Margaret C. Oalmann

Effects of Serum Lipoproteins and Smoking on Atherosclerosis in Young Men and Women

Atherosclerosis begins in childhood and progresses from fatty streaks to raised lesions in adolescence and young adulthood. A cooperative multicenter study (Pathobiological Determinants of Atherosclerosis in Youth [PDAY]) examined the relation of risk factors for adult coronary heart disease to atherosclerosis in 1079 men and 364 women 15 through 34 years of age, both black and white, who died of external causes and were autopsied in forensic laboratories. We quantitated atherosclerosis of the aorta and right coronary artery as the extent of intimal surface involved by fatty streaks and raised lesions and analyzed postmorterm serum for lipoprotein cholesterol and thiocyanate (as an indicator of smoking). The extent of intimal surface involved with both fatty streaks and raised lesions increased with age in all arterial segments of all sex and race groups. Women had a greater extent of fatty streaks in the abdominal aorta than men, but women and men had about an equal extent of raised lesions. Women and men had a comparable extent of fatty streaks in the right coronary artery, but women had about half the extent of raised lesions. Blacks had a greater extent of fatty streaks than whites, but blacks and whites had a similar extent of raised lesions. VLDL plus LDL cholesterol concentration was associated positively and HDL cholesterol was associated negatively with the extent of fatty streaks and raised lesions in the aorta and right coronary artery. Smoking was associated with more extensive fatty streaks and raised lesions in the abdominal aorta. All three risk factors affected atherosclerosis to about the same degree in both sexes and both races. Primary prevention of atherosclerosis by controlling these adult coronary heart disease risk factors is applicable to young men and women and to young blacks and whites.

Relation of a Postmortem Renal Index of Hypertension to Atherosclerosis and Coronary Artery Size in Young Men and Women

In a cooperative multicenter study, the Pathobiological Determinants of Atherosclerosis in Youth, we measured atherosclerosis of the aorta and right coronary artery (RCA) in 2403 black and white men and women 15 through 34 years of age who died of external causes and were autopsied in forensic laboratories. We measured the diameter of the opened, flattened, and fixed RCA and the diameter, intimal thickness, intimal cross-sectional area, medial thickness, and medial cross-sectional area of the pressure-perfused, fixed left anterior descending (LAD) coronary artery. Using the ratio of intimal thickness to outer diameter of the small renal arteries to predict mean arterial pressure during life, we classified the cases as normotensive (mean arterial pressure < 110 mm Hg) or hypertensive (mean arterial pressure > or = 110 mm Hg). The prevalence of hypertension by age, sex, and race corresponded closely with that measured in a survey of the living population. Hypertension had little or no effect on fatty streaks. Hypertension was associated with more extensive raised lesions in the abdominal aortas and RCAs of blacks > 20 years of age and in the RCAs of whites > 25 years of age. At all ages, women had less extensive raised lesions in the RCAs than did men, but the effect of hypertension on raised lesions was similar to that in men. Adjustment for serum lipoprotein cholesterol levels and smoking in a subset of cases yielded results similar to those obtained without adjustment. Hypertension was associated with larger diameters of the RCA and LAD coronary artery and with larger cross-sectional intimal and medial areas of the LAD coronary artery. Hypertension augments atherosclerosis in both men and women primarily by accelerating the conversion of fatty streaks to raised lesions beginning in the third decade of life, and the effect of hypertension increases with age.

Risk factors for atherosclerosis in young subjects: the pday study

The importance of the prevention and treatment of adolescent nutritional disorders is strongly confirmed by the Report of the Expert Panel on Blood Cholesterol Levels in Children and Adolescents from the National Cholesterol Education Program (NCEP). This report documents the significance of blood-cholesterol levels in childhood and adolescence and makes recommendations concerning the population approach and individualized approach to preventing and treating abnormal serum lipid levels and other risk factors for atherosclerosis and coronary heart disease (CHD). The continuing accumulation of data on risk factors associated with the development of atherosclerosis in youth from the Pathobiological Determinants of Atherosclerosis in Youth (PDAY) study provides needed information on this timely subject. The multi-institutional PDAY study was designed to document the natural history of atherosclerosis and its relationship to risk factors and to investigate the pathobiology of lesion development in young subjects. Pathology laboratories in nine centers collected arteries and tissues from more than 3000 persons, ages 15-34 years, whose deaths were attributed to homicides, accidents, or suicides. Arteries were evaluated for lesions, and risk factors were analyzed in a central laboratory. Postmortem risk factors include serum lipoproteins, serum thiocyanate (smoking), glycohemoglobin (diabetes), body mass index (BMI), and thickness of panniculus adiposus (obesity), changes in small renal arteries (hypertension), and apoprotein polymorphisms. Data from the PDAY study document the presence of atherosclerotic lesions at an early age and relate these lesions to known CHD risk factors. These findings provide a strong basis for developing intervention programs for adolescents and young adults in order to reduce risk factors and prevent clinical manifestations of CHD later in life.

A description of two morphologic patterns of aortic fatty streaks, and a hypothesis of their pathogenesis

Two morphologic patterns of fatty streak were identified on examination of 74 aortas from the Pathobiological Determinants of Atherosclerosis in Youth study. Pattern 1, which predominated in 78% of aortas, is characterized by broad bands of intense stain which extend to the proximal edge of ostia. Pattern 2, which predominated in 11%, is characterized by less intense staining which is concave to the associated ostium. Pattern 1 predominated in older subjects and smokers. Aging and smoking decrease arterial elasticity, thereby decreasing the volume and duration of retrograde blood flow in diastole. Doppler ultrasonography of the posterior intercostal arteries and aorta in 42 healthy subjects revealed that retrograde blood flow in late systole/early diastole is normal in subjects in the 15-34 age group. Transition from retrograde to antegrade flow was associated with transient blood stasis. This stasis should prolong the residence time of lipid-rich particles, enhancing diffusion into the vessel wall. A region of lower flow velocity was noted in the periostial region in all patients during diastole. The anatomic, hemodynamic, and risk factor data suggest that the morphology of fatty streaks is determined by interaction of retrograde with antegrade blood flow as modulated by arterial elasticity.

Atherosclerosis in youth: are hypertension and other coronary heart disease risk factors already at work?

Abstract. The purposes of this review were to describe the natural history of atherosclerosis in youth, discuss the role of adult coronary heart disease (CHD) risk factors in the development of atherosclerosis  –  particularly in the young  –  and present the relationship between atherosclerosis and hypertension. Evidence is presented that, by age 15 years, 100% of the youth have aortic atherosclerosis and about one-half have coronary atherosclerosis. Risk factors for adult CHD, including lipoproteins, smoking, glycohemoglobin (a marker for diabetes), obesity, and hypertension, are associated with extent and prevalence of atherosclerosis in young people. Hypertension seems to play its role mainly by converting early atherosclerotic lesions (fatty streaks) to more advanced lesions (raised lesions).