Atherosclerosis in human populations

Atherosclerosis Elsevier Publishing

Company,

ATHEROSCLEROSIS

JACK

Amsterdam

IN HUMAN

-

193

Printed in The Netherlands

POPULATIONS*

P. STRONG

Louisiana

State University Medical

(Received

January 25th, 1972)

Center, New Orleans, La. (U.S.A.)

SUMMARY

similar

This report presents a comparison of atherosclerotic lesions in populations ethnic origin but in diverse environmental settings. The large differences

of in

average extent of atherosclerosis among the white populations and among the Negro populations suggest that environmental conditions may be important determinants of the prevalence and extent of atherosclerotic lesions.

Key words:

Atherosclerosis - Populations - Lesioms - Envirommental

- Ethnic groups - Aortas - Corortary arteries

INTRODUCTION

A recent symposium has indicated that migrant populations afford unique opportunities for studying the effects of environmental changes on persons of similar ethnic

groupsl.

Although

not strictly

comparable

to most studies

of migrant

popu-

lations, the autopsy populations which were investigated in the International Atherosclerosis Project2 provide a framework for comparing populations of similar ethnic origin in diverse environmental settings. Some of the findings of the International Atherosclerosis Project are presented in this context. BACKGROUND OF THE INTERNATIONAL ATHEROSCLEROSIS PROJECT

In 1959, pathologists from several countries organized a cooperative survey to secure reliable and comparable data on atherosclerosis from different populations. The investigations were supported in part by Grants HL-14496, HL-08974. HL-07913 and HL-04152 from the National Heart Institute, United States Public Health Service to the central laboratories and by many other sources for the other participating institutions. * Presented at meeting of the Working Group of the UICC Committee on Studies of Migrant Populations at the East-West Center in Honolulu, February 5-12, 1969. Atherosclerosis,

1972, 16: 193-201

194

JACK P. STRONG

Table 1 shows the names and locations of the investigators who participated in the survey, and the ethnic groups from which they collected arteries. These investigators met at the Institute of Nutrition of Central America and Panama in Guatemala in 1960 and drafted a standard operating protocol of methods for the studys. They collected a total of 23,000 cases between 1960 and 1965. The methods were simplea. In each laboratory,

technicians dissected the coro-

nary arteries and aortas from persons lo-69 years of age, autopsied in medicolegal services or large general hospitals. The pathologist then submitted these arteries, along with accessory information to a central laboratory. In the central laboratory the arteries were stained with Sudan IV to delineate fatty lesions and repackaged in plastic bags. A team of five pathologists estimated for each of five arteries (three branches of coronary arteries, thoracic and abdominal aorta) the percent intimal surface involved by fatty streaks, fibrous plaques, complicated lesions, and calcified lesions. The supervising statistician introduced procedures to standardize the grading and to estimate -the error of the methods. The investigators were aware of the limitations of autopsy material as a source of information about the living population and attempted to reduce some of the bias due to different causes of deathQ3. First, all cases with diseases known to be associated with more severe atherosclerosis, such as coronary heart disease, stroke, hypertension,

TABLE

1

PARTICIPANTS

IN THE INTERNATIONAL

ATHEROSCLEROSIS

Bogoti Cali

Colombia Colombia

Egon Lichtenberger Pelayo Correa

Caracas

Venezuela

Luis Carbonell

San Jose Durban Guatemala

Costa Rica South Africa Guatemala

Kingston Lima

Jamaica Peru

Jorge Salas John Wainwright Carlos Tejada Carlos Restrepo Miguel Guzmln William B. Robertson Javier Arias-Stella

Manila Mexico New Orleans

Philippines Mexico United States

Norway

Atherosclerosis,

1960-1965

Races

Location

San Juan Santiago S%o Paul0

PROJECT,

Puerto Rico Chile Brasil 1972, 16: 193-201

Benjamin Barrera Ruy Perez Tamayo Henry C. McGill, Jr. Jack P. Strong Douglas A. Eggen C. A. McMahan Lars A. Solberg Aagot C. liken Kristen Arnesen Lorenzo Galindo Sergio Donoso Mario Montenegro

American Indian-white and white American Indian-white, white and American Indian American Indian-white, white, and American Indian White Bantu and Asian Indian American Indian and American Indian-white Negro and mulatto American Indian and American Indian-white Filipino American Indian-white Negro and white

White White, mulatto, and Negro White White, Negro, and mulatto

195

ATHEROSCLEROSIS IN HUMAN POPULATIONS

and diabetes were excluded. The remaining cases were divided into four broad causeof-death

categories,

i.e. accidents,

cancers, infections,

causes. The average extent of involvement

and selected miscellaneous

by each type of atherosclerotic

lesion

was determined in each of these four cause-of-death categories within each location, race, sex, and age subgroup. No consistent differences appeared in relation to causeof-death. Therefore, the four categories were pooled into one large group and major comparisons were made within this group (about 65% of the total pool of 23,000 cases). The major results of this investigation

have been published in the May 1968

issue of Laboratory Investigation 2. This volume described the demographic aspects, methodology, geographic, race and sex comparisons, and other special topics in some detail. For each location-race group an overall mean extent of raised lesions (fibrous plaques plus complicated lesions plus calcified lesions) was computed by averaging the 40 individual means for the five arteries, two sexes and four lo-year-age groups (from 25 to 64 years). Table 2 shows the 19 location-race

groups ranked by this overall mean extent

of raised lesions. The extent of raised lesions ranged from a low of 6.2 o/oin Durban Bantu to a high of 18.3% in New Orleans whites. For convenience the investigators divided these populations into five arbitrary groups of atherosclerotic high, medium high, medium, medium low, and 10~7.

TABLE NINETEEN

involvement:

2 LOCATION-RACE

Location-race

group

New Orleans white Oslo Durban Indian New Orleans negro Manila Caracas SLo Paulo white Puerto Rico white Jamaica Negro Cali Puerto Rico Negro Lima Costa Rica Santiago Mexico SLo Paulo Negro Bogota. Guatemala Durban Bantu

GROUPS

RANKED

Rank

1 2 3 4 5 6 ; 9 10 11 12 13 14 15 16 17 18 19

BY

MEAN*

EXTENT

OF RAISED

LESION

(RL)

Mean percent* of intimal surface involved with RL

Arbitrary classijication

18.3 17.8 14.6 14.5 12.8 12.1 10.8 9.6 9.5 9.1 8.8 8.5 8.4 8.2 7.9 7.4 6.7 6.5 6.2

High High Medium Medium Medium Medium Medium Medium Medium Medium Medium Medium Medium Medium Medium Low Low Low Low

high high

low low low low low low low low low

* See text for method of calculation. Atherosclerosis,

1972, 16: 193-201

196

JACK P. STRONG

These 19location-race in the coronary

groups were also ranked

concluded

that

populations

and stenosis

ATHEROSCLEROSIS

IN

similar rank order was obtained.

with more extensive

tend to have more in the coronary calcification,

of raised lesions

arteries alone, in the aorta alone, in each sex alone, and in each decade

of age alone. In all cases, a substantially gators

by mean extent

arteries

also ranked

SIMILAR

also. Prevalence

populations

ETHNIC

raised

GROUPS

lesions

of complicated

in approximately FROM

The investiin the aorta

DIFFERENT

lesions,

the same order. GEOGRAPHIC

LOCATIONS

For this report, major emphasis is on comparisons of atherosclerosis among “similar” ethnic groups from different geographic regions. The 19 geographically and

ethnically

distant

groups

(location-race

groups,

for convenience)

have

been

separated into broad ethnic groups where possible. It is not claimed that the“similar” groups (“Negro”, “ Indian”, etc.) are genetically identical in all places. This subclassification really provides only the crudest sort of framework for making comparisons within

ethnically

“similar”

populations.

Some obvious

differences

in genetic

back-

ground and possibilities of racial admixture in the different populations of both white and Negro ethnic groups occur to the novice; the expert geneticist, anthropologist, and epidemiologist will be aware of more. Nevertheless, this crude classification social race provides a means of approaching the investigation of atherosclerosis “similar”

ethnic

groups

from different

vironmental backgrounds. The six locations with reasonably clude New Orleans,

Oslo, S5o Paulo,

geographic

locations

large numbers Puerto

and with different

by in en-

of cases classified as white in-

Rico, Costa Rica, and Santiago.

Mean

extent of atherosclerotic raised lesions in the anterior descending branch of the left coronary artery for five age groups varies considerably among the different geographic population groups (Table 3, Section A). The New Orleans and Oslo white men consistently have more raised lesions than the other groups, A slight gradient exists among the four other groups with the cases from SBo Paulo and Puerto Rico somewhat higher than the cases from Costa Rica and Santiago. Five locations had sufficient numbers of cases classified as Negroes for analyses. These locations were New Orleans, Jamaica, Puerto Rico, S%o Paulo, and Durban. Cases classified as mulattos were included in the negro group as were the Bantu which comprised most of the Durban cases in this category. Comparison of mean extent of lesions in the Negro ethnic group (Table 3, Section B) shows that the New Orleans cases are highest, the Durban cases lowest, and the cases from Jamaica, Puerto Rico and S%o Paulo intermediate. The locations in which there were mixed American Indian-whites and American Indians are included in Table 3, Section C. This mixed category also includes some cases classified as white in Caracas, Cali, and Bogota; therefore, the location-race groups in this broad ethnic category may be less comparable than in the preceding groups. Except for the cases from Caracas (the most severely diseased group) there Atherosclerosis,

1972, 16: 193-201

NUMBER

15-24

D Other Durban Manila

Indian

36 40

23 72 162 23 36 92

97 31 49 50 60

B Negro New Orleans Jamaica Puerto Rico SBo Paul0 Durban

C American Indianwhite Caracas Cali Lima Mexico Bogota Guatemala

63 26 150 136 355 76

No. of cases

IN IN

0.6 1.9

2.5 0.9 0.4 0.0 0.3 0.6

2.5 0.6 0.7 0.6 0.8

2.1 1.9 0.9 0.6 0.7 0.6

with RL

involved

surface

Intimal

MEN

PERCENTAGE

ARRANGED

Age group

GROUPS

ARTERY,

MEAN

A White New Orleans Oslo SBo Paul0 Puerto Rico Santiago Costa Rica

group

AND

CORONARY

CASES

LOCATION-RACE

Location-race

19

DESCENDING

3

OF

TABLE OF

46 32

23 81 207 29 51 103

124 29 68 73 153

10 152 131 526 67

84

cases

No. of

25-34

OF

INTIMAL DIED

ETHNICALLY

WHO

SURFACE

involved with RL

surface

8.0 6.1

8.3 1.6 2.5 1.0 1.3 2.4

5.0 3.2 2.7 2.9 2.7

13.6 a.7 4.2 4.2 3.1 2.5

CANCER,

INVOLVED

CATEGORIES

Intimal

SIMILAR

ACCIDENTS,

WITH

35-44

30 32

35 44 207 45 46 114

114 23 60 54 160

110 52 137 116 516 79

cases

No. of

13.1 16.3

13.8 7.6 5.5 5.5 4.3 4.9

11.9 8.0 9.1 7.4 4.4

21.4 22.2 10.8 9.6 7.9 6.6

44 35

26 36 158 46 64 135

120 55 56 27 142

156 52 105 140 434 81

LESIONS

24.5 22.5

12.9 15.4 13.6 14.7 9.6 8.0

18.6 10.5 6.0 9.2 7.2

32.4 31.2 18.3 15.1 14.1 12.4

Intimal surface involved with RL

MISCELLANEOUS

No. of cases

45-54

SELECTED

ATHEROSCLEROTIC AND

Intimal surface involved with RL

RAISED

INFECTIONS,

IN

22 24

30 29 156 24 64 146

110 53 34 17 113

134 112 50 98 284 79

No. of cases

BY

THE

55-64

CAUSES,

(RL) AGE,

LEFT

32.7 33.5

25.3 18.0 18.0 10.3 12.9 11.7

27.5 20.7 18.1 12.6 11.6

34.9 36.1 21.0 19.6 20.4 18.3

Intimal surface involved with RL

WITH

ANTERIOR AND

198

JACK P. STRONG

is little consistent difference in mean involvement with atherosclerosis among these groups. For completeness,

the two remaining location-race

groups, Durban

Indian

and Manila, are included in Table 3, Section D. Both of these groups have greater average involvement with atherosclerosis than any of the Negro groups or American Indian-white groups. It is unfortunate that other populations of Asian origins could not be included in the study. Table 4 shows similar comparisons among the white andNegro ethnic groups for mean extent of raised lesions in different arterial segments. In this table the mean of the eight means for four age groups (25-34, 35-44, 45-54, and 55-64) and two sexes are used for comparison. With only minor variations, the groups rank in about the same order regardless of the arterial segment.

TABLE

4

UNWEIGHTED SCLEROTIC OUS CAUSES AND

WITH

MEANS

LESIONS

OF

(RL)

PERCENTAGE

IN BOTH SEXES LOCATION-RACE

Location-vace

OF

IN CASES WHO DIED

INTIMAL

OF FOUR AGE GROUPS GROUPS

SURFACE

OF ACCIDENTS,

ARRANGED

(25-64

INVOLVED

CANCER,

YEARS)

IN ETHNICALLY

WITH

INFECTIONS,

ACCORDING SIMILAR

RAISED

ATHERO-

AND MISCELLANE-

TO ARTERIAL

SEGMENT

CATEGORIES

Artery (surface involved with RL) Thoracic aorta

Abdominal aorta

Right coronary

Circatmflex coronary

Left anterior de&ending coronary

A White New Orleans Oslo SBo Paul0 Puerto Rico Santiago Costa Rica

12.9 11.7 9.3 7.3 7.3 7.4

29.9 24.9 17.3 14.8 12.0 14.2

16.2 17.1 8.2 8.5 7.1 6.8

13.2 13.8 7.3 6.5 5.5 5.0

19.1 21.3 11.7 10.6 8.9 8.4

B Negro New Orleans Jamaica Puerto Rico Slo Paul0 Durban Bantu

10.7 7.5 8.9 5.2 5.2

20.2 13.8 14.4 12.4 9.3

13.7 8.6 6.1 5.4 5.2

12.4 6.2 6.1 5.3 4.5

15.9 11.0 8.1 8.7 6.4

American Indianwhite Caracas Cali Lima Mexico BogotO Guatemala

10.2 8.3 7.2 8.1 6.0 7.2

20.0 16.8 12.4 12.6 11.4 10.7

10.9 7.2 7.8 7.3 5.5 4.9

7.2 4.0 5.7 4.5 3.5 3.6

11.8 9.1 9.1 7.0 6.9 6.0

D Other Durban Indian Manila

12.0 10.4

18.9 21.4

14.6 10.0

11.3 8.3

16.2 13.8

Atherosclerosis,

1972, 16: 193-201

ATHEROSCLEROSIS

SEX

IN HUMAN

199

POPULATIONS

DIFFERENCES

Fig. 1 depicts

unweighted

mean involvement

for men and women

separately

(four age groups, 25-64 years) in the aorta and in the coronary arteries. Large differences in the extent of coronary atherosclerosis between the sexes in the white groups generally

parallel

respective

the well known sex differences

populations.

lesions within

There

is little

in mortality

sex difference

rates from CHD in the

in advanced

any negro group, even in the New Orleans

coronary

artery

Negro. The relatively

small

sex difference in coronary atherosclerosis is a conspicuous feature of atherosclerosis in the American Negro. In the New Orleans cases, negro women have greater involvement

than

white

men. This finding

women, whereas is consistent

with CHD death rates as revealed

The aorta, unlike the coronaries, lesions between of men compared

Negro men have less involvement has essentially

the sexes in any location-race

no difference

group. Although

white

in vital statistics. in extent

of raised

the coronary

arteries

with those of women appear to be more susceptible Aorto

than

to atherosclerosis

Coronary Arteries M9hm(01. JR’

“*~F.m,ok New Orleans

2

I.

I.

PuertoRico

I,

Cotta

I

Rica

gantioga

I.

I.

Jamaica

1.

Puerto Rico

1.

0

I. L

0

IO

. 20

Per Cent Surface

Involved

Fig. 1. Mean percent of intimal surface of aorta and coronary arteries involved with raised atherosclerotic lesions and ratio of mean for males to that for females. Data shown are calculated as the mean of 12 means for three major coronary arteries in four lo-year age groups (25-64 years) and are not weighted for number of cases in each age group. Atherosclerosis,

1972, 16: 193-201

200

JACK

P. STRONG

in the white groups, this is not true of the aorta. This finding is probably

not the result

of selection

groups

or other

show no sex difference arteries.

The aorta

sampling

race, artery,

seems to respond

Puerto

differently

location-race

to the etiologic

in atherosclerosis

age, type of lesion, and average

or in experimental

many

which

in the coronary

agents

of athero-

arteries.

sex differences

cerned with the sex hormones

COMPARISON

because

in aortic raised lesions show a sex difference

sclerosis than the coronary In summary,

artifact,

animals,

and their relation should

OF DIFFERENT

ETHNIC

thake

are not simple.

severity

of lesions.

to atherosclerosis,

IN THE SAME GEOGRAPHIC

There were four locations with two distinct ethnic Rico, SBo Paulo, and Durban). Differences in extent

con-

either in humans

these complex circumstances

GROUPS

detected between the racial groups was observed in Durban. Durban

They vary with

Investigations

into account. LOCATION

groups (New Orleans, of atherosclerosis were

of these locations. The most striking difference Indians were in the medium-high category of

atherosclerosis and Durban Bantu were the least severely involved with atherosclerosis of all location-race groups. In the geographic locations which included both Negroes

and whites, the whites

consistently

had more extensive

involvement

the Negroes except for the female cases in New Orleans. Such interracial could result from either evinronmental or genetic factors.

than

differences

DISCUSSION

Comparisons

among

populations

broad ethnic group reveal considerable On grouping

the 19 location-race

from different variation

locations

but within

in average extent

groups into 5 arbitrary

categories

the same

of atherosclerosis. of average extent,

we find that atherosclerotic involvement in the white populations is high in New Orleans (U.S.A.) and Oslo (Norway), medium in Sao Paulo (Brasil), and medium low in Puerto Rico, Costa Rica, and Santiago (Chile). Atherosclerosis in the Negro population is medium high in New Orleans, medium low in Jamaica and Puerto Rico, and low in 53.0 Paulo and Durban (South America). There is less variation in average

atherosclerotic

involvement

among

the populations

with varying

mixtures

of white and American Indian. Atherosclerosis in these populations ranged from medium to low. The existence of large differences in average extent of atherosclerosis among white populations and among Negro populations suggests that environmental conditions may be important determinants of the prevalence and extent of atherosclerotic lesions. Conditions that might be considered include habitual diet, physical activity, cigarette smoking, stress, and other factors. In view of its important role in current hypotheses concerning the etiology of atherosclerosis, diet (and particularly the amount and type of fat in the diet) must be considered first. The current state of knowledge about dietary habits of the populaAtherosclerosis,

1972,

16: 193-201

ATHEROSCLEROSIS

tions from which these autopsied SHAW AND GuzMAN~.

ing of populations

There

Detailed

the scope of this report. incomplete

and inadequate

the differences these populations environmental

significant

of atherosclerosis

however,

in atherosclerotic consideration

cases were derived

is a statistically

by amount

(7 = 0.688). It is unlikely, the variability

201

IN HUMAN POPULATIONS

correlation

and percentage

that dietary

involvement

has been summarized

differences

between

by SCRIMthe rank-

of calories from fat

are responsible

for all of

among these populations.

of all environmental

factors of possible concern is beyond

In fact, such information

in most of these populations

for evaluating

in atherosclerotic could provide

their relative

involvement. additional

importance

An intensive

investigation

clues to the relative

is

in determining

importance

of some of of other

factors.

REFERENCES 1 HAENSZEL, W., Report of the working group on studies of cancer and related diseases in migrant populations, Inb. J. Cancer, 1969, 4: 364. s MCGILL, H. C., JR., The Geographic Pathology of Atherosclerosis, Lab. Invest., 1968, 18 (5). 3 Interamerican Atherosclerosis Project, Standard Operating Protocol, Department of Pathology, LSU School of Medicine, New Orleans and Instituto de Nutrition de Centro America y Panama, Guatemala, 1960. 4 GUZMAN, M. A., C. A. MCMAHAN, H. C. MCGILL, JR., J. P. STRONG, C. TEJADA, C. RESTREPO, D. A. EGGEN, W. B. ROBERTSON AND L. A. SOLBERG, Selected methodologic aspects of the International Atherosclerosis Project, Lab. Invest., 1968, 18 (5): 479. 5 MCMAHAN. C. A.. Autopsied cases bv aEe, sex, and “race”, Lab. Invest.. 1968, 18 (5): 468. 6 MONTENE~RO, M.. R. AND J, P. STRO&G, Comparison of athe;osclerosis in iour broad cause-ofdeath groups, Lab. Invest., 1968, 18 (5): 503. 7 TEJADA, C., J. P. STRONG, M. R. MONTENEGRO, C. RESTREPO AND L. A. SOLBERG, Distribution of coronary and aortic atherosclerosis by geographic location, race and sex, Lab. Invest., 1968,

18 (5): 509. 8 SCRIMSHAW,

N. S. AND M. A. GUZMAN, Diet and atherosclerosis, Lab. Invest., 1968, 18 (5): 623. 9 STRONG, J. P., M. L. RICHARDS, H. C. MCGILL JR., D. A. EGGEN AND M. T. MCMURRY, On the association of cigarette smoking with coronary and aortic atherosclerosis, J. Atheroscler. Res., 1969, 10: 303.

Atherosclerosis,

1972, 16: 193-201