**5. Regarding atherosclerotic plaque establishment**

Atherosclerotic plaque formation has been suggested to be thoroughly related to a shrinkage in the outflow to inflow area ratio [6]. This information has been sustained in several studies [9, 18, 21, 28–30].

Fisher and Fieman, and Schultz et al., publicized that the bifurcation anatomy stimuli the blood flow that produces the endothelial destruction [9, 20]. Mortensen also declared endothelial impairment and clarified that a quantity of a pulse wave reaching a bifurcation is reflected, and the higher the quantity of reflection, the more the hemodynamic stress might progress locally. The increase in the pressure could lead to endothelial destruction and support atherosclerotic plaque improvement [19]. In terms of endothelial damage, findings presented parallel results to the literature [3].

Initial examinations of this geometric risk theory were assessed in part, owing to relatively small sample sizes. Fisher and Fieman studied the conclusions of bifurcation angle and area ratio asymmetry on the improvement of atherosclerosis [6, 9, 21]. Also, it had limited samples because of the difficulties in obtaining human cadavers [3].

It has been shown that in early lesions of the atherosclerosis, fatty streaks progress very early in fetal period [3, 4]. The creation of fatty streaks also depends on many dynamics such as the susceptibility of the arteries and genetic factors, and the maternal hypercholesterolemia. The locations of a lesion demonstrate variability, and the fatty streaks tend to occur focally in certain predisposed regions while sparing neighboring unaffected sections [3]. Abdominal aorta and common carotid are much more prone to the development of fatty streaks [4]. The intracranial arteries are less prone to laceration enlargement than extra-cranial arteries; hence, the initial lesions develop in extra-cranial arteries rather than in intracranial ones [4].

**6. Potential limitations and implications for these types of diameter** 

(and/or local hemodynamics) is a risk factor for initial carotid wall solidifying.

studies are needed to underline the other factors, potentials, and mechanisms.

Address all correspondence to: bahar.uslu.md.phd@gmail.com

In newborns, the results showed that the outflow to inflow area ratio was very close to optimum. Recent data can be very helpful for understanding the anatomical variations of the CCA, ECA, and ICA. The correlations between area ratios and the histologic assessments of cerebral vessels of newborn cadavers specify that the early stage of atherosclerosis began in early embryologic life. Last results encourage the hypothesis that carotid bifurcation anatomy is among the main risk factors for the early onset of atheroma plaques. Still, supplementary

[1] Narverud I, Retterstøl K, Iversen PO, et al. Markers of atherosclerotic development in children with familial hypercholesterolemia: A literature review. Atherosclerosis. 2014;**235**:

Numerical changes were convincing, but not perfect. Studies were retrospective, comparatively small, and focused on an inadequate number of newborn cadavers. Sample availability was insufficient for both affected groups and controls. It should also be noted that studies were not planned to be an epidemiological study, and therefore, groups did not signify the characteristics of a wide-ranging population. Recognition of blood cells and fibrin on the endothelial surface are interpreted as pathological definitions. Conversely, there might be problems with the poor fixation of specimens, that is, blood could not be washed out from the arterial lumen before fixation procedure. Lastly, scanning electron microscopy (SEM) studies can be associated with various kinds of artifacts. The authors then hope to approve their pathological findings using transmission electron microscopy in upcoming studies. Despite the above possible limitations, the current studies seem to establish a modest upper bound on the influence of local versus known or unknown systemic cardiovascular risk factors on wall setting. Thus, last results are parallel with the earlier ones to support theory that carotid bifurcation geometry

Early Stages of Atherosclerosis Documented in Early Embryologic Life

http://dx.doi.org/10.5772/intechopen.77381

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**calculations**

**7. Conclusion**

**Author details**

Yale University, New Haven, USA

Bahar Uslu

**References**

299-309

The purpose why certain arteries are more disposed to atherosclerotic changes is not well understood. The hemodynamic factors and morphologic features of the artery may play a role [9, 12, 14, 20, 21]. It has been concentrated on the carotid bifurcation [3].

Shultz et al. outcomes [16] demonstrated that variation in carotid bifurcation anatomy is not restricted to differences in absolute vessel dimension. In addition, vessel diameter and area ratios diverge between and within individuals [20].

Selected studies, which have studied the relation between bifurcation's luminal geometry and the occurrence of cerebral artery aneurysms on angiographic images, have localized atherosclerotic lesions at the bifurcations of human cerebral arteries on autopsy cases. However, in this study, there were no available data on the endothelial topography in bifurcation geometry of newborn cadavers in the CCA and its major branches. For this motivation, histologic assessment makes last studies more valuable [3, 31].

Gosling et al. analyzed the optimal area ratio of an arterial bifurcation, producing the least reflection of pressure to be 1.15. That proportion can be close to ideal in human infants; however, in the long term, the decrease in outflow to inflow area ratio can lead to atherosclerotic plaque development. Gosling et al. studied 19 cases, with ages ranging from 0 to 10 and the outflow to inflow area ratio was found to be 1.11 ± 0.02 at 0 age group. Uslu's consequences were closer to the optimum ratio [3, 12].

Sitzer attempted to deliver a mechanistic link by proposing that their angle or rotation of ICA origin may be related to the ICA angle of insertion (comparable with the ICA-CCA angle of Lee et al.), which has been linked to flow turbulences [2, 25].

There are several studies on the diameters of CCA, ICA, and ECA in adults, but few studies are on newborns. To our knowledge, there are no earlier documents available on the relationship between the diameter of newborn cadavers and the CCA, ICA, and ECA [6].

Sehirli reported the mean outflow to inflow area ratio as 1.10 ± 0.33 mm in female and 1.18 ± 0.22 mm in male newborn cadavers for the common carotid artery bifurcation [6]. The consequences of Uslu's study on intracranial bifurcations show that the means of the outflow to inflow area ratio in fetal material are close to the optimum value in fetal material for the cerebral vessels.

Consistent with the results, the luminal geometry of arterial bifurcations impacts the blood flow that produces endothelial damage [3, 9, 13, 26].
