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Jack Perry Strong, MD
Boyd Professor
Department of Pathology
Russell L. Holman, Henry C. McGill, Jr., MD,
Jack P. Strong, MD and Jack C. Geer, MD
From the Department of Pathology,
Louisiana State University School of Medicine and Charity Hospital of Louisiana,
New Orleans, LA
Reprinted from The American Journal of Pathology, 1958, XXXIV, No. 2, pp. 209-235
Jack P. Strong, MD and Henry C. McGill, Jr., MD
From the Department of Pathology,
Louisiana State University School of Medicine
New Orleans, LA
Reprinted from Vol. 40, No. 1, January 1962
The American Journal of Pathology
Natural History of Atherosclerosis
Myocardial
infarct
Cerebral
infarct
Gangrene
of extremities
Abdominal
Aortic
aneurysm
Age in Years
Clinical horizon
Calcification
Complication lesion –
hemorrhage, ulceration,
thrombosis
Fibrous plaque
Fatty streak
Pathology
The Value of Autopsy Studies of Atherosclerosis in
Human Subjects as We Approach the 21st Century
Study of Soldiers Killed in the Korean War
Early Studies of Natural History in New Orleans
Middle of
20th Century
International Atherosclerosis Project
1960’s
Community Pathology of Atherosclerosis in New Orleans
1970’s
Studies of Atherosclerosis and Risk Factors in Hisayama
The Akita Pathology Study
1970’s-1980’s
Comparison of Atherosclerosis in Tokyo, New Orleans and
Oslo Nationwide Study of Atherosclerosis in
Infants and Children and Young Adults in Japan
1980’s
Bogalusa Hearty Study- Atherosclerosis in Children
and Youth Histological Classification of Coronary
Atherosclerosis in Young Subjects
1980’s-1990’s
Pathobiological Determinants of Atherosclerosis in Youth
1980’s 1990’s
Coronary and Aortic Atherosclerosis in
Young Men from Tokyo and New Orleans
Toshiharu Ishii, William P. Newman III, Miguel A. Guzman,
Yahuhiro Hosoda , Jack P. Strong
Laboratory Investigation 1986; 54:561-565
Coronary Atherosclerosis in New Orleans and Japan,
Men 25-44 Years of Age
Percent Intimal Surface Involvement
with Atherosclerotic Lesions
Right Coronary Artery
Circumflex Left Coronary Artery
20
20
0
0
NO Black
NO White
Japan
Fatty Streaks
Raised Lesions
Left Anterior Descending Coronary
20
10
10
0
0
NO White
Japan
NO White
Japan
Combined Coronary Arteries
20
NO Black
NO Black
NO Black
NO White
Japan
PDAY
Pathobiological Determinants of
Atherosclerosis in Youth
Nationwide study of atherosclerosis
in autopsied persons,
15-34 years old,
conducted by 14 cooperating centers.
PDAY Study Subjects
 Males and females aged 15-34
 Death due to external causes
(accidents, homicides, suicides)
 2876 cases collected
Institutions Participating in the Multicenter Cooperative Study,
Pathobiological Determinants of Atherosclerosis in Youth
University of Alabama
Birmingham
Medical College of Georgia
Augusta
Albany Medical College
Albany
University of Nebraska Medical Center
Omaha
Baylor College of Medicine
Houston
The Ohio State University
Columbus
University of Chicago
Chicago
Southwest Foundation for Biomedical Research
San Antonio
The University of Illinois
Chicago
The University of Texas Health Science Center
San Antonio
Louisiana State University Medical Center
New Orleans
Vanderbilt University
Nashville
University of Maryland
Baltimore
West Virginia State University
Morgantown
PDAY Methods of
Evaluating Atherosclerosis
Visual estimate of surface involved by fatty
streaks and raised lesions in Sudan-IV-stained
arteries by three pathologists (LSU)
Computerized image analysis of lesions in
photographs of arteries (OSU)
Computerized image analysis of histologic
sections (OSU)
Risk Factors Measured in Autopsied Persons
Risk Factor
Marker
• Serum lipoprotein cholesterol and
apolipoprotein concentrations
• Total cholesterol, HDL cholesterol, and
apolipoproteins in post mortem serum
• Smoking
• Thiocyanate in post mortem serum
• Blood pressure
• Wall thickness of renal arteries
• Diabetes mellitus
• Glycosylated hemoglobin in post
mortem red blood cells
• Obesity
• Body mass index and panniculus
adiposus
• DNA Polymorphisms
• RFLP’s in liver DNA
F85025
32 Year Old
Black Male
F88513
31 Year Old
White Male
Males
White
Females
Black
White
Black
Thoracic Aorta
40
Raised Legions
Percent Intimal Surface
20
Fatty Streaks
0
Abdominal Aorta
60
40
20
0
Raised Legions
Fatty Streaks
Right Coronary
30
20
10
0
Raised Legions
Fatty Streaks
Intimal Surface of Right Coronary Artery involved by
Athersclerosis in 351 Males at Two Risk Levels
Effects* on Percentage Total Surface Involvement of
Abdominal Aorta, Adjusted for other Variables
Variable
Unit
Effect
Age
5 years
5.0
Race
Black-White
6.6
VLDL+LDL-C
45 mg/dl
5.4
HDL-C
20 mg/dl
-3.1
Smoking
Smoker-Nonsmoker
6.9
Apo B
40 mg/dl
3.9
Apo A-I
35 mg/dl
-3.6
* Estimated from multiple regression analysis of 533 cases (except for Apo B and
A-I 255 cases) all males – PDAY, 1990
Raised Lesions and Fatty Streaks in Three Arterial Segment for
Normal (N) Borderline (B) and Definite Hypertensive (H)
Aorta
50
Thoracic
Percent Intimal Surface
45
Right Coronary
Abdominal
40
Fatty Streaks
35
Raised Lesions
30
25
20
15
10
5
0
P Values
Total Lesions
Raised Lesions
N
B
0.9421
0.0001
H
N
B
0.3116
0.0001
H
N
B
0.0159
0.0001
H
Raised Lesions in Right Coronary Artery of
30-Year-Old White Males by Risk Factor Status
20
PDAY, 1994
Percent Surface Involved
18
16
14
12
10
8
6
4
2
0
Smoking
Blood Pressure
Cholesterol
No
Yes
No
Yes
Normal
High
________________________
No
Yes
No
Yes
Normal
High
________________________
Normal
High
F38604
30 Year Old
Black Female
F7166
23 Year Old
Black Male
Human Template – Half Aorta
PDAY Abdominal Aorta
Sudan Probability
PDAY Abdominal Aorta
Raised Probability
PDAY Right Coronary
Sudan Probability
PDAY Right Coronary
Raised Probability
PDAY Abdominal Aorta
Sudan Probability
PDAY Abdominal Aorta
Raised Probability
PDAY Coronary Artery
Sudan Probability
PDAY Coronary Artery
Raised Probability
PDAY Abdominal Aorta
Sudan Probability
PDAY Abdominal Aorta
Raised Probability
PDAY Abdominal Aorta
Sudan Probability
PDAY Abdominal Aorta
Raised Probability
PDAY Right Coronary
Sudan Probability
PDAY Right Coronary
Raised Probability
PDAY Abdominal Aorta
Sudan Probability
PDAY Abdominal Aorta
Raised Probability
PDAY Right Coronary
Sudan Probability
PDAY Right Coronary
Raised Probability
PDAY, 1994
70
Percent Surface Involved
N = 1,309
60
Fatty Streaks
P = 0.752
50
40
Raised Lesions
P = 0.025
30
20
10
0
Glycoemoglobin: Normal High
Age:
15-19
Normal High
20-24
Normal High
25-29
Normal High
30-34
PDAY, 1994
50
Percent Surface Involved
45
40
35
30
25
N = 1,275
Fatty Streaks
P = 0.010
Raised Lesions
P = 0.0003
20
15
10
5
0
Glycohemoglobin:
Age:
Normal High
15-19
Normal High
20-24
Normal High
25-29
Normal High
30-34
Percent Surface Involved
14
N = 1,455
Fatty Streaks
P = 0.0001
12
10
Raised Lesions
P = 0.0045
8
6
4
2
0
BMI:
Sex:
<25
25-30
>30
_________________________
Male
<25
25-30
>30
___________________________
Female
PDAY, 1994

E2
Least common
receptor binding domain:
112 CYS 158 CYS

E3
MOST COMMON
112 CYS 158 ARG

E4
112 ARG 158 ARG
Total Serum Cholesterol mg/dl)
P = 0.03
200
150
188.2
166.4
179.0
(78.4-198.5)
(153.4-180.5)
(172.4-185.8)
155.3
147.3
160.2
(132.4-185.8)
(107.6-201.7)
(133.5-192.3)
100
50
N=3
N=45
N=12
0
E2
E2
N=223
N=107
N=9
E2 E3
E2 E4
E3 E3
APO E Genotype
E3 E4
E4 E4
50
P = 0.0001
Percent Surface Involved
45
40
35
30.1
27.8-32.5
30
25
20
15
20.5
21.5
17.4-24.0
16.2-28.5
33.5
29.8-37.6
27.0
19.5-37.3
8.7
(5.5-13.6)
10
5
0
E2 E2
E2 E3
E2 E4
E3 E3
APO E Genotype
E3 E4
E4 E4

Atherosclerosis begins in childhood with the
appearance of aortic fatty streaks.

Coronary fatty steaks begin to form in
adolescence

Most persons have coronary
fatty streaks by the
age 20-29 years.

In the PDAY study, the association of
serum lipoprotein levels with
atherosclerotic lesions in young persons
15-34 years of age supports the view that
control the hyperlipoproteinemia will
retard the progression of atherosclerosis
in the young.

There is strong evidence for the effects
of smoking on atherosclerosis in this
young age group.

The association of a hypertensive index
to clinically significant raised arterial
lesions is also well established in this
young age group, 15-34 years of age.

Elevated glycohemoglobin levels and
obesity are associated with accelerated
atherosclerosis in the third and fourth
decades of life.

Control Programs to prevent coronary
heart disease should be directed
toward individuals in the twenties and
thirties for maximum benefits

Early detection and control of
hypercholesterolemia hypertension,
hyperglycemia and obesity in young
persons should reduce the risk of
atherosclerotic disease later in life.

Dietary and other habits that retard
atherosclerosis should be established
in childhood.

Richard S. Vander Heide, MD, PhD

Jack P. Strong, MD

Gray T. Malcom, PhD

Arthur W. Zieske, MD

Dana A. Troxclair, MD

Grace B. Athas, PhD

Cynthia J. Sprow, BS

Penelope H. Strenge, MS, MT (ASCP)