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Ann Thorac Surg 1995;59:1594-1603
© 1995 The Society of Thoracic Surgeons

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Current Review

Pressure-Induced Arterial Wall Stress and Atherosclerosis

Heineman Medical Research Laboratory, Carolinas Medical Center, Charlotte, North Carolina

	Abstract

Top Footnotes Abstract Introduction Anatomic Patterns of... Atherosclerosis and Arterial... Stress Concentration at the... Ostial Lesions Aortic Bifurcation Lesions Carotid Bifurcation Lesions Absence of Lesions in... Pattern of Atherosclerosis in... Effect of Blood Pressure... How Stress and Stretch... Summary Acknowledgments References

 
We present the hypothesis that high wall stress and accompanying stretch, particularly that caused by arterial pressure, are the primary factors responsible for the topography of atherosclerotic lesions. In our view the pattern in the localization of atherosclerotic lesions indicates that the artery behaves as both a pressure vessel and a conduit of blood flow. The phenomenon of ``stress concentration'' in the artery wall is described and the area of pressure-induced high stress is related to the sites of atherosclerotic plaques. Data are presented indicating that reduction of pressure-induced stress may lead to absence of atherosclerotic changes. The proposed mechanism explains the prevalence of atherosclerotic lesions at the ostia of major arterial branches, at the aortic bifurcation, at the carotid bifurcation, and in the descending thoracic aorta, and also explains the absence of atherosclerosis in the intramyocardial coronary arteries and in the intraosseal portions of the vertebral vessels and why a reduction in heart rate, blood pressure, or wall stress by external support reduces the occurrence of atherosclerosis. The effect of wall stress and stretch on atherosclerosis could be mediated by the endothelial cells, the smooth muscle cells, and the penetration of low-density lipoproteins. The comprehensive presentation made in this article could lead to a better understanding of atherosclerosis, its treatment, and its prevention.

	Introduction

Top Footnotes Abstract Introduction Anatomic Patterns of... Atherosclerosis and Arterial... Stress Concentration at the... Ostial Lesions Aortic Bifurcation Lesions Carotid Bifurcation Lesions Absence of Lesions in... Pattern of Atherosclerosis in... Effect of Blood Pressure... How Stress and Stretch... Summary Acknowledgments References

 
Atherosclerosis is a multifactorial disease in which conditions such as high cholesterol level, high blood pressure and diabetes are recognized to exacerbate the disease. Certain mechanical factors such as pressure-induced wall stress and blood flow disturbances also are considered important in the disease process because the disease has a predilection for the sites of arterial branching and bifurcations.

The purpose of this article is to present the hypothesis that arterial wall stress and accompanying stretch, produced by intraluminal pressure, are major contributing factors to the localization of atherosclerotic lesions and to show that this proposed mechanism may explain many observations concerning atherosclerosis.

	Anatomic Patterns of Atherosclerosis

Top Footnotes Abstract Introduction Anatomic Patterns of... Atherosclerosis and Arterial... Stress Concentration at the... Ostial Lesions Aortic Bifurcation Lesions Carotid Bifurcation Lesions Absence of Lesions in... Pattern of Atherosclerosis in... Effect of Blood Pressure... How Stress and Stretch... Summary Acknowledgments References

 
Atherosclerosis commonly affects the artery only at certain well-defined locations rather than through its entire course. In the human, atherosclerotic lesions usually predominate at the origins of tributaries, bifurcations, and curvatures [1, 2] (Fig 1). Some authors [3–9] have thought this focal nature of the disease could be explained by local disturbances in blood flow. Both the high [3–5] and low shear [6–8] areas have been considered as primary sites of atheroma formation. Contrary to these views, it is our contention that shear due to blood flow is probably not the major factor influencing atherosclerosis, but that blood pressure–induced arterial wall stress is the principal factor in the localization of the disease.

View larger version (44K): [in this window] [in a new window]   Fig 1. . Distribution of atherosclerotic occlusive disease in humans. (Reproduced from the Annals of Surgery 1985;201:116 with permission from the J. P. Lippincott Company, Philadelphia, PA, and Dr Michael E. DeBakey.)

	Atherosclerosis and Arterial Function

Top Footnotes Abstract Introduction Anatomic Patterns of... Atherosclerosis and Arterial... Stress Concentration at the... Ostial Lesions Aortic Bifurcation Lesions Carotid Bifurcation Lesions Absence of Lesions in... Pattern of Atherosclerosis in... Effect of Blood Pressure... How Stress and Stretch... Summary Acknowledgments References

 
To serve as a simple conduit to blood flow is only one of the basic functions of the artery. The other basic function is to sustain blood pressure. The artery is therefore both a conduit of blood flow and a container of pressure (pressure vessel). Although the first function has been studied in great detail, the artery as a pressure vessel scarcely has been the subject of investigation. In this study we attempt to show that a key to understanding atherosclerosis is to consider the artery as a pressure vessel, and as such consider two phenomena relevant to atherosclerosis that occur in a pressure vessel: (1) stress concentration at branches and (2) wall fatigue due to pulsatile blood pressure.

	Stress Concentration at the Arterial Branch Origins

Top Footnotes Abstract Introduction Anatomic Patterns of... Atherosclerosis and Arterial... Stress Concentration at the... Ostial Lesions Aortic Bifurcation Lesions Carotid Bifurcation Lesions Absence of Lesions in... Pattern of Atherosclerosis in... Effect of Blood Pressure... How Stress and Stretch... Summary Acknowledgments References

 
Generally speaking, the stress in the arterial wall produced by luminal pressure may be calculated by the law of Laplace. Accurate determination of stress, however, is complex because the arterial tissue is inhomogeneous and nonlinear, and the artery undergoes significant luminal enlargement when the pressure is applied.

Figure 2a shows a rectangular piece of arterial tissue with a central circular hole under tension. In this situation the stress exerted upon the tissue is not uniform, but it is concentrated adjacent to the hole at points A and B, which for the same reason will have a predilection to tear.

View larger version (37K): [in this window] [in a new window]   Fig 2. . Stress concentration at the arterial branch origins. (a) Stress distribution in a rectangular plate with a circular hole. c and l represent, respectively, stresses in the circumferential and longitudinal directions in the artery. The stress in the plate increases toward the hole and reaches a maximum value (max) at points A and B. (b) Schematic presentation of the artery with a branch. When the artery is opened in the longitudinal direction, the ostium of the branch appears similar to the hole in a plate. Points A and B at the ostium are similar to those in (a). (c) Maximum principal isostress contours on the inner surface of a bovine circumflex coronary arterial branch. The wall stress increases from one contour to the next toward the distal and the proximal lips of the ostium. The stress was determined in vitro for a pressure increase from 80 to 120 mm Hg using a finite element analysis method. (d) Maximum principal isostress contours on the inner surface of a canine iliofemoral arterial bifurcation. The stress concentration occurs at the distal and the proximal lips of the branch ostium. The stress was determined in vivo for a pressure increase from 80 to 120 mm Hg using the finite element analysis.

One of the most important consequences of stress concentration at the branch origins is that it produces a greater stretch at that location. In our experiments we both measured and analytically calculated the stretch in the branch area (Fig 3). The increase in intravascular pressure from 80 to 120 mm Hg led to an increment in the stretch of 5% to 7% in the branch region and of only 2% to 3% in other regions [11]. Thus, with each arriving pulse of pressure (120/80 mm Hg) the branch region experiences double the amount of stretch compared with nonbranch regions. This increased stretch in the branch area could influence atherosclerosis through processes such as enhanced low-density lipoprotein penetration or enhanced proliferation of smooth muscle cells.

View larger version (16K): [in this window] [in a new window]   Fig 3. . Distribution of strain around the ostium of a bovine circumflex coronary arterial branch. Experimentally measured strains near both the distal and the proximal lips of the ostium are as high as 5% to 7%, whereas those away from the ostium are 2% to 3%. The analytic strains were obtained from finite element analysis. The strains are for the pressure increase from 80 to 120 mm Hg.

	Ostial Lesions

Top Footnotes Abstract Introduction Anatomic Patterns of... Atherosclerosis and Arterial... Stress Concentration at the... Ostial Lesions Aortic Bifurcation Lesions Carotid Bifurcation Lesions Absence of Lesions in... Pattern of Atherosclerosis in... Effect of Blood Pressure... How Stress and Stretch... Summary Acknowledgments References

	Aortic Bifurcation Lesions

Top Footnotes Abstract Introduction Anatomic Patterns of... Atherosclerosis and Arterial... Stress Concentration at the... Ostial Lesions Aortic Bifurcation Lesions Carotid Bifurcation Lesions Absence of Lesions in... Pattern of Atherosclerosis in... Effect of Blood Pressure... How Stress and Stretch... Summary Acknowledgments References

 
Atherosclerotic lesions in the aortic bifurcation occur at both the ``crotch'' and the ``hip'' of the aortic bifurcation (Figs 1, 4). As shown on the bifurcation geometry (see Fig 4) the wall stress is very high at the crotch on the basis of the analysis presented earlier in Figure 2. Wall stress at the crotch is increased in a manner similar to that at the distal lip of the ostium where the branch angle is small.

View larger version (34K): [in this window] [in a new window]   Fig 4. . (A) Photograph of a human aortic bifurcation showing atherosclerotic lesions at the crotch of the bifurcation. (Reproduced from Texon M, Hemodynamic basis of atherosclerosis. Washington, DC: Hemisphere Publishing Corporation/Taylor & Francis Inc, 1980, Platen 10A, with permission. All rights reserved.) (B) Schematic presentation showing various geometric parameters that may lead to uneven distribution of stress at the bifurcation. The stresses are high at both the crotch and the hip of the bifurcation.

View larger version (28K): [in this window] [in a new window]   Fig 5. . (Top) Circumferential stress in the wall of the artery and its relationship to pressure (P), radius (R), and thickness (t) of the artery. At the hips of the aortic bifurcation the stress is greater than that in the main artery because the length (2a) of the major axis of the ellipse at the bifurcation is greater than the diameter (2R) of the main vessel. (Bottom) The elliptical cross-section at the bifurcation has a tendency to become circular under pressure. Strip AB tends to bend back to become A`B`, which produces a maximum bending stress at points M and N.

The last stress-enhancing factor we must consider is the arterial curvature [14]. What we usually see is that arteriosclerotic plaques often develop on the inner curve of the aortic arch and the inner curve of the tortuous segments of any arteries [15] (Fig 6A). The outer curve is a surface similar to that of a sphere with centers of the two principal radii of curvatures on the same side of the surface (Fig 6B). Such surfaces are called synclastic [16]. The inner surface, on the other hand, has the centers of the two principal radii of curvatures on the opposite sides of the surface. This horse-saddle type of a surface is called anticlastic. It has been well established by Burton [16] and other texts of reference [17] that due to its geometry the pressure-induced wall stress is much higher on the inner than on the outer curve. This correlates with the observations that atherosclerotic lesions usually favor the inner curve.

View larger version (24K): [in this window] [in a new window]   Fig 6. . (A) Longitudinal section of the right carotid siphon, which illustrates the location of intimal cushion (IC). In childhood the subendothelial elastic layer is well developed along the outer walls (OC) of the curvatures, whereas prominent intimal cushions (arrows) consisting mainly of loose connected tissue and sparse elastic elements are present along the inner walls of the curvatures. Inset shows a cross section of the vessel at the site of the arrows. (Reproduced from Wolf S, Werthessen NT, eds. Dynamics of arterial flow. Advances in experimental medicine and biology, vol 115. New York: Plenum, 1976:357, with permission.) (B) Stress distribution in a curved artery: 1 and 2 represent, respectively, the circumferential and longitudinal stresses. The outer curve is part of a sinclastic surface and the inner curve is part of an anticlastic surface. P represents luminal pressure and t represents wall thickness. Circumferential stresses are higher on the inner curve than on the outer curve.

	Carotid Bifurcation Lesions

Top Footnotes Abstract Introduction Anatomic Patterns of... Atherosclerosis and Arterial... Stress Concentration at the... Ostial Lesions Aortic Bifurcation Lesions Carotid Bifurcation Lesions Absence of Lesions in... Pattern of Atherosclerosis in... Effect of Blood Pressure... How Stress and Stretch... Summary Acknowledgments References

 
Studying the pathologic anatomy of carotid bifurcation lesions we found that most frequently the less advanced lesions occurred in the sinus bulb area whereas the more advanced atheromas involved the crotch as well as the entire bifurcation [18] (Fig 7A). These observations agree with those reported in the literature (see Fig 1) [19, 20] and may be explained readily by the distribution of wall stress.

View larger version (141K): [in this window] [in a new window]   Fig 7. . (A) (Top) Atherosclerotic plaque removed from a human carotic artery bifurcation. (Bottom) Locations of atherosclerotic disease at the carotid bifurcation. 56% indicates the relative frequency of occlusive lesions in the brachiocephalic vascular system. Most often, the occlusive lesions occur involving the entire carotid bifurcation as shown at the top. (B) (Left) Schematic presentation of the carotid bifurcation indicating that the stresses are high at the crotch and in the sinus bulb region. Also, the parameters that result in the high stresses are shown. (Right) Maximum principal isostress contours at the human carotid artery bifurcation. The stresses are high at all three locations B, A, and C, being the highest at B. The stress contours were obtained from the finite element analysis for a pressure (pulse) loading of 40 mm Hg.

We performed stress analysis on human carotid artery bifurcation using the method of ``finite element analysis'' [18]. The results of this analysis are shown in Figure 7B. We found that the highest stress occurs at the crotch of bifurcation, then in a decreasing order at the sinus bulb over a substantially large area, and finally at the wall opposite the sinus bulb. Thus, the early lesions in the sinus bulb area as well as the advanced lesions involving the crotch and the entire bifurcation correlate well with the areas of high wall stress.

	Absence of Lesions in Intramyocardial Coronary Arteries and the Intraosseal Portion of the Vertebral Arteries

Top Footnotes Abstract Introduction Anatomic Patterns of... Atherosclerosis and Arterial... Stress Concentration at the... Ostial Lesions Aortic Bifurcation Lesions Carotid Bifurcation Lesions Absence of Lesions in... Pattern of Atherosclerosis in... Effect of Blood Pressure... How Stress and Stretch... Summary Acknowledgments References

 
We have studied in more than 200 patients the occurrence of atherosclerotic lesions in coronary arteries in the course of coronary bypass operations [21]. In about 10% of the patients a major branch of the coronary artery was found to have an intramyocardial course. These branches arise from the circumflex coronary artery just after the origin of the left anterior descending artery. In the great majority of patients we found the intramyocardial branches to be completely free of atherosclerosis, despite the fact that the rest of the coronary arterial tree had severe diffuse atherosclerotic lesions [21]. Atherosclerotic changes involving the epicardial portion of the coronary artery abruptly stopped at the point where the artery entered the myocardium (Fig 8). Similar observations were made by other investigators [22].

View larger version (32K): [in this window] [in a new window]   Fig 8. . (A) Photograph taken intraoperatively showing the atherosclerotic lesion in the coronary artery in humans. The incision in the myocardium exposes the place of entry of the coronary artery into the myocardium. Severely occlusive atherosclerotic plaque has developed in the epicardial segment, but the artery is completely normal in the intramyocardial segment. The atherosclerotic lesion abruptly stops at the entry of the artery into the myocardium. (B) Typical recordings of the left ventricular chamber pressure and the intramyocardial pressure in subepicardial, midwall, and subendocardial regions in canine hearts.

The intraosseal portion of the vertebral arteries are known to show an alternating pattern of atherosclerotic changes; the lesions occur in the segments that are free to expand, but are absent where the artery segment is passing through the bone canal and thus is not free to expand with the systolic pulse pressure (Fig 9) [23]. The surrounding bone seems to act as support and prevents the increase of stress due to systolic stretch in that segment. This function is similar to the support given to the arteries surrounded by myocardium. The portions of the vertebral arteries that lie between the bony canals do not have this protection and therefore are susceptible to the development of high stress and high stretch.

View larger version (43K): [in this window] [in a new window]   Fig 9. . (Right) Rhythmic distribution of atherosclerotic lesions in the vertebral artery. The star indicates the presence of lipids in the regions where the artery is between the two bone canals. The artery in the bone canal (white) is free of the disease. (Reproduced from Wolf S, Werthessen NT, eds. Dynamics of arterial flow. Advances in experimental medicine and biology, vol 115. New York: Plenum, 1976:378, with permission.) (Left) Schematic presentation of the course of the vertebral artery.

	Pattern of Atherosclerosis in the Descending Thoracic Aorta

Top Footnotes Abstract Introduction Anatomic Patterns of... Atherosclerosis and Arterial... Stress Concentration at the... Ostial Lesions Aortic Bifurcation Lesions Carotid Bifurcation Lesions Absence of Lesions in... Pattern of Atherosclerosis in... Effect of Blood Pressure... How Stress and Stretch... Summary Acknowledgments References

 
In the descending thoracic aorta also there is a well-defined pattern of atherosclerotic lesion development. Cornhill and associates [2] and others [27] have described that lesions in this segment occur in the form of two parallel streaks that run along the sides of the intercostal arteries (Fig 10). Flow pattern does not explain this localization, but the wall stress hypothesis suggests that because the descending thoracic aorta is tethered to the spine by means of several pairs of intercostal arteries the wall stress may be responsible for this phenomenon. These pairs act as anchors for the aorta so that when the aorta bends during body movement it changes shape along the two parallel lines by the sides of the intercostal arteries as shown in Figure 10. Thus, once again the parallel lines of mechanical deformation of the aorta correlate with the parallel streaks of atherosclerotic lesions.

View larger version (39K): [in this window] [in a new window]   Fig 10. . (Left) Distribution of atherosclerotic lesions in the thoracic aorta in humans. The lesions are present along two parallel lines just on the outside of the pairs of intercostal arteries. (Reproduced from Liepsch DW, ed. Blood flow in large arteries: applications to atherogenesis and clinical medicine: topography of human aortic sudanophilic lesion. Basel: Karger, 1990;15:Platen I, with permission from Dr J. Fredrick Cornhill.) (Right) Thoracic aorta in the cross section where the intercostal arteries originate. Any lateral movement of the aorta will be achieved by deformation of the aorta in regions A and B, ie, deformation along the two parallel lines. These parallel lines correspond to those along which atherosclerotic lesions develop as shown on the left.

	Effect of Blood Pressure and Heart Rate on Atherosclerosis (Artery Fatigue due to Pulsatile Pressure)

Top Footnotes Abstract Introduction Anatomic Patterns of... Atherosclerosis and Arterial... Stress Concentration at the... Ostial Lesions Aortic Bifurcation Lesions Carotid Bifurcation Lesions Absence of Lesions in... Pattern of Atherosclerosis in... Effect of Blood Pressure... How Stress and Stretch... Summary Acknowledgments References

It also has been reported that a decrease either of the mean blood pressure or of the pulse pressure reduces atherosclerotic lesions in rabbits [29, 30], sheep [31], and monkeys [32], and a decrease in the heart rate reduces atherosclerotic lesions in rabbits [33] and monkeys [34, 35] (Table 1). In humans, a decrease in mean blood pressure [36] and a decrease in the heart rate [37, 38] is reported to reduce mortality and morbidity originating from atherosclerotic disease. To understand these observations, we must consider the concept of cumulative arterial injury caused by artery fatigue. As mentioned in the Atherosclerosis and Arterial Function section, fatigue is one of the phenomena that occur in all vessels under pressure, particularly when the pressure is pulsatile [10]. The phenomenon of fatigue failure is well understood in many nonbiological materials. It is said that ``In pressure vessels virtually all failures are a result of fatigue- fatigue in areas of high localized stress'' [10]. This type of fatigue damage has been considered by Born and Richardson [39] in relation to rupture of atherosclerotic plaques. We propose that this phenomenon occurs in the artery wall itself because the artery has both areas of high localized stress and pulsatile blood pressure.

View larger version (31K): [in this window] [in a new window]   Fig 11. . (Top) Distribution of stress contours in the arterial branch indicating that at both the distal lip (D) and the proximal lip (P) of the ostium the stresses are high and localized. Fatigue failure is expected to occur at either of these two locations mainly as a result of the pulsatile pressure experienced by the artery. (Bottom) Typical fatigue behavior of a nonbiological material. We propose that this also qualitatively represents the fatigue behavior of an artery. Point A indicates that for the systemic pressure of 120/80 mm Hg a certain number of cardiac cycles are required to produce fatigue damage in the artery. Point B indicates that for a greater amount of pulse pressure, but for the same mean pressure, the number of cardiac cycles required to produce fatigue damage is less. Point C indicates that for the same pulse pressure, but a higher mean blood pressure, the fatigue damage could occur at a lower number of cardiac cycles. In qualitative terms, increasing either the mean blood pressure or the pulse pressure would produce the fatigue damage in fewer cardiac cycles, ie, atherosclerotic disease will occur sooner. Similarly, for a given period, decreasing the heart rate decreases the fatigue damage, ie, decreases cumulative arterial injury and hence atherosclerosis.

	How Stress and Stretch Might Influence Atherosclerosis

Top Footnotes Abstract Introduction Anatomic Patterns of... Atherosclerosis and Arterial... Stress Concentration at the... Ostial Lesions Aortic Bifurcation Lesions Carotid Bifurcation Lesions Absence of Lesions in... Pattern of Atherosclerosis in... Effect of Blood Pressure... How Stress and Stretch... Summary Acknowledgments References

Low-density lipoprotein uptake in the artery also has been studied by us [46] and by others [47]. We observed that low-density lipoprotein accumulation in the artery is greater in the branch region than in the nonbranch region. We also found that treatment with beta-blockers, which reduce the heart rate, also decrease low-density lipoprotein accumulation in the artery, particularly in the branch region [48].

The effect of cyclic stretch on smooth muscle cell proliferation also has been studied. We have observed smooth muscle cell proliferation of several folds when the artery was deendothelialized and stretched by a balloon compared with when the artery was only deendothelialized but not stretched [49]. Similar observations have been reported by others [50]. Cell culture studies on smooth muscle cells also have established that the cell orientation [51] and other cell functions are influenced by the cyclic stretch [52].

These observations suggest a strong relationship between wall stress, wall stretch, cyclic stress, cyclic stretch, and many cellular processes that are a part of atherosclerosis.

	Summary

Top Footnotes Abstract Introduction Anatomic Patterns of... Atherosclerosis and Arterial... Stress Concentration at the... Ostial Lesions Aortic Bifurcation Lesions Carotid Bifurcation Lesions Absence of Lesions in... Pattern of Atherosclerosis in... Effect of Blood Pressure... How Stress and Stretch... Summary Acknowledgments References

 
It is postulated that high wall stress and accompanying stretch produced by the arterial pressure are primary factors contributing to the localization of atherosclerotic lesions. The areas where branches arise have high wall stress and high wall stretch, as well as cyclic variations of both in each cardiac cycle. The branch area and other areas of high wall stress thus are exposed to endothelial injury and increased low-density lipoprotein uptake. Increased cyclic stretch in these regions already provides a stimulus for increased smooth muscle cell proliferation. When the injury to these regions is enhanced by either high blood pressure, high plasma level of low-density lipoproteins, or other stimuli such as diabetes, atherosclerotic plaques may develop. This proposed mechanism explains the occurrence of lesions at the ostia of major arterial branches, at the aortic bifurcation, at the carotid bifurcation, and in the descending thoracic aorta, and also solves the enigma of absence of lesions in the intramyocardial coronary and in the intraosseal portions of the vertebral arteries. The mechanism also explains why the reduction of heart rate, blood pressure, or wall stress by external support reduces the arterial injury and reduces the development of atherosclerotic lesions.

	Acknowledgments

Top Footnotes Abstract Introduction Anatomic Patterns of... Atherosclerosis and Arterial... Stress Concentration at the... Ostial Lesions Aortic Bifurcation Lesions Carotid Bifurcation Lesions Absence of Lesions in... Pattern of Atherosclerosis in... Effect of Blood Pressure... How Stress and Stretch... Summary Acknowledgments References

 
Doctor Thubrikar would like to acknowledge the support and encouragement of Dr Stanton P. Nolan, Department of Surgery, University of Virginia, in this research.

	Footnotes

Top Footnotes Abstract Introduction Anatomic Patterns of... Atherosclerosis and Arterial... Stress Concentration at the... Ostial Lesions Aortic Bifurcation Lesions Carotid Bifurcation Lesions Absence of Lesions in... Pattern of Atherosclerosis in... Effect of Blood Pressure... How Stress and Stretch... Summary Acknowledgments References

 
Address reprint requests to Dr Thubrikar, Heineman Medical Research Laboratory, Carolinas Medical Center, 1000 Blythe Blvd, Charlotte, NC 28203.

	References

Top Footnotes Abstract Introduction Anatomic Patterns of... Atherosclerosis and Arterial... Stress Concentration at the... Ostial Lesions Aortic Bifurcation Lesions Carotid Bifurcation Lesions Absence of Lesions in... Pattern of Atherosclerosis in... Effect of Blood Pressure... How Stress and Stretch... Summary Acknowledgments References

 

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