Social environment as a factor in diet-induced atherosclerosis.

Rabbits on a 2 percent cholesterol diet were individually petted, held, talked to, and played with on a regular basis. Measurements of aortic affinity for a Sudan stain, serum cholesterol levels, heart rate, and blood pressure were made at the end of the experimental period. Compared to control groups, which were given the same diet and normal laboratory animal care, the experimental groups showed more than a 60 percent reduction in the percentage of aortic surface area exhibiting sudanophilic lesions, even though serum cholesterol levels, heart rate, and blood pressure were comparable.

Effect of alpha-tocopherol on restenosis after angioplasty in a model of experimental atherosclerosis.

The ability of alpha-tocopherol to reduce restenosis after angioplasty was tested in a rabbit model in which angioplasty was performed on established atherosclerotic lesions. Lesions induced by 4 wk of cholesterol feeding after focal desiccation of femoral arteries were balloon dilated. 3 wk after angioplasty, angiographically determined minimum luminal diameters were less in the untreated group (0.80 +/- 0.51 mm) than in the group treated with oral alpha-tocopherol beginning 19 d before angioplasty (1.38 +/- 0.29 mm; P < 0.01). The cross-sectional area of the intima-media was greater in the untreated group (1.18 +/- 0.48 mm2) than in the alpha-tocopherol group (0.62 +/- 0.25 mm2, P < 0.0001). These differences were not due to vasoconstriction or altered plasma cholesterol. Alpha-tocopherol thus reduced restenosis after angioplasty in this model. In rabbit vascular smooth muscle cells, oxidized low density lipoprotein stimulated DNA synthesis. Alpha-tocopherol treatment inhibited DNA synthesis stimulated by oxidized low density lipoprotein, but not by serum. The findings are consistent with the hypothesis that oxidized lipids can stimulate hyperplasia and that antioxidants may limit hyperplasia by inhibiting either the oxidation or the proliferative effects of oxidants on cells.

Macrophage-mediated 15-lipoxygenase expression protects against atherosclerosis development.

Oxidative modification of LDL increases its atherogenicity, and 15-lipoxygenase (15-LO) has been implicated in the process. To address this issue, we generated transgenic rabbits that expressed 15-LO in a macrophage-specific manner and studied their susceptibility to atherosclerosis development when they were fed a high-fat, high-cholesterol (HFHC) diet (Teklad 0533 rabbit diet 7009 with 10% corn oil and 0.25% cholesterol) for 13.5 wk. Transgenic and nontransgenic rabbits developed similar degrees of hypercholesterolemia and had similar levels of triglyceride, VLDL, LDL, and HDL. Quantitative morphometric analysis of the aortic atherosclerosis indicated that the transgenic animals (n = 19) had significantly smaller lesion areas (9.8+/-6.5%, mean+/-SD) than their littermate controls (n = 14, 17.8+/-15.0%) (P < 0.05). In a subgroup (n = 9) of transgenic rabbits that received the HFHC diet plus the antioxidant N',N '-diphenyl-phenylenediamine (1%), the extent of lesion involvement (9.8+/-7.5%) did not differ from the subgroup (n = 10) that received the regular HFHC diet (9.7+/-5.9%). Since the results were unexpected, we repeated the experiments. Again, we found that the nontransgenic littermates (n = 12) had more extensive lesions (11.6+/-10.6%) than the transgenic rabbits (n = 13; 9.5+/-7.8%), although the difference was not significant. In a third set of experiments, we crossed 15-LO transgenic rabbits with Watanabe heritable hyperlipidemic (WHHL) rabbits and found that the lesion area in the 15-LO transgenic/heterozygous WHHL rabbits (n = 14) was only about one third (7.7+/-5.7%) that found in nontransgenic heterozygous WHHL littermate controls (n = 11, 20.7+/-19.4%) (P < 0.05). These data suggest that overexpression of 15-LO in monocytes/macrophages protects against lipid deposition in the vessel wall during early atherogenesis in these rabbit models of atherosclerosis.

Increase in atherosclerosis and adventitial mast cells in cocaine abusers: an alternative mechanism of cocaine-associated coronary vasospasm and thrombosis.

Coronary vasospasm has been implicated as a cause of myocardial ischemia and sudden cardiac death in cocaine abusers. However, the mechanism or mechanisms remain unknown. Autopsy records (n = 5,871) from the medical examiner's files at Baltimore, Maryland and northern Virginia were examined and 495 persons (8.4%) were identified with positive toxicologic findings for cocaine. Of these, six subjects (1.2%) had total thrombotic occlusion, involving primarily the left anterior descending coronary artery. The mean number of adventitial mast cells per coronary segment and the degree of atherosclerosis were determined. These observations were compared with findings in age- and gender-matched subjects who died from cocaine overdose and in patients who had sudden cardiac death (acute thrombosis) without a history of illicit drug abuse. There were significantly more mast cells in subjects with cocaine-associated thrombosis than in the other groups. The number of mast cells showed a significant correlation with the degree of cross-sectional luminal narrowing (r = 0.68) in subjects with cocaine-associated thrombosis but not in subjects with sudden death due to thrombosis (r = 0.34, p less than 0.03). Subjects with cocaine-associated thrombosis also had significant coronary atherosclerosis without plaque hemorrhage (five had one or more vessels with greater than 75% cross-sectional area luminal narrowing) despite a mean age of 29 +/- 2 years. These findings suggest that adventitial mast cells may potentiate atherosclerosis and vasospasm, thrombosis and premature sudden death in long-term cocaine abusers.

A quantitative study of the localization of atherosclerotic lesions in the rabbit aorta.

A quantitative study of the size and location of early sudanophilic lesions has been carried out on the aortae of five rabbits. The atherosclerotic lesions were induced by feeding an average of 114 (+/- 3.7) egg yolks over an average period of 83 (+/- 1.7) days. The aortic lesions were visualuized by gross staining with Sudan III and measured by the polar coordinate method. The lesions were almost entirely around orifices: their size was directly proportional to the area of the associated ostium (P less than 0.005). The sudanophilic deposits were located downstream from the ostia in areas believed to experience high shear stresses. The area of the intercostal ostia increased as one proceeded down the thoracic aorta (P less than 0.005). A deviation from the distal distribution pattern was observed where local flow and shear stresses were disturbed. The coronary lesions completely surrounded the ostia, the coeliac lesions had significant proximal components and the left renal and inferior mesenteric lesions were skewed to the right. The study suggests that hemodynamic forces and particularly high shear stress is of considerable importance in both the initiation and localization of early atherosclerotic lesions.

A quantitative study of the development of sudanophilic lesions in the aorta of rabbits fed a low-cholesterol diet for up to six months.

Eighteen New Zealand white rabbits were placed on a diet containing 0.25% cholesterol and 6% corn oil for periods of up to 6 months. The animals were divided into 4 gours and sacrificed after 2, 3, 4, and 6 months. The aortae were removed, stained with Sudan III, and analyzed with the polar coordinate technique. While the periorificial lesions developed more slowly on this diet than on the diet with 2% cholesterol and 6% corn oil we had used previously, there was no differences in either the location or the shape of the lesions. In the descending thoracic aorta, lesions developed initially distal to orifices; however, significant lateral and proximal components were observed as atherogenesis progressed. The coronary lesions completely surrounded the ostia in all stages of development. The total area of the lesions was more related to time (r = 0.74, P less than 0.01), than to serum cholesterol (r - 0.51, P less than 0.05) or to cholesterol-time product (r = 0.69, P less than 0.01).

The effect of the duration of cholesterol feeding on the development of sudanophilic lesions in the rabbit aorta.

Polar coordinate mapping was used to determine the rate of growth of individual sudanophilic lesions on the aortic wall around several major branches of the aortae of cholesterol fed rabbits. Four groups, with 6 8-month old male albino white rabbits in each, were used in the study. One group served as a control and the remaining 3 were fed a diet of 2% cholesterol and 6% heated corn oil mixed with ground rabbit pellets for 4, 8, and 10 weeks each. Animals were sacrificed, the aortae removed, stained with Sudan III, pinned at in vivo dimensions, and mapped by the polar coordinate method. No sudanophilic lesions were observed in the control animals. In the experimental groups, the early lesions, except the coronaries, were almost entirely distal to the orifices, and maintained roughly the same contour while spreading around the orifice. The coronary lesions completely encircled the orifices as described previously. As lesions progressed, they became elevated and often granular, so that the lesions themselves may have affected flow profiles around the orifices. Lesions around adjacent orifices were fused in 48% of the cases after 10 weeks on the diet, as opposed to 2% after 4 weeks on the diet. More prolonged experiments were not possible with this diet as the animals developed jaundice and diarrhea. Hemodynamically, these results suggest that early sudanophilic lesions in cholesterol-fed rabbits develop on the aortic wall in areas of high shear stress.

Quantitative study of the localization of sudanophilic coeliac lesions in the White Carneau pigeon.

Polar coordinate mapping was used to determine the rate of progression of spontaneous sudanophilic coeliac lesions on the aortic wall in White Carneau pigeons. Three age groups of 5 pigeons were studied (approximately 1, 4 approximately 4 and approximately 6.5 years). Serum cholesterol was found to decrease with age (r = 0.69, P less than 0.01). Lesion area was found to increase with both age (r = 0.86, P less than 0.01) and the age--serum cholesterol product (r = 0.92, P less than 0.01). Lesions developed initially in the proximal sector (270 degrees leads to 90 degrees) with two relative maxima (approximately 20 degrees and approximately 320 degrees). Lesions then grow proximally and radially. The immediately proximal inflow region (340 degrees leads to 360 degrees) was spared in all 3 age groups. Little sudanophilic material was observed on the distal flow divider (90 degrees leads to 270 degrees) even in the oldest birds. The mode of spontaneous coeliac sudanophilic lesion development in the White Carneau pigeon is in sharp contrast to that observed both in spontaneous lesions in human infants and in experimental lesions in the hypercholesterolemic rabbit where lesion development is in the distal sector (90 degrees leads to 270 degrees).

Localization of atherosclerotic lesions in the human basilar artery.

The topography of atherosclerotic lesions in the human basilar arteries has been studied quantitatively by digitizing images of the excised vessels and producing contour probability maps. Fifteen basilar arteries were obtained at autopsy (age--61 +/- 2; males--6, females--9; black--6, white--9), fixed in formalin, opened along the ventral aspect and stained grossly with Sudan IV to delineate fat-containing lesions. Photographs of the flattened arteries were analyzed and the presence or absence of sudanophilic lesions was determined at approximately 1000 identical sites on all vessels. The probability of finding a lesion at each site was determined and a contour probability map was constructed. Fifty-two percent of the area of the mean contour map was involved with lesions. The extent of the sudanophilic lesions decreased as one proceeded distally from the origin of the basilar artery at the confluence of the vertebral branches (i.e. proximal 1/3--56%; middle 1/3--49%; distal 1/3--43%; P less than 0.04). Significantly more sudanophilic material was observed on the ventral (outer curvature) as opposed to the dorsal (inner curvature) surfaces (55%, 43% respectively; P less than 0.03). These data suggest that hemodynamic forces associated with confluent flow and curvature may be important in the localization of sudanophilic lesions in the proximal and ventral aspects of the human basilar artery.

Vascular casting. A new method for the study of the arterial endothelium.

Vascular casts of the rat aorta were made using modified Batson's No. 17 anatomical corrosion compound. The outline of the silver-stained endothelial cell boundaries were clearly visible on the cast when examined using both scanning electron and light microscopy. The physical properties of the injectate were determined. The exothermic nature of the polymerization of the injectate did not grossly damage the endothelial cells. A method was developed for recovery, without damage, of the arterial tissue surrounding the cast. The technique of vascular casting appears to be a powerful tool for the study of the arterial endothelium which avoids shrinkage artifacts and maintains 3-dimensional geometry.

Cocaine: an independent risk factor for aortic sudanophilia. A preliminary report.

Several recent autopsy reports indicate an increased prevalence of coronary atherosclerosis in ischemic heart disease temporally associated with cocaine abuse. The objective of this study was to conduct a retrospective analysis of sudanophilic lesions in young asymptomatic individuals who abused cocaine. Twenty-six cases (15-34-year-old black males) were examined from the Pathobiological Determinants of Atherosclerosis in Youth (PDAY) study. Sixteen subjects (mean age 25 +/- 1 years) had a positive toxicologic screen for cocaine and/or its major metabolites at autopsy and were confirmed habitual cocaine abusers. The remaining 10 cases (mean age 24 +/- 2 years) were subjects with a negative toxicologic screen at autopsy and no history of illicit drug abuse. Post-mortem blood was collected for lipoprotein analysis and determination of smoking status. The aorta and right coronary arteries were stained with Sudan IV and the degree and extent of sudanophilia was quantitated by image analysis. Multiple linear regression analysis of cocaine, age, smoking status, VLDL+LDL-C/HDL-C ratio and HDL-C as predictor variables of percentage intimal surface involvement, revealed an association between cocaine abuse and the extent of sudanophilia in both the thoracic and abdominal aorta (P = 0.002 and 0.049, respectively). Analysis of risk factors or of cocaine abuse as predictors of sudanophilia did not achieve statistical significance in the right coronary artery. These preliminary results suggest that habitual use of cocaine, through unknown mechanism(s), increases aortic sudanophilia independent of traditional risk factors.

Effect of age, race, body surface area, heart weight and atherosclerosis on coronary artery dimensions in young males.

Compensatory arterial enlargement in response to atherosclerosis has been demonstrated for the left main coronary artery. Only limited data is available on the interaction of patient characteristics and atherosclerosis with coronary artery dimensions. The purpose of the present study was to evaluate the influence of age, race, body habitus, heart weight and atherosclerosis on coronary artery dimensions of young males. Hearts from 137 young men (age 32 +/- 8 years; 78 black, 59 white) with unnatural deaths (homicide, suicide, accident, drug overdose) were perfusion-fixed, and histologic sections were obtained from the left main, proximal left anterior descending and left circumflex coronary arteries. Computerized planimetry was performed on Movat stained sections. Multiple regression analysis was used to evaluate the relative contribution of plaque size, age, race, heart weight and body surface area on coronary dimensions and compensatory enlargement in response to atherosclerosis. In the left anterior descending and left main coronary arteries, black race, body surface area and age were independent predictors of increased lumen area. In the left circumflex, age was a predictor of lumen area. Plaque area, black race and body surface area independently predicted increased area enclosed by the internal elastic lamina area. There was compensatory enlargement of internal elastic lamina with increasing plaque size in both races in the three arteries, but the percent luminal stenosis was greater in whites due to smaller artery size. Luminal narrowing did not develop until plaques occupied 30% of internal elastic lamina area. Among a population of young men with non-cardiac deaths, blacks have larger lumen and area enclosed by internal elastic lamina than whites. Age and body surface area are major determinants of lumen areas, and compensatory arterial enlargement was seen in all examined arteries in the present study.

Quantitative study of the rabbit aortic endothelium using vascular casts.

A quantitative study of the en face size and shape of rabbit endothelial cells from the ventral mid-thoracic and ventral infrarenal abdominal aorta has been carried out in 6 rabbits. Photomicrographs were taken from vascular casts of the rabbit aorta and the endothelial cell outlines were analyzed quantitatively using a digitizer and digital computer. The morphology of the endothelial cells was described using 8 calculated parameters (area, perimeter, length, width, angle of orientation, width:length ratio, axis intersection ratio and shape index). The endothelial cells in both locations had the same surface area (P greater than 0.30); however, the cells in the abdominal aorta were longer (P less than 0.01) and narrower (P less than 0.01) than those in the thoracic aorta. This fact is reflected by the smaller value for the shape index and width : length ratio in the abdominal aorta (P less than 0.01). Cells in both the thoracic and abdominal aorta were aligned with the flow direction.

An aortic--left ventricular pulse duplicator used in testing prosthetic aortic heart valves.

A pulse duplicator for the testing of prosthetic valves has been produced which accurately simulates physiological pressure and flow wave forms in the left ventricle and ascending aorta. The model consists of two components--the ventricle and the artificial systemic circulation. The ventricle is a collapsible bag which is externally pressurized and produces an accurate ventricular pressure-time history. The artificial circulation is externally pressurized and produces an accurate ventricular pressure-time history. The artificial circulation is a development of the lumped parameter model of Westerhof13 in which the physiological input impedance is modeled by a characteristic resistance, a capacitance, and a peripheral resistance connected in series. The model allows for a wide range of heart rates, systolic-diastolic ratios, mean pressures, flow rates, and fluid viscosity. A Fourier analysis of the model pressure and flow waves shows excellent quantitative agreement with physiological data, as does the vascular input impedance. The Oxford aortic heart valve exhibited a regurgitation of 1.9 per cent and no measureable pressure drop or power loss.

Technical and economic feasibility of reusing disposable perfusion cannulas.

OBJECTIVE(S): The reuse of disposable devices is a potential source of significant cost savings to hospitals. Venous and arterial perfusion cannulas under new and reused conditions were selected to identify the clinical, safety, technical, logistic, and economic issues that must be addressed to realize these savings. METHODS: Single- and dual-stage venous and arterial cannulas from two manufacturers were tested when new, after initial clinical use, and after a single clinical use plus up to nine simulated reuses. Reuse was simulated by end-to-end bending, coupling and uncoupling of the connectors, and by two 1-hour soaks in plasma at 4 degrees and 40 degrees C, respectively. Cannulas were decontaminated and then processed by a peracetic acid-based liquid chemical sterilization system after each use/reuse. Sterilization was validated by eliminating Bacillus subtilis spores from the cannulas on each of five consecutive cycles. Cannulas were tested for physical changes, functional integrity, biocompatibility, and in vivo performance in sheep. A cost analysis was also performed. RESULTS: Sterilization was successfully achieved. Mechanical changes were less than 20% on all variables studied and were undetectable by experienced cardiac surgeons in selective evaluation. No clinically important differences were found between new and reused cannulas, even after nine simulated reuses. Reusing cannulas four times would reduce the cost per procedure from $53 to $19 (64%). CONCLUSIONS: Preliminary data suggest that the perfusion cannulas tested can be safely and efficaciously used five times. Limited reuse of these disposable cannulas is technically feasible and cost-effective. Cannula reuse would result in a small incremental savings; however, with more expensive devices and higher-volume sterilization procedures, the savings could be considerably greater. This program provides a model for evaluation of other single-use medical devices for reuse.

Late failure of porcine valve heterografts in children.

Heterograft porcine valves have gained wide acceptance in replacement of diseased cardiac valves, and their clinical performance in adults has been very satisfactory over follow-up periods of up to 8 years. Valve replacement in children is relatively infrequent and experience with porcine xenografts is necessarily small. Our combined experience at three university hospitals has been with 25 children, 17 months to 16 years of age, who have been followed for 10 to 54 months (mean follow-up 33 months). Porcine valves were used to replace the aortic valve in nine, the mitral valve in seven, both valves in two, the tricuspid valve in two, and the pulmonary valve in five patients. Severe bioprosthetic valve dysfunction has occurred in five (20%) of these patients so far and necessitated replacement because of severe stenosis in mitral (two) or aortic (three) valve prostheses at 18 to 45 months after implantation; one postoperative death occurred among the five reoperations. Pathological examination showed extensive fragmentation of collagen with focal heavy calcification and degeneration. In addition we have encountered deterioration and calcification of two porcine valves in 23 valved conduits followed for 12 to 70 months (mean 43 months), requiring removal and replacement of the valves 65 and 67 months after implantation. This experience indicates a disquietingly high incidence of relatively early failure of porcine xenograft valves in children. This is significantly higher than the failure rate observed in adult patients. The failure rate is not consistently related to the small size of an implanted valve which becomes relatively narrow with the growth of the patient, leading to excessive turbulence and trauma to the prosthesis. Other factors, including increased turnover of calcium and accelerated rejection in growing children, may contribute to these failures and should be examined in order to improve long-term results. A satisfactory performance would make heterografts the ideal valvular prosthesis in children, since anticoagulation is avoided.

Gastric vascular ectasia in patients undergoing bone marrow transplantation.

The authors reviewed all gastric biopsy specimens from patients who had undergone bone marrow transplantation at our institution between 1986 and 1991. Ten of 28 patients had gastric vascular ectasia (GVE), a distinct lesion consisting of telangiectatic vessels within the superficial gastric mucosa. All patients undergoing bone marrow transplantation had received a standard chemotherapeutic transplantation regimen consisting of busulfan and cyclophosphamide without total-body irradiation. Eight of the 10 patients with GVE had evidence of upper gastrointestinal tract bleeding, as compared with 4 of 18 patients without GVE. In all 10 patients with GVE, the results of liver chemistry analyses were abnormal. Five patients had hepatic veno-occlusive disease, and 8 patients had graft-versus-host disease. Endoscopic biopsy samples of GVE showed markedly dilated vascular spaces similar to those seen in gastric antral vascular ectasia and diffuse antral vascular ectasia. However, no thrombi were identified in these enlarged vessels. Digital morphometry showed the mean cross-sectional area of GVE vessels was significantly greater (P < .001, Wilcoxon's rank-sum test) than the mean vessel areas of 10 chemical gastritis and 10 normal antral (control) biopsy samples. Gastric vascular ectasia may be a significant cause of gastrointestinal bleeding in patients undergoing bone marrow transplantation. The pathogenesis of GVE is unknown; transplantation regimen toxicity may play a role.

Quantitative analysis of inflammatory cells in aortic atherosclerosis of young adults.

Cellular analysis of aortic atherosclerotic lesions has been pursued extensively in recent years, although most of these investigations have involved the detection of inflammatory cells in chronically diseased tissue or artificially induced atherosclerosis in an animal model. Few studies have attempted to quantify accurately, using computer analysis systems, the degree of cellular infiltration in a statistically significant number of samples, in tissue from young adults. In this study, segments of human aortae were collected at autopsy from 29 individuals ranging in age from 15 to 35 years. The tissue was embedded in paraffin and stained using routine histological and automated immunohistochemical staining techniques. The sections were evaluated using advanced image analysis techniques to investigate the differences in cellular composition and cell activation between the dorsal and ventral aspects of the human aorta and to correlate these findings to the age of the subjects. These regions have been previously shown to have a high (dorsal) and low (ventral) probability of developing sudanophilic lesions. Our data demonstrated that statistically different cell populations exist in the dorsal and ventral regions of each vessel. The dorsal aspect (i.e., high-probability region) had a greater number of HAM56(+) (36.9% increase,p = 0.0002) and HLA-DRα(+) cells (44.2% increase,p = 0.0035) than did the ventral surface (i.e., low-probability region), although there were no significant differences in the number of CD43(+) lymphocytes. When grouped according to age, results showed significant increases in the dorsal region when considering HAM56(+) and HLA-DRα(+) cells (p = 0033 and 0.046, respectively). Morphologically, a greater number of foam cell aggregates were found to occur in the dorsal region of the vessel than in the ventral portion. Our results indicate that the microarchitecture and cellular composition of the dorsal and ventral aorta are significantly different, with these variations becoming more marked with age.

The weighted-distance scheme: a globally optimizing projection ordering method for ART.

The order in which the projections are applied in the algebraic reconstruction technique (ART) has a great effect on speed of convergence, accuracy, and the amount of noise-like artifacts in the reconstructed image. In this paper, a new projection ordering scheme for ART is presented: the weighted-distance scheme (WDS). It heuristically optimizes the angular distance of a newly selected projection with respect to an extended sequence of previously applied projections. This sequence of influential projections may incorporate the complete set of all previously applied projections or any limited time interval subset thereof. The selection algorithm results in uniform sampling of the projection access space, minimizing correlation in the projection sequence. This produces more accurate images with less noise-like artifacts than previously suggested projection ordering schemes.

Age-related development of atherosclerotic plaque stress: a population-based finite-element analysis.

BACKGROUND: In order to identify those age-related factors in the development of coronary atherosclerosis that would affect the stability of the plaque system, we have developed idealized, finite-element, cross-sectional models of the arterial wall and associated lesions, derived from population-based data. METHODS: The physical development and morphology of coronary plaques was documented in the Pathobiological Determinants of Atherosclerosis in Youth histological study. Using this database, finite-element analysis models were created for five age groups (15-19, 20-24, 25-29 and 30-34 years) and for the 25 largest lesions. Cosmos (Structural Research, Inc., Los Angeles, California, USA) was used to create and analyze the models. RESULTS: The area of greatest stress shifted from the intima opposite the lesion in the 15-19 years age group to the edge of the cap and adjacent healthy tissue in the later age groups. Increasing age had a strong positive correlation with the shoulder stress level (r = 0.95) and the per cent stenosis correlated well with shoulder stress (r = 0.99, P < 0.002). Increasing the cap stiffness from a soft cap to a fibrous cap in the 30-34 year age group model resulted in a localized increase in shoulder surface stress by 10%. A calcified cap increased this shoulder surface stress by 30%. CONCLUSIONS: This finite-element analysis of the population-based data shows that the increase in stress appears to be closely related to the impaired load-bearing capability of the lipid pool that develops with age. The shoulder area of the lesion has been shown to be the location of most of the plaque fractures.