IN the 19th century there were two major hypotheses to explain the pathogenesis of atherosclerosis: the "incrustation" hypothesis and the "lipid" hypothesis. The incrustation hypothesis of von Rokitansky,1 proposed in 1852 and modified by Duguid,2 suggested that intimal thickening resulted from fibrin deposition, with subsequent organization by fibroblasts and secondary lipid accumulation. The lipid hypothesis, proposed by Virchow3 in 1856, suggested that lipid in the arterial wall represented a transduction of blood lipid, which subsequently formed complexes with acid mucopolysaccharides; lipid accumulated in arterial walls because mechanisms of lipid deposition predominated over those of removal. The two hypotheses are now . . .

https://www.nejm.org/doi/pdf/10.1056/NEJM199201233260406?articleTools=true

The pathogenesis of coronary artery disease and the acute coronary syndromes (1).

This report is the continuation of two earlier reports that defined human arterial intima and precursors of advanced atherosclerotic lesions in humans. This report describes the characteristic components and pathogenic mechanisms of the various advanced atherosclerotic lesions. These, with the earlier definitions of precursor lesions, led to the histological classification of human atherosclerotic lesions found in the second part of this report. The Committee on Vascular Lesions also attempted to correlate the appearance of lesions noted in clinical imaging studies with histological lesion types and corresponding clinical syndromes. In the histological classification, lesions are designated by Roman numerals, which indicate the usual sequence of lesions progression. The initial (type I) lesion contains enough atherogenic lipoprotein to elicit an increase in macrophages and formation of scattered macrophage foam cells. As in subsequent lesion types, the changes are more marked in locations of arteries with adaptive intimal thickening. (Adaptive thickenings, which are present at constant locations in everyone from birth, do not obstruct the lumen and represent adaptations to local mechanical forces). Type II lesions consist primarily of layers of macrophage foam cells and lipid-laden smooth muscle cells and include lesions grossly designated as fatty streaks. Type III is the intermediate stage between type II and type IV (atheroma, a lesion that is potentially symptom-producing). In addition to the lipid-laden cells of type II, type III lesions contain scattered collections of extracellular lipid droplets and particles that disrupt the coherence of some intimal smooth muscle cells. This extracellular lipid is the immediate precursor of the larger, confluent, and more disruptive core of extracellular lipid that characterizes type IV lesions. Beginning around the fourth decade of life, lesions that usually have a lipid core may also contain thick layers of fibrous connective tissue (type V lesion) and/or fissure, hematoma, and thrombus (type VI lesion). Some type V lesions are largely calcified (type Vb), and some consist mainly of fibrous connective tissue and little or no accumulated lipid or calcium (type Vc).

A Definition of Advanced Types of Atherosclerotic Lesions and a Histological Classification of Atherosclerosis A Report From the Committee on Vascular Lesions of the Council on Arteriosclerosis, American Heart Association

To help determine if coronary angiography can predict the site of a future coronary occlusion that will produce a myocardial infarction, the coronary angiograms of 42 consecutive patients who had undergone coronary angiography both before and up to a month after suffering an acute myocardial infarction were evaluated. Twenty-nine patients had a newly occluded coronary artery. Twenty-five of these 29 patients had at least one artery with a greater than 50% stenosis on the initial angiogram. However, in 19 of 29 (66%) patients, the artery that subsequently occluded had less than a 50% stenosis on the first angiogram, and in 28 of 29 (97%), the stenosis was less than 70%. In every patient, at least some irregularity of the coronary wall was present on the first angiogram at the site of the subsequent coronary obstruction. In only 10 of the 29 (34%) did the infarction occur due to occlusion of the artery that previously contained the most severe stenosis. Furthermore, no correlation existed between the severity of the initial coronary stenosis and the time from the first catheterization until the infarction (r2 = 0.0005, p = NS). These data suggest that assessment of the angiographic severity of coronary stenosis may be inadequate to accurately predict the time or location of a subsequent coronary occlusion that will produce a myocardial infarction.

Can coronary angiography predict the site of a subsequent myocardial infarction in patients with mild-to-moderate coronary artery disease?

Information obtained during the past decade suggests the need to reexamine the possibility that the onset of myocardial infarction and sudden cardiac death is frequently triggered by daily activities. The importance of physical or mental stress in triggering onset of coronary thrombosis is supported by the findings that 1) the frequencies of onset of myocardial infarction, sudden cardiac death, and stroke show marked circadian variations with parallel increases in the period from 6:00 AM to noon, 2) transient myocardial ischemia shows a similar morning increase, and episodes are often preceded by mental or physical triggers, 3) a ruptured atherosclerotic plaque, often nonobstructive by itself, lies at the base of most coronary thrombi, 4) a number of physiologic processes that could lead to plaque rupture, a hypercoagulable state or coronary vasoconstriction, are accentuated in the morning, and 5) aspirin and beta-adrenergic blocking agents, which block certain of these processes, have been shown to prevent disease onset. The hypothesis is presented that occlusive coronary thrombosis occurs when 1) an atherosclerotic plaque becomes vulnerable to rupture, 2) mental or physical stress causes the plaque to rupture, and 3) increases in coagulability or vasoconstriction, triggered by daily activities, contribute to complete occlusion of the coronary artery lumen. Recognition of the circadian variation--and the possibility of frequent triggering--of onset of acute disease suggests the need for pharmacologic protection of patients during vulnerable periods, and provides clues to mechanism, the investigations of which may lead to improved methods of prevention.

Circadian variation and triggers of onset of acute cardiovascular disease.

The establishment of a prognosis and the approach to the treatment of many diseases is aided greatly by a logical classification. For example, classification of a wide variety of neoplasms by anatomic extent, microscopic appearance, and the presence of special markers now forms the basis for selecting appropriate therapy. In cardiology, the classification of patients with acute myocardial infarction and congestive heart failure has been of enormous value in following the progress and in selecting therapy of individual patients and in comparing the outcome of similar patients treated at different locations and at different times. The purpose of this article is to provide a classification of unstable angina. This classification is designed to facilitate communication about these patients, to aid in the decision regarding diagnostic measures and therapy of individual patients, and to provide a more precise basis for including patients in and for evaluating the outcome of clinical trials.

Unstable angina : a classification

To visualize intracoronary lesions in patients with different clinical expressions of coronary disease, we performed coronary angioscopy during coronary-artery bypass surgery in 10 patients with unstable angina and 10 patients with stable coronary disease. We examined a total of 32 vessels, using flexible fiberoptic angioscopes. Twenty-two vessels had no acute intimal lesion; three had complex plaques, six had thrombi, and one had both. Coronary angiography correctly identified the absence of complex plaque and thrombus in 22 vessels, but it detected only one of four complex plaques and one of seven thrombi. On angioscopy, none of the 17 arteries in the patients with stable coronary disease had either a complex plaque or thrombus. In the "offending" arteries of the patients with unstable angina, all three patients with accelerated angina had complex plaques and all seven with angina at rest had thrombi. We conclude that angioscopy frequently reveals complex plaques or thrombi not detected by coro...

Coronary Angioscopy in Patients with Unstable Angina Pectoris

Percutaneous peripheral excimer-laser angioplasty at 308 nm was used for treatment of 30 patients with peripheral vascular disease. Twenty-eight patients underwent laser-assisted balloon angioplasty, and two patients underwent laser angioplasty alone. Acute angiographic and clinical success was achieved in 24 of 31 (77%) femoropopliteal stenoses and occlusions. Seven of nine (78%) stenoses, six of seven (86%) short (0-5 cm) occlusions, seven of eight (88%) medium-length (6-10 cm) occlusions, three of four (75%) long (11-15 cm) occlusions, and one of three (33%) extreme (greater than 15 cm) occlusions were successfully treated. Inability to treat total occlusions was in each case related to a failure to maintain coaxial position and subintimal passage of the fiber. These cases demonstrate the feasibility of safely performing percutaneous peripheral excimer-laser or excimer-laser-assisted angioplasty. The overall frequency of restenosis after a mean follow-up period of 9.1 months was 29%. The data suggest t...

A. Hickey

Papers

Coronary Angioscopy in Patients with Unstable Angina Pectoris

Percutaneous excimer-laser and excimer-laser-assisted angioplasty of the lower extremities: results of initial clinical trial.

Cardiac angioscopy in acute ischemic syndromes