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The Natural History of Coronary Atherosclerosis
The Natural History of Coronary Atherosclerosis" K.
S.
MATHUR, M.D.,
V.
KUMAR, M .D. AND
S.
K . KASHYAP, M.B .
Agra, India
T
They were drawn almost equally from both urban and rural population. The three main coronary arteries, namely the right coronary, left anterior descending branch with its main trunk and the left circumflex coronary arteries were cut transversely at intervals of 1 to 1 Y:z ern. and opened longitudinally. The vessels were studied both before and after staining with Sudan IV as described by Holman et aC and in the technical report of WHO.· The amount and severity of atherosclerosis and the atherosclerotic narrowing were assessed by the methods recommended by Gore and Tejada" in their atherosclerosis index. The atherosclerotic indices and the narrowing indices were calculated in each case for the coronary arterial bed and also for its main branches.
H E GEOGRAPHIC, RACIAL AND SEX DIF-
ferences in the prevalence of ischemic heart disease has focused attention on the study of atherosclerosis of the coronary arteries, which has been shown to be the most significant factor in determining the risk of occlusive episodes in a population. The earliest manifestations of atherosclerotic lesions commence in the intima of coronary vessels in the early decades and continue to progress silently and steadily. Gradually the lumen of the vessel is encroached upon and narrowed. The evolution of these mural changes constitutes the natural history of atherosclerosis of coronary arteries. In the present study, atherosclerotic lesions have been analyzed in the main arteries of the coronary system on gross inspection at necropsy, and the extent and severity of atherosclerosis has been quantitated. An estimation of the narrowing of the coronary vessels at different sites has been made. The probable course and sequence of events resulting in the atherosclerotic narrowing of the coronary arteries has been constructed from these data.
RESULTS
Table I summarizes the distribution of 200 cases and incidence of coronary atherosclerosis in relation to age and sex. TABLE I-INCIDENCE OF CORONARY ATHEROSCLEROSIS BY AGE AND SEX
Males
MATERIAL AND METHODS
Coronary arteries were removed in situ with the heart in 200 consecutive medicolegal necropsies performed at Sarojini Naidu Medical College, Agra, on cases dying of traumatic wounds and head injuries (89), suspected poisoning (53), gun shot and stab wounds (28), burns (15), drowning (1 1) and hanging (4) without showing any morphologic evidence of atherosclerotic catastrophe. This included 157 men and 43 women ranging from newborn to 80 years in age. Seventy-two per cent of them belonged to low socioeconomic group, 27 per cent to middle and 1 per cent to high socioeconomic group.
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The earliest evidence of atherosclerosis of the coronary arteries in the form of lipid spots and streaks was found in a 19-yearold man. The men were afllicted a decade earlier than women. After the age of 40
*From the Department of Medicine, Sarojini Naidu Medical College.
70
Volume 46. No .1 July 1964
NATURAL HISTORY OF CORONARY ATHEROSCLEROSIS
TABLE 2-ExTENT OF CORONARY ARTERY INTIMAL SURl'ACE INVOLVEMENT WITH ATHEROSCLEROSIS Extent of Surface Involvement (Number of Cases in Each Group) ABC D
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In Table 2 is given the extent of coronary artery intimal surface involvement by the atherosclerotic process. The mean surface area of the coronary arteries involved by atherosclerosis increased with age. Most of the cases below 40 years showed 0 to 15 per cent intimal surface involvement j none of them had more than 33 per cent surface involved. TABLE 3-MEAN CORONARY ARTERY SURFACE INVOLVEMENT BY ATHEROSCLEROSIS Per Cent Intimal Surface Involved by
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In the fifth and sixth decades, 16 to 50 per cent surface was afflicted with atherosclerotic process in the majority of cases. The largest number of cases showing more than 50 per cent surface involvement was found in persons over 70 years of age (Fig. 1) . The percentage of intimal surface involvement by different types of lesions is given in Table 3. CORONARY ARTERY SURFACE INVOLVEMENT WITH ATHEROSCLEROSIS.
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The mean coronary artery surface involved by the atherosclerotic lesions increased from 2.5 per cent in the second decade to 48.0 per cent in the eighth decade. Fatty streaks constituted the sole lesion of atherosclerosis in the second and third decades and the predominant lesion up to the fifth and even the sixth decade. Fibrous plaques which were first detected in a man aged 33 years continued to contribute in progressively increasing proportion to the atherosclerotic process in later years. Complicated and calcified lesions appearing first in the fifth decade involved a maximum percentage of intimal surface in the eighth decade accounting for 8 per cent of total intimal surface (Fig. 2) . The mean of the atherosclerotic indices and the narrowing indices of the coronary arterial bed in each decade are given in Table 4.
Diseases of
MATHUR, KUMAR AND KASHYAP
72
Ctl~DNIIRY '",TIMIIL INYDLV4HENT
TABLE 4-MEAN ATHEROSCLEROTIC INDICES AND NAltitOWINO INDICES OF CORONARY AaTEItlES IN EACH DECADE Coronary Bed Atherosclerotic Index
Age Group (yean)
Narrowing Index
Below 10
0.0035±0.009* ( 0 - 0.03) 0.035±0.07 ( 0-0.33) 0.255±0.314 ( 0 - 1.23) 2.135±2.448 (0.03-15.43) 5.088±4.796 (0.03-15.40) 9.034±10.198 ( 1.83-35.2) 14.092± 6.985 (8.73-17.33)
11-20 21-30 31-40 41-50 51-60 61-70 71-80
the Chest
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0.074±0.43* (0 - 2.59) 2.770±7.49 (0 - 44.00) 5.913±6.76 (0 - 30.67) 12.402± 9.99 (2.67-30.67) 29.46±20.19 (8.67-65.33)
-Indicates standard deviation. Figures in parentheses indicate range.
The mean atherosclerotic indices of the coronary arterial bed rose progressively from 0.0035 in the second decade to 14.092 in the eighth decade. The rate of rise was gradual during the first four decades, but accelerated thereafter. The progression in the mean narrowing indices was uniform throughout from 0.074 in the fourth decade to 29.46 in the eighth decade. The mean atherosclerotic and the narrowing indices of the coronary arteries for
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males and females are given in Table 5. The values of mean atherosclerotic indices and the narrowing indices were higher in males than females in each decade, except in the sixth and the seventh decades where higher values were observed in females. This may be due to the very small number of females as compared to males in these age groups. The means of the atherosclerotic indices
TABLE 5-MEAN ATHEROSCLEROTIC AND NAltitOWINO INDICES OF CORONARY AaTEItlES FOR MALES AND FEMALES IN EACH DECADE Age Group (yean) Below 10
11-20
21-30 31·40 41·50 51-60 61-70 71-80
Atherosclerotic Index
Males Narrowing Index
0.0054 (0-0.03) 0.037 (0-0.33) 0.269 (0-1.23) 2.433 (0.03-15.4) 4.639 (0.03-15.4) 9.326 (01.83-35.2) 14.44 (8.73-17.33)
Figures in parentheses indicate range.
0.089 (0-2.59) 3.194 (0-44.0) 4.527 (0-13.33) 10.831 (2.67-30.67 ) 33.925 ( 13.30-65.33)
Atherosclerotic Index
0.029 (0-0.13) 0.03 (0.03-0.03 ) 0.697 (0.03-1.23) 8.680 (4.83-12.53) 8.015 (2.93-13.10) 12.70 ( ,- )
Females
Narrowing Index
0.721 (0-2.00) 17.00 (3.33-30.67) 17.90 (5.13-30.67) 11.33 ( -
)
Volume 46. No . I July 1964
NATURAL HISTORY OF CORONARY ATHEROSCLEROSIS
73
TABLE 6-MEAN ATHEROSCLEROTIC INDICES OF RIGHT CORONARY LEFT ANTERIOR DESCENDING CORONARY AND THE LEFT CIRCUMFLEX CORONARY ARTERIES IN EACH DECADE
Age Group (years)
Left Anterior Descending Coronary
Right Coronary
Below 10 11-20 21-30 31-40 41-50 51-60 61-70 71-80
0.0015±0.04* (0-0.03) 0.038±0.075 (0-0.33) 0.280±0.34 (0-1.23) 2.794±4.86 (0.03-25.30) 6.700±7.37 (0 .03-28.37 ) 12.122±13.12 (2.13-45.10) 18.412±6.44 (8.73-27.10)
0.022±0.055* (0-0.33) O.125±0.172 (0-0.63) 1.690±4.30 (0-26.30) 3.1l1±3.60 (0-15.40) 6.167±7.10 (1.53-25.33 ) 7.832±4.928 (3.70-17.33)
Left Circumflex Coronary
0.013±0.034* (0-0.33) 0.129±0.194 (0-0.63) 1.023±1.47 (0-7.68) 3.376±3.83 (0-15 .40) 5.328±4.83 ( 1.23-15.40) 11.032±4.17 (5.13-17.33)
*Indicates standard deviation. Figures in parentheses denote range.
highest and there were no marked differences in values for the right coronary and the left circumflex coronary arteries . The mean narrowing indices of the main arteries of the coronary system in each decade are given in Table 7. An appreciable degree of atherosclerotic narrowing in the coronary arterial bed was observed first of all in the left anterior descending coronary artery in the fourth decade and a decade later in the right coronary and the left circumflex arteries. The mean narrowing indices of the coronary arteries showed progression with age up to the eighth decade. The left anterior de-
for the main arteries of the coronary system are given in Table 6. The left anterior descending branch is the first artery to be afHicted with atherosclerosis in the second decade, the mean index being 0.0015 . Atherosclerosis appeared in the right coronary and the left circumflex arteries in the third decade, and the values of the mean atherosclerotic indices were 0.022 and 0.013, respectively. In all the coronary arteries the degree of atherosclerosis progressed with age up to the eighth decade. In any decade, however, the mean atherosclerotic index for the left anterior descending coronary artery was
TABLE 7-MEAN NARROWING INDICES OF RIGHT CORONARY, LEFT ANTERIOR DESCENDING CORONARY AND LEFT CIRCUMFLEX ARTERIES IN EACH DECADE
Age Group
Right Coronary
Below 10 11-20 21-30 31-40 41-50 51-60 61-70 71-80
Left Anterior Descending Coronary
Left Circumflex Coronary
0.074±2.49*
( 1.753±7.07* (0-42.70) 1.629±2.02 (0-7.33) 4.592±4.12 (1.33-13.33 ) 11.866±8.09 (4.67-26.67 )
-
)
1.447±1.83 (0-9.33) 4.666±5.89 (0-26.67) 11.035±9.51 ( 1.33-30.67) 20.00±8.509 (7.33-30.61)
*Indicate standard deviation. Figures in parentheses denote range.
0.456±0.79* (0-3.33) 1.865±2.45 (0-9.33) 4.596±3.83 ( 1.33-13.33) 12.126±8.20 (4 .00-26.67 )
MATHUR, KUMAR AND KASHYAP
74
scending coronary artery showed more marked degree of narrowing as compared to other branches in each age group . COMMENTS
The results of the present study indicate that the mural lesions of atherosclerosis of the coronary arteries comprise a series of changes which commence early in life beginning as early as the second decade in a few cases. As age advances, these lesions are found in an increasingly larger proportion of individuals until by about the fifth decade, they are present in all cases. The extent and severity of atherosclerotic lesions varies from person to person and also, in the individual arteries, but no adult in that age group could be classed as free from atherosclerosis. Strong and McGill" from the United States reported that among the white and Negro adults of their population, the prevalence of grossly visible lesions had also become universal in the fifth decade. However, in the United States, whites showed a much more severe degree of coronary atherosclerosis in any decade than ours. The influence of age on the extent and severity of atherosclerosis indicates that the process advances with increasing years as reported by us earlier." A similar relationship in age and coronary atherosclerosis has been observed by other workers."?" The rate of rise of the mean atherosclerotic index appears to be very gradual in the first four decades, but became accelerated thereafter . Part of this lack of uniformity in the rate of rise could be explained on the basis of logarithmic weighting employed for the purpose of converting the atherosclerotic profile into the atherosclerotic index. However, the results may also be interpreted to mean that after the initial foci of lipid deposition in the form of lipid spots and streaks have occurred in the intima, a number of factors beside the original ones which laid the foundation of the atherosclerotic process come into play, and the process develops a tendency to progress more rapidly. Lober" had reported that
Diseasesof the Chest
atherosclerosis In coronary arteries progresses at a nearly uniform rate, but this has not been substantiated by our observations. It seems unlikely that a process which passes through so many different phases in the course of its natural history should have a uniform rate of progression. Analysis of the extent of intimal involvement in different decades shows that this increases with age. This extension has also been observed in other studies.tt As the process of atherosclerosis advances, the newer lesions seem to encroach upon the unaffected regions. It is likely that as the early lesions are being transformed into the more advanced types, crops of early grades of lesions continue to appear throughout life. According to Gore et al.tt there are geographic differences in the rate of this extension, which is reportedly slower in Japanese and maximum in whites of the United States. The incidence of fatty streaks, which first appeared at the age of 19 years, continues to rise until the sixth decade and declines thereafter. After the fifth decade, the fibrous plaques contribute most predominantly towards the atherosclerotic process. The fibrous plaques appear almost 15 to 20 years later than the fatty streaks, which are supposed to act as an analogue for the formation of the fibrous plaques. According to Holman et al.tl it takes about 20 years for fatty streaks to convert into the fibrous plaques in the aorta. Our observations for the coronary arteries are in conformitv with their views. The complicated and calcified atherosclerotic lesions which predispose to occlusion of coronary lumen and correlate with the risk of ischemic heart disease, have been noticed much less frequently in our cases as compared to those reported by Strong and McGill." These complicated lesions were noticed earliest in the fifth decade about 20 years after they are seen in the white population of the United States (Gore et al.tt). These lesions increased in proportion from 4 per cent in the fifth decade to 16 per cent in the eighth decade. Even then at all age
Volume 46, No.1 July 1964
NATURAL HISTORY OF CORONARY ATHEROSCLEROSIS
periods they were the least prevalent of all the other types of atherosclerotic lesions, i.e. fatty streaks and fibrous plaques. These observations confirm the view that the progression of the severity of atherosclerosis in different geographic regions is variable. The geographic variations in the prevalence of coronary atherosclerosis re-emphasizes the importance of environmental factors in atherogenesis. All the stages in the process of the evolution of atherosclerosis seem to come up at an earlier age in the men than in the women. The magnitude of difference for various types of lesions remains almost the same between the two sexes and it appears that the pace at which the earlier lesions are transformed into the subsequent more advanced types does not differ in the two sexes, but rather the process in its initial form commences later in females. The degree of atherosclerosis when compared in three main branches was such that the process, in most of the cases, appeared a decade earlier and was more advanced in the left anterior descending branch than in the other two branches. This is in agreement with the findings of Lober,' Roberts et al.' and Wig et al" The latter two groups believe that the right coronary and the left anterior descending coronary artery generally contain the most severe coronary atherosclerosis. However, this has not been observed in our cases for the right coronary artery . These differences in the degree of atherosclerosis in the three main arteries of the coronary system were more evident in the women than in the men. This finding when viewed in conjunction with the observation that the extent and severity of atherosclerosis in men in any decade is greater than in women, becomes important when correlated with much higher incidence of clinical episodes of ischemic heart disease in men as compared to women. Young et al" have reported that the degree of atherosclerosis in any artery varies directly with its radius. Our observations as discussed above have shown that
75
the degree of atherosclerosis increases progressively with age. We have also noticed in our study that the mean "narrowing index" of the coronary artery increases with age. This may be related to the concomitant increase in the size of the coronary arteries, which is supposed to take place with advancing age. The severest narrow ing was observed in the left anterior descending artery. The more frequent occurrence of infarcts in the region of the blood supply of this artery, reported by one of us (K. S. Mathur) 14 could be attributed to this fact. SUMMARY
The natural history of coronary atherosclerosis has been reconstructed from data gathered from 200 consecutive medicolegal necropsies. Coronary atherosclerosis in men commences in the second decade in the form of fatty spots which are most frequent in the anterior descending branch of the left coronary artery . The earliest evidence of atherosclerosis in women was seen in the third decade. The atherosclerotic process does not progress beyond grade I in the second decade. The extent and severity of atherosclerosis increases progressively with age, without a terminal decline in the mean atherosclerotic index. Atherosclerosis is present in all cases above 40 years. Fibrous plaques are first noticed in the fourth decade. Complicated lesions are seen for the first time in the fifth decade. The narrowing index of the coronary arteries also progresses with age from the fourth decade onwards, no significant narrowing being detectable earlier. The proces." of atherosclerosis is consistently more advanced in the anterior descending branch of the left coronary artery than in the circumflex branch or the right coronary artery. The extent and severity of atherosclerosis is less in women than in the men in each decade and the proces" commences a decade later. RESUMEN
La historia natural de aterosclerosis corona ria ha sido recontruida gracias a los datos reunidos de 200 casas consecutivos de necropsias medico-
MATHUR, KUMAR AND KASHYAP
legales. La aterosclerosis coronaria en los hombres comienza en la segunda decada en la forma de puntos grasosos que son mas frecuentes en la rama anterior descendente de la coronaria izquierda. La mas temprana evidencia de aterosclerosis en las mujeres fue vista en la tercera decada. El proceso ateroscleroso no progresa mas alla del grado I en la segunda decada, La extensi6n y la gravedad de la aterosclerosis aumenta progresivamente con la edad, sin declinaci6n terminal media del Indice ateroscler6tico. La aterosclerosis esta presente en todos los casos arriba de 40 afios, Las pia cas fibrosas se notaron primeramente en la cuarta decada, EI Indice de estrechamiento de las coronarias tarnbien progresa con la edad desde la cuarta decada en adelante. Antes no se encontr6 estrechamiento de significaci6n. EI proceso de la aterosclerosis es constantemente mas avanzado en la rama anterior decendente de la arteria coronaria izquierda que en la rama circunfleja de la coronaria derecha. La extensi6n y gravedad de la aterosclerosis es menor en las mujeres que en los hombres en cada decada y eI proceso empieza una decada mas tarde. RESUME L'evolution naturelle de l'atherosclerose coronarienne a ete reconstituee a partir de renseignements rassernbles de 200 autopsies medico-Iegeles consecutives. L'atherosclerose coronarienne chez I'homme commence dans la deuxieme decenie sous forme de taches grasseuses qui sont surtout frequentes dans l'artere interventriculaire anterieure. La preuve la plus precoce d'atherosclerose chez la femme a ete observee dans la troisieme decenie, Le processus atherosclerotique ne depasse pas Ie grade I dans la deuxierne decenie. L'extension et la severite de l'atherosclerose augmentent progressivement avec I'age, sans chute terminale dans I'index atherosclerotique moyen. L'atherosclerose est presente dans tous les cas au-dessus de l'age de 40 ans, Les plaques fibreuses sont rernarquees pour la premiere fois dans la quatrierne decenie, Les lesions compliquees sont vues pour la premiere fois dans la cinquierne decenie. L'index de retrecissernent des arteres coronaires augmente egalement avec rage a partir de la quatrierne decenie, aucun retrecissernent significatif n'etant detectable plus tot. Le processus atherosclereux est nettement plus avance dans l'artere interventriculaire anterieure que dans la circonflexe ou dans l'artere coronaire droite. L'extension et la severite de l'atherosclerose est moindre chez les femmes que chez l'homme dans chacune des decenies, et Ie processus commence une decenie plus tard.
Diseasesof the
Ch~SI
ZUSAMMENFASSUNG Die Pathogenese der coronaren Arteriosklerose wurde aufgebaut aus einem an 200 aufeinanderfolgenden Sektionen. Die coronare Arteriosklerose bei Mannern beginnt in der zweiten Dekade in Form fettiger Fleckbildungen, die am haufigsten in dem anterioren absteigenden Ast der linken Coronararterie vorkommen. Die friihesten Anzeichen fUr eine Arteriosklerose bei Frauen liellen sich in der dritten Dekade erkennen. Der arteriosklerotische Prozess schreitet iiber die erste Stufe in der zweiten Dekade nicht hinaus. AusmaJ3 und Schwere der Arteriosklerose nimmt fortschreitend mit dem Alter zu, ohne terminalen Abfall im mittleren arteriosklerotischen Index. Die Arteriosklerose besteht in allen Fallen iiber 4{) Jahre. Fibrose Veriinderungen werden zuerst in der vierten Dekade beobachtet. Komplizierte Lasionen kann man erstmals in der 5. Dekade erkenen. Der Verengerungsindex der Coronararterien schreitet eben falls mit dem Alter von der 4. Dekade an fort, ohne daJ3 man eine signifikante Verengerung schon friiher bemerken kann. Der Prozess der Arteriosklerose ist gewohnllch starker fortgeschritten im anterioren absteigenden Ast der linken Coronararterie als in dem zirkularen Ast oder der rechten Coronararterie. AusmaJ3 und Schwere der Arteriosklerose sind geringer bei Frauen als bein Mannern in jedem Lebensabschnitt, und der Prozess beginnt eine Dekade spater,
2 3
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REFERENCES HOLMAN, R. L., MCGILL, H . C., JR., STRONO, J . P. AND GEER, J. C.: "Technics for Studying Atherosclerotic Lesions," Lab. Inuest ., 7 : 42, 1958. World Health Organization Technical Report Series No. 143, WHO Geneva, 1958. GoRE, I. AND TEJADA, C.: "The Quantitative Appraisal of Atherosclerosis," Am. ]. Path., 33 :875 , 1957. STRONO, J . P. AND MCGILL, H. C., JR. : "The Natural H istory of Coronary Atherosclerosis," Am. ]. Path ., 40:37, 1962. MATHUR, K . S., PATNEY, N. L. AND KUMAR. V.: "Atherosclerosis in India. An Autopsy Study of the Aorta and the Coronary, Cerebral, Renal and Pulmonary Arteries," Circulation, 24 :68, 1961. ACKERMAN, R . F., DRY, T. J. AND EDWARD, J. E. : "Relationship of Various Factors to the Degree of Coronary Atherosclerosis in Women," Circulation, 1: 1345, 1950. WHITE, N. K., EDWARD, J. E. AND DRY, T. J .: "The Relationship of the Degree of Coronary Atherosclerosis with Age in Men," Circulation , 1: 645, 1950. LoBER, P. H . : "Pathogenesis of Coronary Sclerosis," Arch . Path., 55: 359, 1953. ROBERTS, J. C., JR., MOSES, C. AND WILKINS, R. H .: "Autopsy Studies in Atherosclerosis . I. Distribution and Severity of Atherosclerosis in Patients Dying without Morphologic Evidence of Atherosclerotic Catastrophe," Circulation, 20:511, 1959.
Volume 46. No .1 July 1964
NATURAL HISTORY OF CORONARY ATHEROSCLEROSIS
10 WIG, K. L ., MALHOTRA, R. P., CHITKARA,
77
of Atherosclerosis. The Early Aortic Lesions as Seen in New Orleans in the Middle of the 20th Century," Am. I . Path ., 34 :209, 1958.
N . L . AND GUPTA, S. P.: "Prevalence of Coronary Atherosclerosis in Northern India," Brit. Med. I ., 2 :510, 1962 . II GoRE, I., ROBERTSON, W . B., HIRST, A. E., HADLEY, G. G . AND KOSSEKI, Y. : "Geographic Differences in the Severity of Aortic and Coronary Atherosclerosis. The United States, Jamaica, W . I., South India and Japan," Am. J. Path ., 36 : 559, 1960.
13 YOUNG, W. , GOFMAN, J. W ., TANDY, R., MALAMUD, N . AND WATERS, E . S. G .: "The Quantitation of Atherosclerosis. I. Relationship to Artery Size ," Am. J. Cardial., 6: 288, 1960. 14 MATHUR, K . S. : "Coronary Artery Occlusion," Indian I. Med. 13:7, 1959.
12 HOLMAN, R . L ., MCGILL, H . C ., Ja., STRONG, J. P. AND GEER, J. C. : "The Natural History
For reprints, please write Dr. Mathur, S. N. Medical College, Agra, U.P., Ind ia .
sa;
INVESTIGATION OF TUBERCULOSIS Following the discovery of a far advanced active case of tuberculosis In a pupil In a high school with an enrollment of 940 students. It was found that 31.2 per cent of the students had slgnlflcant tuberculin reactions and that among his close school contacts, the rate was 90 per cent. The epidemiologic Investigation revealed no other sources of contact with the disease and points of airborne spread In the school environment. Six members of the student body . Including the
sister of the Index case, developed reinfection type tuberculosis following exposure at school to the Index case . The attack rate among the students who had classroom contact at school with the Index case Is equal to that of young persons 15 to 24 years of age who had household exposure to an open case.
BRYANT, W. F.• JR., HUTCHESON. R. H . AND DILLON, A. : .. An Epidemiologic Investigation of Tuberculosis in a Ten nessee H igh School following Discovery of a Student Case." t . T''''''1Je' M.d. Asso( ., ~7 :42 . 1964.
ANGIOFOLLICULAR LYMPH NODE HYPERPLASIA A 27-year-old asymptomatic woman had a mass In the anterior mediastinum which was confused with a cardiovascular defect based on the results of physical examination and the flndlngs In routine roentgenograms. selective angiocardiography demonstrated the mass to be extracardlovascular. At surgical exploration. the mass was found to be an example of med iastinal anglofolllcular lymph node hyperplasla-a rate, benign lymph nodal enlargement of unknown cause. In the 47 cases of this entity which have been reported, both sexes have been equally affected ; the ages ranged from 13 through 58 years at the time of diagnosis. Sixty per
cent of the patients were less than 31 years of age . Of the 47 tumors, 35 (74 per cent) were thoracic and 12 (23 per cent) were extrathoracic. Most of the tumors within the thorax were asymptomatic mediastinal or hllar masses that were readily apparent on standard roentgenograms of the thorax. The extrathoraclc tumor usually presented as palpable masses In the soft tissues of the neck or of an upper extremity.
VENEZIELE. C. M •• SHERIDAN, L. A., PAYNE, W . S. AND HARRISON, E. G. : " Angiofoll icular Lymph Node Hyper· plas ia of the Mediastinum ," [ . T'bor, " ..d C",dio""s. S",g ., 47:111 .1964.
PENICILLIN HYPERSENSITIVITY The clinician faced with the problem of penicillin sensitivity complicating subacute bacterial endocarditis does not have to subject his patient to a known risk of an acute allergic reaction. While positive penicillin skin tests signify likely penicillin anaphylaxis, a negative response does not preclude anaphylaxis or other serious allergic reactions. Effective
alternate antibiotic regimens are at his disposal. Only after these have failed would penicillin desensitization seem justlfled. GRIECO, M. H .. DUBIN, M. R., ROBINSON. J. L. AND SCHWARTZ, M. J.: " Pen icill in Hypersensitivity in Patients with Bacterial Endocarditis ." A...., / ..t , M.tJ ., 60 :204. 1964.
S.
MATHUR, M.D.,
V.
KUMAR, M .D. AND
S.
K . KASHYAP, M.B .
Agra, India
T
They were drawn almost equally from both urban and rural population. The three main coronary arteries, namely the right coronary, left anterior descending branch with its main trunk and the left circumflex coronary arteries were cut transversely at intervals of 1 to 1 Y:z ern. and opened longitudinally. The vessels were studied both before and after staining with Sudan IV as described by Holman et aC and in the technical report of WHO.· The amount and severity of atherosclerosis and the atherosclerotic narrowing were assessed by the methods recommended by Gore and Tejada" in their atherosclerosis index. The atherosclerotic indices and the narrowing indices were calculated in each case for the coronary arterial bed and also for its main branches.
H E GEOGRAPHIC, RACIAL AND SEX DIF-
ferences in the prevalence of ischemic heart disease has focused attention on the study of atherosclerosis of the coronary arteries, which has been shown to be the most significant factor in determining the risk of occlusive episodes in a population. The earliest manifestations of atherosclerotic lesions commence in the intima of coronary vessels in the early decades and continue to progress silently and steadily. Gradually the lumen of the vessel is encroached upon and narrowed. The evolution of these mural changes constitutes the natural history of atherosclerosis of coronary arteries. In the present study, atherosclerotic lesions have been analyzed in the main arteries of the coronary system on gross inspection at necropsy, and the extent and severity of atherosclerosis has been quantitated. An estimation of the narrowing of the coronary vessels at different sites has been made. The probable course and sequence of events resulting in the atherosclerotic narrowing of the coronary arteries has been constructed from these data.
RESULTS
Table I summarizes the distribution of 200 cases and incidence of coronary atherosclerosis in relation to age and sex. TABLE I-INCIDENCE OF CORONARY ATHEROSCLEROSIS BY AGE AND SEX
Males
MATERIAL AND METHODS
Coronary arteries were removed in situ with the heart in 200 consecutive medicolegal necropsies performed at Sarojini Naidu Medical College, Agra, on cases dying of traumatic wounds and head injuries (89), suspected poisoning (53), gun shot and stab wounds (28), burns (15), drowning (1 1) and hanging (4) without showing any morphologic evidence of atherosclerotic catastrophe. This included 157 men and 43 women ranging from newborn to 80 years in age. Seventy-two per cent of them belonged to low socioeconomic group, 27 per cent to middle and 1 per cent to high socioeconomic group.
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The earliest evidence of atherosclerosis of the coronary arteries in the form of lipid spots and streaks was found in a 19-yearold man. The men were afllicted a decade earlier than women. After the age of 40
*From the Department of Medicine, Sarojini Naidu Medical College.
70
Volume 46. No .1 July 1964
NATURAL HISTORY OF CORONARY ATHEROSCLEROSIS
TABLE 2-ExTENT OF CORONARY ARTERY INTIMAL SURl'ACE INVOLVEMENT WITH ATHEROSCLEROSIS Extent of Surface Involvement (Number of Cases in Each Group) ABC D
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years, all cases, irrespective of age and sex, showed evidence of coronary atherosclerosis.
In Table 2 is given the extent of coronary artery intimal surface involvement by the atherosclerotic process. The mean surface area of the coronary arteries involved by atherosclerosis increased with age. Most of the cases below 40 years showed 0 to 15 per cent intimal surface involvement j none of them had more than 33 per cent surface involved. TABLE 3-MEAN CORONARY ARTERY SURFACE INVOLVEMENT BY ATHEROSCLEROSIS Per Cent Intimal Surface Involved by
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9.9 15.8 16.5
0.8 6.0 12.6
0.6 1.8
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61-70 71·80
37 .2 48.0
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In the fifth and sixth decades, 16 to 50 per cent surface was afflicted with atherosclerotic process in the majority of cases. The largest number of cases showing more than 50 per cent surface involvement was found in persons over 70 years of age (Fig. 1) . The percentage of intimal surface involvement by different types of lesions is given in Table 3. CORONARY ARTERY SURFACE INVOLVEMENT WITH ATHEROSCLEROSIS.
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The mean coronary artery surface involved by the atherosclerotic lesions increased from 2.5 per cent in the second decade to 48.0 per cent in the eighth decade. Fatty streaks constituted the sole lesion of atherosclerosis in the second and third decades and the predominant lesion up to the fifth and even the sixth decade. Fibrous plaques which were first detected in a man aged 33 years continued to contribute in progressively increasing proportion to the atherosclerotic process in later years. Complicated and calcified lesions appearing first in the fifth decade involved a maximum percentage of intimal surface in the eighth decade accounting for 8 per cent of total intimal surface (Fig. 2) . The mean of the atherosclerotic indices and the narrowing indices of the coronary arterial bed in each decade are given in Table 4.
Diseases of
MATHUR, KUMAR AND KASHYAP
72
Ctl~DNIIRY '",TIMIIL INYDLV4HENT
TABLE 4-MEAN ATHEROSCLEROTIC INDICES AND NAltitOWINO INDICES OF CORONARY AaTEItlES IN EACH DECADE Coronary Bed Atherosclerotic Index
Age Group (yean)
Narrowing Index
Below 10
0.0035±0.009* ( 0 - 0.03) 0.035±0.07 ( 0-0.33) 0.255±0.314 ( 0 - 1.23) 2.135±2.448 (0.03-15.43) 5.088±4.796 (0.03-15.40) 9.034±10.198 ( 1.83-35.2) 14.092± 6.985 (8.73-17.33)
11-20 21-30 31-40 41-50 51-60 61-70 71-80
the Chest
'Y DIFFERENT
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0.074±0.43* (0 - 2.59) 2.770±7.49 (0 - 44.00) 5.913±6.76 (0 - 30.67) 12.402± 9.99 (2.67-30.67) 29.46±20.19 (8.67-65.33)
-Indicates standard deviation. Figures in parentheses indicate range.
The mean atherosclerotic indices of the coronary arterial bed rose progressively from 0.0035 in the second decade to 14.092 in the eighth decade. The rate of rise was gradual during the first four decades, but accelerated thereafter. The progression in the mean narrowing indices was uniform throughout from 0.074 in the fourth decade to 29.46 in the eighth decade. The mean atherosclerotic and the narrowing indices of the coronary arteries for
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males and females are given in Table 5. The values of mean atherosclerotic indices and the narrowing indices were higher in males than females in each decade, except in the sixth and the seventh decades where higher values were observed in females. This may be due to the very small number of females as compared to males in these age groups. The means of the atherosclerotic indices
TABLE 5-MEAN ATHEROSCLEROTIC AND NAltitOWINO INDICES OF CORONARY AaTEItlES FOR MALES AND FEMALES IN EACH DECADE Age Group (yean) Below 10
11-20
21-30 31·40 41·50 51-60 61-70 71-80
Atherosclerotic Index
Males Narrowing Index
0.0054 (0-0.03) 0.037 (0-0.33) 0.269 (0-1.23) 2.433 (0.03-15.4) 4.639 (0.03-15.4) 9.326 (01.83-35.2) 14.44 (8.73-17.33)
Figures in parentheses indicate range.
0.089 (0-2.59) 3.194 (0-44.0) 4.527 (0-13.33) 10.831 (2.67-30.67 ) 33.925 ( 13.30-65.33)
Atherosclerotic Index
0.029 (0-0.13) 0.03 (0.03-0.03 ) 0.697 (0.03-1.23) 8.680 (4.83-12.53) 8.015 (2.93-13.10) 12.70 ( ,- )
Females
Narrowing Index
0.721 (0-2.00) 17.00 (3.33-30.67) 17.90 (5.13-30.67) 11.33 ( -
)
Volume 46. No . I July 1964
NATURAL HISTORY OF CORONARY ATHEROSCLEROSIS
73
TABLE 6-MEAN ATHEROSCLEROTIC INDICES OF RIGHT CORONARY LEFT ANTERIOR DESCENDING CORONARY AND THE LEFT CIRCUMFLEX CORONARY ARTERIES IN EACH DECADE
Age Group (years)
Left Anterior Descending Coronary
Right Coronary
Below 10 11-20 21-30 31-40 41-50 51-60 61-70 71-80
0.0015±0.04* (0-0.03) 0.038±0.075 (0-0.33) 0.280±0.34 (0-1.23) 2.794±4.86 (0.03-25.30) 6.700±7.37 (0 .03-28.37 ) 12.122±13.12 (2.13-45.10) 18.412±6.44 (8.73-27.10)
0.022±0.055* (0-0.33) O.125±0.172 (0-0.63) 1.690±4.30 (0-26.30) 3.1l1±3.60 (0-15.40) 6.167±7.10 (1.53-25.33 ) 7.832±4.928 (3.70-17.33)
Left Circumflex Coronary
0.013±0.034* (0-0.33) 0.129±0.194 (0-0.63) 1.023±1.47 (0-7.68) 3.376±3.83 (0-15 .40) 5.328±4.83 ( 1.23-15.40) 11.032±4.17 (5.13-17.33)
*Indicates standard deviation. Figures in parentheses denote range.
highest and there were no marked differences in values for the right coronary and the left circumflex coronary arteries . The mean narrowing indices of the main arteries of the coronary system in each decade are given in Table 7. An appreciable degree of atherosclerotic narrowing in the coronary arterial bed was observed first of all in the left anterior descending coronary artery in the fourth decade and a decade later in the right coronary and the left circumflex arteries. The mean narrowing indices of the coronary arteries showed progression with age up to the eighth decade. The left anterior de-
for the main arteries of the coronary system are given in Table 6. The left anterior descending branch is the first artery to be afHicted with atherosclerosis in the second decade, the mean index being 0.0015 . Atherosclerosis appeared in the right coronary and the left circumflex arteries in the third decade, and the values of the mean atherosclerotic indices were 0.022 and 0.013, respectively. In all the coronary arteries the degree of atherosclerosis progressed with age up to the eighth decade. In any decade, however, the mean atherosclerotic index for the left anterior descending coronary artery was
TABLE 7-MEAN NARROWING INDICES OF RIGHT CORONARY, LEFT ANTERIOR DESCENDING CORONARY AND LEFT CIRCUMFLEX ARTERIES IN EACH DECADE
Age Group
Right Coronary
Below 10 11-20 21-30 31-40 41-50 51-60 61-70 71-80
Left Anterior Descending Coronary
Left Circumflex Coronary
0.074±2.49*
( 1.753±7.07* (0-42.70) 1.629±2.02 (0-7.33) 4.592±4.12 (1.33-13.33 ) 11.866±8.09 (4.67-26.67 )
-
)
1.447±1.83 (0-9.33) 4.666±5.89 (0-26.67) 11.035±9.51 ( 1.33-30.67) 20.00±8.509 (7.33-30.61)
*Indicate standard deviation. Figures in parentheses denote range.
0.456±0.79* (0-3.33) 1.865±2.45 (0-9.33) 4.596±3.83 ( 1.33-13.33) 12.126±8.20 (4 .00-26.67 )
MATHUR, KUMAR AND KASHYAP
74
scending coronary artery showed more marked degree of narrowing as compared to other branches in each age group . COMMENTS
The results of the present study indicate that the mural lesions of atherosclerosis of the coronary arteries comprise a series of changes which commence early in life beginning as early as the second decade in a few cases. As age advances, these lesions are found in an increasingly larger proportion of individuals until by about the fifth decade, they are present in all cases. The extent and severity of atherosclerotic lesions varies from person to person and also, in the individual arteries, but no adult in that age group could be classed as free from atherosclerosis. Strong and McGill" from the United States reported that among the white and Negro adults of their population, the prevalence of grossly visible lesions had also become universal in the fifth decade. However, in the United States, whites showed a much more severe degree of coronary atherosclerosis in any decade than ours. The influence of age on the extent and severity of atherosclerosis indicates that the process advances with increasing years as reported by us earlier." A similar relationship in age and coronary atherosclerosis has been observed by other workers."?" The rate of rise of the mean atherosclerotic index appears to be very gradual in the first four decades, but became accelerated thereafter . Part of this lack of uniformity in the rate of rise could be explained on the basis of logarithmic weighting employed for the purpose of converting the atherosclerotic profile into the atherosclerotic index. However, the results may also be interpreted to mean that after the initial foci of lipid deposition in the form of lipid spots and streaks have occurred in the intima, a number of factors beside the original ones which laid the foundation of the atherosclerotic process come into play, and the process develops a tendency to progress more rapidly. Lober" had reported that
Diseasesof the Chest
atherosclerosis In coronary arteries progresses at a nearly uniform rate, but this has not been substantiated by our observations. It seems unlikely that a process which passes through so many different phases in the course of its natural history should have a uniform rate of progression. Analysis of the extent of intimal involvement in different decades shows that this increases with age. This extension has also been observed in other studies.tt As the process of atherosclerosis advances, the newer lesions seem to encroach upon the unaffected regions. It is likely that as the early lesions are being transformed into the more advanced types, crops of early grades of lesions continue to appear throughout life. According to Gore et al.tt there are geographic differences in the rate of this extension, which is reportedly slower in Japanese and maximum in whites of the United States. The incidence of fatty streaks, which first appeared at the age of 19 years, continues to rise until the sixth decade and declines thereafter. After the fifth decade, the fibrous plaques contribute most predominantly towards the atherosclerotic process. The fibrous plaques appear almost 15 to 20 years later than the fatty streaks, which are supposed to act as an analogue for the formation of the fibrous plaques. According to Holman et al.tl it takes about 20 years for fatty streaks to convert into the fibrous plaques in the aorta. Our observations for the coronary arteries are in conformitv with their views. The complicated and calcified atherosclerotic lesions which predispose to occlusion of coronary lumen and correlate with the risk of ischemic heart disease, have been noticed much less frequently in our cases as compared to those reported by Strong and McGill." These complicated lesions were noticed earliest in the fifth decade about 20 years after they are seen in the white population of the United States (Gore et al.tt). These lesions increased in proportion from 4 per cent in the fifth decade to 16 per cent in the eighth decade. Even then at all age
Volume 46, No.1 July 1964
NATURAL HISTORY OF CORONARY ATHEROSCLEROSIS
periods they were the least prevalent of all the other types of atherosclerotic lesions, i.e. fatty streaks and fibrous plaques. These observations confirm the view that the progression of the severity of atherosclerosis in different geographic regions is variable. The geographic variations in the prevalence of coronary atherosclerosis re-emphasizes the importance of environmental factors in atherogenesis. All the stages in the process of the evolution of atherosclerosis seem to come up at an earlier age in the men than in the women. The magnitude of difference for various types of lesions remains almost the same between the two sexes and it appears that the pace at which the earlier lesions are transformed into the subsequent more advanced types does not differ in the two sexes, but rather the process in its initial form commences later in females. The degree of atherosclerosis when compared in three main branches was such that the process, in most of the cases, appeared a decade earlier and was more advanced in the left anterior descending branch than in the other two branches. This is in agreement with the findings of Lober,' Roberts et al.' and Wig et al" The latter two groups believe that the right coronary and the left anterior descending coronary artery generally contain the most severe coronary atherosclerosis. However, this has not been observed in our cases for the right coronary artery . These differences in the degree of atherosclerosis in the three main arteries of the coronary system were more evident in the women than in the men. This finding when viewed in conjunction with the observation that the extent and severity of atherosclerosis in men in any decade is greater than in women, becomes important when correlated with much higher incidence of clinical episodes of ischemic heart disease in men as compared to women. Young et al" have reported that the degree of atherosclerosis in any artery varies directly with its radius. Our observations as discussed above have shown that
75
the degree of atherosclerosis increases progressively with age. We have also noticed in our study that the mean "narrowing index" of the coronary artery increases with age. This may be related to the concomitant increase in the size of the coronary arteries, which is supposed to take place with advancing age. The severest narrow ing was observed in the left anterior descending artery. The more frequent occurrence of infarcts in the region of the blood supply of this artery, reported by one of us (K. S. Mathur) 14 could be attributed to this fact. SUMMARY
The natural history of coronary atherosclerosis has been reconstructed from data gathered from 200 consecutive medicolegal necropsies. Coronary atherosclerosis in men commences in the second decade in the form of fatty spots which are most frequent in the anterior descending branch of the left coronary artery . The earliest evidence of atherosclerosis in women was seen in the third decade. The atherosclerotic process does not progress beyond grade I in the second decade. The extent and severity of atherosclerosis increases progressively with age, without a terminal decline in the mean atherosclerotic index. Atherosclerosis is present in all cases above 40 years. Fibrous plaques are first noticed in the fourth decade. Complicated lesions are seen for the first time in the fifth decade. The narrowing index of the coronary arteries also progresses with age from the fourth decade onwards, no significant narrowing being detectable earlier. The proces." of atherosclerosis is consistently more advanced in the anterior descending branch of the left coronary artery than in the circumflex branch or the right coronary artery. The extent and severity of atherosclerosis is less in women than in the men in each decade and the proces" commences a decade later. RESUMEN
La historia natural de aterosclerosis corona ria ha sido recontruida gracias a los datos reunidos de 200 casas consecutivos de necropsias medico-
MATHUR, KUMAR AND KASHYAP
legales. La aterosclerosis coronaria en los hombres comienza en la segunda decada en la forma de puntos grasosos que son mas frecuentes en la rama anterior descendente de la coronaria izquierda. La mas temprana evidencia de aterosclerosis en las mujeres fue vista en la tercera decada. El proceso ateroscleroso no progresa mas alla del grado I en la segunda decada, La extensi6n y la gravedad de la aterosclerosis aumenta progresivamente con la edad, sin declinaci6n terminal media del Indice ateroscler6tico. La aterosclerosis esta presente en todos los casos arriba de 40 afios, Las pia cas fibrosas se notaron primeramente en la cuarta decada, EI Indice de estrechamiento de las coronarias tarnbien progresa con la edad desde la cuarta decada en adelante. Antes no se encontr6 estrechamiento de significaci6n. EI proceso de la aterosclerosis es constantemente mas avanzado en la rama anterior decendente de la arteria coronaria izquierda que en la rama circunfleja de la coronaria derecha. La extensi6n y gravedad de la aterosclerosis es menor en las mujeres que en los hombres en cada decada y eI proceso empieza una decada mas tarde. RESUME L'evolution naturelle de l'atherosclerose coronarienne a ete reconstituee a partir de renseignements rassernbles de 200 autopsies medico-Iegeles consecutives. L'atherosclerose coronarienne chez I'homme commence dans la deuxieme decenie sous forme de taches grasseuses qui sont surtout frequentes dans l'artere interventriculaire anterieure. La preuve la plus precoce d'atherosclerose chez la femme a ete observee dans la troisieme decenie, Le processus atherosclerotique ne depasse pas Ie grade I dans la deuxierne decenie. L'extension et la severite de l'atherosclerose augmentent progressivement avec I'age, sans chute terminale dans I'index atherosclerotique moyen. L'atherosclerose est presente dans tous les cas au-dessus de l'age de 40 ans, Les plaques fibreuses sont rernarquees pour la premiere fois dans la quatrierne decenie, Les lesions compliquees sont vues pour la premiere fois dans la cinquierne decenie. L'index de retrecissernent des arteres coronaires augmente egalement avec rage a partir de la quatrierne decenie, aucun retrecissernent significatif n'etant detectable plus tot. Le processus atherosclereux est nettement plus avance dans l'artere interventriculaire anterieure que dans la circonflexe ou dans l'artere coronaire droite. L'extension et la severite de l'atherosclerose est moindre chez les femmes que chez l'homme dans chacune des decenies, et Ie processus commence une decenie plus tard.
Diseasesof the
Ch~SI
ZUSAMMENFASSUNG Die Pathogenese der coronaren Arteriosklerose wurde aufgebaut aus einem an 200 aufeinanderfolgenden Sektionen. Die coronare Arteriosklerose bei Mannern beginnt in der zweiten Dekade in Form fettiger Fleckbildungen, die am haufigsten in dem anterioren absteigenden Ast der linken Coronararterie vorkommen. Die friihesten Anzeichen fUr eine Arteriosklerose bei Frauen liellen sich in der dritten Dekade erkennen. Der arteriosklerotische Prozess schreitet iiber die erste Stufe in der zweiten Dekade nicht hinaus. AusmaJ3 und Schwere der Arteriosklerose nimmt fortschreitend mit dem Alter zu, ohne terminalen Abfall im mittleren arteriosklerotischen Index. Die Arteriosklerose besteht in allen Fallen iiber 4{) Jahre. Fibrose Veriinderungen werden zuerst in der vierten Dekade beobachtet. Komplizierte Lasionen kann man erstmals in der 5. Dekade erkenen. Der Verengerungsindex der Coronararterien schreitet eben falls mit dem Alter von der 4. Dekade an fort, ohne daJ3 man eine signifikante Verengerung schon friiher bemerken kann. Der Prozess der Arteriosklerose ist gewohnllch starker fortgeschritten im anterioren absteigenden Ast der linken Coronararterie als in dem zirkularen Ast oder der rechten Coronararterie. AusmaJ3 und Schwere der Arteriosklerose sind geringer bei Frauen als bein Mannern in jedem Lebensabschnitt, und der Prozess beginnt eine Dekade spater,
2 3
4 5
6
7
8 9
REFERENCES HOLMAN, R. L., MCGILL, H . C., JR., STRONO, J . P. AND GEER, J. C.: "Technics for Studying Atherosclerotic Lesions," Lab. Inuest ., 7 : 42, 1958. World Health Organization Technical Report Series No. 143, WHO Geneva, 1958. GoRE, I. AND TEJADA, C.: "The Quantitative Appraisal of Atherosclerosis," Am. ]. Path., 33 :875 , 1957. STRONO, J . P. AND MCGILL, H. C., JR. : "The Natural H istory of Coronary Atherosclerosis," Am. ]. Path ., 40:37, 1962. MATHUR, K . S., PATNEY, N. L. AND KUMAR. V.: "Atherosclerosis in India. An Autopsy Study of the Aorta and the Coronary, Cerebral, Renal and Pulmonary Arteries," Circulation, 24 :68, 1961. ACKERMAN, R . F., DRY, T. J. AND EDWARD, J. E. : "Relationship of Various Factors to the Degree of Coronary Atherosclerosis in Women," Circulation, 1: 1345, 1950. WHITE, N. K., EDWARD, J. E. AND DRY, T. J .: "The Relationship of the Degree of Coronary Atherosclerosis with Age in Men," Circulation , 1: 645, 1950. LoBER, P. H . : "Pathogenesis of Coronary Sclerosis," Arch . Path., 55: 359, 1953. ROBERTS, J. C., JR., MOSES, C. AND WILKINS, R. H .: "Autopsy Studies in Atherosclerosis . I. Distribution and Severity of Atherosclerosis in Patients Dying without Morphologic Evidence of Atherosclerotic Catastrophe," Circulation, 20:511, 1959.
Volume 46. No .1 July 1964
NATURAL HISTORY OF CORONARY ATHEROSCLEROSIS
10 WIG, K. L ., MALHOTRA, R. P., CHITKARA,
77
of Atherosclerosis. The Early Aortic Lesions as Seen in New Orleans in the Middle of the 20th Century," Am. I . Path ., 34 :209, 1958.
N . L . AND GUPTA, S. P.: "Prevalence of Coronary Atherosclerosis in Northern India," Brit. Med. I ., 2 :510, 1962 . II GoRE, I., ROBERTSON, W . B., HIRST, A. E., HADLEY, G. G . AND KOSSEKI, Y. : "Geographic Differences in the Severity of Aortic and Coronary Atherosclerosis. The United States, Jamaica, W . I., South India and Japan," Am. J. Path ., 36 : 559, 1960.
13 YOUNG, W. , GOFMAN, J. W ., TANDY, R., MALAMUD, N . AND WATERS, E . S. G .: "The Quantitation of Atherosclerosis. I. Relationship to Artery Size ," Am. J. Cardial., 6: 288, 1960. 14 MATHUR, K . S. : "Coronary Artery Occlusion," Indian I. Med. 13:7, 1959.
12 HOLMAN, R . L ., MCGILL, H . C ., Ja., STRONG, J. P. AND GEER, J. C. : "The Natural History
For reprints, please write Dr. Mathur, S. N. Medical College, Agra, U.P., Ind ia .
sa;
INVESTIGATION OF TUBERCULOSIS Following the discovery of a far advanced active case of tuberculosis In a pupil In a high school with an enrollment of 940 students. It was found that 31.2 per cent of the students had slgnlflcant tuberculin reactions and that among his close school contacts, the rate was 90 per cent. The epidemiologic Investigation revealed no other sources of contact with the disease and points of airborne spread In the school environment. Six members of the student body . Including the
sister of the Index case, developed reinfection type tuberculosis following exposure at school to the Index case . The attack rate among the students who had classroom contact at school with the Index case Is equal to that of young persons 15 to 24 years of age who had household exposure to an open case.
BRYANT, W. F.• JR., HUTCHESON. R. H . AND DILLON, A. : .. An Epidemiologic Investigation of Tuberculosis in a Ten nessee H igh School following Discovery of a Student Case." t . T''''''1Je' M.d. Asso( ., ~7 :42 . 1964.
ANGIOFOLLICULAR LYMPH NODE HYPERPLASIA A 27-year-old asymptomatic woman had a mass In the anterior mediastinum which was confused with a cardiovascular defect based on the results of physical examination and the flndlngs In routine roentgenograms. selective angiocardiography demonstrated the mass to be extracardlovascular. At surgical exploration. the mass was found to be an example of med iastinal anglofolllcular lymph node hyperplasla-a rate, benign lymph nodal enlargement of unknown cause. In the 47 cases of this entity which have been reported, both sexes have been equally affected ; the ages ranged from 13 through 58 years at the time of diagnosis. Sixty per
cent of the patients were less than 31 years of age . Of the 47 tumors, 35 (74 per cent) were thoracic and 12 (23 per cent) were extrathoracic. Most of the tumors within the thorax were asymptomatic mediastinal or hllar masses that were readily apparent on standard roentgenograms of the thorax. The extrathoraclc tumor usually presented as palpable masses In the soft tissues of the neck or of an upper extremity.
VENEZIELE. C. M •• SHERIDAN, L. A., PAYNE, W . S. AND HARRISON, E. G. : " Angiofoll icular Lymph Node Hyper· plas ia of the Mediastinum ," [ . T'bor, " ..d C",dio""s. S",g ., 47:111 .1964.
PENICILLIN HYPERSENSITIVITY The clinician faced with the problem of penicillin sensitivity complicating subacute bacterial endocarditis does not have to subject his patient to a known risk of an acute allergic reaction. While positive penicillin skin tests signify likely penicillin anaphylaxis, a negative response does not preclude anaphylaxis or other serious allergic reactions. Effective
alternate antibiotic regimens are at his disposal. Only after these have failed would penicillin desensitization seem justlfled. GRIECO, M. H .. DUBIN, M. R., ROBINSON. J. L. AND SCHWARTZ, M. J.: " Pen icill in Hypersensitivity in Patients with Bacterial Endocarditis ." A...., / ..t , M.tJ ., 60 :204. 1964.