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Biomedical subjects

Richard E Tracy

Publications and source records attributed to Richard E Tracy.

14 recordsLinked to original sources

PDAY risk score predicts advanced coronary artery atherosclerosis in middle-aged persons as well as youth.

A risk score formula to estimate the probability of advanced atherosclerosis using coronary heart disease (CHD) risk factors was developed for persons 15-34 years of age by the Pathobiological Determinants of Atherosclerosis in Youth (PDAY) study. We applied the PDAY risk score to autopsied individuals from the Community Pathology Study (CPS), a different population that included middle-aged as well as young subjects. The PDAY risk score was associated with extent of raised lesions in the coronary arteries of CPS cases 15-34 years of age. The PDAY risk score computed from only the modifiable risk factors was associated with extent of raised lesions in the coronary arteries of subjects 35-54 years of age. The association of the PDAY risk score with lesions in 15-34 year old CPS subjects validates the PDAY risk score. The associations in both younger (15-34 years) and older (35-54 years) subjects suggest a seamless progression of the effects of the modifiable risk factors on atherosclerosis from 15 to 54 years of age. These results support the proposal that early control of risk factors is likely to prevent or delay the onset of CHD.

Adolescent↗

Common carotid arterial interadventitial distance (diameter) as an indicator of the damaging effects of age and atherosclerosis, a cross-sectional study of the Atherosclerosis Risk in Community Cohort Limited Access Data (ARICLAD), 1987-89.

BACKGROUND: The effect of age on common carotid artery diameter is unclear for varying atherosclerosis risk levels. METHODS: Cross-sectional data from the Atherosclerosis Risk in Communities Limited Access Data set were used to estimate the association of age with B-mode ultrasound common carotid artery diameter for three atherosclerosis risk levels. Based on information from clinical examinations, B-mode ultrasounds, questionnaires, blood and other tests, participants were categorized into three groups: pre-existing disease (prevalent stroke and/or coronary heart disease), high risk group (no pre-existing disease, but prevalent diabetes, hypertension, plaques/shadowing, body mass index > or = 30, current smoking, or hyperlipidemia), and a low risk group (no pre-existing disease, no plaques/shadowing, and no major elevated risk factors). Multivariable linear regression analyses modeled the common carotid artery diameter relationship with age. RESULTS: Age was positively and significantly associated with common carotid artery diameter after risk factor adjustment in the overall sample, but age had a larger effect among persons with evidence of atherosclerosis (interaction p < 0.05). Each year of older age was associated with 0.03 mm larger diameter/year among persons with pre-existing disease, with 0.027 mm larger diameter/year in the high risk group, but only 0.017 mm/year among the low risk group. Results were qualitatively similar using plaques/shadowing status to indicate atherosclerosis severity. CONCLUSION: The significant impact of age on common carotid artery diameter among low risk, middle-aged, black and white men and women suggests arterial remodelling may occur in the absence of identified risk factors. The significantly larger impact of age among persons with, compared to persons without identified atherosclerosis or its risk factors, suggests that arterial remodelling may be an indicator of exposure duration.

Adult↗

Pathobiological determinants of atherosclerosis in youth risk scores are associated with early and advanced atherosclerosis.

OBJECTIVES: Atherosclerosis begins in childhood and progresses during adolescence and young adulthood. The Pathobiological Determinants of Atherosclerosis in Youth Study previously reported risk scores to estimate the probability of advanced atherosclerotic lesions in young individuals aged 15 to 34 years using the coronary heart disease risk factors (gender, age, serum lipoprotein concentrations, smoking, hypertension, obesity, and hyperglycemia). In this study we investigated the relation of these risk scores to the early atherosclerotic lesions. METHODS: We measured atherosclerotic lesions in the left anterior descending coronary artery, right coronary artery, and abdominal aorta and the coronary heart disease risk factors in persons 15 to 34 years of age who died as a result of external causes and were autopsied in forensic laboratories. RESULTS: Risk scores computed from the modifiable risk factors were associated with prevalence of microscopically demonstrable lesions of atherosclerosis (American Heart Association grade 1) in the left anterior descending coronary artery and with the extent of the earliest detectable gross lesion (fatty streaks) in the right coronary artery and abdominal aorta. Risk scores computed from the modifiable risk factors also were associated with prevalence of lesions of higher degrees of microscopic severity (intermediate as well as advanced) in the left anterior descending coronary artery and with extent of lesions of higher degrees of severity (intermediate and raised lesions) in the right coronary artery and abdominal aorta. CONCLUSIONS: Risk scores calculated from traditional coronary heart disease risk factors to identify individual young persons with high probability of having advanced atherosclerotic lesions also are associated with earlier atherosclerotic lesions, including the earliest anatomically demonstrable atherosclerotic lesion. These results support lifestyle modification in youth to prevent development of the initial lesions and the subsequent progression to advanced lesions and, thereafter, to prevent or delay coronary heart disease.

Adolescent↗

Risk scores predict atherosclerotic lesions in young people.

BACKGROUND: Atherosclerosis begins in childhood and progresses through young adulthood to form the lesions that cause coronary heart disease. These preclinical lesions are associated with coronary heart disease risk factors in young persons. METHODS: The Pathobiological Determinants of Atherosclerosis in Youth study collected arteries and samples of blood and other tissues from persons aged 15 to 34 years who died of external causes and underwent autopsy in forensic laboratories. We measured the coronary heart disease risk factors and atherosclerotic lesions in the coronary arteries (CAs) (n = 1117) and the abdominal aorta (n = 1458). RESULTS: We developed risk scores, normalized so that a 1-unit increase was equivalent to a 1-year increase in age, to estimate the probability of advanced atherosclerotic lesions in the CAs and the abdominal aorta from age, sex, serum lipoprotein concentrations, smoking, hypertension, obesity, and hyperglycemia. Odds ratios for a 1-unit increase in the risk scores were 1.18 (95% confidence interval, 1.14-1.22) for the CAs and 1.29 (95% confidence interval, 1.23-1.35) for the abdominal aorta. These risk scores had good discrimination (c-indexes: 0.78 for the CAs and 0.84 for the abdominal aorta) and were calibrated. The presence of abdominal aortic lesions increased the likelihood of having CA lesions. CONCLUSION: Risk scores calculated from traditional coronary heart disease risk factors provide a tool for identifying young individuals with a high probability of having advanced atherosclerotic lesions.

Adolescent↗

Evidence concerning resistance to atheroma by media-like islands in the intima of coronary arteries.

Coronary arteries with and without atheroma are compared histologically to ask what kind of artery encourages atheroma. When atheroma obliterates the structures that preceded and invited its intrusion, the sites remaining for observation form a censored data set. How to assess media-like island effects using the censored data set is the objective here. Full length of right coronary artery is prepared for H&E-stained paraffin sections. At sites lacking atheroma, measurements are taken for intimal thickness (FT), SMC numbers (CT), and their ratio, fibroplastic thickness per SMC, FC = FT/CT. Arteries with atheroma tend to have greater values for all three variables, FC, FT, and CT. Mathematical models compensating for data set censoring imply that atheroma selectively favors sites with much fibroplasia and few SMCs, i.e. high FC. Frequently encountered media-like islands in the coronary intima showed ambiguous evidence of weakly repelling atheroma. Fibroplastic intimal thickening measured by FC progresses relentlessly with age. The sites with the greatest fibroplasia seem to be the most prone to selective obliteration by atheroma. Media-like islands seem to protect only the local sites and not the whole artery from atheroma.

Adult↗

ACE insert/delete polymorphism and atherosclerosis.

We report on the results of a large autopsy study focusing upon the hypothesis that deletion of the Alu insert in the angiotensin converting enzyme (ACE) gene is associated with: (a) greater prevalence or extent of atherosclerosis in the aorta and coronary arteries; and (b) microscopic qualities of established atherosclerotic plaques in the coronary arteries. This study was conducted in young US black (n=290) and white (n=379) males using available materials and data from the Pathobiological Determinants of Atherosclerosis in Youth (PDAY) study, a multi-center cooperative autopsy study organized in 1985 to explore the relationships of known cardiovascular risk factors to atherosclerosis in victims of accidents, homicides, or suicides in the age range of 15-34 years. The results provide strong evidence that ACE genotype may not be a predictor of either the prevalence or the extent of the lesions of atherosclerosis in the right coronary artery or the aorta of young adults, an observation that confirms previous studies that estimated the prevalence and extent of atherosclerosis using coronary angiography. In addition, the results suggest that ACE genotype does not contribute to the formation of atherosclerotic lesions that have the characteristics of vulnerable plaques in the left anterior descending coronary artery of young adults.

Adolescent↗

Smoking is associated with advanced coronary atherosclerosis in youth.

Smoking is linked to atherosclerosis and coronary heart disease (CHD) in older adults. However, evidence that smoking affects coronary atherosclerosis in young people is incomplete. The Pathobiological Determinants of Atherosclerosis in Youth (PDAY) Study collected arteries, blood, and other tissues from persons 15 to 34 years of age dying of external causes and autopsied in forensic laboratories. Lesions in the proximal left anterior descending coronary arteries (LAD) from 1127 subjects were graded microscopically according to the American Heart Association criteria. Among individuals with advanced lesions (Grade 4 or 5), smokers had a greater prevalence of Grade 5 lesions than non-smokers (odds ratio 9.61, 95% confidence interval 2.34-39.57), a difference suggesting that smoking accelerates the transition from Grade 4 to Grade 5 lesions. This association occurred among both men and women, and among persons with and without other CHD risk factors. The difference in qualities of advanced lesions suggests that smoking possibly accelerates the transition from Grade 4 to Grade 5 lesions by promoting thrombosis and accretion on the intimal surface of the plaque.

Adolescent↗

Lipid fixation for fat staining in paraffin sections applied to lesions of atherosclerosis.

A new method to fix lipids for staining in paraffin sections was applied here to early lesions of atherosclerosis to test comparability with similar results using frozen-section fat stains. Small blocks of formalin-fixed human coronary artery were exposed to an emulsion of linoleic acid and lecithin in 70% ethylene glycol at 56 degrees C for 3 days. The unsaturated fatty acids partitioned into the tissue lipids for later fixation by chromic acid and could then be processed through paraffin-section for fat staining. Blocks of tissue from the same specimens were also processed for standard frozen-section fat staining. The types of early atherosclerotic lesions described by the American Heart Association Lesions Committee--types I, II, III, and IV--were demonstrated equally well using the two methods. Additional newly described patterns of lipid deposits were also revealed by both methods. The paraffin method showed no indication of omitting or adding anything compared with frozen sections. The surprising finding of unexpected patterns of lipid distribution in human coronary artery suggests that the method may prove to be useful. Those novel patterns were first observed with the more flexible paraffin method and later confirmed by the more tedious and demanding frozen-section method.

Adult↗

Determination of elements in native and bypass human coronary artery plaque deposits from the same heart using inductively coupled plasma-mass spectrometry.

As part of an ongoing study on atherosclerotic arteries, the concentrations of 12 elements in a native and by-pass human coronary artery plaque deposits from five human hearts were determined using inductively coupled plasma-mass spectrometry (ICP-MS). These elements were Ca, P, Na, K, Mg, Zn, Cu, Pb, Fe, Al, Si, and S. For Zn, Ca, Pb, Fe, Al, and Si, the levels were at the fractional micromol/g levels and they probably played an unimportant role in plaque development. Sulfur levels varied from 23 to 140 micromols indicative of the possible presence of homocysteine, but there appeared to be no consistent relationship between by-pass and native concentrations. The calcium and phosphorus concentrations were relatively high in all cases, but the ratio of their molecular concentrations did not correspond to hydroxyapatite, which is conventionally considered to be the chemical form of calcium in heart plaque. In the mature native plaque, high calcium/phosphorus ratios indicated calcium in chemical forms other than hydroxyapatite. In undeveloped by-pass plaque, the phosphorus concentration was too high to be as hydroxyapatite but may be phospholipids. Because it is difficult to get suitable samples, only five heart samples were available. Therefore, these results should be treated as preliminary.

Arteriosclerosis↗

High resolution three-dimensional visualization and characterization of coronary atherosclerosis in vitro by synchrotron radiation x-ray microtomography and highly localized x-ray diffraction.

Human atherosclerotic plaques in both native and bypass arteries have been visualized using microtomography to provide additional information on the nature of coronary artery disease. Plaques contained within arteries removed from three white males aged 51, 55 and 70 are imaged in three-dimensions with monochromatic synchrotron x-ray radiation. Fields of view are 658 x 658 x 517 voxels. with cubic voxels ranging from 12 to 13 microm on a side. X-ray energies range from 11 to 15 keV (bandpass approximately 10 eV). At lower energies, high local absorption tends to generate reconstruction artefacts, while at higher energies the arterial wall is scarcely visible. At all energies, calcifications are clearly visible and differences are observed between plaques in native arteries (lifetime accumulations) versus bypass arteries (plaques developing in the interval between the heart bypass operation and the autopsy). In order to characterize coronary calcification, a microfocused, 50 microm2, 25 keV x-ray beam was used to acquire powder diffraction data from selected calcifications. Also, large calcifications were removed from the native arteries and imaged with 25 keV x-ray energy. Calcifications are composed of hydroxyapatite crystallites and an amorphous phase. In summary, native calcifications are larger and have a higher fraction of hydroxyapatite than calcifications from the bypass arteries.

Aged↗

Obesity accelerates the progression of coronary atherosclerosis in young men.

BACKGROUND: Obesity is a risk factor for adult coronary heart disease and is increasing in prevalence among youths as well as adults. Results regarding the association of obesity with atherosclerosis are conflicting, particularly when analyses account for other risk factors. METHODS AND RESULTS: The Pathobiological Determinants of Atherosclerosis in Youth (PDAY) study collected arteries, blood, and other tissue from approximately 3000 persons aged 15 to 34 years dying of external causes and autopsied in forensic laboratories. We measured gross atherosclerotic lesions in the right coronary artery (RCA), American Heart Association (AHA) lesion grade in the left anterior descending coronary artery (LAD), serum lipid concentrations, serum thiocyanate (for smoking), intimal thickness of renal arteries (for hypertension), glycohemoglobin (for hyperglycemia), and adiposity by body mass index (BMI) and thickness of the panniculus adiposus. BMI in young men was associated with both fatty streaks and raised lesions in the RCA and with AHA grade and stenosis in the LAD. The effect of obesity (BMI>30 kg/m(2)) on RCA raised lesions was greater in young men with a thick panniculus adiposus. Obesity was associated with non-HDL and HDL (inversely) cholesterol concentrations, smoking (inversely), hypertension, and glycohemoglobin concentration, and these variables accounted for approximately 15% of the effect of obesity on coronary atherosclerosis in young men. BMI was not associated with coronary atherosclerosis in young women although there was trend among those with a thick panniculus adiposus. CONCLUSIONS: Obesity is associated with accelerated coronary atherosclerosis in adolescent and young adult men. These observations support the current emphasis on controlling obesity to prevent adult coronary heart disease.

Adipose Tissue↗

The action of aging upon coronary intima and renal microvasculature in USA and Andes populations.

Full lengths of right coronary artery obtained at autopsy and examined in hematoxylin and eosin stained paraffin sections sometimes reveal the presence of at least one instance of atheroma (YesA specimens). YesA specimens are nearly always those with generalized intimal fibroplasia, measured by excessive intimal thickness per smooth muscle cell. Accumulating evidence suggests that aging governs the progression of fibroplasia, and that this fibroplasia is what aging does to the coronary artery in preparation for atheroma. Hyalinization of renal arterioles was previously found to correlate strongly with the presence of coronary atheroma and with the progression of the fibroplasia of aging in race, sex, age matched comparisons of subjects within a population (forensic autopsies in New Orleans). The data reported here reveal the correlation of arteriolar hyalinization with fibroplasia and atheroma to persist in comparisons across geographically diverse populations. The outcome suggests that aging of coronary intima, in so far as it bears upon preparation for atheroma, may vary in rate between populations. This source of variation could offer clues about environmental factors that may modify rates of aging.

Adolescent↗

Influence of arteriolar hyalinization on arterial intimal fibroplasia in the renal cortex of subjects in the United States, Peru, and Bolivia, applicable also to other populations.

Microvasculopathies of nephrosclerosis progress with age in contrasting patterns. Arterial intimal fibroplasia (R(r) and R(c), respectively, in small and large interlobular arteries) previously showed close linkages to hypertension and to "nephrosclerosis," defined by fibrous replacement of atrophied nephrons, whereas hyalinization of arterioles (Hy) failed to show consistent linkages. In this study, renal samples from seven populations, three newly assembled and four reassessed from archived data, were evaluated for R(r), R(c), and Hy in forensic autopsies of basal subjects (ie, those lacking conditions known to correlate with hypertension or nephrosclerosis, mostly deaths by violence). The patterns of progression on age were alike in all populations, but the rates of progression differed greatly. The observed ranges indicate a 547% higher rate for Hy in the fastest compared with the slowest population, a 49% higher rate for R(c), and a 107% higher rate for R(r). About one third of variation in R(r) and R(c) between populations can be attributed to the correlation with Hy, leaving a substantial residual effect independent of Hy. The findings suggest that the etiology propelling hyalinization in arterioles seems somehow to accelerate the progression of intimal fibroplasia in arteries. The reverse direction, fibroplasia somehow accelerating hyalinization, seems unreasonable, because the presumed consequence, Hy, fails to increase notably with age after 40 years, whereas the presumed causes, R(r) and R(c), rise unremittingly into old age. The etiologies of the population differences are of great consequence to public health but remain unknown.

Adolescent↗

A method for quantifying adrenocortical nodular hyperplasia at autopsy: some use of the method in illuminating hypertension and atherosclerosis.

Quantifying the severity of adrenocortical nodular hyperplasia at autopsy or surgery has much potential practical value. For instance, this inquiry explores the correlation of adrenal nodularity with features of atherosclerosis in coronary arteries and microvascular features of hypertension in the renal cortex. Tissue retrieved from forensic autopsies in 96 men and women ages 16 to 88 years were evaluated for adrenal nodularity, coronary atheroma, and hypertensive renal microvasculopathies. Formalin-fixed adrenal glands were cut into 0.5-cm thick slices and fixed to plastic sheets with SuperGlue (Ross Products, Inc, Columbus, OH). After ranking the specimens on increasing nodularity, they were judged to fall into 10 distinguishable grades of increasing severity; photographs of a representative in each grade were arranged onto a panel. Each gland was then assigned the grade of the photograph it most resembled. Coronaries and kidneys were evaluated in paraffin sections. Weight and nodularity of adrenal glands increased with age. Men with at least one instance of atheroma in the coronary sample had heavier and more nodular glands (age-adjusted) than in men without atheroma. The differences held stronger statistical significance for nodularity than for weight because nodularity continued to show significance even within age groups sometimes represented by few cases. Hypertensive renal microvasculopathies failed to correlate with any of the adrenal features. Women were too few for the analysis. Findings made with the panel of photographs now available for grading adrenocortical nodular hyperplasia showed interesting correlations with coronary atherosclerosis in this data set, suggesting that use of this method might offer some insight into cardiovascular disease.

Adolescent↗