The critical role of hemodynamics in the development of cerebral vascular disease

A review

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Atherosclerosis and intracranial saccular aneurysms predictably localize in areas with complex arterial geometries such as bifurcations and curvatures. These sites are characterized by unique hemodynamic conditions that possibly influence the risk for these disorders. One hemodynamic parameter in particular has emerged as a key regulator of vascular biology—wall shear stress (WSS). Variations in geometry can change the distribution and magnitude of WSS, thus influencing the risk for vascular disorders. Computer simulations conducted using patient-specific data have suggested that departures from normal levels of WSS lead to aneurysm formation and progression. In addition, multiple studies indicate that disturbed flow and low WSS predispose patients to extracranial atherosclerosis, and particularly to carotid artery disease. Conversely, in the case of intracranial atherosclerosis, more studies are needed to provide a firm link between hemodynamics and atherogenesis. The recognition of WSS as an important factor in cerebral vascular disease may help to identify individuals at risk and guide treatment options.

Abbreviations used in this paper: BA = basilar artery; CA = carotid artery; CFD = computational fluid dynamics; ECA = external CA; eNOS = endothelial nitric oxide synthase; ICA = internal CA; iNOS = inducible NO synthase; ISA = intracranial saccular aneurysm; MAPK = mitogen-activated protein kinase; MCA = middle cerebral artery; NF-κB = nuclear factor–kappa B; VA = vertebral artery; WSS = wall shear stress.

Article Information

Address correspondence to: Bauer E. Sumpio, M.D., Ph.D., Department of Vascular Surgery, Yale University School of Medicine, 333 Cedar Street, BB 204, New Haven, Connecticut 06520. email:

Please include this information when citing this paper: published online November 27, 2009; DOI: 10.3171/2009.10.JNS09759.

© AANS, except where prohibited by US copyright law.



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    Left: Distribution of aneurysms in the circle of Willis. Approximately 90% of aneurysms occur in the anterior circulation, and most commonly (30–35%) in the anterior communicating artery (ACoA) complex (see Bonneville et al.). The darker color indicates the presence of saccular aneurysms. Right: Distribution of atherosclerosis in the intracranial vasculature. Dark color denotes areas afflicted by atherosclerosis, which usually involves the CA siphon. ACA = anterior cerebral artery; AICA = anterior inferior cerebellar artery; PCA = posterior cerebral artery; PCoA = posterior communicating artery; PICA = posterior inferior cerebellar artery; SCA = superior cerebellar artery.

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    Computed tomography angiography images demonstrating the origin of intracranial aneurysms (red arrows) at the junction of asymmetrical ACAs (white arrows). Please note that the aneurysm points away from the dominant ACA. Thick-cut maximum intensity projection images (A and C) and 3D reconstructions (B and D) of different ruptured aneurysms are shown.

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    Variations in bifurcation angles may influence the risk of aneurysm initiation and atherosclerosis. An increase in bifurcation angles has been associated with aneurysm formation. As the angles get wider, blood flow from the parent artery is obstructed, and as a result the WSS levels rise around the CA apex. A recent study by Lee et al. has linked variations in the proximal area ratio to disturbed flow patterns in the CA.

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    An idealized aneurysm forming on the outer curve of a curved artery. Due to centrifugal forces, blood enters through the distal aneurysm neck and impacts on the aneurysm wall. The site of impact experiences a local increase of wall stress (normal stress), whereas areas directly adjacent to the impact site experience high levels of WSS. Increases in curvature (1/R), or in the diameter of the neck may increase the levels of WSS. After impact, blood flow may follow the outline of the aneurysm and exit at the proximal neck. It should be noted that not all aneurysms conform to this flow pattern. Blood can enter through the proximal neck, and the site of flow impingement and maximal WSS may vary (for examples of an aneurysm dome see Castro et al., Cebral et al.,17 and Tateshima et al.).

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    The interplay between systemic factors and mechanical factors may lead to aneurysm formation.

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    Disturbed laminar flow includes flow patterns such as separation and recirculation. Endothelial cells sense changes in the hemodynamic environment and change their gene expression profile, possibly in an attempt to normalize WSS levels. Expression of NO is suppressed and release of various proinflammatory and prothrombotic factors ensues. IFN-γ = interferon-γ; IL-1 = interleukin-1; TNF = tumor necrosis factor.

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    The CA bifurcation is a common site for atherosclerotic lesions. The presence of the CA sinus promotes the generation of secondary flow patterns. Early lesions localize at the outer wall of the ICA, which correlates accurately with areas of disturbed flow (see Ku et al. and Zarins et al.). The outer wall of the ECA can also be affected. The apex and the inner walls of the ICA and ECA are exposed to normal or high levels of WSS and are thus spared in the early stages of atherogenesis. If stenosis occurs, then the flow patterns change and the aforementioned areas might be at risk (see Kaazempur-Mofrad et al.).



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