Coronary Intimal Thickening Begins in Fetuses and Progresses in Pediatric Population and Adolescents to Atherosclerosis


Coronary Intimal Thickening Begins in Fetuses and Progresses in Pediatric Population and Adolescents to Atherosclerosis.

Guerri-Guttenberg R, Castilla R, Cao G, Azzato F, Ambrosio G, Milei J.

Angiology. 2020 Jan;71(1):62-69. doi: 10.1177/0003319719849784. Epub 2019 May 14.

PMID: 31088126

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Take Home Points:

  • Coronary intimal thickening (IT) can be found in infants, children and adolescents.
  • The prevalence of IT is higher with older age.
  • IT is rarely seen in fetuses, suggesting that it is probably not related to embryological or fetal development.

Comment from Dr. Inga Voges (Kiel, Germany), section editor of Fetal Cardiology Journal Watch: In this autopsy study the authors assessed the prevalence of coronary intimal thickening (IT) and types of coronary alterations in 63 hearts from fetuses, infants, older children (1-11 y) and adolescents (11-18 y) without structural heart disease. None of the deaths were related to coronary artery alterations.

Histomorphometric and planimetric analyses were performed and maximal intima thickness, media thickness, as well as intima to media ratio were measured. IT was defined as musculoelastic thickening characterized by proliferation of smooth muscle cells, scarce monocytes and lymphocytes embedded by amorphous deposits within the internal elastic membrane and morphologically intact endothelium above the lesion. In addition, immunophenotyping of cells in the vessel wall was performed with monoclonal antibodies against macrophages, smooth muscle cells, transforming growth factor b1 (TGF-b1), apolipoprotein B and endothelial cells. An automated immunohistochemical system was used for stem cells(CD34/CD117), fibroblasts (vimentin), endothelial cells (CD34/vimentin), endothelial cells and monocytes/macrophages (vascular endothelial growth factor), and cellular proliferation (Ki67).

In the group of fetuses (n=20) only two cases were found to have IT. In the group of infants (n=18), older children (n=15) and adolescents (n=10) the authors found an increasing frequency of coronary alterations with increasing age (see Table I and figure I). The extent of IT correlated with patient age (see figure 3) but was not related to gender or causes of death. Intimal thickening was more commonly found near bifurcation sites in the left anterior descending coronary artery and in zones free of bifurcation in the right coronary artery. The authors also found that the thicker the intima, the more disrupted the internal elastic membrane. Immunohistochemical studies with a-SMC actin could demonstrate, that in IT, smooth muscle cells lose polarity and orient in a perpendicular manner towards the internal elastic membrane or in a disarranged form.

The authors nicely summarize that their results suggest that 1) IT is not a “remnant” of changes derived from embryological development, 2) IT cannot be a consequence of alterations in fetal circulation/oxygenation and 3) the effects of maternal risk factors or other maternal conditions during pregnancy are not evident during fetal life.