus was noted in 18 per cent, and obesity was a factor in 27 per cent of the cases. Elevated serum cholesterol (above 250 mg/ 100 m1) was noted in 84 per cent of the cases with a range of 191 to 460 mg/ 100 ml, or an average of 297 mg/1 00 ml. Necropsy in 17 ( 77 per cent) of the 22 deaths revealed a predominant involvement in the left anterior descending coronary artery. Electrocardiographic infarction pattern was found to be as frequently anterior as posterior in distribution with lateral extention about half as frequent. There is no question that myocardial infarction is a more severe and devastating disease in the overall younger age groups than in the older age groups, the current study having shown a 24 per cent instant mortality. The mortality in white women is higher than that of white men, although the incidence of the disease is less. The incidence of the disease in the Negro is almost equal in men and women, but the mortality rate in the Negro, particularly women, approaches 100 per cent.
Disuses of
ARTHUR S. KAPLAN RESUMEN
Este trabajo consiste en Ia presentaci6n de 50 casos de infano cardiaco cllnicamente probados en sujetos menores de 35 anos y revision de Ia literatura sobre infarto del miocardia en individuos menores de 40 anos. El grupo consiste en 46 hombres de Ia raza blanca, de los que 12 ( 26 por ciento) fallecieron, cuatro mujeres blancas, de las que 2 (50 por ciento) murieron, 5 hombres de raza negra de los que 4 (80 por ciento) sucumbieron y 4 mujeres negras; de las que ( 4 por ciento) fallecieron. En 34% de los casos se comprob6 hipertensi6n, diabetes mellitus en 18% y obesidad como factor en 27%. La elevaci6n del colesterol sangufneo (sobre 250 mgm por den mi.) fut> comprobada en el 84%, con niveles variables entre 191 a 460 mgm por cien mililitros. La autopsia, practicada en 17 ( 77 por ciento) de las 22 muenes, revel6 una panicipaci6n predominante de Ia A. coronaria descendente anterior. Los trazados ECG indicativos de infano fueron de distribuci6n anterior o posterior con igual frecuencia, con extension lateral aproximadamente en Ia mitad de los casos. No cabe duda que el infano del miocardia es mas grave y devastador entre el grupo joven que entre los de mayor edad, observ.indose en el presente estudio una mortalidad inmediata de un 50%. La monalidad entre las mujeres blancas es mayor que entre los hombres blancos, si bien Ia jncidencia de Ia afecci6n es menor. La incidencia entre los de raza negra es igual en ambos sexos, aunque Ia mortalidad en esta raza particulannente entre las mujeres se aproxima al 100%. REsuME
d'une serie de 59 cas d'infarctus myocardiques cliniquement trouves chez des rnalades ayant 35 ans et au-dessous; et revue de Ia litterature sur le sujet de l'infarctus du myocarde chez les sujets au-dessous de 40 ans. Le groupe consistait en 46 hommes blancs dont 12 ( 26 pour cent ont succomb); 4 femmes blanches. dont 2 (50 pour cent) sont mones; 5 hommes noirs dont 4 (80 pour cente son mons; et 4 femmes noires, doot 4 ( 100 pour cent) ont succombee. L'hypertension a ete notee dans 34 pour cent des cas. Le diabete sucre dans 18 pour cent, et l'obesite jouait un role dans 27 pour cent des cas. Une elevation du cholesterol dans le serum ( au-dessus de 250 mg/ 100 mi.) a ete note dans 84 pour cent des cas, avec des chiffres extremes de 191 a 460 mg/ 100 ml, ou une moyenne de 297 mg. P~ntation
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L'autopsie ches 17 (77 pour cent} des 22 cas monals a montre une atteinte predominante de l'anere interventriculaire anterieure. Le type electrocardiographique d'infarctus etait aussi souvent anterieur que posterieur dans sa distribution, avec une extension laterale environ dans Ia moitie des cas. II n'y a pas de doute que l'infarctus du myocarde est une maladie plus severe et mutilante dans le groupe d'age jeune que dans les groupes d'age plus age, l'etude presente ayant montre une monalite precoce de 24 pour cent. La mortalite chez les femmes blanches est plus fone que ceUe des hommes blancs, quoique Ia frequence de Ia maladie soit moindre. La frequence de Ia maladie chez les noirs est a penu pres equivalente chez les hommes et les femmes, mais le taux de mortalite chez le noir, particulierement dans le sexe feminin, approche 100 pour cent. ZusAMMENFASSUNG
Bericht tiber eine Reihe von 59 Fallen klinisch bestiitigten Herzinfarktes bei Patienten im Alter von 35 Jahren und weniger mit Literaturiibersicht iiber die Berichte einer solchen Erkrankung bei Patienten von weniger als 40 Jahren. Die Gruppe hestand als 46 WeiPen mannlichen Geschlechtes, von denen 12 ( 26%) starben, 4 weiPen Frauen, von denen 2 (50%) starben 5 mannlichen Negern, von denen 4 (80%) starben und 4 weiblichen Negem, von denen 4 ( 100%) starben. Eine Hypertension wurde bei 34% der Faile festgestelh. Ein Diabetes mellitus wurde bei 18% beobachtet, und Fettsucht war ein begleitender Faktor bei 27% der Faile. Erhohtes Serum Cholesterin (mehr als 200 mg/100 ml) wurde bei 84% der Faile beobachtet mit einer Schwankungsbreite von 191-460 mg/ I00 mi. bei einem Durchschnittswen von 297 mg/100 mi. Die Sektion von 17 ( 77%) der 22 Todesfalle ergab einen iiberwiegenden Befall der linken vorderen absteigenden Coronar-arterie. Elektrokardiographische Infarktzeichen wurden ebenso haufig im vorderen wie im riickwanigen Anteil gefunden, bei einer lateralen Beteiligung in ungefahr der halben Haufigkeit. Es ist keine Frage, daP der Myocardinfarkt eine schwerere und verheerendere Erkrankung bei der insgesamt jiingeren Ahersgruppe ist als bei der aheren Ahersgruppe, wobei die vorliegende Untersuchung eine Mortalitatsziffer zeigt von 24%. Die Sterblichkeit bei weiPen Frauen ist hoher als bei weiPen Mannern, obwohl deren Kranheitshaufigkeit niedriger liegt. Das Vorkommen des Herzinfarktes bei den Negem ist ungefahr gleich haufig bei Mannem wie bei den Frauen, jedoch erreicht die Mortalitat bei dieser Rasse-insbesondere beim weiblichen Geschlecht -100%.
Volu~ 51, No.2 February, 1967
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REFERENCES NoRFOLK ( V a.) Chamber of Commerce Sta.tistical Digest, 1963. SMITH, H. L. AND BARTLES, E. C.: "Coronary thrombosis with myocardial infarction and hypertrophy in young persons," ]AMA, 98: 1072, 1932. YATER, w. M., TRAUM, A. H., BROWN, w. G., FITZGERALD, R. P., GEISLER, M. A., WILCOS, B. B. : "Coronary artery disease in men 18 to 39 yean of age," A mer. Heart ]., 36:334, 481, 683, 1948. BAKER, M. R. AND ScHILLHAMMER, w. R., jR.: "Myocardial infarction in young adults," U. S. Armed Forces Medical ]., 11:75, 1951. FRIEDBERG, C. K.: Diseases of the Heart, 2nd Ed., W. B. Saunden Co., Philadelphia, 1956. WRIGHT, H. B.: "Atherosclerosis and coronary heart disease," Lancet, II: 980, 1960. AcHESON, R. M.: "Atherosclerosis and coronary heart disease," lAncet II. 706, 1960. CRAWFORD, T., DEXTER, D. AND TEARE, R. D.: "Coronary artery pathology in sudden death from myocardial ischaemia. A comparison by age groups," Lancet I: 181, 1961. MoLL, A. AND HAMACHER, F.: Der herzinfarkt in juengeren lebensalter, beitraege zur praktischen medizin, No. 44, F. Enke Verlag, Stuttgart, 1962. YATER, w. M., WELSH, P. P., STAPLETON, J. F. AND CLARK, M. L.: "Comparison of clinical and pathologic aspects of coronary artery disease in men of various age groups," a study of 950 autopsied cases from the Armed Forces Institute of Pathology. Ann. Intern. M ed. 34: 352, 1951. ZINN, W. J., AND CROSBY, R. S.: "Myocardial infarction, statistical analysis of 679 autopsy-proven cases," Amer. ]. Med., 8:169, 1950. CouNTRY, J. C.: '"Myocardial infarction in young men," U.S. Armed Forces Med. J. 5: 688, 1954. NEWMAN, M.: "Coronary occlusion in young adults," Lancet II: 409, 1946. DuNCAN, G. G.: Diseases of Metabolism, 5th Ed., W. B. Saunden Co., Philadelphia, 1964, p. 949, 1030. ORVIS, H. H., TsoHAs, R. E., FAWAL, I. A. AND EVANS, J. M.: "Serum cholesterol in normal males versus males with coronary heart
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disease, difference with respect to age," Am. ]. M. Sc. 241: 167, 1961. BRisTow, J. D., Don-n, C. T., GRiswoLD, H. E. AND KAssEBAUM, D. G.: "Myocardial infarction in a fifteen year old boy," Am. J. Med., 30:961, 1961. STRYKER, W. A.: "Coronary occlusive disease in infants and in children," J. Dis. Child. 71: 280, 1946. COCHRAI'Ii"E, w. A. AND BoWDEN, D. H.: "Calcification of the arteries in infancy and childhood," Pediatrics 14: 222, 1954. TRAISMAN, H. s., LIHPERIS, N. M. TRAISJUN, A. S.: "Myocardial infarction due to calcification of the arteries in an infant," J. Dis. Child. 91:34, 1956. CoHEN, H. AND SIEw, S.: "Aberrant left coronary artery, report of a case and review of the literature," Circulation 20:918, 1959. LJKOFF, W., SEGAL, B. AND DREIFUS, L.: "Myocardial infarction patterns in young subjects with normal coronary arteriograms," Circulation 26:373, 1962. THOMAS, C. B. AND CoHEN, B. H.: "The familial occurrence of hypertension and coronary artery disease with observations concering obesity and diabetes," Ann. Int. Med. 42: 90, 1955. BLACKMAN, N. S. AND KoLOOLU, Y.: "Acute myocardial infarction in women under fifty yean of age," New York J. M ed. 61 : 3079. 1961. CocHRAN, R. AND GWINUP G.: "Coronary artery disease in young females,'' Arch. Int. Med., 110:162, 1962. WuEsT, J. H., DaY, T. J. AND EDWARDS, J. E.: "The degree of coronary atherosclerosis in bilaterally oophorectomized women," Circulation 7:801, 1953. WEINREB, H. L., GERMAN, E., AND RosENBERG, B.: "A study of myocardial infarction in women," Ann. Intern. Med. 46:285, 1957. KEIL, P. G., AND McVAY, L. V., Ja.: "A comparative study of myocardial infarction in the white and negro races," Circulation 13: 712, 1956. Jo~.:L, E. AND GREENSTEIN, M. D.: "Total coronary sclerosis in a boy of ten yean," Lancet, II :659, 1944.
For reprints, please write: Dr. Kaplan, 803 Medical Tower, Norfolk.
MISSILES IN HEART The after-histories of 40 soldiers of World War II with missiles In the heart were recorded. The record Is complete In every case, and all the veterans have survived. Pericarditis was a common accompaniment of the Injury, and an etruslon of considerable degree (sometimes delayed) OttUrred In 25 per cent. Electrocardiograms were helpful In the acute phase and often called attention for the flrst time to the cardiac Injury. In all but 2 cases the tracIngs have returned to a normal pattern. The size of the heart on x-ray examination ls now normal In all except the soldier with aorticvalve InJury. Elective removal of the missile was later attempted In 8 patients. It was successful In 3 but was abandoned In 5. 2 of whom the foreign body could not now be found.
A delayed complication of major importance occurred In a soldier In whom the shell fragment lodged ftrst In the left pulmonary artery, subsequently shifted to the right and 15 years later eroded Into and obstructed a bronchus. necessitatIng pneumonectomy (Burford's case). The subsequent course of the remainder of these veterans has been benign except for the formidable psychologic strain of living with a mlsslle In the heart. All are genuinely concerned about the missile, and 5 are totally Incapacitated by an anxiety neurosis. Subsequent migration. erosion or Infection occurs Infrequently once the foreign body Is flxed ln the myocardium. These complications have not appeared In the 20 years covered by this study.
E. F. AND BE.EBI!, G. W.: "Missiles in the heart" Ntw Engl. }. M,J., 274: 1046, 1966.
BLAND,