Study on the prevalence of eccentric and concentric atherosclerotic plaques in various segments of the coronary arterial tree, in unselected and selected Bucharest population samples.

A study was carried out on the prevalence and distribution of eccentric and concentric atherosclerotic plaques in the coronary arterial tree of 916 unselected apparently healthy subjects who died from accidents and of 150 selected patients who died from coronary heart disease. The results show that the percentages of eccentric and concentric plaques vary with age, sex, anatomical branching pattern and cause of death; there are also differences between major coronary arteries and main branch vessels. In addition to eccentric and concentric plaques, we revealed the existence of mixed (both eccentric and concentric) plaques, mainly located at branch points.

The onset and progression of atherosclerotic plaques as related to arterial wall changes.

The coronary arterial beds from more than 1200 subjects aged 1 to 65 years were investigated by both histopathological, histochemical and morphometric methods. Light microscopic aspects were analysed to reveal if plaque development and progression toward obstructive lesions were associated with arterial wall changes, particularly of the intimal connective tissue adjacent to lesions. Six patterns of plaque development in the coronary arterial tree were delineated, emphasis being placed on the observation that the onset and progression of plaques frequently appeared independent of arterial wall changes, in contrast to fatty streaks, gelatinous lesions, intimal necrotic areas, incorporated microthrombi and intramural thrombi.

Influence of coronary heart disease risk factors (CHDRFs) on the natural history of coronary atherosclerosis as revealed by a post-mortem study.

A postmortem study was carried out on the whole coronary arterial bed of 430 selected apparently healthy subjects, aged 38 to 65 years, in an effort to reveal the influence exerted by coronary heart disease risk factors (CHDRFs) on the development of coronary obstructive plaques. A clear positive correlation was found in 31% of cases and in more than 50% of 28 selected topographic sites of the coronary arterial bed. On the other hand, the subgroup without CHDRFs also exhibited severe coronary narrowings.

Coronary anatomy and microarchitecture as related to coronary atherosclerotic involvement.

A report is given on the authors' main results concerning the anatomy and microarchitecture of human coronary arteries as related to atherosclerotic involvement and to the clinical manifestations of coronary heart disease. The peculiarities of anatomical branching pattern, of the intimal thickening, muscle columns development, of age-related changes, in the intima/media thickness ratio, as well as the segmental characteristics in susceptibility to plaque development and in the plaque pattern are presented. Our results allow to delineate the coronary arterial bed as an entity in anatomical, histological and pathological sense.

Prevalence of thick intimas and of obstructive lesions in the vessels supplying the conduction system of the heart.

A study of the prevalence of thick intimas and of obstructive lesions in the vessels supplying the conduction system of the heart (first septal artery, sinus node artery, atrioventricular node artery, posterior descending artery) was carried out on both non-hospitalized and hospitalized subjects. A total of 932 cases aged 6 to 55 years were investigated. The age period of the onset of both intimal thickenings and atherosclerotic plaques, the percent of cases with intimal thickenings and atherosclerotic plaques in successive age groups and the highest value of the intima thickness/media thickness ratio, were recorded.

Are routine autopsy protocols adequate for accurate appraisal of coronary atherosclerosis?

Atherosclerotic involvement of 1,106 coronary arterial trees was investigated by means of gross inspection, light microscopy, and the method of successive observations of similar topographic sites placed in sequence according to age, sex, cause of death, and anatomic branching pattern. The results obtained, based on strict adherence to routine autopsy protocols, were compared with control studies, which demonstrated that such strict adherence had constrained us to overlook the following aspects: a) existence of particular anatomic branching patterns, such as those of atherogenic character and/or involved in onset of myocardial ischemia; b) development of obstructive plaques in coronary branch vessels; c) presence of obstructive lesions in vessels which supply the conduction system; d) the obstructive character of platelet and fibrin microemboli and thrombi which showered the intramyocardial vessels; e) accurate identification, classification, and grading of atherosclerotic lesions with the aid of routine autopsy protocols, which was not possible in our material.

Role of thrombosis in the onset, progression and obstructive character of coronary atherosclerotic plaques.

A study was carried out on the role of successive microthrombi incorporation and intramural thrombi formation in the onset, progression and obstructive character of coronary atherosclerotic plaques. The coronary arterial tree of 836 apparently healthy subjects 1 to 50 years old who died of accidental causes was investigated. The onset of coronary atherosclerotic plaques having as precursors thrombi could be detected in 10% of advanced lesions.

Anatomoclinical correlations in coronary heart disease: recent advances and unanswered questions.

An attempt is made to summarize the recent available information on anatomoclinical correlations in coronary heart disease. The paper focuses attention on: (a) the role in the pathogenesis of unstable angina pectoris, severe arrhythmias and sudden cardiac death, of repeated cycles of formation, disintegration and peripheral embolization of intramural thrombi or of thrombi developed on preexisting atherosclerotic plaques; (b) a still apparently unsolved problem: which comes first, coronary thrombosis or myocardial infarction? (c) the pathophysiological and clinical significance of the "border zone" of myocardial infarcts; (d) the importance, in the pathogenesis of coronary heart disease and particularly of sudden cardiac death, of obstructive lesions which occur in the vessels supplying the conduction system of the heart.

A further study on the influence exerted by vascular geometry on coronary atherosclerotic involvement.

A further study was carried out on the relationship between coronary artery geometry and atherosclerotic involvement. The results show that: a) the coronary artery geometry may expose an individual at an early age to an increased risk for developing atherosclerotic lesions; b) the presence, in the coronary arterial bed of vessels with large diameters (greater than 2 mm) and the succession of numerous branching points also appeared as atherogenic conditions; c) the type of atherosclerotic lesion (proliferative, insudative, necrotic, lipid-rich) was, in our material strongly influenced by the geometry of branch sites.

The relationship between intimal necrosis and lipid accumulation during the onset and progression of atherosclerotic lesions.

In human coronary arteries, aorta and intracranial arteries, the first areas of intimal necrosis preceded the onset of the first lipid accumulation related to atherosclerotic involvement. Both intra- and extracellular lipid accumulations developed only in preexisting areas of intimal necrosis. Intimal necrosis not only caused an abnormal intraarterial retention of fat, but also caused fat to be deposited preferentially in specific forms and particular locations.

Coronary atherosclerosis: where are we now?

An attempt is made to present and summarize recent results in atherosclerosis research which may aid to a better understanding of atherogenesis, progression of atherosclerotic lesions and occurrence of myocardial ischemia. Based on selected data from the available literature and the authors' experience, the review focuses the attention on: the atherogenic role of hemodynamic stresses; the onset and fate of early coronary atherosclerotic lesions; the development of lesions of possible clinical significance; the concept of "critical stenosis"; the view that atherosclerosis is a hyperplastic and/or neoplastic disease.

Prevalence of the "normal" aspect of the coronary arteries in an unselected population sample of Bucharest aged 1-60 years.

The coronary arterial trees obtained from 640 subjects 1-60 years old were studied grossly and by light microscopy, including morphometric methods. The highest values of of the ratio intima/media thickness were recorded in successive age groups, with special reference to those topographic sites where this ratio acquired an abnormal value. The percent of children, adolescents, young and mature adults free of atherosclerotic plaques, gelatinous lesions and intima necrotic areas, fatty streaks and intramural thrombi was also evaluated.

Method-dependent number and topography of coronary narrowings.

A comparative gross and light microscopic study of the coronary arterial bed carried out on 95 selected male subjects aged 51-55 years, revealed that the number and topography of narrowings (more than 50% luminal insufficiency) showed wide method-dependent variations. If only routine gross inspection of the major coronary arteries was performed (method 1) 52% of the subjects exhibited narrowings; if gross inspection was extended to the proximal segment of the first diagonal, first septal, left marginal, right marginal and posterior descending vessels, the proportion of subjects with coronary narrowings augmented to 61% (method 2); finally the use of the light microscopy to investigate vessels supplying the conduction system and terminal vessels (method 3) augmented this proportion to 73%. Conversely, we recorded the absence of narrowings encroaching more than 50% in 48% of the subjects with method 1, in 39% with method 2 and in only 27% with method 3.

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.

Atherogenic anatomical patterns of coronary arteries branching related to cardiac and non-cardiac causes of death.

A gross and light microscopic study carried out on 102 selected male subjects aged 51-70 who died of ischemic heart disease and on 102 selected, male subjects of similar age, who died of noncardiac causes revealed that: in subjects who died of ischemic heart disease the prevalence of atherogenic deviations from the common type of distribution of the coronary arteries was 2-4 times greater than in subjects who died of non-cardiac causes; subjects who died of ischemic heart disease, with the atherogenic deviations from the common tape of distribution of the coronary arteries showed an increased number of stenotic atherosclerotic plaques and a particular propensity to "clustering" of these lesions, predominantly around branch mouths.

Centrifugal extension of coronary intimal necrotic areas.

The use of serial cross-sections, camera lucida drawings and photographic reconstruction of longitudinally cut samples, revealed that about half of intimal necrotic areas present in the coronary arteries of subjects aged 41-50 years exhibited a longitudinal diameter greater than 1.0 cm, occurring as very long lesions. In the 16 intimal necrotic areas included in a tridimensional study the longitudinal diameter was 7.

Presence of atherosclerotic lesions connected with the coronary artery lumen.

Starting from five accidental observations made on isolated tissue sections on the existence of "anchored" lesions in the coronary arteries of adolescents and young adults, 47 selected coronary artery samples removed from subjects 16-40 years old were submitted to a three-dimensional investigation. Based on serial sections and sequential camera lucida drawings, the geometry, diameters and spatial connections of 42 intimal necrotic areas were recorded. All these lesions appeared in a three-dimensional plane connected with the coronary artery lumen by one or several necrotic bands which seemed to communicate freely with the luminal cavity.

Study of coronary intimal thickening.

A light microscopic study on intimal thickening carried out on 932 subjects 1-50 years old and on 22 selected topographic sites of the coronary arterial bed, revealed: (a) In similar topographic sites intimal thickening developed 5-15 years earlier in subjects with than in subjects without minor deviations from the common type of distribution of the coronary arteries. (b) The most rapid development of the intimal layer was detected in children aged 11-15 years. (c) 6% of children who died of acute diseases (mainly acute peritonitis) showed intimal thickening in both major coronary arteries and branch vessels; in children who died of accidents thickening developed only in the major coronary arteries.

Intimal thickening and atherosclerotic involvement of the left main coronary artery.

A post mortem study carried out on 886 apparently healthy children, adolescents, young and mature adults of an unselected population sample of Bucharest who died of accidental causes, revealed that the left main coronary artery acted as an atherosclerosis-resistant segment of the coronary arterial bed. The importance of this natural resistance was demonstrated by means of a comparative investigation involving the degree of intimal thickness, the intima thickness versus media thickness ratio, the per cent of subjects with atherosclerotic plaques and the obstructive character of these plaques. These parameters were examined in 6 selected topographic sites: (a) at 5 mm distal to the 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.

A method which improves anatomo-clinical correlations in ischemic heart disease.

A study carried out on 595 unselected subjects aged 21-55 years who had died of accidental causes and on 56 selected patients who had died of myocardial infarction showed that the light microscopic examination of coronary branch vessels led to an obvious improvement of anatomo-clinical correlations in ischemic heart disease. These branch vessels included atherosclerotic plaques in 51% of unselected subjects 51-55 years old, dead of accidents and in 73% of selected patients dead of myocardial infarction. Severe stenotic plaques of possible clinical significance were found in 14% of subjects dead of accidents and in 48% of patients dead of myocardial infarction.

Differences in the pattern of atherosclerotic involvement between non-branched regions and adjacent branching points of human coronary arteries.

A light-microscopic study carried out on 816 coronary arterial trees revealed that the variety of atherosclerotic lesions detected in non-branched segments was 3-5 times greater than that recorded in branching points. The fibromuscular and fibronecrotic plaques, small fatty streaks, small intimal necrotic areas, incorporated microthrombi and intramural organized thrombi were recorded in both non-branched regions and branching points. The mucoid, foam cell-rich and necrotic plaques, large fatty streaks with abundant extracellular lipid and large intimal necrotic areas with lipid and fibrin deposition were recorded only in non-branched regions, whereas the fibrohyaline plaques were recorded only in the branching points.

A method for the study of the dynamics of atherosclerotic involvement of human coronary arteries.

A method able to reveal the progression of atherosclerosis from children to mature adults is proposed, based on the successive light microscopic examination of similar selected topographic sites of the coronary arterial tree placed in sequence according to age, sex and branching anatomical pattern. The dynamic reconstruction of thousands of static views revealed a linear and parallel increase in the number of all types of early atherosclerotic lesions: fibromuscular plaques, intimal necrotic areas, incorporated microthrombi and fatty streaks. Some endogenous and exogeneous risk factors for coronary heart disease accelerated this age-related rate of progression and also gave rise to particular cycles of evolution toward lesions of possible clinical significance.

Age and atherosclerosis--related changes occurring in the "intercalated vascular segments" of human coronary arteries.

The term "intercalated vascular segment" is used by the authors to designate a structural accomodation to the existence of diffuse thickened intimas, occurring as local vascular connections between the lumen of the main coronary arteries and the branch mouths of the daughter vessels. They exhibit the light microscopic feature of cylindrical conduits including only an endothelial sheet encased by the intimal connective tissue. The most important change related to aging and atherosclerotic involvement seems to be the conversion of some intercalated vascular segments in rigid, undistensible and narrowed conduits; this might produce local changes similar to those of a fixed stenosis.

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.