1. Jack Perry Strong, MD Boyd Professor Department of Pathology

2. 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

4. Myocardial infarct Cerebral infarct Gangrene of extremities Abdominal Aortic aneurysm Natural History of Atherosclerosis Clinical horizon Calcification Complication lesion – hemorrhage, ulceration, thrombosis Fibrous plaque Fatty streak Age in Years Pathology

11. The Value of Autopsy Studies of Atherosclerosis in Human Subjects as We Approach the 21 st Century Study of Soldiers Killed in the Korean War Middle of Early Studies of Natural History in New Orleans 20 th Century International Atherosclerosis Project1960’s Community Pathology of Atherosclerosis in New Orleans1970’s Studies of Atherosclerosis and Risk Factors in Hisayama1970’s-1980’s The Akita Pathology Study Comparison of Atherosclerosis in Tokyo, New Orleans and Oslo Nationwide Study of Atherosclerosis in Infants and Children and Young Adults in Japan1980’s Bogalusa Hearty Study- Atherosclerosis in Children and Youth Histological Classification of Coronary Atherosclerosis in Young Subjects1980’s-1990’s Pathobiological Determinants of Atherosclerosis in Youth1980’s 1990’s

12. 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

13. Coronary Atherosclerosis in New Orleans and Japan, Men 25-44 Years of Age Percent Intimal Surface Involvement with Atherosclerotic Lesions

14. PDAY Pathobiological Determinants of Atherosclerosis in Youth Nationwide study of atherosclerosis in autopsied persons, 15-34 years old, conducted by 14 cooperating centers.

15. PDAY Study Subjects  Males and females aged 15-34  Death due to external causes (accidents, homicides, suicides)  2876 cases collected

16. Institutions Participating in the Multicenter Cooperative Study, Pathobiological Determinants of Atherosclerosis in Youth University of Alabama Birmingham Albany Medical College Albany Baylor College of Medicine Houston University of Chicago Chicago The University of Illinois Chicago Louisiana State University Medical Center New 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 University Nashville West Virginia State University Morgantown

17. 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)

18. Risk Factors Measured in Autopsied Persons Risk FactorMarker 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

20. F85025 32 Year Old Black Male

21. F88513 31 Year Old White Male

22. Percent Intimal Surface Males WhiteBlack Females WhiteBlack

24. Intimal Surface of Right Coronary Artery involved by Athersclerosis in 351 Males at Two Risk Levels

25. Effects* on Percentage Total Surface Involvement of Abdominal Aorta, Adjusted for other Variables VariableUnitEffect Age5 years5.0 RaceBlack-White6.6 VLDL+LDL-C45 mg/dl5.4 HDL-C20 mg/dl-3.1 SmokingSmoker-Nonsmoker6.9 Apo B40 mg/dl3.9 Apo A-I35 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

26. Raised Lesions and Fatty Streaks in Three Arterial Segment for Normal (N) Borderline (B) and Definite Hypertensive (H) Percent Intimal Surface P Values Total Lesions0.94210.31160.0159 Raised Lesions0.00010.00010.0001 Aorta Right Coronary Thoracic Abdominal

27. Raised Lesions in Right Coronary Artery of 30-Year-Old White Males by Risk Factor Status Percent Surface Involved PDAY, 1994 Smoking Blood Pressure Cholesterol NoYes Normal NoYes High NoYes Normal NoYes High ________________________ Normal ________________________ High

28. F38604 30 Year Old Black Female

29. F7166 23 Year Old Black Male

30. Human Template – Half Aorta

37. PDAY Abdominal Aorta Sudan Probability

38. PDAY Abdominal Aorta Raised Probability

39. PDAY Right Coronary Sudan Probability

40. PDAY Right Coronary Raised Probability

41. PDAY Abdominal Aorta Sudan Probability

42. PDAY Abdominal Aorta Raised Probability

43. PDAY Coronary Artery Sudan Probability

44. PDAY Coronary Artery Raised Probability

45. PDAY Abdominal Aorta Sudan Probability

46. PDAY Abdominal Aorta Raised Probability

47. PDAY Abdominal Aorta Sudan Probability

48. PDAY Abdominal Aorta Raised Probability

49. PDAY Right Coronary Sudan Probability

50. PDAY Right Coronary Raised Probability

51. PDAY Abdominal Aorta Sudan Probability

52. PDAY Abdominal Aorta Raised Probability

53. PDAY Right Coronary Sudan Probability

54. PDAY Right Coronary Raised Probability

55. Percent Surface Involved Glycoemoglobin :NormalHigh 15-19 Age: PDAY, 1994 NormalHigh 20-24 NormalHigh 25-29 NormalHigh 30-34 N = 1,309

56. Percent Surface Involved N = 1,275 Glycohemoglobin: NormalHigh 15-19 Age: PDAY, 1994 NormalHigh 20-24 NormalHigh 25-29 NormalHigh 30-34

57. Percent Surface Involved N = 1,455 BMI: _________________________ Male ___________________________ Female Sex: PDAY, 1994

58.  E 2 Least common receptor binding domain: 112 CYS 158 CYS  E 3 MOST COMMON 112 CYS 158 ARG  E 4 112 ARG 158 ARG

59. Total Serum Cholesterol mg/dl) P = 0.03 N=3 N=45 N=12 N=107 N=9 N=223 E 2 E 2 E 3 E 2 E 4 E 3 E 3 E 4 E 4

60. Percent Surface Involved P = 0.0001 E 2 E 2 E 3 E 2 E 4 E 3 E 3 E 4 E 4

62.  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.

63.  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.

64.  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.

65.  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.

66.  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)