Atherosclerotic Plaques In Coronary Arteries Research Articles

Localization of heparin-binding epidermal growth factor-like growth factor in human coronary arteries. Possible roles of HB-EGF in the formation of coronary atherosclerosis.

Heparin-binding epidermal growth factor (EGF)-like growth factor (HB-EGF) is a newly identified member of the EGF family. Our previous in vitro studies showed that HB-EGF is a potent mitogen and chemoattractant for vascular smooth muscle cells (SMCs), suggesting the role of HB-EGF in the pathogenesis of atherosclerosis. The purposes of the present study were to investigate the localization of HB-EGF in both normal and atherosclerotic human coronary arteries and to elucidate the possible roles of this growth factor in the formation of atherosclerotic lesions. The immunohistochemical localization of HB-EGF, SMCs, macrophages, and EGF receptors (EGFRs) was examined in human coronary arteries obtained at autopsy. The medial SMCs of coronary arteries in neonates, infants, and children consistently synthesized HB-EGF protein. In normal adults, however, the relative number of HB-EGF-positive medial SMCs decreased gradually with age after about 30 years of age. In nonatherosclerotic coronary arteries with diffuse intimal thickening, SMCs of the intima, especially those located in the area of the medial side of the intima, were strongly positive for HB-EGF protein. In atherosclerotic plaques of coronary arteries with eccentric intimal thickening, both SMCs and macrophages in and around the core lesions, in addition to the intimal and medial SMCs located adjacent to the plaque, produced HB-EGF protein. A strong immunostaining of EGFRs was observed in these SMCs, suggesting a close association of HB-EGF and EGFR expression. These data suggest that HB-EGF might play important roles in the migration of SMCs from the media to the intima, the proliferation of intimal SMCs, and the interaction between SMCs and macrophages in the process of coronary atherogenesis.

Adhesion of blood platelets is inhibited by VCL, a recombinant fragment (leucine504 to lysine728) of von Willebrand factor.

VCL, fragment Leu504 to Lys728 of von Willebrand factor (vWF) expressed in Escherichia coli, contains the glycoprotein (GP) Ib-binding domain of vWF. This fragment inhibited ristocetin-induced platelet aggregation with an IC50 of 0.2 mumol/L and botrocetin-induced platelet aggregation with an IC50 of 0.08 mumol/L. We studied the antiadhesive profile of VCL by adding it to blood that was circulated over various adhesive surfaces. VCL inhibited adhesion to endothelial cell matrix, which served as a model of the vessel wall. Maximal inhibition at a high shear rate of 1600 s-1 was stronger (60%) than at a low shear rate of 300 s-1 (40%). Half maximal inhibition was found to be 1.5 mumol/L at both shear rates. The role of various adhesive molecules was investigated in more detail by coating glass coverslips with collagen type I, laminin, fibronectin, or vWF. Fibrinogen was studied as well. Platelet adhesion to laminin and vWF was not inhibited by VCL. Adhesion to collagen, fibronectin, and fibrinogen was particularly inhibited at a high shear rate. VCL coated to a coverslip caused a concentration-dependent adhesion that was blocked by antibodies against GPIb, which block interaction with vWF. Binding studies showed a nonsaturable ristocetin binding of VCL to platelets that was blocked by vWF or inhibitory antibodies against GPIb. Binding to collagen was weak, and VCL did not inhibit binding of vWF at a 5000-fold excess. From these data, we conclude that VCL inhibits adhesion in all cases in which adhesion is vWF dependent by competing for vWF binding to activated GPIb. The lack of inhibition of adhesion to vWF as a single molecule may be explained by assuming that this adhesion is determined by interaction of nonactivated GPIb with vWF that has been changed in conformation by adsorption. Studies investigating thrombus formation on the connective tissue of an atherosclerotic plaque in a human coronary artery showed that VCL was able to partially prevent this thrombus formation. VCL may be of value in preventing adhesion and thrombus formation under conditions in which these processes are dependent on vWF.

Coronary Artery Calcium Area by Electron-Beam Computed Tomography and Coronary Atherosclerotic Plaque Area

Coronary calcium identified by electron-beam computed tomography (EBCT) correlates poorly with luminal atherosclerotic narrowing, but calcium, an intimate part of coronary plaque, may be more directly related to atheromatous plaque area. Thirty-eight coronary arteries from 13 autopsy hearts were dissected, straightened, and scanned with EBCT in 3-mm contiguous increments. Coronary calcium area was defined as one or more pixels with a density > 130 Hounsfield units (0.18 mm2/pixel). Each artery was divided into corresponding 3-mm segments, representative histological sections were stained, and atherosclerotic plaque area per segment (mm2) was quantified. Coronary artery calcium and coronary artery plaque areas were correlated for the hearts as a whole, for individual coronary arteries, and for individual coronary artery segments. The sums of histological plaque areas versus the sums of calcium areas were highly correlated for each heart and for each coronary artery. However, coronary plaque area was on the order of five times greater than calcium area. Furthermore, minimal diffuse segmental coronary plaque could be present despite the absence of coronary calcium detectable by EBCT. This histopathologic study confirms an intimate relation between whole heart, coronary artery, and segmental coronary atherosclerotic plaque area and EBCT coronary calcium area but suggests that there is a threshold value for plaque area below which coronary calcium is either absent or not detectable by this methodology.

Conjunctive antithrombotic therapy for thrombolysis in myocardial infarction

Disruption of an atherosclerotic plaque in coronary arteries with a minor stenosis is the usual stimulus for acute coronary thrombosis and myocardial infarction. In this article the pathogenesis of arterial thrombosis and contributions of local arterial wall substrates, the rheology of blood flow, systemic factors, and the critical role of thrombin in the formation of thrombus are discussed. More potent antithrombotic therapy may accelerate exogenous thrombolysis, allows endogenous thrombolysis, and should reduce recurrent infarction and ischemia and death, as well as need for coronary revascularization. Maximal antithrombotic therapy for acute myocardial infarction includes an intravenous bolus of heparin at 100 U/kg followed by an intravenous infusion—at 1,200 U/hr for patients weighing 60–80 kg, 1,300 U/hr for those weighing >80 kg, and 1,000 U/hr for those weighing < 60 kg (or 17 U/kg/hr)—to maintain the activated partial thromboplastin time at 2–3 times control (60–90 sec) for at least 5–7 days. To convert intravenous to subcutaneous administration, use 14,000–17,000 U every 12 hours and initially overlap the intravenous infusion by 2 hours. The loading dose of aspirin on admission to the hospital is 160 mg followed by 80 mg/day. High-risk patients should be considered for conversion of heparin to warfarin therapy for at least 3 months at an international normalized ratio of 2.5–4.0 for the prevention of recurrent ischemia, reinfarction, death, thromboembolism, reactivation of thrombosis, and reduced necessity for revascularization.

Comparison in women versus men of composition of atherosclerotic plaques in native coronary arteries and in saphenous veins used as aortocoronary conduits

Objectives. This study quantifies and compares the components of atherosclerotic plaques in native coronary arteries and in saphenous vein grafts used for aortocoronary bypass surgery in women versus those in men.Background. Plaque composition has been described in various manifestations of fatal coronary artery disease and after the bypass operation, but no reports have investigated this composition according to gender.Methods. A total of 979 5-mm segments of native coronary arteries and 842 5-mm segments of saphenous vein grafts were examined by computerized planimetric technique in 11 women and 11 men who were matched for survival time after the bypass operation.Results. Comparison of the plaque components revealed that atherosclerotic plaques in women, compared with those in men, contained significantly more cellular fibrous tissue, both in native coronary arteries (mean 38% vs. 4%, p < 0.001) and in saphenous vein grafts (mean 70% vs. 36%, p < 0.05). In contrast, the proportion of dense fibrous tissue was significantly less in the atherosclerotic plaques of women than in those of men, both in native coronary arteries (mean 50% vs. 85%, p < 0.001) and in saphenous vein grafts (mean 25% vs. 57%, p < 0.05).Conclusions. Cellular fibrous tissue is often found at an early stage of plaque development, whereas dense fibrous tissue is a major component in later stages. Thus, the plaque composition of the native coronary arteries and saphenous venous conduits differed in men and women, with the plaques of the women appearing younger than those of the men.

Angiogenic processes in the pathogenesis of human coronary atherosclerosis.

Intimai neovascularization, which represents the newly formed vasa vasorum, has been recognized in atherosclerotic plaques of human coronary arteries for many years (Winternitz et al. 1938; Barger et al. 1984; Kamat et al. 1987). Nevertheless, there are still several unresolved questions regarding the origin and pathogenesis of these newly formed blood vessels as well as their pathophysiologic significance in the progression and/or regression of atherosclerosis, and especially the development of its sequelae such as thrombi and intimal hemorrhage. It is well known that neovascularization is a ubiquitous and vital response in various physiologic and pathologic conditions such as embryonic development, the inflammatory-repair process, and the growth of solid cancer (Folkman 1990).

Composition of atherosclerotic plaques in the epicardial coronary arteries in juvenile (Type I) diabetes mellitus

The composition of atherosclerotic plaques in 331 five-mm segments of the 4 major (left main, left anterior descending, left circumflex, and right) epicardial coronary arteries of 8 patients with juvenile (mean age at onset, 9 years; mean age at death, 29 years) diabetes mellitus was determined by computerized planimetric analysis. Analysis of all coronary segments disclosed that the plaques consisted primarily of dense (53%) and cellular (38%) fibrous tissue. Pultaceous debris (7%), foam cells (1.2%) and calcific deposits (0.7%) occupied a small percentage of the plaques. Thus, 91% of the coronary plaques in these young diabetic patients consisted of fibrous tissue and nearly all of the remaining 9% consisted of lipid deposits. Analysis of composition according to degrees of cross-sectional luminal narrowing revealed marked increases in dense fibrous tissue (from 31 to 74%), pultaceous debris (from 3 to 12%), and calcific deposits (from 0% to 3%) as the cross-sectional area narrowing increased from ≤ 25% to >75%. Compared with older patients with fatal coronary artery disease, the patients with juvenile diabetes had more dense fibrous tissue and pultaceous debris and less calcific deposits.

Noninvasive definition of anatomic coronary artery disease by ultrafast computed tomographic scanning: A quantitative pathologic comparison study

Objectives. The aim of this study was to determine the relation between coronary artery calcification detected by ultrafast computed tomographic scanning and histopathologic coronary artery disease.Background. Recent studies suggest that discrete coronary artery calcification as visualized by ultrafast computed tomographic scanning may facilitate the noninvasive detection of estimation, or both, of the in situ extent of coronary disease. Such quantitative relations have not been established.Methods. Thirteen consecutive perfusion-fixed outopsy hearts (from eight male and five female patients aged 17 to 83 years) were scanned by ultrafast computed tomographic scanning in contiguous 3-mm tomographic sections. The major epicardial arteries were dissected free, positioned longitudinally and scanned again in cross section. Coronary artery calcification in a coronary segment was defined as the presence of one or more voxels with a computed tomographic density 130 Hounsfleld units. Each epicardial artery was sectioned longitudinally, stained and measured with a planimeter for quantification of cross-sectional and atherosclerotic plaque areas at 3-mm intervals, corresponding to the computed tomographic scans. A total of 522 paired coronary computed tomographic and histologic sections were studied.Results. Direct relations were found between ultrafast computed tomographic scanning coronary artery calcium burden and atherosclerotic plaque area and percent lumen area stenosis. However, the range for plaque area or percent lumen stenosis, or both, associated with a given calcium burden was broad. Three hundred thirty-one coronary segments showed no calcification by computed tomography. Although atherosclerotic disease was found in several corresponding pathologic specimens,97% of these noncalcified segments were associated with nonobstructive disease (<75% area stenosis); if no calcification was determined in an entire coronary vessel, all corresponding coronary disease was found to be nonobstructive. To determine the relation between arterial calcification and any atheromatous disease, computed tomographic calcium burden for each segment was paired with the histologic absence or presence of disease. Ultrafast computed tomographic scanning had a sensitivity and specificity of 59% and 90% and a negative and positive predictive value of 65% and 87%, respectively. A direct correlation was found (r = 0.99) between total calcium burden calculated from tomographic scans of the heart as a whole and scans of the arteries obtained in cross section.Conclusions. The detection of coronary calcification by ultrafast computed tomographic scanning is highly predictive of the presence of histopathologic coronary disease, but the use of this technique to define the extent of coronary disease may be limited. However, the absence of coronary calcification at any site is highly specific for the absence of obstructive disease.

Composition of atherosclerotic plaques in coronary arteries in women

This study analyzes the composition of atherosclerotic plaques in the 4 major epicardial coronary arteries in 8 women <40 years of age (mean 34) with fatal coronary artery disease (CAD) and compares these data to previous studies of 37 adults >45 years of age (mean 59) with fatal CAD. Histologic sections were taken at 5-mm intervals from the entire lengths of the right, left main, left anterior descending and left circumflex coronary arteries. With the use of a computerized morphometry system, analysis of the 4 major epicardial coronary arteries showed the major component of plaque to be a combination of cellular (mean percent total plaque area = 65%, standard error = 6%) and dense (19%, standard error = 6%) fibrous tissue. Arterial segments narrowed >75% in cross-sectional area from these young women were compared with similarly narrowed arteries from 37 older patients (32 men [86%]) with fatal CAD previously reported by this laboratory, and showed significantly more cellular fibrous tissue and lipid-rich foam cells, and lesser amounts of dense fibrous and heavily calcified tissue. The large amount of lipid-containing foam cells and relative lack of acellular scar tissue in coronary plaques in these young women suggests a greater potential for reversibility of these plaques in this subset of patients with CAD.

Percutaneous valvuloplasty as a treatment for aortic and mitral valve disease

sis in aortocoronary bypass grafts. Morphologic study and risk factor analysis 6-to 12 years after surgery. Arteriosclerosis 1986;6:594-600. 12. Walts AE, Fishbein MC, Matloff JM. Thrombosed, ruptured atheromatous plaques in saphenous vein coronary artery bypass grafts. Ten years experience. AM HEART J 1987;114:71823. 13. Liang BT, Antman EM, Taus R, Collins Jr JJ, Schoen FJ. Atherosclerotic aneurysms of aortocoronary vein grafts. Am J Cardiol 1988;61:185-8. 14. Solymoss BC, Nadeau P, Millette D, Campeau L. Late thrombosis of saphenous vein coronary bypass grafts related to risk factors. Circulation 1988;78:I-140-3. 15. Ratliff NB, Myles JL. Rapidly progressive atherosclerosis in aortocoronary saphenous vein grafts. Possible immune-mediated disease. Arch Pathol Lab Med 1989;113:772-6. 16. Riahi M, Vasu CM, Tomatis LA, Schlasser RJ, Zimmerman G. Aneurysm of saphenous vein bypass graft to coronary artery. J Thorac Cardiovasc Surg 1975;70:358-9. 17. Benchimol A, Harris CL, Desser KB, Fleming H. Aneurysms of an aorta-coronary artery saphenous vein bypass graft--a case report. Vasc Surg 1975;9:261-4. 18. Teja K, Dillingham R, Mentzer RM. Saphenous vein aneurysms after aortocoronary bypass grafting. Post-operative interval and hyperlipidemia as determining factors. AM HEART J 1987;113:1527-9. 19. Movat MZ. Demonstration of all connective tissue elements in a single section. Pentachrome stains. Arch Patho11985;60:28995. 20. Roberts WC. Qualitative and quantitative comparison of amounts of narrowing by atherosclerotic plaques in the major epicardial coronary arteries at necropsy in sudden coronary death, transmural acute myocardial infarction, transmural healed myocardial infarction and unstable angina pectoris. Am J Cardiol 1989;64:324-8. 21. Kragel AH, Reddy SG, Wittes JT, Roberts WC. Morphometric analysis of the composition of atherosclerotic plaques in the four major epicardial coronary arteries in acute myocardial infarction and in sudden coronary death. Circulation 1989; 80:1747-56. 22. Roberts WC, Potkin BN, Solus DE, Reddy SG. Mode of death, frequency of healed and acute myocardial infarction, number of major epicardial coronary arteries severely narrowed by atherosclerotic plaque, and heart weight in fatal atherosclerotic coronary artery disease: analysis of 889 patients studied at necropsy. J Am Coll Cardiol 1990;15:196-203. 23. Roberts WC. Lipid-lowering therapy after an atherosclerotic event. Am J Cardiol 1989;64:693-5.

Qualitative and quantitative comparison of amounts of narrowing by atherosclerotic plaques in the major epicardial coronary arteries at necropsy in sudden coronary death, transmural acute myocardial infarction, transmural healed myocardial infarction and unstable angina pectoris

The amounts of narrowing of the 4 major (left main, left anterior descending, left circumflex and right) epicardial coronary arteries by atherosclerotic plaques were compared in 4 subsets of coronary patients. Of the 129 patients studied at necropsy, an average of 2.7 of the 4 arteries was narrowed >75% in cross-sectional area at some point ( 0.7 4 in controls), and the group with unstable angina pectoris ( 3.2 4 ) had more narrowing than did the groups with sudden coronary death ( 2.8 4 ), acute myocardial infarction ( 2.7 4 ) and healed myocardial infarction ( 2.3 4 ). Each of the 4 major epicardial coronary arteries was divided into 5-mm long segments and a histologic section was prepared and stained by the Movat method of each of the 6,461 segments in the 129 patients and in the 1,849 segments in the 40 control subjects. In the 129 patients, 35% of the 5-mm segments were narrowed 75 to 100% in cross-sectional area (3% in controls) and the group with unstable angina had the highest percent (48%) of segments severely narrowed compared to the groups with sudden coronary death (36%), acute myocardial infarction (34%) and heated myocardial infarction (31%). Thus, of the 4 subsets of patients with fatal coronary artery disease studied at necropsy, those with unstable angina pectoris had the most severe and extensive coronary artherosclerosis.

Morphology of the endothelium over atherosclerotic plaques in human coronary arteries.

The right coronary arteries of six hearts removed from patients with atherosclerosis, who were undergoing cardiac transplantation, were perfused with 2% buffered glutaraldehyde for 20 minutes before preparation for scanning electron microscopy. Perfusion was started within five minutes of explanation. In two patients the artery was angiographically normal, in one it was irregular in outline, and three had focal segments with significant stenosis. None of the patients had concentrations of plasma lipids above 5.5 mmol/l. The endothelial surface showed widespread focal abnormalities ranging from adhesion and migration of monocytes to loss of individual endothelial cells. Larger areas of endothelial denudation with exposure of underlying collagen were also seen consistently. Loss of endothelial cells was associated with accumulation of monocytes, on and deep to the surface, as well as adhesion of platelets to the exposed subendothelial tissue. These results accord with the endothelial damage and platelet adhesion seen in hyperlipidaemic animals fed a high lipid diet.

Morphology of the endothelium over atherosclerotic plaques in human coronary arteries

Morphology of the endothelium over atherosclerotic plaques in human coronary arteries

Atherosclerotic involvement of coronary branch vessels

The atherosclerotic involvement of coronary branch vessels (first diagonal, first septal, posterior descending, left and right marginals, conus and the vessels supplying the conduction system) was investigated in 450 apparently healthy subjects aged 11–55 years who died of accidental causes. In subjects 35–55 years old, 1 out of every 3 persons with atherosclerotic plaques in the major coronary arteries also had atherosclerotic plaques in coronary branch vessels; the respective relation for fatty streaks was 1 out of every 12 subjects, for intimal necrotic areas 1 out of every 7 subjects and for incorporated microthrombi 1 out of every 9 subjects. One out of every 3 subjects 51–55 years old had more than 50% lumen reduction in the undistended major coronary arteries, compared to 1 out of every 6 subjects in undistended coronary branch vessels. A small subgroup (8.2%) showed more severe stenotic lesions in coronary branch vessels than in coronary major arteries. The atherosclerotic plaques of coronary branch vessels appeared as ‘underdeveloped’, lacking a thick fibrohyaline cap, a large detritus cavity, abundant lipid deposition, cholesterol crystals, basal vascularization, intraplaque hemorrhage, ulceration, calcification, occlusive thrombosis. On the other hand the stenotic character of these plaques was often severe (more than 75% lumen reduction). The questionable value of the estimation of the ischemic significance of a coronary stenosis in the absence of available data on the development of a compensatory collateral circulation is discussed.

Natural resistance to atherosclerosis exhibited by the first centimeter of left and right coronary arteries

A combined gross and histologic study carried out on 270 selected male subjects with the common type of distribution of the coronary arteries revealed a natural resistance to intimal thickening and plaque development exhibited by the left main coronary artery and by the first centimeter of the right coronary artery. The importance of this natural resistance in children, adolescents, young and mature adults up to 55 years old was demonstrated by means of a comparative investigation, involving the degree of intimal thickness, the media thickness versus intima thickness ratio and the per cent of subjects with atherosclerotic plaques. These parameters were examined in 6 selected samples: (a) at 5 mm distal to the aortic origin of the left main coronary artery, compared with those detected at 10 mm and 20 mm distal to the point of origin of the anterior descending artery; (b) at 5 mm from the aortic origin of the right coronary artery, compared with those recorded at 20 mm and 30 mm from the same point of origin. The differences between the above-mentioned samples appeared statistically significant in all age groups investigated. The first atherosclerotic lesions developed about three decades later in the left main coronary artery than in the proximal segment of the anterior descending artery. In the age group 51–55 years old, only 13.3% of subjects showed atherosclerotic plaques in the left main coronary artery, compared to 77.6% in the proximal segment of the anterior descending artery. Also only 6.6% of subjects 51–55 years old showed atherosclerotic plaques at 5 mm distal to the aortic origin of the right coronary artery, compared to 50.0% at 30 mm.

Atherosclerosis—Relationship to coronary blood flow

Human atherosclerotic plaques in coronary arteries consist of a variable mixture of lipids, cells and fiber proteins synthesized by the cells. The 2 major space-occupying components of the advanced lesions, which together obstruct the lumen, are the fibrous cap and the necrotic core from which the lesions derive their name. The smooth muscle cells, which make up most cells of the plaque, including the fibrous caps, are produced by migration from the media as well as by proliferation of these cells in the intima. The lipids, mostly supplied by circulating lipoproteins, are present not only in the atheromatous acellular core, but also in the cytoplasm of the cells of the lesion and extracellularly, often attached to 1 or more constituents of the fibrous matrix of the plaque (collagen, elastin and proteoglycans). In both human and rhesus monkey coronary arteries, the lumen becomes more stenotic as the plaque becomes larger and enlarges as the plaque becomes smaller in response to lipid-lowering therapy. Recent studies in other nonhuman primate models of advanced atherosclerosis have questioned the influence of the plaque lesion on coronary blood flow. For example, in the cynomolgus species of macaque ( M. fascicularis), depending on how the plaques are induced, the artery lumens may dilate as the plaques become larger because the outside diameters of the arteries increase. Furthermore, some diseased arteries are found to stenose further when the animals with advanced coronary plaques are treated by measures that substantially reduce the lipids in the plaques. Questions now being studied in several animal models and in human arteries include the relative influence of the degree of medial involvement, of lesion cell types, and of lesion circumferential localization (concentric versus eccentric) on these paradoxical phenomena.

Extravasated erythrocytes, iron, and fibrin in atherosclerotic plaques of coronary arteries in fatal coronary heart disease and their relation to luminal thrombus: Frequency and significance in 57 necropsy patients and in 2958 five mm segments of 224 major epicardial coronary arteries

The presence of extravasated erythrocytes (EE), iron (I), and fibrin (F) within coronary atherosclerotic plaques and their relation to intraluminal coronary thrombus was determined in 2958 five-mm segments of 224 major epicardial coronary arteries in 57 patients with fatal coronary heart disease and in 1290 five-mm segments of 103 coronary arteries in 27 control (c) subjects. Intraplaque EE were present in 10% of the segments (controls [c] = 1%), In 35% of the arteries (c = 5%), and in 84% of the patients (c = 19%); I was present in 4% of the segments (c = < 1%), in 14% of the arteries (c = 4%), and in 57% of the patients (c = 22%); intraplaque F was present in 2% of the segments (c = < 1%), in 17% of the arteries (c = 3%), and in 63% of the patients (c = 7%). Intraluminal thrombus, present only in the patients with acute myocardial infarction and in none of the controls, occurred in 3% of the segments, in 8% of the arteries and in 26% of the patients. Intraplaque hemorrhage or EE occurred usually in the absence of intraluminal thrombus and conversely intraluminal thrombus occurred more frequently without than with underlying plaque hemorrhage. The frequency of intraplaque EE, I, and F was proportional to the amount of coronary atherosclerotic plaque present. Intraplaque I and F infrequently were observed in the absence of EE. The significance of extravasated erythrocytes, iron, and fibrin in atherosclerotic plaques remains unclear.

SERUM LIPIDS AND CEREBROVASCULAR DISEASE.

The composition of serum lipids is characteristically altered in patients with atherosclerosis. High concentrations of triglyceride were found more often than elevated concentrations of cholesterol and phospholipids in a study of patients with cerebral, coronary, and aortic atherosclerosis. 1 It has been recently established 1-6 that a defect in the metabolism of triglyceride, with the accumulation of this substance in the plasma, may be the most common lipid derangement in patients with coronary artery disease. The similarity between lipid content of atherosclerotic plaques in cerebral and coronary arteries, 7 as well as the frequent coexistence of these lesions, 8,9 suggests the possibility of certain common factors in the pathogenesis of such atheromas. The present study extends previous work 5 dealing with the relationship of serum lipids and coronary artery disease to the problem of cerebrovascular disease. Methods and Material Sixty-three male patients observed in the wards and outpatient clinics of the