Risk factors for atherosclerosis in young subjects: the PDAY Study. Pathobiological Determinants of Atherosclerosis in Youth.
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Biomedical subjects
J P Strong
Publications and source records attributed to J P Strong.
The PDAY Study: natural history, risk factors, and pathobiology. Pathobiological Determinants of Atherosclerosis in Youth.
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Adolescent↗
Difference in atherosclerosis between the populations of a fishing and a farming village in Japan.
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Adult↗
Atherosclerosis in youth: are hypertension and other coronary heart disease risk factors already at work?
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).
Adolescent↗
Effects of serum lipoproteins and smoking on atherosclerosis in young men and women. The PDAY Research Group. Pathobiological Determinants of Atherosclerosis in Youth.
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.
Adolescent↗
Cardiovascular risk factors and hyalinization of renal arterioles at autopsy. The Honolulu Heart Program.
Nephrosclerosis, commonly found in subjects with hypertension and diabetes, is marked by hyalinization of arterioles and fibroplasia of small arteries in the renal cortex. Cardiovascular risk factors that predicted subsequent hyalinization of renal arterioles at autopsy were identified, using data from the Honolulu Heart Program, a prospective epidemiological study of cardiovascular disease (CVD) in Japanese-American men. Among 8006 participants at baseline, 1381 died between 1965 and 1982; 285 of these had a protocol autopsy, and 150 had assessments of arteriolar hyalinization from renal tissue. Subjects were categorized into four groups on the basis of the number of hyalinized arterioles per square centimeter of renal tissue, and CVD risk factor levels and proportions were compared across these groups with the use of general linear models and logistic regression. Multivariate assessment using logistic regression demonstrated that diastolic blood pressure (DBP) and glucose level were positively associated and alcohol intake was negatively associated with an elevated degree of renal arteriolar hyalinization, independent of other CVD risk factors. The odds ratios for elevated hyalinization associated with a 10-mm Hg increase in DBP, a 20-mg/dL increase in glucose level, and a 30-mL/d increase in alcohol intake were 1.97 (95% confidence interval [CI] = 1.24-3.12), 1.23 (95% CI = 1.07-1.41), and 0.24 (95% CI = 0.11-0.55), respectively. Associations were similar when prevalent cases of CVD were excluded and when autopsy selection bias was taken into account. Renal arteriolar hyalinization was also more strongly associated with atherosclerosis in the larger cerebral vessels (Spearman's r = .59, P < .001) than in the coronary arteries (r = .16, P = .073) and aorta (r = .24, P = .022). Hyalinization was significantly related to cardiovascular-renal mortality, and this association was accounted for by other CVD risk factors. These findings suggest that blood pressure, glucose level, and alcohol intake are independent predictors of hyalinization in renal arterioles and that this type of renal vasculopathy may be a marker for atherosclerosis in other vascular regions, particularly the cerebral vessels. The protective association involving alcohol and the possibility that renal arteriolar hyalinization may be an indicator of cerebral atherosclerosis may warrant investigation in other populations.
Age Factors↗
Predictors of myocardial lesions in men with minimal coronary atherosclerosis at autopsy. The Honolulu heart program.
Some cardiovascular risk factors are associated with clinical coronary heart disease but not with autopsy evidence of coronary atherosclerosis. To determine whether these risk factors might operate through mechanisms other than atherosclerosis, we examined associations between cardiovascular risk factors and subsequent intramural myocardial lesions assessed by protocol autopsy between 1965 and 1984 in 120 Japanese-American men from the Honolulu Heart Program who had minimal coronary atherosclerosis (American Heart Association (AHA) panel score < 3 on scale of 1 to 7). Age-adjusted prevalence of myocardial lesions was related to smoking status (P < 0.01), as well as amount, duration, and pack-years of smoking (P < 0.03). In a multiple logistic model, smoking (20 pack-years) was directly associated and fish intake (> or = 2 times/wk) was inversely associated with myocardial lesions independently of age, cholesterol, systolic blood pressure, body mass index, alcohol, diabetes, total calories, and animal protein intake (odds ratio (OR) = 1.5, 95% confidence intervals (CI) = 1.1 to 2.0 and OR = 0.35, 95% CI = 0.2 to 0.9, respectively). The protective effect of fish intake was most evident among men who did not have hypertension at baseline. Indices of obesity, body fat distribution, and physical activity and levels of triglyceride and alcohol intake were not associated with myocardial lesions. Thus, the adverse effects of smoking and the protective effects of fish consumption may extend to individuals relatively free of coronary atherosclerosis, possibly through hemostatic mechanisms or effects on small intramural arteries.
Aged↗
Renovasculopathies of nephrosclerosis in relation to atherosclerosis at ages 25 to 54 years.
Renovasculopathies of hypertension include arteriolar hyalinization and arterial intimal fibroplasia. Atherosclerotic features of coronary arteries and aorta include fatty streaks and raised lesions. Data were obtained from a series of 573 autopsies of black and Caucasian males and females aged 25 to 54 years, who died of violent and natural causes unrelated to atherosclerosis. Analysis showed positive correlations of coronary and aortic raised lesions with arteriolar hyalinization. Arterial intimal fibroplasia correlated positively with raised lesions in the aorta but only weakly and inconsistently in the coronary arteries. The extent of fatty streaks in the coronaries, as in the aorta, did not correlate with either form of renovasculopathy. These results provide evidence that hyalinization of renal arterioles may be a marker for young people who have the most advanced coronary atherosclerosis, and who therefore have an early start upon a course toward coronary heart disease later in life.
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Histologic features of atherosclerosis and hypertension from autopsies of young individuals in a defined geographic population: the Bogalusa Heart Study.
Histologic features of arterial intima have been quantified at autopsy by morphometric methods in 66 individuals aged 6-30 years, in whom cardiovascular risk factors had been measured prospectively prior to death. Measures of serum cholesterol were found to correlate significantly with the extent of foam cell infiltration seen in paraffin sections and the intensity of lipid staining in frozen sections of the abdominal and thoracic segments of the aorta. A similar correlation in the coronary arteries was weak and inconsistent. Blood pressure was significantly correlated with foam cells and stainable lipid in the abdominal but not the thoracic segment of the aorta. A similar correlation in the coronary arteries was significant, but only in males, and most consistently in the black males. Intimal thickness of the coronary arteries showed sporadic and weak correlations with blood pressure and lipids; however, a strong and consistent correlation was seen between coronary intimal thickness and hyalinization of renal arterioles. With many statistical tests carried out on a limited data set, some particular details are, no doubt, spuriously significant; however, some persistent patterns are beginning to emerge. The reproducible findings support the concept that prospective measurements of blood pressure and serum lipids are associated with a degree of structural characteristics present in children and young adults. Moreover, the observed structural characteristics, specifically the deposition of lipids in the intima of coronary arteries and aorta, are likely to reflect variations in the rates of progression of atherosclerosis.
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Environmental and genetic risk factors in early human atherogenesis: lessons from the PDAY study. Pathobiological Determinants of Atherosclerosis in Youth.
A multi-institutional study 'Pathobiological Determinants of Atherosclerosis in Youth' (PDAY) was initiated to document the natural history of atherosclerosis, its relationship to risk factors, and pathobiology of lesion development in young subjects. Pathology laboratories in nine centers collected arteries and tissues from over 2000 persons from 15 through 34 years of age whose deaths were attributed to homicides, accidents, or suicides. Arteries were evaluated for lesions, and risk factors were analyzed in a central laboratory. Post-mortem risk factors included serum lipoproteins, serum thiocyanate (smoking), glycohemoglobin (diabetes), thickness of panniculus adiposus (obesity), small renal artery changes (hypertension) and apoprotein isoforms. This study documents the development of atherosclerosis at an early age. It also shows that the recognized risk factors for coronary heart disease are associated with lesion development in the arteries of these young subjects. The PDAY study has a counterpart in Japan where the development of atherosclerosis has been studied in young subjects. This Japanese study, in a population in which coronary heart disease has not yet become a major epidemic, has findings quite similar to the findings from the PDAY study. Studies of atherosclerosis in both Japan and the USA provide strong justification for reducing risk factors in young persons.
Arteriosclerosis↗
Relation of a postmortem renal index of hypertension to atherosclerosis in youth. The Pathobiological Determinants of Atherosclerosis in Youth (PDAY) Research Group.
In a cooperative multicenter study, Pathobiological Determinants of Atherosclerosis in Youth, of 1164 young men 15 through 34 years of age who died of external causes and were autopsied in forensic laboratories, we measured atherosclerosis of the aorta and the right coronary artery. Using the ratio of intimal thickness to outer diameter of the small renal arteries to predict mean arterial pressure (MAP) during life, we classified the cases as either normotensive (MAP < 110 mm Hg) or hypertensive (MAP > or = 110 mm Hg). By this criterion, the prevalence of hypertension in blacks was 16%; in whites, 12%. Hypertension was associated directly with blood level of glycohemoglobin (an indicator of blood glucose concentration) and with body mass index (BMI) but inversely with thickness of the panniculus adiposus. Among hypertensive compared with normotensive cases, the extent of raised lesions (mainly fibrous plaques) was greater in the aortas of 30- to 34-year-old men and in the right coronary arteries of 25- to 34-year-old men. The prevalence of raised lesions involving 5% or more of the intimal surface was twofold greater in the aortas and right coronary arteries of hypertensive men throughout the 15-to-34-year age span of the study cases. The association of hypertension with raised lesions was not accounted for by adjusting for glycohemoglobin level, BMI, or thickness of the panniculus adiposus. Hypertension is associated with accelerated atherosclerosis in youth.
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Relation of glycohemoglobin and adiposity to atherosclerosis in youth. Pathobiological Determinants of Atherosclerosis in Youth (PDAY) Research Group.
In a cooperative multicenter study (Pathobiological Determinants of Atherosclerosis in Youth, PDAY) of 1532 young persons 15 through 34 years of age who died of external causes and were autopsied in medical examiners' laboratories, we quantified atherosclerosis of the aorta and the right coronary artery. We analyzed postmortem blood cells for glycohemoglobin and postmortem serum for lipoprotein cholesterol and thiocyanate (as an indicator for smoking). We measured the thickness of the panniculus adiposus and the body mass index (weight per height squared) as indicators of adiposity. Glycohemoglobin levels exceeding 8% were associated with substantially more extensive fatty streaks and raised lesions in the right coronary artery in persons more than 25 years of age and with more extensive raised lesions in the aorta in persons more than 30 years of age. Both thickness of the panniculus adiposus and body mass index were associated with more extensive fatty streaks and raised lesions in the right coronary artery. The associations of atherosclerotic lesions with glycohemoglobin and adiposity were not explained by a less favorable lipoprotein profile or smoking. The results show that atherosclerosis in young adults is associated with the prediabetic or early diabetic state, as indicated by elevated glycohemoglobin levels, and with obesity.
Adipose Tissue↗
Natural history and risk factors for early human atherogenesis. Pathobiological Determinants of Atherosclerosis in Youth (PDAY) Research Group.
A multi-institutional study, Pathobiological Determinants of Atherosclerosis in Youth (PDAY), was initiated to document the natural history of atherosclerosis, its relationship to risk factors, and the pathobiology of lesion development in young subjects. Pathology laboratories in nine centers collected arteries and tissues from > 2000 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), thickness of panniculus adiposus (obesity), changes in small renal arteries (hypertension), and apoprotein isoforms. This PDAY study documents the development of atherosclerosis at an early age and shows that the recognized risk factors for coronary heart disease are associated with lesion development in the arteries of these young subjects. The findings provide a strong justification for reducing risk factors in young persons.
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Long-term induction and regression of diet-induced atherosclerotic lesions in rhesus monkeys. II. Morphometric evaluation of lesions by light microscopy in coronary and carotid arteries.
Atherosclerotic lesions were induced in rhesus monkeys (Macaca mulatta) by feeding them a high-saturated fatty acid and high-cholesterol diet. After 5.4 years the extent of lesions in three major coronary arteries and the right carotid artery was evaluated morphometrically by light microscopy in one group of animals (group P). The remaining animals were switched to a low-cholesterol diet that remained high in saturated fatty acids and provided the same percentage of total calories as did the atherogenic diet. Lesion regression was then evaluated in one group of monkeys 1.9 years (group R4) and in another group of monkeys 3.7 years (group R5) after withdrawal of cholesterol alone from the diet. In group P, the mean intimal thickness varied between 26 and 47 microns, maximum intimal thickness between 70 and 92 microns, and luminal reduction between 9% and 12% in the three major coronary arteries. Luminal reduction varied between 1% and 11% in right carotid artery segments. After 1.9 years of consuming the basal diet, group R4 animals were no different from group P animals with respect to morphometric measures. Total intimal and medial areas of the left anterior descending (LAD) coronary artery in groups P and R4 were also similar. In contrast, after 3.7 years of consuming the basal diet, group R5 animals showed consistently although not statistically significantly lower values than those in group P for the morphometric measures in coronary arteries and total intimal area in the LAD. Similar results were obtained for the common carotid and external carotid arteries. Thus, our study shows that long-term diet-induced lesions in coronary arteries and in common and external segments of the right carotid artery regressed only when the animals were fed the basal diet for 3.7 years. We conclude that atherosclerotic lesions induced in coronary and carotid arteries can regress toward normal to a certain extent, but they require a longer time for regression than do other arterial segments. These findings support the results of clinical trials in human subjects.
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Long-term induction and regression of diet-induced atherosclerotic lesions in rhesus monkeys. I. Morphological and chemical evidence for regression of lesions in the aorta and carotid and peripheral arteries.
Atherosclerotic lesions were induced in rhesus monkeys by feeding a high-saturated fatty acid and high-cholesterol diet. After 5.4 years the extent of fatty streaks and raised lesions was evaluated in one group of animals (group P) by visual estimation in 10 arterial segments and chemically in four arterial segments. The remaining animals were switched to a basal regression diet low in cholesterol but high in saturated fatty acids for up to 3.7 years. Regression of lesions was evaluated in one group for 1.9 years (group R4) and in another for 3.7 years (group R5) after deleting cholesterol from the diet. The atherogenic diet increased serum cholesterol levels in all animals from a mean of 150 mg/dL to a mean of about 430 mg/dL. The atherogenic diet produced lesions in group P in all arterial segments (involving up to 50% of the arterial intimal surface) and increased cholesterol content in four arterial segments (varying between 443 and 506 micrograms/cm2). Switching to the basal regression diet decreased serum cholesterol levels to normal after 12 to 18 weeks. The switch to the basal diet significantly decreased the extent of fatty streaks in most arterial segments in both groups. Although differences in the mean extent of raised lesions among groups were not statistically significant, 7 of 10 arterial segments in group R4 and 9 of 10 segments in group R5 showed a lesser extent of raised lesions than in group P. Cholesterol content was lower (P < .05) in all four arterial segments in group R5 than in group P.(ABSTRACT TRUNCATED AT 250 WORDS)
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Association of diabetes mellitus with coronary atherosclerosis and myocardial lesions. An autopsy study from the Honolulu Heart Program.
While the excess risk of clinical cardiovascular disease among persons with diabetes mellitus is well established, most autopsy studies have not been able to elucidate reasons for the excess, to assess potential selection bias, or to adjust for other cardiovascular risk factors. The purpose of this study was to examine the predictive relation between diabetes and autopsy evidence of coronary atherosclerosis and myocardial lesions. Among 8,006 Japanese-American men examined at baseline in 1965-1968 as part of the Honolulu Heart Program, 7,591 were free of cardiovascular disease, and 1,515 of these men died over a 17-year follow-up period. Protocol autopsies were performed for 83 diabetic men and 159 nondiabetic men. Diabetes status was defined using self-reported history and treatment at several examinations, as well as physician diagnoses during hospitalization between 1965 and 1984. An excess of coronary artery atherosclerosis, assessed by mean panel score (3.4 vs. 3.0, p = 0.017) and percentage of intimal surface with raised lesions (56.6% vs. 47.4%, p = 0.024), was present among diabetic men but diminished to nonsignificant levels (3.3 vs. 3.0, p = 0.102, and 53.9% vs. 48.8%, p = 0.183, respectively) after adjustment for other cardiovascular risk factors. Myocardial lesions (acute, healing, or fibrotic) occurred significantly more frequently among diabetics than among nondiabetics (77.7% vs. 63.4%, p = 0.035), even after adjustment for other risk factors. Potential autopsy selection bias assessed in several ways appeared minimal. Among men with mild atherosclerosis, diabetics had more small and large myocardial lesions than did nondiabetics, although differences were not statistically significant (p < 0.10). It appears that the more adverse risk factor profile among diabetics accounts for some of the observed excess of coronary atherosclerosis. However, diabetes was independently associated with myocardial lesions, and these findings suggest a role for nonatherosclerotic mechanisms, such as clotting abnormalities or microvascular disease, in accounting for the excess clinical heart disease found in persons with diabetes.
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Atherosclerosis in young white males: arterial collagen and cholesterol.
As part of a multicenter study on atherosclerosis, we examined defined segments of thoracic and abdominal aortas from 118 white males, age 15-34 years, who died from external causes. One half of each aorta specimen was graded for lesions. Intima-media preparations were assayed for collagen and cholesterol in two standardized regions (dorsal and ventral) derived from the alternate half of each segment. Even though the mean extent of intimal surface involvement with raised lesions remained minimal (0-6%), the data revealed a remarkable transition in vessel wall chemistry over this time span. For example, the amount of collagen per unit surface area increases with age in all vessel segments except the ventral domain of the thoracic aorta. The amount of collagen as a percent of total vessel protein rises with age only in the ventral and dorsal regions of the abdominal aorta. Free and esterified cholesterol levels per unit surface area increase with age in all vessel segments. There is a significant correlation between collagen and esterified cholesterol per unit surface area in all vessel regions with the exception of the abdominal ventral segment. In the latter segment increases in collagen per unit surface area occur without a corresponding increase in cholesterol level suggesting that connective tissue proliferation may actually precede lipid deposition in the genesis of atherosclerosis. Esterified cholesterol is present at higher levels in the dorsal domains of the thoracic and abdominal aortas than in the ventral domains. These findings provide chemical data confirming that the dorsal domains is the most lesion-prone region of these vessel segments.(ABSTRACT TRUNCATED AT 250 WORDS)
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Nephrosclerosis in three cohorts of black and white men born 1925 to 1944, 1934 to 1953, and 1943 to 1962.
The prevailing levels of blood pressure among black and white men of ages 25 to 54 years were examined by two independent approaches in this study. Data on blood pressure obtained in national health surveys (National Health and Nutrition Examination Surveys, NHANES) do not show any appreciable upward or downward trend between 1960 and 1980 in men of these ages. The histologic examination of kidney samples obtained from coroner's autopsies offers an indirect way of estimating the levels of blood pressure that prevail in populations because of statistical relationships between nephrosclerosis and blood pressure. Samples of kidney tissues archived in New Orleans from 1968 to 1986 were evaluated by quantitative morphometry for the severity of the renovasculopathies that accompany high blood pressure. The outcome showed no significant secular trend among black and white men, confirming blood pressure survey findings that show no change in the hypertensive status of the population. The black-white difference in incipient signs of hypertension was seen to be well-established by ages 25 to 34 years in all cohorts of New Orleans subjects, as well as in the NHANES survey data. These result suggest that the adolescent and young adult ages are especially important in establishing the black-white difference in hypertension.
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