Chapter 14. Atherosclerosis of the aorta and coronary arteries in coronary heart disease

Chapter 14. Atherosclerosis of the aorta and coronary arteries in coronary heart disease A. M. VIHERT Aortic and coronary atherosclerosis and the prevalence of coronary stenosis and thrombosis were studied in subjects who had died offresh or recurrent myocardial infarction or had sufferedfrom myocardial infarction in the past. In general, severe atherosclerosis of the coronary arteries with stenosis and calcification was almost a prerequisite for the development of coronary heart disease. The frequency of coronary heart disease varied widely both in different countries and in different towns in the same country. Considerable variations were found among the various towns in the frequency of stenosis and thrombosis in those who had died of coronary heart disease. This finding indicates that although atherosclerosis is indeed a prerequisite for the development of myocardial infarction, other factors may play a significant role in its occurrence. The weight of the heart in persons (excluding hypertensives) with coronary stenosis or a first fresh myocardial infarction was considerably greater than that in the low atherosclerosis group. Coronary atherosclerosis is encountered as early as in the 15-19-year age-group (see Chapter 3). However, its severity must usually reach a high level before manifestations of disturbances in the cor- onary blood circulation appear and even more so before myocardial infarction develops. The purpose of this chapter is to elucidate the interrelationship between the severity of athero- sclerosis or its various manifestations on the one hand and myocardial infarction on the other, and to compare the frequency of myocardial lesions in the five towns. MATERIAL AND METHODS The aorta and the three main coronary arteries were collected during 5 years from about 7000 men and 6000 women who died from natural causes. The myocardium was scrutinized for fresh and old lesions. Table 42 shows the number of cases with myocardial lesions, by age and sex, and Table 43 shows the frequency of myocardial lesions as a proportion of non-violent deaths. There were a further 75 males and 19 females with myocardial infarction among the violent deaths. FREQUENCY OF MYOCARDIAL LESIONS On the basis of the findings indicated in Table 43, it may be concluded that from the beginning of the Table 42. Number of cases with myocardial lesions (all towns combined) by age and sex (violent deaths excluded) Age group Males Females 10-19 1 0 20-29 7 0 30-39 48 3 40-49 143 25 50-59 531 144 60-69 964 503 70-79 818 706 Total 2512 1381 third decade of life onwards coronary heart disease is a hazard of the male population, since, at this age 6% of all subjects who died natural deaths had died from, or had previously suffered from, myocardial infarction. This proportion increases with age. Myo- cardial infarction is now becoming a problem not only for the elderly but also for the young and middle-aged, since in the 30-39 age group the num- ber of men with atherosclerotic changes in the myocardium is twice that in the earlier decades of life and the various manifestations of coronary heart disease were found in about 15 % of men of this age BULL. WORLD HEALTH ORGAN., Vol. 53, 19763477 -585- A. M. VIHERT Table 43. Prevalence (%) of myocardial lesions (all towns combined) by age and sex (violent deaths excluded) mFresh Recurrent myoargel Al ye mycrilmyocardial moada ye Age group infarcion infarction scar only of lesion M F M F M F M F 10-19 0 0 0 0 2.0 0 2.0 0 20-29 0.9 0 0.9 0 4.3 0 6.0 0 30-39 5.2 0.5 4.0 1.0 5.5 0 14.8 1.5 40-49 8.1 1.7 6.9 1.1 8.1 2.6 23.1 5.4 50-59 7.3 4.3 8.7 3.5 16.0 6.1 32.0 13.9 60-69 6.7 6.7 10.4 6.1 20.9 10.7 37.9 23.5 70-79 7.1 8.3 9.3 7.6 26.1 16.9 42.6 32.9 Total 6.9 6.1 8.9 5.5 19.0 10.9 34.7 22.5 group. In the decade 40-49 this proportion rose to 23 %, and 7% died from recurrent myocardial infarc- tion. The prevalence of fresh myocardial infarction remained at roughly the same level (7-8%) only from the fifth decade of life onwards. The frequency of recurrent myocardial infarction as a cause of death increased gradually in the fifth, sixth, and seventh decades of life. From the sixth decade onwards 9-10% of all men dying of natural causes died of a recent myocardial infarction. Thus, in the five towns as a whole, fresh and recurrent myocardial infarction were the causes of death in 15-16% of cases from the fifth decade of life onwards. The frequency of myocardial infarction in men, however, was considerably greater than in women since it must be taken into account that a great number of men had previously had myocardial infarction, sometimes more than once, without dying of it, as is shown by the high percentage of men with large myocardial scar. In the seventh and eighth decades of life nearly 40% of men had some change or other connected with disturbances of the coronary blood circulation, i.e., two out of every five men either died of myo- cardial infarction or had suffered from it in the past. In women, none of these changes was encountered before the age of 30. In the fourth and fifth decades of life they were uncommon but nevertheless about 1.5% of these women who died of natural causes died of fresh or recurrent myocardial infarction and 1.8 % had a large myocardial scar. The frequency of fresh myocardial infarction in women attained the level of that in men only in the seventh decade of life and the frequency of recurrent myocardial infarction was much lower in women at all ages. In other words, myocardial infarction as a cause of death was recorded in women less frequently than in men. In all decades of life large myocardial scars were en- countered far less frequently in women than in men. Thus the problem is not as acute in women, but nevertheless manifestations of coronary heart disease were observed in more than one fifth of all female subjects (Table 43). There were considerable geographical differences in the frequency of myocardial infarction and large myocardial scar among men and women in the different towns (Table 44). Myocardial infarction was found significantly less often in men from Yalta than in men from the other towns and was also less frequent in men from Ryazan and Tallin than in those from Malmo. In women the findings were very similar. The frequency of myocardial infarction was higher in women from Malm6 and Prague than in those from Ryazan; the frequency in Yalta and Tallin occupied an intermediate position. On the other hand, it is interesting to note that large myocardial scar was observed with similar frequency in all towns except Ryazan, where it was found 3-4 times less often than elsewhere. Women differed slightly from this general rule in that large myocardial scar was most frequent in Yalta. These data show that coronary heart disease was observed much less frequently among men and women from Ryazan than among those from the other four towns. Yalta was the only town where the frequency of myocardial infarction was the same in men and women. AORTIC AND CORONARY LESIONS Coronary arteries The anatomical basis of coronary heart disease is severe coronary atherosclerosis. The intimal surface area occupied by raised lesions was twice as large in men and women who died from myocardial infarc- tion as in the low atherosclerosis group, larger than in the standardized average atherosclerosis group, and even significantly larger than in the high athero- sclerosis group. The biggest area of raised lesions in both sexes was found in cases with recent myocardial infarc- tion, whereas in cases with fresh myocardial infarc- 586 ATHEROSCLEROSIS IN CORONARY HEART DISEASE Table 44. Frequency (%) of fresh myocardial infarction (FMI), recurrent myocardial infarction (RMI), post-infarction scars (LSc), and all types of lesion in five towns (age-standardized values) Town FMI only ~R Ml (FMI All types of All LSc (with All types ofTown only witth LSc) myocardial LSc only or without lesionWIinfarction FMI) Males aged 30-79 years Malmo (M) 8.6 10.8 19.2 15.4 26.2 34.6 Prague (P) 5.8 9.0 14.8 16.8 25.8 31.6 Ryazan (R) 7.1 5.2 12.3 5.5 10.8 17.8 Yalta (Y) 4.9 3.9 8.8 16.8 20.7 25.6 Tallin (T) 6.5 7.3 13.8 16.5 23.8 30.6 Statistical M> R,T, M> P,T> M> P,T, P,Y,T, M,P,T>R M,P,T>Y>R significance P>Y >R>Y R>Y M>R M>Y M>T Females aged 40-79 years Malmo 5.8 5.6 11.4 9.2 14.8 20.6 Prague 5.7 5.1 10.8 9.2 14.8 20.6 Ryazan 4.4 2.1 6.5 3.3 5.4 9.8 Yalta 4.8 4.6 9.4 14.2 18.8 23.6 Tallin 5.5 3.5 9.0 9.4 12.9 18.4 Y,M,P, Statistical M,P. M,P>T> R M> R,T Y>T, Y> M,P, T>R significance T>R Y>R P>R M,P> R T>R Y>T tion and large myocardial scar the differences were practically absent. Moreover, there was rela- tively little difference in the extent of such lesions in men and women in the corresponding groups. In the low and standardized average atherosclerosis groups the area of raised lesions was lower in every case and the differences between most groups were statisti- cally significant (P <0.001). The area of calcified lesions with fresh myocardial infarction and large myocardial scar was 21/2-4 times as great as in the low atherosclerosis group; it was also much greater than in the standardized average group, and almost reached the level of the high atherosclerosis group. When the three coronary arteries were compared in myocardial infarction deaths, there was little asso- ciation between raised lesions and coronary stenosis but a strong association was found between the extent of calcified lesions and the frequency of stenosis. The extent of calcified lesions in the left anterior descending coronary artery was two or three times higher than in the right coronary and left circumflex coronary arteries and stenosis was found Table 45. Extent of raised and calcified lesions (% of surface) and prevalence (%) of stenosis in three coronary arteries in subjects with fresh myocardial infarction (all towns combined), males (age-stan- dardized values) Extent Coronary_______artery____ PrevalenceCoronary artery raised calcified of stenosis lesions lesions Right 61.7 3.5 32.0 Left anterior descending 59.0 6.8 54.3 Left circumflex 50.3 3.4 27.0 twice as frequently in the left anterior descending artery as in the other two arteries (Table 45). There were no large inter-town differences in the extent of raised lesion in males with different mani- festations of coronary heart disease (Table 46). The values for Ryazan were similar to those for the other 587 A. M. VIHERT Table 46. Extent of raised and calcified lesions in the average coronary artery and prevalence of stenosis (50 % or more) in any coronary artery in subjects with fresh (FMI) or recent myocardial infarction (RMI) or large myocardial scar (LSc) Extent of raised lesions Extent of calcified lesions Prevalence of stenosis Town in subjects with in subjects with in subjects with FMI only RMI LSc only FMI only RMI LSc only FMI only RMI LSc only Males aged 30-79 Malmo (M) 47.7 61.9 51.6 2.7 5.4 5.2 67.6 83.9 55.5 Prague (P) 57.8 70.9 55.1 4.2 4.4 5.3 57.5 79.5 50.5 Ryazan (R) 50.2 64.3 59.0 2.0 4.8 5.0 40.8 67.3 36.5 Yalta (Y) 50.0 63.8 40.3 1.8 4.9 4.3 57.1 78.6 39.3 Tallin (T) 49.5 64.1 58.2 6.5 6.5 6.6 43.3 63.2 54.5 All towns combined 50.5 63.6 52.2 3.4 5.5 5.3 54.7 74.0 50.3 Statistical significance - P > M R, T, P, T> M, R - - M > T M > T M,T> Y M >Y Females aged 40-79 Malmo 36.4 66.0 38.8 3.1 7.4 2.2 38.2 85.7 37.0 Prague 36.7 - 49.0 2.7 - 3.2 22.8 - 30.0 Ryazan - - - - - - - - - Yalta - 47.8 33.2 - 4.3 3.2 - 73.8 35.9 Tallin 51.4 - 39.5 3.2 - 3.6 29.1 - 23.6 All towns combined 39.2 56.8 39.4 2.6 5.2 2.8 31.6 64.8 31.0 Statistical significance - - - - - - - - - towns. In women from Ryazan, however, raised lesions in the coronary arteries were less extensive than in women from elsewhere. The area of calcified lesions was the lowest in both men and women from Ryazan, where the frequency of stenosis was simi- larly lower (see below). However, women often had more extensive calcified lesions than men in different types of myocardial lesions. Aorta In subjects who had fresh or recent myocardial infarction or large myocardial scar, raised lesions occupied a greater area not only in the coronary arteries but also in the aorta (Table 47). In contrast to the findings in the coronary arteries, the area of raised lesions in the aorta was the same or greater in women than in men, apparently because of the greater area of calcified lesions in the aorta in women (Table 47). Raised and calcified lesions in all three myocardial infarction groups were consider- ably more extensive than in the low and standard- ized average and often the high atherosclerosis groups. Inter-town differences in raised and calcified lesions of the aorta were similar for the various myocardial infarction lesions (Table 47). The small- est area of lesions was found among men and women from Ryazan, followed by those from Yalta and Tallin. The largest areas of raised lesions were found among men from Prague and women from Malmo, and the biggest areas of calcified lesions among the inhabitants of Malmo (Table 47). Calci- fied lesions were considerably more extensive in the women from all the towns, so that raised lesions were also frequently more extensive in women. 588 ATHEROSCLEROSIS IN CORONARY HEART DISEASE Table 47. Extent of raised and calcified lesions in the average aorta in subjects with fresh (FMI) or recent myocardial infarction (RMI) or large myocardial scar (LSc) (age-standardized values) Raised lesions in subjects with Calcified lesions in subjects with Town FMI only RMI LSc only FMI only RMI LSc only Males Malmo (M) 46.0 47.9 47.4 2.3 1.7 2.1 Prague (P) 51.2 51.4 48.2 1.3 1.9 2.3 Ryazan (R) 33.8 43.1 39.9 1.5 1.4 1.0 Yalta (Y) 37.4 41.9 45.8 1.0 1.4 2.2 Tallin (T) 42.1 51.8 47.3 2.2 1.9 3.0 All towns combined 42.6 49.1 46.5 1.7 1.8 2.4 Statistical significance M>R - - - - T,P,Y,M>R T>M Females Malmo 50.0 64.7 46.0 4.0 5.8 3.7 Prague 39.5 - 53.5 1.7 - 2.3 Ryazan - 39.0 - - 1.1 - Yalta - 50.4 46.0 - 4.9 3.7 Tallin 42.9 - 40.1 2.6 - 3.4 All towns combined 38.0 53.0 44.6 2.3 4.1 3.3 Statistical significance - - - - - - STENOSIS OF CORONARY ARTERIES IN CORONARY HEART DISEASE The main anatomical basis of myocardial infarc- tion is stenosis of coronary arteries, which was found in men aged 20-25 years with coronary heart disease 9-10 times more often than in the low atherosclero- sis group. At older ages the differences between the groups was not so marked. Coronary stenosis was found in the overwhelming majority of subjects with fresh or recurrent myocar- dial infarction or large myocardial scar (Table 46). Stenosis occurred considerably more frequently in those with recent myocardial infarction than in the other two groups, where the frequency of stenosis was in turn greater than in the low and standardized average atherosclerosis groups. In women it was greater than in the high atherosclerosis group. Sten- osis was somewhat less frequent in women who had died of fresh myocardial infarction or who had a large myocardial scar than among men, but in subjects with recent myocardial infarction the differ- ence between the sexes was negligible. Stenosis of one artery was found in 30% of men with fresh myocardial infarction, of two arteries in 20.4%, and of all three arteries in 10.5%. The corresponding figures for women were 27.3 %, 14.4%, and 9.2%. The frequency of stenosis of one artery was some- what lower among both men and women with recurrent myocardial infarction (26.3% and 24.3%, respectively), but the frequency of stenosis of two arteries (30.0% and 22.7%, respectively) and parti- cularly of all three arteries (23.1 % and 27.2 %, respectively) was increased. When only large myocardial scar was present the frequency of stenosis of one, two, or three arteries was similar to that in subjects with fresh myocardial 589 A. M. VIHERT infarction (23.3%, 20.0%, and 17.5% in men, and 18.1 %, 15.6%, and 13.8% in women). Nevertheless, the frequency of stenosis in two or three arteries was somewhat higher in this group than in subjects with fresh myocardial infarction, apparently because some of the post-infarction scars were connected not only with fresh but also with recurrent myocardial infarction and consequently accompanied by the stenosis of a larger number of arteries. In men coronary stenosis was encountered as early as the 20-29-year age group (2 out of 9 deaths) and in the 30-39-year age group it was found in as many as one-third of the cases (16 out of 49). In women there was no stenosis in those age groups and in the 40-49-year age group it was infrequent (4 out of 22). There were some differences in the frequency of coronary stenosis among the population of the vari- ous towns (Table 46). The highest frequency of stenosis in all groups occurred in men and women in Malm6 and the lowest in Ryazan. This finding was in agreement with the observation that atherosclero- sis was most extensive in Malmo and least extensive in Ryazan. PREVALENCE OF CORONARY THROMBOSIS AND NON-THROMBOTIC CORONARY OCCLUSION IN CORONARY HEART DISEASE Coronary thrombosis was found in 35.5 % of males with fresh myocardial infarction, and in 41.9% of males with recurrent myocardial infarc- tion, the corresponding figures for women being 39% and 34.1 %, respectively (Table 48). The most frequent site of thrombosis among men was the left anterior descending coronary artery, which ac- counted for 43% of all thrombosis subjects with fresh and 41 % of subjects with recurrent infarction. The next most frequent site was the right coronary artery, the corresponding figures being 31 % and 38 %. In women with fresh infarction the left ante- rior descending coronary artery was most commonly thrombosed (53% of all thrombosis), followed by the left circumflex artery (25 %), and the right cor- onary artery (22 %), whereas in women with recurrent infarction the findings were right coronary artery 44 %, left anterior descending coronary artery 36 %, and left circumflex artery 36%. Thrombosis of two arteries was very rarely encountered (2-5 % of cases of coronary heart disease). Thrombosis was often observed in subjects with only large myocardial scar but no fresh myocardial Table 48. Prevalence (%) of coronary thrombosis and non-thrombotic occlusion in subjects with coronary heart disease (all towns combined, age-standardized values) Thrombosis Non-thrombotic Group occlusion M F M F Fresh myocardial infarction only 35.5 39.0 15.3 13.8 Recurrent myocardial infarction 41.9 34.1 25.7 24.1 Large myocardial scar only 11.2 7.8 19.9 15.2 All types of myocardial lesion 23.2 21.4 20.4 16.9 lesion, who thus probably died suddenly. In such cases thrombosis was found in 11% of men and 7.8% of women (Table 48). In both men and women the right coronary artery was thrombosed most often (41 % and 47% of cases, respectively) followed by the left anterior descending artery (38% and 33 %). There were considerable inter-town differences in the frequency of thrombosis, particularly in men. Thrombosis was encountered least commonly in men from Ryazan and Tallin and most frequently in those from Yalta. In women thrombosis was also frequent in Yalta, followed by Malmo, with Ryazan and Tallin showing the lowest prevalence. The differ- ence in frequency of thrombosis in the different towns were less marked in subjects with recurrent than those with fresh myocardial infarction. Non-thrombotic coronary occlusion was found in 15% of men and 14% of women with fresh infarc- tion; the corresponding figures for recurrent infarc- tion were 25% and 28% and for large myocardial scar, 20% and 15% (Table 48). The left anterior descending coronary artery was most frequently affected in all types of myocardial change (40-45% of all non-thrombotic occlusions); the frequency of such occlusions in both the left circumflex and right coronary arteries was about 30 %. Non-thrombotic occlusion was most frequent among men and women from Prague, followed by Malmo, and 2-3 times as frequent as in Ryazan. HEART WEIGHT IN CORONARY HEART DISEASE The weight of the heart in men and women was greatest in cases of recurrent myocardial infarction, somewhat less when only large myocardial scar was present, and lowest of all in cases of fresh infarction. 590 ATHEROSCLEROSIS IN CORONARY BEART DISEASE In all three groups the heart weight was much greater than in the low atherosclerosis group, and even greater than in the high atherosclerosis group, the differences being statistically significant (P <0.001). In people with coronary heart disease the mean heart weight, even in cases of fresh myocardial infarction and without hypertension, was much greater than in the low atherosclerosis group (420 g in men and 365 g in women), which suggests that the insufficiency of coronary blood circulation per se stimulated the increase in the heart muscle mass. This suggestion was supported by observations of heart weight in subjects with coronary stenosis but without myocardial infarction or scar and without hypertension or diabetes. The age-standardized mean heart weight in such subjects was 355 g in men and 330 g in women, compared with 325 g and 282 g, respectively, for the low atherosclerosis group (P <0.001). There were considerable inter-town differences in heart weight among the three infarction groups, especially in men, but no consistent trends were observed. RUPTURE OF THE HEART Rupture of the heart in myocardial infarction occurred in 10% of men and 16% of women (ratio 1: 1.6-P <0.001) (Table 49). Hypertension and Table 49. Prevalence (%) of rupture of the heart in subjects with fresh myocardial infarction, with or without myocardial scar (age-standardized values) Males Females Subjects Subjects Group Total ruwith Total with No. rupture No. rupture No. % No. % Infarction without hypertension or diabetes 781 78 10.0 396 62 15.7 Infarction with hyper- tension but without diabetes 352 33 9.4 313 49 15.7 Infarction with diabetes but without hyper- tension 58 0 0 65 3 4.6 Infarction with both hypertension and dia- betes 36 1 2.8 53 6 11.3 diabetes apparently had no influence on the fre- quency of heart rupture. In men it occurred most frequently in the seventh, eighth, and ninth decades (12%, 9%, and 13%, respectively) and in women in the sixth, seventh, and eighth decades (11 %, 19%, and 13 %, respectively). In men heart rupture occur- red most frequently in Tallin (13% of subjects with myocardial infarction). Among women it was most common in Yalta (56%, i.e., 20 out of 36 subjects with myocardial infarction). SUDDEN DEATH IN MYOCARDIAL INFARCTION The prevalence of sudden death in patients with different types of myocardial infarction was within the range 38-44% for men and 23-34% for women (Table 50). The prevalence in men was 2-3 times higher in the younger age groups. In women this trend was present but was not so marked. CORONARY HEART DISEASE AND HYPERTENSION Of 2511 male coronary heart disease deaths, 753 (31 %) were known to be hypertensive. In women the proportion was 44%. But not all the hypertensives among these deaths were known. Of 5722 male normotensive deaths, 1758 (30%) died of coronary heart disease. In women the proportion was 17% (837 out of 4755 known normotensives). For known hypertensives the proportion of coronary heart dis- ease deaths was 52% in men (753 of 1461 deaths) and 40% in women (540 of 1348 deaths). DISCUSSION It is generally recognized that the age range of 50-59 years and the two subsequent decades are the most dangerous for men in respect of myocardial infarction (7, 51, 58). Most authors (1, 5, 30, 40, and many others) note that men predominate in cases of myocardial infarc- tion, particularly in the younger age groups. The male: female case ratios in studies of myocardial infarction range from 3: 1 (13) to 7: 1 (4). Accord- ing to Berinskaja's data, in the age group 41-50 years the male:female ratio was 5.1: 1, at age 5140 it was 2: 1, and at age 61-70 it decreased to 1.5: 1. This feature was confirmed by the present investiga- tion. It was only in the seventh decade of life that the frequency of infarction as a cause of death became the same in men and women. 591 A. M. VIHERT Table 50. Frequency (%) of sudden deaths among cases of myocardial infarction, combined) by age and sex (all towns Fresh myocardial infarction Recurrent myocardial infarction Large myocardial scar withoutinfarction Age group No. Sudden % No. Sudden % No. Sudden %death death death Males 10-19 0 0 - 0 0 - 1 0 - 20-29 1 0 - 1 1 100.0 5 3 60.0 30-39 17 1 1 64.7 13 10 76.9 18 8 44.4 40-49 50 33 66.0 43 19 44.2 50 35 70.0 50-59 121 63 52.1 145 62 42.8 265 142 53.6 60-69 170 73 42.9 263 108 41.1 531 216 40.7 70-79 137 42 30.7 179 55 30.7 502 143 28.5 80-89 31 8 25.8 46 11 23.9 171 40 23.4 90-99 1 1 100.0 4 1 25.0 15 1 6.7 528 231 43.8 694 267 38.5 1558 588 37.7 Females 10-19 0 0 - 0 0 - 0 0 - 20-29 0 0 - 0 0 - 0 0 - 30-39 1 0 - 2 0 - 0 0 - 40-49 8 1 12.5 5 2 40.0 12 6 50.0 50-59 45 15 33.3 36 13 36.1 63 21 33.3 60-69 144 57 39.6 130 35 26.9 229 68 29.7 70-79 179 54 30.2 164 45 27.4 363 68 18.7 80-89 45 16 35.6 61 20 32.8 215 43 20.0 90-99 4 2 50.0 1 0 - 23 5 21.7 426 145 34.0 399 115 28.8 905 211 23.3 During the last few decades there has been a tendency to the development of myocardial infarc- tion at an earlier age (41, 44, 50, 51). WHO data indicate a large number of fatal cases of ischaemic heart disease in young men; in the period 1955-1964 mortality from cardiovascular disease, mainly ischaemic heart disease, in men aged 35-44 rose by 60% and even in those under 31 years of age it rose by 5-15 %. Occasional cases of myocardial infarction among teenagers have been described (20, 39, 55). The occurrence of occasional cases of myocardial infarction among men in the age groups 10-19 and 20-29 years in our material is therefore not sur- prising. Epidemiological surveys during the last few de- cades have shown that the frequency of coronary heart disease varies widely both in different coun- tries (35) and in different towns in the same country (14,58). Some inter-town differences in the fre- quency of myocardial infarction were therefore to be expected in this study. Ryazan and Tallin, similar to each other in living conditions, differed greatly in the frequency of coronary heart disease and women from Yalta, a health resort, had almost as high a frequency of myocardial infarction as those from Malmo and Prague. On the other hand, men in Yalta had the lowest frequency of myocardial infarc- tion. 592 ATHEROSCLEROSIS IN CORONARY HEART DISEASE 593 The frequency of coronary thrombosis in cases of myocardial infarction reported by authors varies from 30% (11, 52) to 92% (56). The mean figure for a large number of studies is 55-60%, higher than in this study. The frequency of thrombosis in subjects, parti- cularly in men, with fresh myocardial infarction also differed among the five towns. Meanwhile there were practically no differences between men and women in the frequency of thrombosis in myocardial infarc- tion (Table 48). On the basis of the data quoted it may evidently be assumed that not more than 50-60% of myocardial infarctions are directly linked with the development of thrombosis in one of the coronary arteries. The differences between the sexes in cases with large myocardial scar apparently arise from the fact that thrombosis was found mainly in cases of sudden death and was the cause of it, and that sudden death was more frequent among men (see Chapter 5). In the case of subjects dying from fresh myocardial infarction, however, it has been pointed out that those without coronary thrombosis or occlusions more often die suddenly than those with it (34, 54, 60). The absence of sudden heart deaths from a series might thus increase the preva- lence of subjects with thrombosis. Thrombosis and occlusion are found most fre- quently in the left anterior descending coronary artery, apparently because of the greater extent of atherosclerosis, particularly calcified lesions, in that artery. This finding is in agreement with the data of other authors (29, 38, 52, 54). Coronary stenosis a was found in 60-80% of men and 50-75% of women with myocardial infarction (Table 46). These figures are close to those of the International Atherosclerosis Project study, in which stenosis was found on the average in 60% of persons who had died of coronary heart disease. In that study stenosis was found most frequently in white women in the 54-64 and 65-69 age groups in New Orleans (83% and 87% of all cases, respective- ly-close to the frequency of stenosis in Malmo and Yalta in cases of recurrent myocardial infarction). In men in the International Atherosclerosis Project study the frequency of stenosis was highest in New Orleans and Oslo (60-75%), which roughly cor- responded to the findings of the present study, with the exception of Ryazan, where stenosis was some- what less common (Table 46). It may be that the longitudinal method of dissecting the coronary arte- a In this study only stenosis >50 Y. of the lumen was taken into account (see Chapter 1). ries adopted in both studies resulted in low figures for the frequency of coronary stenosis. Indeed, in studies at the Mjasnikov Institute of Cardiology of the Academy of Medical Sciences of the USSR, of 320 persons who had died of myocardial infarction, 82% had stenosis of over 50% in one of the arteries (59). Proudfit et al. (48) using selective cor- onary angiography found stenosis of over 30% in 94% of patients who had suffered from angina pectoris and in 99% of those who had had myocar- dial infarction. In both the International Atherosclerosis Project and the present studies, considerable inter-town variations were found in the frequency of stenosis in those who had died of coronary heart disease. For example (Table 46), in men from Malmo, Prague, and Yalta the frequency of coronary stenosis was very similar, yet myocardial infarction was found twice as often in men from Malmo as in those from Yalta, and men from Prague had half as many myocardial infarctions again as those from Yalta. In women from Yalta and Malm6, the frequency of coronary artery stenosis was high (Table 46) and in women from Tallin it was much lower, but the frequency of all types of myocardial infarction in women from Yalta was significantly lower than in two other towns (Table 44). This indicates that, although atherosclerosis was indeed a prerequisite for the development of myocardial infarction, other factors may also have played a significant role in its occur- rence. These include functional factors, hormonal influences, constitutional features, etc. (12, 28, 49). The frequency of stenosis in the low atherosclerosis group was significantly lower than in subjects with all forms of myocardial infarction. The extent of raised lesions in the coronary arte- ries in persons who had died from myocardial infarction was roughly twice that in the low athero- sclerosis group, and the extent of calcified lesions was 4-41/2 times as great. The large extent of raised lesions in subjects with coronary heart disease was also in line with the data obtained in the Interna- tional Atherosclerosis Project study and by Stern- by (54). In the WHO survey, as in the International Atherosclerosis Project study, some variations were noted in the extent of raised lesions in the coronary arteries in the different towns, particularly in Ryazan women, whose raised lesions were the least extensive. Calcified lesions were also least extensive in the inhabitants of Ryazan. The extent of raised lesions in the average cor- onary artery in men and women in the WHO study A. M. VIHERT was similar to that found in New Orleans and Oslo. The differences in the extent of raised lesions among inhabitants of the various towns covered by the International Atherosclerosis Project study were greater than the differences among the towns of the WHO survey. For example, among men aged 45-54 the extent of raised lesions was 60% in New Orleans, 19% in Costa Rica, and 14% in Bogota. The prevalence of stenosis also varied widely. Stenosis was present in 70% of white men aged 55-64 in New Orleans and 27% in Guatemala. In this study, as in the International Athero- sclerosis Project study, the differences in the extent of the raised and calcified lesions between the fresh myocardial infarction and large myocardial scar groups were small or almost non-existent, but both types of lesions were more extensive in the recurrent myocardial infarction group (Table 46). Both raised and calcified lesions were always more common in the different myocardial lesion groups than in the low atherosclerosis and standardized average athero- sclerosis groups. Thus, atherosclerosis of the coronary arteries and the aorta is very extensive in persons who have died from myocardial infarction or who have had myo- cardial infarction in the past, which suggests that severe atherosclerosis of the coronary arteries with stenosis and calcification is almost a prerequisite for the development of coronary heart disease. The majority of authors who have considered the prob- lem agree with this view (6, 19, 22, 26, 33, 35, 37, 46, 57, 59, 60, and others). The weight of the heart was significantly greater in subjects who had died of myocardial infarction than in those in the low and standardized average athero- sclerosis groups. Since the myocardial infarction groups also included persons with arterial hyperten- sion, the effect of hypertension was studied separ- ately. It was shown that the weight of the heart in both men and women with myocardial infarction but without arterial hypertension and in those with coronary stenosis without myocardial infarction, hypertension, or diabetes was considerably greater than that in the low atherosclerosis group but lower than in persons with both myocardial infarction and hypertensive disease. This suggests that the insuffi- ciency of the coronary blood circulation per se stimulated the increase of the heart muscle mass. An increase in heart weight in persons with severe coronary atherosclerosis and coronary heart disease but without myocardial infarction has also been reported by other authors (15, 16, 21, 54). However, in the International Atherosclerosis Project study no such relationship was detected; neither the heart weight nor its ratio to body weight were regularly higher in subjects with severe coronary athero- sclerosis or in subjects with coronary stenosis. The findings of van Peenen & Gersll were similar (47). There are thus different opinions on whether or not severe atherosclerosis without myocardial infarction affects heart weight. The findings in the present study support the view that coronary atherosclerosis per se increases the heart weight in subjects with coronary stenosis or a first fresh myocardial infarc- tion; in them, the heart weight was higher and the increase had apparently taken place before the infarction developed. The frequency of myocardial rupture, according to the findings of the present study, does not in general exceed the limits quoted in the literature (24, 43, 58). It is also generally accepted that the fre- quency of rupture of the heart is higher in women than in men. This feature was noted first by Beres- ford & Earl (9) and later by others (42, 45, 62). Crawford et al. state that during the period 1957-1958 there were 600 cases of myocardial rup- ture among 3 250 000 inhabitants of London. In the middle-aged group myocardial rupture occurred twice as frequently among men but in the older age groups it was twice as frequent among women, so that overall there was equality of the sexes in this respect. The findings of the Mjasnikov Institute of Cardiology-rupture occurring in 10% of male and 16% of female cases of myocardial infarction-are quite similar to those of the present study. The greater frequency of myocardial rupture in women has been ascribed to the weak development of collateral blood circulation in women because of the less marked nature of coronary atherosclerosis (45). Another important factor is considered to be the presence of hypertensive disease, which is more frequent in women (23, 41). However, according to the data obtained in the present study neither hyper- tension nor diabetes can really be considered as factors that promote rupture in myocardial infarc- tion. 594 ATHEROSCLEROSIS IN CORONARY HEART DISEASE 595 RtSUMt CHAPITRE 14. L'ATHEROSCLLROSE DE L'AORTE ET DES ARTtRES CORONAIRES DANS LA CARDIOPATHIE CORONARIENNE L'atheroscl6rose aortique et coronarienne, et la pre- valence de la st6nose et de la thrombose coronariennes ont ete 6tudiees chez des sujets d6c&d6s d'infarctus myo- cardique recent ou d'une rechute d'infarctus, ou qui avaient souffert d'infarctus du myocarde dans le passe. En g6neral, 1'existence d'une ath6roscl6rose severe des arteres coronaires avec st6nose et calcification est une condition presque indispensable au developpement de la cardiopathie coronarienne. La frequence de celle-ci varie largement a la fois dans les divers pays et dans les differentes villes d'un meme pays. Des variations consi- derables ont 6te observees entre les diverses villes dans la frequence de la st6nose et de la thrombose chez les sujets d6cedes de cardiopathie coronarienne. 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