Evolution and progression of atherosclerotic lesions in coronary arteries of children and young adults

Author

Stary HC Reference

Arteriosclerosis 1989; 9(Supp): I-19-I-32 Abstract

In an autopsy study of the evolution of atherosclerotic lesions in young people, we obtained the coronary arteries and aortas of 1160 male and female subjects who died between full-term birth and age 29 years. In this article, we report the light and electron microscopic observations of the coronary arteries of 565 of these subjects in which we fixed the coronary arteries by perfusion with glutaraldehyde under pressure. From birth, the intima was always thicker in the half of the coronary artery circumference opposite the flow-divider wall of a bifurcation (eccentric thickening). In cases where we found lipid in the intima, there was always more in eccentric thickening. Isolated macrophage foam cells in the intima of infants were the earliest sign of lipid retention. These cells occurred in 45% of infants in the first 8 months of life but decreased subsequently. At puberty, more substantial accumulations of macrophage foam cells reappeared in more children. Foam cells were now accompanied by lipid droplets in existing smooth muscle cells and by thinly scattered extracellular lipid. Sixty-five percent of children between ages 12 and 14 years had such lesions. An additional 8% of children had progressed beyond this early stage and had developed advanced preatheroma or atheroma stages. Such advanced lesions, located only in areas of eccentric thickening, were characterized by the addition of massive extracellular lipid that displaced normal cells and matrix and, thus, damaged and weakened the arterial wall.

Summary

This paper describes a large series of coronary histology data from 565 human subjects who died between full-term birth and 29 years of age. At the time of this study, there was controversy regarding the extent of atherosclerosis in the young and at what age dietary interventions to reduce atherosclerosis should be instituted. The left main, proximal left anterior descending and proximal circumflex arteries were analysed. Based on the findings of this series, a classification system was developed to characterize development of atherosclerotic lesions. Type 1 lesions consist of isolated macrophage foam cells in the proteoglycan layer with no extracellular lipid or vascular smooth muscle cells. These lesions were seen in some infants as early as the first week of life and appeared to be decreased after the first year. Type II lesions are fatty streaks composed of layers of cells with lipid droplet-inclusions. More macrophages are present than type I lesions. These lesions were noted beginning from late in the first decade of life. A type III lesion is a preatheroma that is intermediate between the fatty streak and the atheroma. These lesions contain all the components of a fatty streak with a marked increase in the number of extracellular lipid particles. They appear grossly as a small white elevation and are typically seen beginning in the mid second decade of life. Type IV lesions were seen in subjects beginning at the end of puberty

Figure 1 (a) Outer wall at the level of the left main coronary artery just proximal to the main bifurcation. Extracellular lipid (arrows) is abundant and concentrated in the musculoelastic layer (me) of eccentric thickening and displaces some structural intimal smooth cells. Macrophage foam cells (fc) and lipid-laden smooth muscle cells are layered above the extracellular aggregates. Such lipid deposits were classified as preatheroma (type III lesion). From a 25-year-old white man who died in a motorcycle accident. (b) Outer wall at the LAD 1 level with eccentric thickening now metamorphosed into a lesion classified as atheroma (type IV lesion). Extracellular lipid now forms a confluent core in the musculoelastic layer of eccentric thickening. While this lipid deposit thickens the intima, it also weakens the wall as it displaces structural smooth muscle cells. From a 19-year-old white man who committed suicide. Pgc: proteoglycan intima; M: media; and A: adventitia.

Figure 1 (a) Outer wall at the level of the left main coronary artery just proximal to the main bifurcation. Extracellular lipid (arrows) is abundant and concentrated in the musculoelastic layer (me) of eccentric thickening and displaces some structural intimal smooth cells. Macrophage foam cells (fc) and lipid-laden smooth muscle cells are layered above the extracellular aggregates. Such lipid deposits were classified as preatheroma (type III lesion). From a 25-year-old white man who died in a motorcycle accident. (b) Outer wall at the LAD 1 level with eccentric thickening now metamorphosed into a lesion classified as atheroma (type IV lesion). Extracellular lipid now forms a confluent core in the musculoelastic layer of eccentric thickening. While this lipid deposit thickens the intima, it also weakens the wall as it displaces structural smooth muscle cells. From a 19-year-old white man who committed suicide. Pgc: proteoglycan intima; M: media; and A: adventitia.

and consisted of large lipid or necrotic cores. Macrophage foam cells were seen bordering the lipid core on the luminal aspect of the lesion. A type V lesion is a fibroatheroma in which the proteogly-can layer has changed in composition with an increased number of smooth muscle cells embedded in a dense matrix of collagen and capillaries. This layer of smoothmuscle cells becomes a fibrous cap. These lesions were typically seen beginning in the mid third decade of life.

Stary described the frequency of the various lesions at different ages and this data established that vascular lesions are quite common even in young children. This study raised many questions regarding the sequence of events that would lead to a fatty streak at such young ages and subsequent progression of lesion complexity.

Citation Count 15

Key message

Vascular lesions consistent with early atherosclerosis begin very early in life and appear to progress in complexity through a series of defined stages.

Strengths

Detailed, extensive histological examination of very young human subjects. The idea that lesion growth occurs through predictable stages representing various cellular and molecular events set a framework for future investigations.

Weaknesses

Descriptive study. Although this classification system has been useful to facilitate our understanding of atherogenesis, the staging of atherosclerotic lesions may be an oversimplification of the underlying pathophysiology and not take into account the marked heterogeneity of atherogenesis between individuals.

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