J Chron Dis Vol. 31, pp. 313-319 0 Pergamon Press Ltd. 1978. Printed
0021-9681/78/0501-03f3802.00/0 in Great
Britain
CLINICOPATHOLOGICAL CORONARY FROM
STUDY
ARTERIES
THE COMMUNITY PERIOD-I.
OF THE
HEART
OF AUTOPSIED
OF HISAYAMA
ISCHEMIC
MYOCARDIAL
AND
CASES
DURING
A 10YR
LESIONS
YUICHI HIYOSHI,* TERUO OMAE, YASUO HIROTA,? MORIYUKI TAKESHITA, KAZUO UEDA and SHIBANOSUKE KATSUKI’C Second
Department
of Internal Medicine, Faculty of Medicine, Kyushu Maidashi 3-l-1, Higashiku, Fukuoka 812, Japan
University,
and KENZO First
and Second
TANAKA
and MUNETOMO
ENJOJI
Departments of Pathology, Faculty of Medicine, Kyushu Maidashi 3-l-1, Higashiku, Fukuoka 812, Japan (Received in revised
University,
form 26 July 1977)
Abstract-A clinicopathological study of myocardial infarction was m,ade in a Japanese community with autopsy rate of approximately 82% during 1Oyr (from 1 November 1961 to 31 October 1971). Myocardial infarct (1 cm or more in 1 dimension) was found in 12.4 and 10.8% of 193 males and 167 females, aged 20 yr or over, respectively. Frequency of myocardial infarct among the autopsied cases remained almost constant in the 6th through 9th decade of life in both sexes. Approximately one half of the larger infarcts (5 cm or more in 1 dimension) and all of the smaller infarcts were found initially by postmortem examination. Unequivocal cardiac pain was found in one half of the patients with larger infarcts. Approximately one fourth of the larger infarcts and more than one half of the smaller infarcts were asymptomatic. This emphasizes the importance of close follow-up of cohorts in the epidemiological study of coronary heart disease.
INTRODUCTION
Ischemic myocardial lesions, especially myocardial infarction, are one of the most important problems of epidemiological as well as pathological study. The term “myocardial infarction” implies ischemic myocardial necrosis due to coronary occlusion. Evidence and opinions regarding the pathogenesis of coronary thrombosis and myocardial infarction, however, are conflicting. It is well known that hospital autopsy series are biased by many antemortem and postmortem selection factors. Epidemiological study might not reveal the true incidence of myocardial infarction in any population, because there are surprisingly common unrecognized myocardial infarctions [ 1,2]. This study intends to present the frequency of ischemic myocardial lesions among the autopsied cases in a Japanese community with high autopsy rate and accuracy of diagnosis of myocardial infarction in field survey. This work was supported in part by U.S.A. Public Health Service Grant, NB-03642 from the National Institute of Neurological Diseases and Blindness. Address for reprints: Teruo Omae, MD, Second Department of Internal Medicine, Faculty of Medicine, Kyushu University, Maidashi 3-l-1, Higashiku, Fukuoka 812, Japan. *Present address: First Department of Internal Medicine, School of Medicine, Fukuoka University, Nanakuma 34, Nishiku, Fukuoka 814, Japan. tPresent address: Department of Internal Medicine, Kyushu Dental College, Kitakyushu, Japan. fPresent address: Medical College of Miyazaki, Miyazaki, Japan. 313
YUICHI HIYOSHI et al.
314
MATERIALS
AND
METHODS
Epidemiological study on cerebrovascular diseases in Hisayama town started November 1 1961. This is a farming community adjoining Fukuoka city, Kyushu island, Japan. The population in this community by national census was 6521 in 1960, 7140 in 1965, and 7154 in 1970. Residents, aged 40 yr or over, comprised 27.6, 30.0 and 33.2% of the whole population, respectively. Population distribution by age and sex in this community was not substantially different from that of all Japan (Fig. 1). Residents, aged 40yr or over, underwent biennial and interposed annual medical examinations including electrocardiograms. Efforts were made to obtain autopsy on all of the dead in this community. The autopsy rate rose sharply in the first 2yr of the study, and exceeded 80% in the 3rd yr. Excluding those under 20 yr of age, the mean autopsy rate was approximately 82% during the first lOyr, from 1 November 1961 to 31 October 1971. This figure is high enough when compared with the autopsy rate among deaths in the hospitals of medical schools and of medical colleges in Japan in 1971 (n 50, median 51.8x, range 15.3-92.8x) [3]. Table 1 presents age and sex distribution of autopsied cases by 10 yr age groups. All of them were Japanese. After fixation in 10% formalin, the extramural coronary arteries were cut in situ transversely at 2-3 mm intervals. Sites of stenosis, gross visual estimate of luminal stenosis, and presence or absence of thrombus, intimal hemorrhage and calcification were recorded on a diagram. At least one most narrowed segment of each major coronary artery was removed, dehydrated, cleaned, imbedded in paraffin and cut. The myocardium was sectioned transversely from the apex to the atrioventricular groove. The slices of approximately 1 cm in thickness were examined, and gross findings were recorded on diagrams. Histologic sections were prepared from at least one of the slices containing papillary muscles. Sections were stained with hematoxylin and eosin, PAS, and elasticaVan Gieson methods. Occasional sections were stained with Mallory-Heidenhain method. AGE
(WE.)
NALE
FEMALE
1960 CNNSUS ALL JAPAN
1,000
0
0
1,m
AGE (Yrs.)
so-
i
lz$$ .,dg 1970 CENSUS 1,000
20-29 30-39 40-49 50-59 60-69 70-79 10-19 0- 9
0
0
l.ooO
per 10,000 Population
FIG. 1. Population
distribution
by age and sex. Comparison
between Hisayama
and all Japan.
Ischemic TABLE
1. AGE
AND
Myocardial
Lesions
Men Women Total
20-29 1 2 3
10 YR AGE
SEX DISTRIBUTION OF AUTOPSIED CASES BY GROUPS Age groups,
Sex
315
3G-39 40-49 11 7 18
13 8 21
5&59
60-69
yr 70-79
80-89
90-99
Total
20 18 38
54 28 82
64 55 119
23 41 64
7 8 I5
193 167 360
As gross visual estimation of luminal stenosis is subject to considerable inter- and intra-observer variations, assessment was made on histologic sections using a micrometer, and degree of luminal stenosis was given as relative stenosis to the diameter composed of internal elastic lamina. Distinction between organized thrombus and atherosclerotic plaque is difficult and arbitrary. In this paper, an occluded or severely stenosed segment of the coronary artery passed through by several channels was considered organized and recanalized thrombus. Myocardial infarct was defined as a zone of necrosis or scarring at least 1 cm in the greatest dimension. Larger myocardial infarct was defined as the infarct of 5 cm or more in one dimension and smaller one as the lesion less than 5 cm in the greatest dimension. Subendocardial infarct was defined as the lesion limited to the inner one half of the ventricular wall. Transmural infarct was defined as the lesion which involved more than one half of the ventricular wall. Histological age of the lesion was determined, using the criteria described by Mallory et al. [4]. Lesions, the age of which was 4 weeks or less, were considered acute. Grossly visible lesion less than 1 cm in the greatest dimension was called small lesion. RESULTS
There were 42 cases of myocardial infarct (24 men and 18 women) (Table 2). Relative frequency of cases of myocardial infarct among the autopsied cases was 0, 11.5, 8.0, 10.3, 11.4, 14.6, 8.9, 13.3, 21.1, and 6.7% in the lst, 2nd, 3rd, 4th, 5th, 6th, 7th, 8th, 9th, and 10th yr, respectively. Significant increase in frequency of myocardial infarct in recent years was not observed. Figure 2 diagrammatically illustrates the distribution of cases with myocardial infarct, those with small lesion and those with microscopic foci of necrosis or scarring by sex and 10 yr age groups. The youngest case with myocardial infarct was a man of 30yr. Relative frequency of myocardial infarct among cases, aged 20 or over, was slightly higher in males (mean 12.4%) than in females (mean 10.8%) and remained almost constant in the 6th through 9th decade of life in both sexes. Table 3 gives the details of age of cases, and size, type and histological age of infarcts. Cases where myocardial infarct was probably caused by coronary embolism and where it was caused by dissecting aneurysm of the ascending aorta (one case each) were eliminated from this Table. One man had a large right ventricular infarct due to the right TABLE 2. DISTRIBUTION OF CASES OF MYOCARDIAL SEX
INFARCTION BY AGE AND
Age groups,
Sex Men Women Total
2&29
3C39
40-49
1 1
1 1
50-59 3 2* 5
yr 6tk-69 7G79 7 3 10
9 6 15
8(f89 3 6t 9
90-99 1 1
Total 24 18 42
*Myocardial infarct in one case was probably due to severe compression to the main stem of the left coronary artery by dissecting aneurysm of the ascending aorta. tMyocardial infarct in one case with bacterial endocarditis was probably due to emboli in intramural coronary branches.
YUICHI HIYOSHI et al.
316 M 11931
Aae
F
(167)
-1 “’
23
‘.‘.’
64 54
“’
‘,
..',.. : .. .: ., ., :.I. : ..: :1.:.: ',;,. :.:.. '.'. ::.
I
6%
50
100 -
M’
I
0
50 m
St
100%
,,“F
FIG. 2. Distribution of cases with ischemic myocardial lesions by age and sex. Figure in the column indicates number of autopsied cases. M = male; F = female; MI = myocardial infarct (a zone of myocardial necrosis of scarring 1 cm or more in one dimension); SL = small lesion (a zone of myocardial necrosis or scarring less than 1 cm in the maximum dimension); MF = microscopical foci of myocardial necrosis or scarring.
coronary artery thrombosis. Old infarct was more frequent in larger subendocardial as well as transmural categories. Clinical diagnosis presented to pathologist at autopsy is summarized in Table 4. All of the smaller infarcts and about one half of the larger infarcts had not been recognized until postmortem examination. Larger transmural infarcts were more likely to be unrecognized than larger subendocardial ones. A plausible explanation for this finding is the longer survival period of the latter indicated by histological age. Type and size of the lesion, and symptoms or signs of the 40 cases are summarized in Table 5. Unequivocal cardiac pain was recognized in only one half of the patients TABLE 3. DISTRIBUTIONOF TYPES,SIZE AND AGE OF INFARCTSBY 10 YR AGE GROUPS
Age groups, yr 2G29 30-39 40-49 50-59 6&69 lo-19 80-89 9G99 Total
Subendocardial Old Acute
0021-9681/78/0501-03f3802.00/0 in Great
Britain
CLINICOPATHOLOGICAL CORONARY FROM
STUDY
ARTERIES
THE COMMUNITY PERIOD-I.
OF THE
HEART
OF AUTOPSIED
OF HISAYAMA
ISCHEMIC
MYOCARDIAL
AND
CASES
DURING
A 10YR
LESIONS
YUICHI HIYOSHI,* TERUO OMAE, YASUO HIROTA,? MORIYUKI TAKESHITA, KAZUO UEDA and SHIBANOSUKE KATSUKI’C Second
Department
of Internal Medicine, Faculty of Medicine, Kyushu Maidashi 3-l-1, Higashiku, Fukuoka 812, Japan
University,
and KENZO First
and Second
TANAKA
and MUNETOMO
ENJOJI
Departments of Pathology, Faculty of Medicine, Kyushu Maidashi 3-l-1, Higashiku, Fukuoka 812, Japan (Received in revised
University,
form 26 July 1977)
Abstract-A clinicopathological study of myocardial infarction was m,ade in a Japanese community with autopsy rate of approximately 82% during 1Oyr (from 1 November 1961 to 31 October 1971). Myocardial infarct (1 cm or more in 1 dimension) was found in 12.4 and 10.8% of 193 males and 167 females, aged 20 yr or over, respectively. Frequency of myocardial infarct among the autopsied cases remained almost constant in the 6th through 9th decade of life in both sexes. Approximately one half of the larger infarcts (5 cm or more in 1 dimension) and all of the smaller infarcts were found initially by postmortem examination. Unequivocal cardiac pain was found in one half of the patients with larger infarcts. Approximately one fourth of the larger infarcts and more than one half of the smaller infarcts were asymptomatic. This emphasizes the importance of close follow-up of cohorts in the epidemiological study of coronary heart disease.
INTRODUCTION
Ischemic myocardial lesions, especially myocardial infarction, are one of the most important problems of epidemiological as well as pathological study. The term “myocardial infarction” implies ischemic myocardial necrosis due to coronary occlusion. Evidence and opinions regarding the pathogenesis of coronary thrombosis and myocardial infarction, however, are conflicting. It is well known that hospital autopsy series are biased by many antemortem and postmortem selection factors. Epidemiological study might not reveal the true incidence of myocardial infarction in any population, because there are surprisingly common unrecognized myocardial infarctions [ 1,2]. This study intends to present the frequency of ischemic myocardial lesions among the autopsied cases in a Japanese community with high autopsy rate and accuracy of diagnosis of myocardial infarction in field survey. This work was supported in part by U.S.A. Public Health Service Grant, NB-03642 from the National Institute of Neurological Diseases and Blindness. Address for reprints: Teruo Omae, MD, Second Department of Internal Medicine, Faculty of Medicine, Kyushu University, Maidashi 3-l-1, Higashiku, Fukuoka 812, Japan. *Present address: First Department of Internal Medicine, School of Medicine, Fukuoka University, Nanakuma 34, Nishiku, Fukuoka 814, Japan. tPresent address: Department of Internal Medicine, Kyushu Dental College, Kitakyushu, Japan. fPresent address: Medical College of Miyazaki, Miyazaki, Japan. 313
YUICHI HIYOSHI et al.
314
MATERIALS
AND
METHODS
Epidemiological study on cerebrovascular diseases in Hisayama town started November 1 1961. This is a farming community adjoining Fukuoka city, Kyushu island, Japan. The population in this community by national census was 6521 in 1960, 7140 in 1965, and 7154 in 1970. Residents, aged 40 yr or over, comprised 27.6, 30.0 and 33.2% of the whole population, respectively. Population distribution by age and sex in this community was not substantially different from that of all Japan (Fig. 1). Residents, aged 40yr or over, underwent biennial and interposed annual medical examinations including electrocardiograms. Efforts were made to obtain autopsy on all of the dead in this community. The autopsy rate rose sharply in the first 2yr of the study, and exceeded 80% in the 3rd yr. Excluding those under 20 yr of age, the mean autopsy rate was approximately 82% during the first lOyr, from 1 November 1961 to 31 October 1971. This figure is high enough when compared with the autopsy rate among deaths in the hospitals of medical schools and of medical colleges in Japan in 1971 (n 50, median 51.8x, range 15.3-92.8x) [3]. Table 1 presents age and sex distribution of autopsied cases by 10 yr age groups. All of them were Japanese. After fixation in 10% formalin, the extramural coronary arteries were cut in situ transversely at 2-3 mm intervals. Sites of stenosis, gross visual estimate of luminal stenosis, and presence or absence of thrombus, intimal hemorrhage and calcification were recorded on a diagram. At least one most narrowed segment of each major coronary artery was removed, dehydrated, cleaned, imbedded in paraffin and cut. The myocardium was sectioned transversely from the apex to the atrioventricular groove. The slices of approximately 1 cm in thickness were examined, and gross findings were recorded on diagrams. Histologic sections were prepared from at least one of the slices containing papillary muscles. Sections were stained with hematoxylin and eosin, PAS, and elasticaVan Gieson methods. Occasional sections were stained with Mallory-Heidenhain method. AGE
(WE.)
NALE
FEMALE
1960 CNNSUS ALL JAPAN
1,000
0
0
1,m
AGE (Yrs.)
so-
i
lz$$ .,dg 1970 CENSUS 1,000
20-29 30-39 40-49 50-59 60-69 70-79 10-19 0- 9
0
0
l.ooO
per 10,000 Population
FIG. 1. Population
distribution
by age and sex. Comparison
between Hisayama
and all Japan.
Ischemic TABLE
1. AGE
AND
Myocardial
Lesions
Men Women Total
20-29 1 2 3
10 YR AGE
SEX DISTRIBUTION OF AUTOPSIED CASES BY GROUPS Age groups,
Sex
315
3G-39 40-49 11 7 18
13 8 21
5&59
60-69
yr 70-79
80-89
90-99
Total
20 18 38
54 28 82
64 55 119
23 41 64
7 8 I5
193 167 360
As gross visual estimation of luminal stenosis is subject to considerable inter- and intra-observer variations, assessment was made on histologic sections using a micrometer, and degree of luminal stenosis was given as relative stenosis to the diameter composed of internal elastic lamina. Distinction between organized thrombus and atherosclerotic plaque is difficult and arbitrary. In this paper, an occluded or severely stenosed segment of the coronary artery passed through by several channels was considered organized and recanalized thrombus. Myocardial infarct was defined as a zone of necrosis or scarring at least 1 cm in the greatest dimension. Larger myocardial infarct was defined as the infarct of 5 cm or more in one dimension and smaller one as the lesion less than 5 cm in the greatest dimension. Subendocardial infarct was defined as the lesion limited to the inner one half of the ventricular wall. Transmural infarct was defined as the lesion which involved more than one half of the ventricular wall. Histological age of the lesion was determined, using the criteria described by Mallory et al. [4]. Lesions, the age of which was 4 weeks or less, were considered acute. Grossly visible lesion less than 1 cm in the greatest dimension was called small lesion. RESULTS
There were 42 cases of myocardial infarct (24 men and 18 women) (Table 2). Relative frequency of cases of myocardial infarct among the autopsied cases was 0, 11.5, 8.0, 10.3, 11.4, 14.6, 8.9, 13.3, 21.1, and 6.7% in the lst, 2nd, 3rd, 4th, 5th, 6th, 7th, 8th, 9th, and 10th yr, respectively. Significant increase in frequency of myocardial infarct in recent years was not observed. Figure 2 diagrammatically illustrates the distribution of cases with myocardial infarct, those with small lesion and those with microscopic foci of necrosis or scarring by sex and 10 yr age groups. The youngest case with myocardial infarct was a man of 30yr. Relative frequency of myocardial infarct among cases, aged 20 or over, was slightly higher in males (mean 12.4%) than in females (mean 10.8%) and remained almost constant in the 6th through 9th decade of life in both sexes. Table 3 gives the details of age of cases, and size, type and histological age of infarcts. Cases where myocardial infarct was probably caused by coronary embolism and where it was caused by dissecting aneurysm of the ascending aorta (one case each) were eliminated from this Table. One man had a large right ventricular infarct due to the right TABLE 2. DISTRIBUTION OF CASES OF MYOCARDIAL SEX
INFARCTION BY AGE AND
Age groups,
Sex Men Women Total
2&29
3C39
40-49
1 1
1 1
50-59 3 2* 5
yr 6tk-69 7G79 7 3 10
9 6 15
8(f89 3 6t 9
90-99 1 1
Total 24 18 42
*Myocardial infarct in one case was probably due to severe compression to the main stem of the left coronary artery by dissecting aneurysm of the ascending aorta. tMyocardial infarct in one case with bacterial endocarditis was probably due to emboli in intramural coronary branches.
YUICHI HIYOSHI et al.
316 M 11931
Aae
F
(167)
-1 “’
23
‘.‘.’
64 54
“’
‘,
..',.. : .. .: ., ., :.I. : ..: :1.:.: ',;,. :.:.. '.'. ::.
I
6%
50
100 -
M’
I
0
50 m
St
100%
,,“F
FIG. 2. Distribution of cases with ischemic myocardial lesions by age and sex. Figure in the column indicates number of autopsied cases. M = male; F = female; MI = myocardial infarct (a zone of myocardial necrosis of scarring 1 cm or more in one dimension); SL = small lesion (a zone of myocardial necrosis or scarring less than 1 cm in the maximum dimension); MF = microscopical foci of myocardial necrosis or scarring.
coronary artery thrombosis. Old infarct was more frequent in larger subendocardial as well as transmural categories. Clinical diagnosis presented to pathologist at autopsy is summarized in Table 4. All of the smaller infarcts and about one half of the larger infarcts had not been recognized until postmortem examination. Larger transmural infarcts were more likely to be unrecognized than larger subendocardial ones. A plausible explanation for this finding is the longer survival period of the latter indicated by histological age. Type and size of the lesion, and symptoms or signs of the 40 cases are summarized in Table 5. Unequivocal cardiac pain was recognized in only one half of the patients TABLE 3. DISTRIBUTIONOF TYPES,SIZE AND AGE OF INFARCTSBY 10 YR AGE GROUPS
Age groups, yr 2G29 30-39 40-49 50-59 6&69 lo-19 80-89 9G99 Total
Subendocardial Old Acute
