jack perry strong, md boyd professor department of pathology

Atherosclesosis in Youth:The PDAY Study

Jack Perry Strong, MDBoyd Professor Department of Pathology

The Natural History of Atherosclerosis

The Early Aortic Lesions as seen in New Orleans

in the middle of the 20th Century*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

The Natural History of Coronary Atherosclerosis

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 1962The American Journal of Pathology

Myocardial infarct

Cerebral infarct

Gangreneof extremities

AbdominalAortic

aneurysm

Natural History of Atherosclerosis

Clinical horizon

CalcificationComplication lesion – hemorrhage, ulceration, thrombosis

Fibrous plaque

Fatty streak

Age

in Y

ears

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 Middle ofEarly Studies of Natural History in New Orleans 20th Century

International Atherosclerosis Project 1960’s

Community Pathology of Atherosclerosis in New Orleans 1970’s

Studies of Atherosclerosis and Risk Factors in Hisayama 1970’s-1980’sThe Akita Pathology Study

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 AgePercent Intimal Surface Involvement

with Atherosclerotic Lesions

NO Black NO White Japan0

10

20

Right Coronary Artery

Fatty StreaksRaised Lesions


10

20

Circumflex Left Coronary Artery


101520

Left Anterior Descending Coronary


101520

Combined Coronary Arteries

PDAYPathobiological 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 YouthUniversity of Alabama

Birmingham

Albany Medical CollegeAlbany

Baylor College of MedicineHouston

University of ChicagoChicago

The University of IllinoisChicago

Louisiana State University Medical CenterNew Orleans

University of Maryland Baltimore

Medical College of Georgia Augusta

University of Nebraska Medical Center Omaha

The Ohio State University Columbus

Southwest Foundation for Biomedical Research

San Antonio

The University of Texas Health Science Center

San Antonio

Vanderbilt UniversityNashville

West Virginia State UniversityMorgantown

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

• Smoking

• Blood pressure

• Diabetes mellitus

• Obesity

• DNA Polymorphisms

• Total cholesterol, HDL cholesterol, and apolipoproteins in post mortem serum

• Thiocyanate in post mortem serum

• Wall thickness of renal arteries

• Glycosylated hemoglobin in post mortem red blood cells

• Body mass index and panniculus adiposus

• RFLP’s in liver DNA

F8502532 Year

Old Black Male

F8851331 Year Old White Male

15-19

20-24

25-29

30-34

15-19

20-24

25-29

30-34

15-19

20-24

25-29

30-34

15-19

20-24

25-29

30-34

010203040

Thoracic Aorta

Raised LegionsFatty Streaks

15-19

20-24

25-29

30-34

15-19

20-24

25-29

30-34

15-19

20-24

25-29

30-34

15-19

20-24

25-29

30-34

0

20

40

60Abdominal Aorta


15-19

20-24

25-29

30-34

15-19

20-24

25-29

30-34

15-19

20-24

25-29

30-34

15-19

20-24

25-29

30-34

0

10

20

30

Right Coronary


Perc

en

t In

tim

al S

urf

ace

MalesWhite Black

FemalesWhite Black

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 VariablesVariable 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)

0

5

10

15

20

25

30

35

40

45

50

N B H N B H N B H

Fatty Streaks

Raised Lesions

Perc

en

t In

tim

al S

urf

ace

P ValuesTotal Lesions 0.9421 0.3116 0.0159Raised Lesions 0.0001 0.0001 0.0001

Aorta Right CoronaryThoracic Abdominal

Raised Lesions in Right Coronary Artery of 30-Year-Old White Males by Risk Factor Status

0

2

4

6

8

10

12

14

16

18

20

Perc

en

t S

urf

ace I

nvolv

ed PDAY, 1994

SmokingBlood Pressure

Cholesterol

No YesNormal

No YesHigh

No YesNormal

No YesHigh________________________

Normal

________________________

High

F3860430 Year Old Black Female

F716623 Year Old Black Male

Human Template – Half Aorta

PDAY Abdominal Aorta Sudan Probability

PDAY Abdominal AortaRaised Probability

PDAY Right CoronarySudan Probability

PDAY Right CoronaryRaised Probability

PDAY Abdominal Aorta Sudan Probability

PDAY Abdominal Aorta Raised Probability

PDAY Coronary ArterySudan Probability

PDAY Coronary ArteryRaised Probability

PDAY Abdominal AortaSudan Probability

PDAY Abdominal AortaRaised Probability

Atherosclerosis of Abdominal Aortaby Age and GlycohemoglobenAdjusted for Race and Sex

0

10

20

30

40

50

60

70

Fatty Streaks P = 0.752

Raised Lesions P = 0.025

Perc

en

t S

urf

ace I

nvolv

ed

Glycoemoglobin:

NormalHigh

15-19Age:

PDAY, 1994

Normal

High20-24

NormalHigh

25-29

NormalHigh

30-34

N = 1,309

Atherosclerosis of Right Coronary Artery by Age and GlycohemoglobenAdjusted for Race and Sex

0

5

10

15

20

25

30

35

40

45

50



Perc

en

t S

urf

ace I

nvolv

ed N = 1,275

Glycohemoglobin: NormalHigh

15-19

Age:

PDAY, 1994

Normal

High20-24

NormalHigh

25-29

NormalHigh

30-34

Atherosclerosis of Right Coronary Artery by Body Mass Index and Sex Adjusted for Race and Age

<25 25-30 >30 <25 25-30 >300

2

4

6

8

10

12

14



Perc

en

t S

urf

ace I

nvolv

ed N = 1,455

BMI: _________________________Male

___________________________FemaleSex:

PDAY, 1994

APO E Isoforms

E2 Least common receptor binding domain: 112 CYS 158 CYS

E3 MOST COMMON 112 CYS 158 ARG

E4 112 ARG 158 ARG

0

50

100

150

200

147.3(107.6-201.7)

166.4(153.4-180.5)155.3

(132.4-185.8)

179.0(172.4-185.8)

188.2(78.4-198.5)

160.2(133.5-192.3)

APO E Genotype

Total Serum Cholesterol by APO E GenotypeAdjusted for Age and Race

Tota

l S

eru

m C

hole

ste

rol m

g/d

l) P = 0.03

N=3

N=45 N=1

2N=107 N=

9

N=223

E2 E2

E2 E3E2 E4

E3 E3E3 E4

E4 E4

Lesions in Abdominal Aorta by Apo E Genotype adjusted for age and Race

0

5

10

15

20

25

30

35

40

45

50

8.7(5.5-13.6)

20.517.4-24.0

21.516.2-28.5

30.127.8-32.5

33.529.8-37.6

27.019.5-37.3

APO E Genotype

Perc

en

t S

urf

ace

Involv

ed

P = 0.0001

E2 E2

E2 E3E2 E4

E3 E3E3 E4

E4 E4

Summary and Conclusions

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.

The LSU PDAY Team 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)

jack perry strong, md boyd professor department of pathology

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