Cardiac myocyte sizes in right compared with left ventricle during overweight and hypertension.

Evidence is sparse concerning hypertrophy of cardiomyocytes in left and right ventricles (LV, RV). LV and RV from 105 forensic autopsies were weighed. Cross sectioned cardiac myocyte thicknesses were measured in hematoxylin and eosin-stained paraffin sections. Overweight (OW) is body weight >104.3 kg and hypertension (HT) is mean arterial pressure >106.7 mm Hg assessed from renal histology. Mean RV weights and cardiomyocyte thicknesses held nearly perfect proportionality to the LV values. Exceptions to these patterns were (1) myocytes were slightly thicker than expected in RV of the 27 specimens with the smallest myocyte thicknesses; (2) weights were slightly greater than expected in RV of hypertensives; and (3) myocytes were slightly smaller than expected in RV of OW subjects. Myocyte hypertrophy appears to affect LV and RV equally, preserving constant proportionality between them in a number of conditions which include OW, HT, and perhaps some cardiomyopathies. Ischemic, valvular, and right ventricular disorders determined at autopsy are specifically omitted from this provisional conclusion. The three exceptions from this principle were of small magnitude and unimpressive statistical significance which calls for cautious interpretation. Neither OW nor HT appears to act predictably upon the heart as exclusively volume or pressure overload.

Eccentric may differ from concentric left ventricular hypertrophy because of variations in cardiomyocyte numbers.

BACKGROUND: When overweight or hypertension is present, some patients at first examination exhibit left ventricular (LV) dilation and others concentric hypertrophy that persists indefinitely. Perhaps the ventricles with the fewest myocytes could enter systolic dysfunction with dilation and those with more myocytes may sustain persistent concentric hypertrophy. METHODS AND RESULTS: Cardiomyocyte numbers, MyN, were counted in paraffin sections of left ventricles from 99 forensic autopsies, excluding instances of coronary heart disease. MyN lacked statistically significant relationships with age, race, sex, height, weight, LV mass, and mean arterial pressure estimated from renal histology. Specimens with the fewest myocytes, however, did manifest significant dilation and thinner chamber walls. CONCLUSIONS: The tendency toward an eccentric pattern of hypertrophy in ventricles with the fewest myocytes is a clear conclusion, but has an ambiguous interpretation. This is the pattern expected from the initial hypothesis, but it also has other possible explanations. This ambiguity arises chiefly from limitations in the methods used for estimating MyN. These limitations are accessible to control in future studies. Our findings failed to contradict the hypothesis introduced here. These conclusions are implicit in the underlying observations of MyN constancy across such groupings as sex, height, weight, and LV mass, which provide the less speculative findings.

Bilateral common carotid artery ultrasound for prediction of incident strokes using intima-media thickness and external diameter: an observational study.

BACKGROUND: External common carotid artery (CCA) diameter and intima-media thickness (IMT) are independently associated with incident stroke and other cardiovascular events. Arterial geometry such as large IMT and large diameter may reflect vulnerable plaques and so impact stroke risk. Finally, arterial changes that exist bilaterally may increase stroke risk. METHOD: We studied middle-aged men and women (n=7276) from a prospective observational study who had right (R) and left (L) CCA IMT and external diameters measured via B-mode ultrasound (1987-89) in order to categorize CCA geometry. Using side- and gender-specific IMT and diameter medians, we categorized each measurement as large (≥ median) vs. not large (< median) and defined four geometries: both IMT and diameter were large, only one parameter was large, or neither was large (reference group). Participants were followed for first time stroke through December 31, 1999. We used proportional hazards models to assess associations between right and left CCA geometries with new stroke. We also calculated positive and negative likelihood ratios (+LR and -LR) for CCA bilateral phenotypes as a measure of diagnostic accuracy. RESULTS: Presence of both large CCA IMT and large diameter on one side was associated with strong stroke risk even after risk factor adjustment (men: RCCA hazard ratio [HR]=3.7 95% confidence interval [CI]=1.9-7.4; LCCA HR=2.4 95% CI=1.4-4.4; women: RCCA HR=4.0 95% CI=1.5-10.5; LCCA HR=5.7 95% CI=1.7-19.0). Presence of both large IMT and large diameter bilaterally was the strongest predictor of stroke identifying 64% of women and 44% of men who developed strokes. This phenotype showed potential for predicting stroke among individuals (women: +LR=3.1, 95% CI=2.6-3.8; men: +LR=2.3, 95% CI=1.8-2.8). CONCLUSION: Bilateral carotid artery geometries may be useful for stroke risk prediction.

Cardiomyocyte size estimated from noninvasive measurements of left ventricular wall thickness and chamber diameter.

Noninvasive measurements of left ventricular wall thickness (LVT) and left ventricular chamber diameter (LVD) allow calculation of expected left ventricular weight (LVW), but not of myocyte breadth (MyB), so that specification of left ventricular hypertrophy (LVH) is not optimal. Hypertrophied hearts, excluding coronary heart disease, and comparison specimens without hypertrophy were compiled into a series of 78 forensic autopsies, wherein LVT, LVD, and LVW were measured. MyB was measured in hematoxylin and eosin-stained paraffin sections. A series of clinical cases tabulating LVD and LVT was assembled from readily available publications. From postmortem data, a regression equation was derived to predict MyB from LVD and LVT. Applying this equation to the clinical data produced a scatter plot closely resembling that in the postmortem dataset. The equation derived here appears to provide valid predictions of cardiomyocyte sizes expected in histological measurements. The finding is the first of its kind and requires further testing for validation or rejection. This is offered as a provisional way to improve the determination of LVH using noninvasive measurements. How this improvement might enhance understanding of the mechanisms for hypertrophy is briefly explored, thus generating working hypotheses.

Histologically measured cardiomyocyte hypertrophy correlates with body height as strongly as with body mass index.

Cardiac myocytes are presumed to enlarge with left ventricular hypertrophy (LVH). This study correlates histologically measured myocytes with lean and fat body mass. Cases of LVH without coronary heart disease and normal controls came from forensic autopsies. The cross-sectional widths of myocytes in H&E-stained paraffin sections followed log normal distributions almost to perfection in all 104 specimens, with constant coefficient of variation across the full range of ventricular weight, as expected if myocytes of all sizes contribute proportionately to hypertrophy. Myocyte sizes increased with height. By regression analysis, height(2.7) as a proxy for lean body mass and body mass index (BMI) as a proxy for fat body mass, exerted equal effects in the multiple correlation with myocyte volume, and the equation rejected race and sex. In summary, myocyte sizes, as indexes of LVH, suggest that lean and fat body mass may contribute equally.

Renal vasculature in essential hypertension: a review of some contrarian evidence.

This chapter reviews a body of evidence concerning the anatomic pathology, pathogenesis, epidemiology and possible etiologic agents of benign essential hypertension in human populations. A core finding serves as the starting point for further reasoning: intimal fibroplasia of renal interlobular arteries (arteriosclerosis) increases with age at varying rates in all populations around the world, and the rise of mean arterial pressure (MAP) with age is closely tied to this process. The weight of evidence favors the view that fibroplasia progresses for wholly unknown reasons, is not accelerated by elevations in MAP, and that it raises MAP in proportion to its severity by creating nephron heterogeneity that initiates Goldblatt mechanisms. This form of hypertension has been designated type 2 to distinguish it from a less common form, called type 1, where the fibroplasia is of mild or minimal degree. This chapter reviews evidence that indicates type 1 does not evolve into type 2 because hypertension is not accelerating the process.Experimental models of hypertension include the Goldblatt model, which resembles some aspects of type 2, and spontaneous genetic models, which mimic some aspects of type 1 hypertension. There is currently no persuasive evidence that type 2 hypertension, as it naturally develops in the human during aging of 50 years or more, can be reproduced in laboratory animals. Clues to the etiology of the arterial fibroplasia that appears to underlie most instances of essential hypertension would best be sought in the study of variations among human populations around the world, and especially of their migrants.

Coronary artery circumferential stress: departure from Laplace expectations with aging.

Normal, youthful arteries generally maintain constant radius/wall thickness ratios, with the relationship being described by the Laplace Law. Whether this relationship is maintained during aging is unclear. This study first examines the Laplace relationships in postmortem coronary arteries using a novel method to correct measurements for postmortem artifacts, uses data from the literature to provide preliminary validation, and then describes histology associated with low circumferential stress. Measurements of radius and wall thickness, taken at sites free from atheromas, were used with national population estimates of age-, gender-, and race-specific blood pressure data to calculate average circumferential stress within demographic groups. The estimated circumferential stress at ages 55-74 years was about half that at ages 18-24 years because of a disproportionate increase of wall thickness relative to artery radius at older ages, violating the expected relationships described by the Laplace Law. Arteries with low circumferential stress (estimated at sites distant from atherosclerosis) had more necrotic atheromas than arteries with high stress. At sites with low stress and intimal thickening, smooth muscle cells (SMCs) were spread apart, thereby diminishing their density within both the intima and media. Thus, older arteries displayed both low circumferential stress and abundant matrix of low cellularity microscopically. Such changes might alter SMC-matrix interactions.

Associations of arterial tissue lipids with coronary heart disease risk factors in young people.

OBJECTIVE: To examine the associations of the coronary heart disease (CHD) risk factors with lipid composition of arterial tissue in 397 autopsied subjects 15-34 years of age from the Pathobiological Determinants of Atherosclerosis in Youth (PDAY) study. METHODS AND RESULTS: We measured esterified cholesterol, free cholesterol, and phospholipid in the left circumflex coronary artery and two segments of the abdominal aorta, one of which is more susceptible to advanced atherosclerosis than the other, and also measured the major CHD risk factors. Non-HDL cholesterol concentration was positively associated, and HDL cholesterol concentration was negatively associated, with tissue lipids in the left circumflex coronary artery and the abdominal aorta. Hypertension was positively associated with tissue lipids in both arteries. Hyperglycemia was associated with tissue lipids in the left circumflex coronary artery and smoking with lipids in the abdominal aorta. PDAY risk scores summarize the effects of the CHD risk factors on advanced atherosclerosis. These risk scores, computed from the mutable risk factors, were associated with tissue lipids in the left circumflex coronary artery and both segments of the abdominal aorta. CONCLUSIONS: The CHD risk factors are associated with lipids in arterial tissue just as they are associated with gross and microscopic lesions. These results support the proposal that early control of risk factors is likely to prevent or delay progression of atherosclerosis and prevent or delay the onset of CHD.

B-mode ultrasound common carotid artery intima-media thickness and external diameter: cross-sectional and longitudinal associations with carotid atherosclerosis in a large population sample.

BACKGROUND: Arterial diameter and intima-media thickness (IMT) enlargement may each be related to the atherosclerotic process. Their separate or combined enlargement may indicate different arterial phenotypes with different atherosclerosis risk. METHODS: We investigated cross-sectional (baseline 1987-89: n = 7956) and prospective (median follow-up = 5.9 years: n = 4845) associations between baseline right common carotid artery (RCCA) external diameter and IMT with existing and incident carotid atherosclerotic lesions detected by B-mode ultrasound in any right or left carotid segments. Logistic regression models (unadjusted, adjusted for IMT, or adjusted for IMT and risk factors) were used to relate baseline diameter to existing carotid lesions while comparably adjusted parametric survival models assessed baseline diameter associations with carotid atherosclerosis progression (incident carotid lesions). Four baseline arterial phenotypes were categorized as having 1) neither IMT nor diameter enlarged (reference), 2) isolated IMT thickening, 3) isolated diameter enlargement, and 4) enlargement of both IMT and diameter. The association between these phenotypes and progression to definitive carotid atherosclerotic lesions was assessed over the follow-up period. RESULTS: Each standard deviation increment of baseline RCCA diameter was associated with increasing carotid lesion prevalence (unadjusted odds ratio [OR] = 1.54, 95% confidence interval [CI] = 1.47-1.62) and with progression of carotid atherosclerosis (unadjusted hazards ratio (HR) = 1.37, 95% CI = 1.28-1.46); and the associations remained significant even after adjustment for IMT and risk factors (prevalence OR = 1.11, 95% CI = 1.04-1.18; progression HR = 1.11, 95% CI = 1.03-1.19). Controlling for gender, age and race, persons with both RCCA IMT and diameter in the upper 50th percentiles had the greatest risk of progressing to clearly defined carotid atherosclerotic lesions (all HR = 1.71, 95% CI = 1.47-2.0; men HR = 1.88, 95% CI = 1.48-2.39; women HR = 1.59, 95% CI = 1.31-1.95) while RCCA IMT or diameter alone in the upper 50th percentile produced significantly lower estimated risks. CONCLUSION: RCCA IMT and external diameter provide partially overlapping information relating to carotid atherosclerotic lesions. More importantly, the RCCA phenotype of coexistent wall thickening with external diameter enlargement indicates higher atherosclerotic risk than isolated wall thickening or diameter enlargement.

Comparison of coronary heart disease risk factors in autopsied young adults from the PDAY Study with living young adults from the CARDIA study.

BACKGROUND: Disease is sometimes best studied by examination of tissue obtained from autopsied individuals. Results derived from autopsied persons are considered biased because many factors influence the decision to perform an autopsy, and variables measured postmortem may be affected by changes immediately prior to death and emergency medical treatment. METHODS: The Pathobiological Determinants of Atherosclerosis in Youth (PDAY) study measured coronary heart disease risk factors postmortem in autopsied young adults 23-34 years of age dying from external causes (accidents, homicides, suicides). The Coronary Artery Risk Development in Young Adults (CARDIA) study measured risk factors in living subjects of similar ages. RESULTS: Within sex, race, and age groups, the differences in body mass index between PDAY and CARDIA were significant but small. The prevalences of hyperglycemia/diabetes within sex, race, and age groups were similar in PDAY and CARDIA; overall, blacks in PDAY, but not in CARDIA, had a higher prevalence than whites. Serum lipoprotein concentrations were slightly and significantly higher and significantly more variable in PDAY subjects than in CARDIA subjects; the greater variability was interpreted as due primarily to emergency medical treatment. Prevalences of smoking and hypertension were substantially higher in PDAY subjects. CONCLUSIONS: Although there were statistically significant differences, the overall similarity of the risk factors in the two studies supports the validity of investigating associations of risk factors measured postmortem with anatomically determined arterial lesions in autopsied young adults dying from external causes. The greater variability in postmortem serum measurements attenuates but does not obscure associations.

Low smooth muscle cell densities characterize sites with isolated interstitial lipid in coronary artery intima.

CONTEXT: The initial step in the development of atherosclerotic lesions is suggested to be the retention of low-density lipoprotein. This suggestion would seem to imply that some interval of time ought to intervene between the initial retention of interstitial lipid and subsequent influx of fatty streak cellular elements. Yet no evidence for such a waiting interval has been offered. OBJECTIVE: To describe findings from application to coronary arteries from forensic autopsy specimens of a new method for staining lipids in paraffin sections. DESIGN: Isolated interstitial lipid (IIL) (extracellular lipid pools accompanied by no perceptible intracellular lipid or other fatty streak elements at the affected sites) was identified in various intimal compartments, and smooth muscle cell (SMC) numbers were counted at these sites. RESULTS: Isolated interstitial lipid was a surprisingly frequent finding after age 35 years, seen in 87 (84%) of 104 cases. The number of SMCs per unit area of sectioned intima was high in specimens lacking IIL (15.5 SMCs/[100 microm]2), lowest at sites displaying IIL (8.3 SMCs/[100 microm]2), and intermediate at sites lacking IIL in specimens that do contain IIL at some other location (12.6 SMCs/[100 microm]2). CONCLUSIONS: These findings plus other evidence support the proposal that retention of lipid most often happens, in aging arteries, at sites where the architecture was previously altered by diluting of constant SMC numbers by expanding collagenous matrix, thereby lowering SMC densities.

Common carotid artery wall thickness and external diameter as predictors of prevalent and incident cardiac events in a large population study.

BACKGROUND: Arterial diameters enlarge in response to wall thickening, plaques, and many atherosclerotic risk factors. We hypothesized that right common carotid artery (RCCA) diameter would be independently associated with cardiac disease and improve risk discrimination. METHODS: In a middle-aged, biracial population (baseline n = 11225), we examined associations between 1 standard deviation increments of baseline RCCA diameter with prevalent myocardial infarction (MI) and incident cardiac events (MI or cardiac death) using logistic regression and Cox proportional hazards models, respectively. Areas under the receiver operator characteristic curve (AUC) were used to estimate model discrimination. RESULTS: MI was present in 451 (4%) participants at baseline (1987-89), and incident cardiac events occurred among 646 (6%) others through 1999. Adjusting for IMT, RCCA diameter was associated with prevalent MI (female OR = 2.0, 95%CI = 1.61-2.49; male OR = 1.16, 95% CI = 1.04-1.30) and incident cardiac events (female HR = 1.75, 95% CI = 1.51-2.02; male HR = 1.27, 95% CI = 1.15-1.40). Associations were attenuated but persisted after adjustment for risk factors (not including IMT) (prevalent MI: female OR = 1.73, 95% CI = 1.40-2.14; male OR = 1.14, 95% CI = 1.02-1.28, and incident cardiac events: female HR = 1.26, 95% CI = 1.08-1.48; male HR = 1.19, 95% CI = 1.08-1.32). After additional adjustment for IMT, diameter was associated with incident cardiac events in women (HR = 1.18, 95% CI = 1.00-1.40) and men (HR = 1.17, 95% CI = 1.06-1.29), and with prevalent MI only in women (OR = 1.73; 95% CI = 1.37-2.17). In women, when adjustment was limited, diameter models had larger AUC than other models. CONCLUSION: RCCA diameter is an important correlate of cardiac events, independent of IMT, but adds little to overall risk discrimination after risk factor adjustment.

Age trends of renal arteriolar hyalinization explored with the aid of serial sections.

BACKGROUND: Hyalinized renal arterioles (Hy) can be counted per unit area of PAS-stained paraffin sections. The percentages of nephrons having hyalinized afferent and efferent arterioles can be assessed in serial sections. METHODS: Slides of renal tissue were assessed for Hy in 559 basal forensic autopsies, i.e. those with no condition known to correlate with hypertension. Serial sections in a series of 20 cases were used to measure afferent and efferent arterioles and determine formulas to relate afferent and efferent arterioles to Hy. The formulas were used in the 559 cases to assess the trends on age of Hy in terms of percentage of affected nephrons. RESULTS: Hy increased rapidly from ages 15 to 34 years, but stabilized from ages 35 to 102 years at levels implying afferent arterioles of about 2/5 of nephrons and efferent arterioles of about 1/5. Most of the nephrons in the kidney were deduced to be supplied by hyalinized afferent arterioles in nearly half of all subjects from ages 35 to 102 years, and the rates were the same at all ages. CONCLUSION: These data provide for the first time provisional estimates for the prevalence of Hy to be used as baselines for biopsy comparisons. Failure of numerous kidneys to enter end-stage nephrosclerosis in spite of several decades of involvement by hyalinization in half or more of their arterioles does not support the view that hyalinization induces ischemic nephron atrophy.

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.

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.

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.

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.

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.

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.

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.