Author + information
- Arnold P.G. Hoeks, PhD⁎ (, )
- Koen D. Reesink, PhD,
- Evelien Hermeling, MSc and
- Robert S. Reneman, MD, PhD
- ↵⁎Department of Biophysics, Cardiovascular Research Institute Maastricht, University Maastricht, P.O. Box 616, 6200 MD Maastricht, the Netherlands
A recent article (1) published in the Journalcorroborates the hypothesis that shear stress triggers fibrous cap rupture. In 20 patients with considerable lumen narrowing (maximum area reduction of 80 ± 7%), ulcerative plaque rupture preferentially occurred in areas with locally high wall shear stresses (WSS), estimated by means of computational modeling. However, the authors of this study do not answer the basic question of whether local WSS distribution is indeed related to plaque rupture.
Hemodynamics is an interplay between pressure, flow, and morphology. The study by Fukumoto et al. (1) mainly considers the interaction between flow and morphology under steady-state conditions. Compared with an unaffected site, the increase in WSS around a plaque can be estimated to be a factor of 10 assuming simple circular geometries. For a normal WSS of 0.6 Pa (2), the mean WSS within the stenosis will remain <10 Pa, which might be too low to initiate plaque rupture directly, as acknowledged by the authors.
The article does not fully appreciate the influence of local blood pressure within a stenosis, although this pressure was calculated as well. Let us consider the hemodynamics in the vicinity of a stenosis (3), where in a steady-state situation the sum of potential energy (local blood pressure) and kinetic energy (local blood velocity) is constant (Bernoulli equation): an increase in velocity induced by geometry decreases local pressure (3). An area reduction of 80% converts to an increase in velocity by a factor of 5, and the associated pressure decrease will be 1.1 kPa (8.4 mm Hg), which is 100 times greater than the WSS. In the longitudinal direction, the pressure gradient across the wall also goes down by 8.4 mm Hg and is partially restored distal to the stenosis.
Now let us assume that the vasa vasorum function properly (4). Then, within the arterioles supplying the plaque, blood pressure highly depends on the blood pressure proximal to the stenosis, despite frictional losses along the arterioles. Because of high stenotic blood flow velocities, not only a high WSS but also a substantial pressure gradient develops across the wall towards the lumen. This situation is opposite to normal conditions where the transmural pressure gradient is directed outward.
Pulsatile conditions aggravate the situation. High-grade stenoses cause strong pulse wave reflections, increasing the proximal pulse pressure by almost a factor of 2. The pulsatile transmural pressure and the longitudinal pressure gradient into the stenosis contribute to (position-dependent) wall and plaque deformation. Because of the fragility of plaque structures (5), this deformation will very likely contribute to cap rupture. The pressure gradient across a plaque may contribute to the release of thrombogenic material into the lumen.
Wall shear stress plays an important role in atherogenesis but is merely coincidental with plaque rupture. The combination of high velocities due to lumen narrowing, the vasa vasorum, plaque composition, and structure and pressure wave reflection induce longitudinal and transmural pressure gradients and plaque deformation, contributing to plaque rupture. A small residual lumen generates high inward pressure gradients and inward “bleeding.”
- American College of Cardiology Foundation
- Fukumoto Y.,
- Hiro T.,
- Fujii T.,
- et al.
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