(Circulation. 1996;94:3257-3262.)
© 1996 American Heart Association, Inc.
Articles |
Association Between Intima-Media Thickness and Wall Shear Stress in Common Carotid Arteries in Healthy Male Subjects
the University of Reggio Calabria, Dipartimento di Medicina Sperimentale e Clinica, Centro Aterosclerosi, Catanzaro, Italy.
Correspondence to Agostino Gnasso, MD, Policlinico Mater Domini, via T. Campanella, 88100 Catanzaro, Italy.
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Abstract |
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Background Atherosclerotic lesions lie in regions of low wall shear stress. No relationship between wall shear stress and intima-media thickness in vivo has been reported. Aims of the present study were to verify the reproducibility of wall shear stress measurement in vivo and to evaluate its association with intima-media thickness in the common carotid artery in healthy subjects.
Methods and Results Wall shear stress was calculated according to the following formula: Shear Stress=Blood ViscosityxBlood Velocity/Internal Diameter. Blood viscosity was measured by use of a cone/plate viscometer. Blood velocity, internal diameter, and intima-media thickness were measured by high-resolution echo Doppler. Twenty-one healthy male subjects were investigated. Peak and mean shear stress values were 29.5±8.2 and 12.1±3.1 dynes/cm-2 (mean±SD), respectively. Peak shear stress was inversely related to intima-media thickness (r=.62), age (r=.77), systolic blood pressure (r=.61), and body mass index (r=.59) (P<.0001 for all coefficients). Mean shear stress yielded similar results. The relationship between shear stress and intima-media thickness was independent of age, blood pressure, and body mass index. The reproducibility, calculated by Kendall's W test, was statistically significant.
Conclusions Our results demonstrate that common carotid artery wall shear stress measurement in vivo is reproducible. It inversely relates to intima-media thickness, age, systolic blood pressure, and body mass index. These findings confirm in vivo the role of shear stress in intima-media thickening.
Key Words: carotid arteries • hemodynamics • atherosclerosis • shear stress
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Introduction |
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According to current knowledge, the vessel wall is considered an integrated organ capable of detecting hemodynamic stimuli and releasing vasoactive substances.1 Levels of the vasodilators prostacyclin and nitric oxide and of the vasoconstrictor endothelin-1 are strongly influenced by shear stress.2 3 4 5 6 An overall vessel structure remodeling can occur in the long term.7 8 9 10
For a long, slender, relatively straight artery, such as the common carotid, wall shear stress, that is, the frictional force exerted by the circulating blood column on the intimal surface of the arteries,11 is directly proportional to blood flow velocity and inversely proportional to the vessel diameter. The intact endothelium is able to sense shear stress and to induce luminal diameter modifications to keep shear stress constant at a predetermined level.12 13
Pathological investigations14 15 16 17 18 19 20 21 22 23 have demonstrated that preferential sites for LDL deposition and atherosclerotic lesions lie in regions of low shear stress. Furthermore, high shear stresses prevent atherogenesis in vivo in the cholesterol-fed monkey.24
In vivo measurement of wall shear stress has long been hindered by technical difficulties, ie, accurate vessel diameter and flow velocity estimates. Current echo-Doppler instruments allow the accurate determination of these parameters. Aims of the present study were to verify the reproducibility of wall shear stress measurement in vivo and to evaluate its association with IMT measured in the common carotids in healthy volunteers.
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Methods |
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To test the reproducibility of the shear stress calculation, we studied five healthy male volunteers (aged >18 years) three to five times in a period of 6 to 8 weeks. The subjects were nonsmokers, did not use any drug, and had no plaque or stenosis of the carotid tree. For each subject, the average of the several examinations was calculated, and the ratio between each individual value and the average value was determined.
In the second part of the study, 16 additional subjects with the same characteristics were enrolled and studied once. Because right and left common carotid arteries were analyzed separately, the correlation between IMT and wall shear stress was calculated on 42 arteries.
Blood pressure, height, and weight were measured by routine methods. BMI was computed as weight (in kilograms) divided by height (in meters squared).
Echo-Doppler examination for arterial diameter, IMT, and blood flow velocity measurement was performed by use of an ECG-triggered high-resolution ATL ultramark 9 HDI instrument (Advanced Technology Laboratories Inc) equipped with a 5- to 10-MHz multifrequency linear probe. The examinations were performed in the morning in a room at 22°C; the subjects had fasted since the previous evening. Coffee was not allowed. The subjects were kept in the supine position with their heads slightly extended. All measurements were performed in the common carotid arteries 1 to 2 cm proximal to the bulb. The common carotids were studied in longitudinal and transverse planes with anterior, lateral, and posterior approaches. The sonographer, who was the same throughout the study, recorded the examination on a videotape. A reader, who was the same throughout the study and who was blinded with regard to the subject investigated, performed the measurement of ID and IMT.
ID was defined as the distance between the leading edge of the echo produced by the intima-lumen interface of the near wall and the leading edge of the echo produced by the lumen-intima interface of the far wall. ID was measured at the R wave (IDR) and T wave (IDT) of the cardiac cycle. IDR, obtained just before the systolic wave passage, was the narrowest luminal diameter; IDT, obtained during the systolic wave passage, was the largest. Diameters used in the analysis represent the mean of the diameters measured in the lateral and posterior projections.
IMT was measured as previously described.25 Briefly, images selected from video recordings of the ultrasound scan were displayed on a computer screen by the use of a video maker card (Vitec) and analyzed by a software program that allows quantitative evaluation of the IMT. For each participant, three measurements pertaining to the anterior, lateral, and posterior projections of the far wall were performed on each side. The average of the three measurements was used to calculate the IMT.
Systolic blood flow velocity was detected with the sample volume reduced to the smallest possible size (1 mm) and placed in the center of the vessel. The angle between the ultrasound beam and the longitudinal vessel axis (
) was kept between 44° and 56°. After 1 minute for stabilization, VSP and VM were recorded as the mean of the last three cardiac cycles. In the first part of the study, blood flow velocity was recorded four times at 5-minute intervals in each subject. The records became stable after the subjects had been resting 5 to 10 minutes. It was therefore decided to leave the subjects resting 10 minutes before examination.
On the same day as the echo-Doppler examination and within 2 hours of blood withdrawal from an antecubital vein, blood viscosity (
) was measured in vitro at 37°C by use of a cone/plate viscometer (Wells-Brookfield DV III) equipped with a cp-40 spindle. The blood was anticoagulated with heparin (35 IU/mL). Blood viscosity, measured at shear rates between 1.1 and 450 s-1, reached almost a plateau at a shear rate of 90 s-1. Because the measurement at a shear rate of 450 s-1 was not feasible in all subjects, results obtained at a shear rate of 225 s-1 were used. At this shear rate, blood may be regarded as a newtonian fluid.26
Peak (
P) and mean (M) wall shear stresses were calculated according to the formulas
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S and M represent the systolic and mean wall shear rates, respectively. Wall shear rates are not directly measured in this model but can be calculated by use of a poiseuillean parabolic model of velocity distribution across the arterial lumen,27 according to the formulas
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We have measured the VM and used this value for M calculation. Other authors26 measured mean cross-sectional blood velocity and assumed VM to be twice as great according to the formula M (s-1)=8·VM/ID. However, we also measured mean cross-sectional blood velocity by sizing the sample volume to embrace the entire vessel lumen and found a strong relationship with VM (r=.91), although the absolute values were slightly higher than VM/2.
It has been demonstrated that for large arteries, Poiseuille flow provides a useful estimate of wall shear for both steady and oscillating regimens of flow.28 We evaluated flow velocity distribution in all subjects by measuring the velocity in five different points across the common carotid lumen; a typical profile is shown in Fig 1
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The Reynolds number was calculated according to the following: R=
·vm·r/, where is the blood density (assumed to be between 1.056 and 1.060x103 kg/m3), vm is the mean velocity of the blood (in meters per second), r the radius of the vessel (in millimeters), and the blood viscosity (in centipoise). A Reynolds number value <1000 is usually considered characteristic of laminar flow.
The Pearson correlation coefficient was used to test the association between wall shear stress, IMT, age, SBP, and BMI and to verify the relationship between the first and the repeat results of shear stress measurement. CVs were calculated to test the reproducibility of ID, blood velocity, blood viscosity, and shear stress measurements. For P and M, Kendall's W coefficient of concordance was also calculated. To allow for the independent contribution of shear stress, age, SBP, and BMI to IMT, stepwise multiple regression analyses were performed. The cutoff value for variables entering the model was set at P<.1. Regression analysis was also used to adjust shear stress values for age.
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Results |
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A typical blood flow profile recorded in the common carotid artery is illustrated in Fig 1
. Fig 1a shows the position of the sample volume within the arterial lumen, Fig 1b the corresponding peaks, and Fig 1c the flow profile drawn according to recorded velocities.
Table 1 shows clinical and biochemical characteristics, values of ID, blood flow velocity, shear stress, and Reynolds number of the five subjects participating in the first part of the study.
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Table 2 shows the reproducibility data for ID, blood viscosity, blood flow velocity, and wall shear stress. The mean CV represents the average of the CVs calculated in each subject. The variation was very low for ID and blood viscosity and slightly higher for peak and mean blood velocities. As expected, P and M variabilities were higher, but they never exceeded 9%. Pearson correlation coefficients were .98 and .97 for P, .93 and .95 for M (all P<.05), first versus second and first versus third measurements, respectively. The Kendall's W coefficients of concordance computed for P and M were highly significant: W0.05,5,3=11.4 (P<.001) and W0.05,5,3=8.8 (P<.01), respectively.
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Table 3 shows the clinical and biochemical characteristics of the 21 subjects who participated in the second part of the study. The range of P and M values was quite widespread. P and M were strongly correlated (r=.82, P<.0001).
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Figs 2 and 3 show the regression lines between P and M, respectively, and IMT, age, SBP and BMI. P and M were inversely and significantly related to IMT, age, SBP, and BMI, although the correlation coefficients were slightly lower for M.
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IMT was significantly correlated with age (r=.70, P<.0001), SBP (r=.56, P<.0002), and BMI (r=.70, P<.0001).
The results of the stepwise regression analyses are reported in Table 4. BMI and shear stress were independently associated with IMT, whereas age and SBP did not significantly improve the regression model. We have further adjusted shear stress values for age and found these values significantly inversely correlated with IMT (adjusted P: r=.35, P=.02; adjusted M: r=.39, P=.01) (Fig 4).
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Discussion |
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The results of the present study show that the in vivo measurement of wall shear stress in the common carotid arteries of healthy men is reproducible.
P and M are inversely related to age, SBP, and BMI and also to IMT, independently of age, SBP, and BMI. These findings confirm in vivo the role of shear stress in intima-media thickening and support the hypothesis that the known relationship between IMT and age, SBP, and BMI might be mediated, at least in part, by wall shear stress. The determination of wall shear stress in vivo, as described in the present study, is based on several assumptions that need to be discussed.
First, blood has been assumed to be a newtonian fluid. The presence of cells, however, can strongly influence the rheological properties of the blood. Furthermore, erythrocyte aggregation is known to play a key role in the pathophysiology of blood circulation.29 Adhesive, repulsive, and mechanical forces account for the equilibrium between aggregation and disaggregation of red blood cells.30 31 At the shear rate of 225 s-1, used for in vitro blood viscosity measurement in the present study, erythrocytes are likely to be completely disaggregated, and the blood can be regarded as newtonian.32
Second, blood velocity has been calculated assuming that arterial flow is parallel to the long axis of the vessel, but it is well known that nonaxial flow exists in several vascular beds, including the extracranial carotid circulation.33 34 Helical flow patterns do not allow exact knowledge of the angle between the axis of the flowing blood and that of the ultrasound beam and might therefore result in overestimation or underestimation of blood velocity. This phenomenon is certainly important in the region around and above the flow divider, whereas disturbed flow in the common carotid arteries, at the level at which we measured blood velocity and arterial diameter, should be negligible.35 The flow profile in the segment of the common carotid examined was parabolic, as shown in Fig 1 and as would be expected 
10 diameters distal to the origin of the carotid artery and several diameters proximal to its bifurcation. The Reynolds number, a predictor of turbulence, was constantly <1000.
Finally, shear stress has been calculated according to Poiseuille's law and equation. Poiseuille's law applies only to constant laminar flow of a newtonian fluid in a straight rigid tube of a uniform bore. It has been demonstrated that a poiseuillean parabolic model of velocity distribution across the arterial lumen provides a useful estimate of wall shear.27
The results of the first part of the study demonstrate that the measurement of both P and M in the common carotid artery is reproducible. Because wall shear stress is calculated from blood viscosity, blood velocity, and arterial diameter, its reproducibility reflects the variability of the constituents. Because shear stress calculation has been performed within a period of 6 to 8 weeks, the reported variabilities reflect both operator and intraindividual variability. Of the three determinants of shear stress, blood velocity showed the highest variability. We found that much of this variability could be eliminated by having the subjects rest for at least 10 minutes before examination.
Because arterial flow is pulsatile, shear stress varies during the cardiac cycle. The highest shear value (P) is recorded at the blood flow velocity acme and the lowest value just before. The difference between these two values is referred to as pulse shear stress and is sometimes used as a further measure of wall shear stress, especially when reverse flow occurs.35 Furthermore, the frequency at which the vessel wall experiences P over time (that is, heart rate–adjusted P) might play a role. We have calculated heart rate–adjusted P and pulse shear stress, although reverse flow was never detected in our population, and found these variables strictly related to P and M. We think that in our population, P and M can reasonably account for wall shear stress and have therefore used only these parameters for further analysis.
In the second part of the study, we calculated the wall shear stress in the 42 carotid arteries examined. Mean P was similar to that reported by Ku and coworkers35 in an acrylic plastic model of the carotid tree, using a laser Doppler velocimeter to measure flow velocity. The range, however, was quite large, thus demonstrating for the first time that shear stress can vary widely in the same arterial district among individuals. The relationship between wall shear stress and IMT was highly statistically significant, although IMT values were contained within a narrow range because only healthy and relatively young subjects were investigated. This relationship was independent of age, SBP, and BMI in multiple regression analysis. Furthermore, age-adjusted shear stress was still significantly associated with IMT. The mechanisms by which low shear stresses induce intimal thickening and atherosclerotic lesions might be diverse. Low shear stress probably contributes to an increased fluid residence time, which in turn may result in increased transport of atherogenic particles or interfere with endothelial metabolism.36 37 Platelets and macrophages, key elements of atherosclerotic lesions, are more likely to adhere to the arterial wall in regions of increased residence time,38 and the TPA secretion rate of human endothelial cells decreases with decreasing values of shear stress, at least in experiments in vitro.39 In addition, recent evidence suggests that shear stress modulates the transcription of genes for nitric oxide synthase, platelet-derived growth factor, and transforming growth factor-ß1, all factors involved in vascular remodeling.4 40 41 42 43 44 45 46 The end effect of low shear stress seems to be increased local production of mitogenic substances. Furthermore, it must be pointed out that in the present study, shear stress was measured only once, whereas wall shear stress history for each patient is likely to play an important role in intimal thickening and may account for some of its variance.
An inverse relation between vessel wall shear stress and atherosclerosis progression in human coronary arteries has been described in vivo.47 However, in that study, only the vessel diameter was measured by means of quantitative angiography, whereas flow rate and viscosity values were assumed to be constant. It can be calculated that a 15% variation in blood viscosity within the normal range causes a wall shear stress variation of the same magnitude. Because alterations of blood flow velocity and viscosity might contribute to wall shear stress modifications and, as a result, to arterial wall thickness, we believe that their measurement is mandatory to calculate wall shear stress.
Carotid arteries are frequently a seat of atherosclerotic lesions. One puzzling aspect of this involvement is the asymmetry of lesions between the left and right carotids, despite both districts being exposed to identical "systemic" risk factors such as hyperlipidemia, hypertension, diabetes mellitus, and cigarette smoking. Local factors, mainly the geometry of the carotid arteries, have been hypothesized to play a role in determining atherosclerotic lesion localization.48 Indeed, the geometry of the vessel influences the blood flow pattern and hence the wall shear stress,49 and that might offer a possible explanation for the asymmetry of lesions between left and right districts.
Intriguing as well is the observation that classic cardiovascular risk factors all determine intima-media thickening of the common carotid artery,25 50 51 52 although the hypothesized mechanisms of action would be greatly different. In the present study, wall shear stress was found to be significantly and inversely correlated to age, blood pressure, and BMI. The inverse relationship with age was mainly sustained by a reduction of flow velocity, which might reflect decreased cardiac output and increased peripheral resistances.53 ID increased with increasing values of blood pressure and BMI, and this, together with a reduction of flow velocity, accounts for the inverse correlation of these variables with wall shear stress. Blood viscosity was not significantly associated with any variable.
Although the findings of our study apply only to healthy subjects, it might be speculated that aging, hypertension, overweight, and possibly other coronary heart disease risk factors induce arterial wall thickening at least in part through a reduction of wall shear stress. Alterations of wall shear stress might offer a unique explanation for the effects produced by different risk factors.
In conclusion, we describe a method for in vivo wall shear stress measurement in the common carotid arteries. Repeated examinations, performed in five subjects, demonstrate that reproducibility is good, although wall shear stress calculation is based on several assumptions and results from the interaction of three variables, ie, blood velocity, vessel diameter, and blood viscosity. In healthy subjects, both P and M are strongly and inversely related to IMT, age, SBP, and BMI. These findings confirm in vivo an important role for shear stress in intima-media thickening and can help explain, at least in part, the observed relationship between IMT and age, SBP, and BMI.
Because the described method is noninvasive and repeatable, it can be used to monitor wall shear stress variations over time in the same individual and can be applied easily to larger populations.
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Selected Abbreviations and Acronyms |
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Received April 16, 1996; revision received July 29, 1996; accepted August 8, 1996.
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 F. M.A. Box, J. van der Grond, A. J.M. de Craen, I. H. Palm-Meinders, R. J. van der Geest, J. W. Jukema, J. H.C. Reiber, M. A. van Buchem, G. J. Blauw, and for the PROSPER Study Group Pravastatin Decreases Wall Shear Stress and Blood Velocity in the Internal Carotid Artery Without Affecting Flow Volume: Results From the PROSPER MRI Study Stroke, April 1, 2007; 38(4): 1374 - 1376. [Abstract] [Full Text] [PDF]
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L. Kadem and D. Garcia Are We Using the Right Fluid Mechanics Principles? Ann. Thorac. Surg., January 1, 2007; 83(1): 354 - 354. [Full Text] [PDF]
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K. Yoshida, S. Tobe, and M. Yamaguchi Reply Ann. Thorac. Surg., January 1, 2007; 83(1): 354 - 355. [Full Text] [PDF]
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E. Touze, C. P. Warlow, and P. M. Rothwell Risk of Coronary and Other Nonstroke Vascular Death in Relation to the Presence and Extent of Atherosclerotic Disease at the Carotid Bifurcation Stroke, December 1, 2006; 37(12): 2904 - 2909. [Abstract] [Full Text] [PDF]
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 V. Tuka, M. Slavikova, J. Svobodova, and J. Malik Diabetes and distal access location are associated with higher wall shear rate in feeding artery of PTFE grafts Nephrol. Dial. Transplant., October 1, 2006; 21(10): 2821 - 2824. [Abstract] [Full Text] [PDF]
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 R. Elosua, J. M. Ordovas, L. A. Cupples, C.-Q. Lai, S. Demissie, C. S. Fox, J. F. Polak, P. A. Wolf, R. B. D'Agostino Sr., and C. J. O'Donnell Variants at the APOA5 locus, association with carotid atherosclerosis, and modification by obesity: the Framingham Study J. Lipid Res., May 1, 2006; 47(5): 990 - 996. [Abstract] [Full Text] [PDF]
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 T. Nagaoka and A. Yoshida Noninvasive evaluation of wall shear stress on retinal microcirculation in humans. Invest. Ophthalmol. Vis. Sci., March 1, 2006; 47(3): 1113 - 1119. [Abstract] [Full Text] [PDF]
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K. Yoshida, S. Tobe, M. Kawata, and M. Yamaguchi Acquired and Reversible von Willebrand Disease With High Shear Stress Aortic Valve Stenosis Ann. Thorac. Surg., February 1, 2006; 81(2): 490 - 494. [Abstract] [Full Text] [PDF]
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 K. E Pyke and M. E Tschakovsky The relationship between shear stress and flow-mediated dilatation: implications for the assessment of endothelial function J. Physiol., October 15, 2005; 568(2): 357 - 369. [Abstract] [Full Text] [PDF]
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 A. Chandiwal, V. Balasubramanian, Z. K. Baldwin, M. S. Conte, and L. B. Schwartz Gene Therapy for the Extension of Vein Graft Patency: A Review Vascular and Endovascular Surgery, January 1, 2005; 39(1): 1 - 14. [Abstract] [PDF]
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R. Elosua, J. M. Ordovas, L. A. Cupples, C. S. Fox, J. F. Polak, P. A. Wolf, R. A. D'Agostino Sr., and C. J. O'Donnell Association of APOE genotype with carotid atherosclerosis in men and women: the Framingham Heart Study J. Lipid Res., October 1, 2004; 45(10): 1868 - 1875. [Abstract] [Full Text] [PDF]
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C. Irace, C. Cortese, E. Fiaschi, C. Carallo, E. Farinaro, and A. Gnasso Wall Shear Stress Is Associated With Intima-Media Thickness and Carotid Atherosclerosis in Subjects at Low Coronary Heart Disease Risk Stroke, February 1, 2004; 35(2): 464 - 468. [Abstract] [Full Text] [PDF]
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S. Q. Liu, C. Tieche, D. Tang, and P. Alkema Pattern formation of vascular smooth muscle cells subject to nonuniform fluid shear stress: role of PDGF-{beta} receptor and Src Am J Physiol Heart Circ Physiol, August 7, 2003; 285(3): H1081 - H1090. [Abstract] [Full Text] [PDF]
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 R. Ceravolo, R. Maio, A. Pujia, A. Sciacqua, G. Ventura, M. C. Costa, G. Sesti, and F. Perticone Pulse pressure and endothelial dysfunction in never-treated hypertensive patients J. Am. Coll. Cardiol., May 21, 2003; 41(10): 1753 - 1758. [Abstract] [Full Text] [PDF]
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R. Dammers, F. Stifft, J. H. M. Tordoir, J. M. M. Hameleers, A. P. G. Hoeks, and P. J. E. H. M. Kitslaar Shear stress depends on vascular territory: comparison between common carotid and brachial artery J Appl Physiol, February 1, 2003; 94(2): 485 - 489. [Abstract] [Full Text] [PDF]
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C. S. Fox, J. F. Polak, I. Chazaro, A. Cupples, P. A. Wolf, R. A. D'Agostino, and C. J. O'Donnell Genetic and Environmental Contributions to Atherosclerosis Phenotypes in Men and Women: Heritability of Carotid Intima-Media Thickness in the Framingham Heart Study Stroke, February 1, 2003; 34(2): 397 - 401. [Abstract] [Full Text] [PDF]
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T. Drueke, V. Witko-Sarsat, Z. Massy, B. Descamps-Latscha, A. P. Guerin, S. J. Marchais, V. Gausson, and G. M. London Iron Therapy, Advanced Oxidation Protein Products, and Carotid Artery Intima-Media Thickness in End-Stage Renal Disease Circulation, October 22, 2002; 106(17): 2212 - 2217. [Abstract] [Full Text] [PDF]
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C. Irace, A. Gnasso, F. Cirillo, G. Leonardo, M. Ciamei, A. Crivaro, A. Renzulli, and M. Cotrufo Arterial Remodeling of the Common Carotid Artery After Aortic Valve Replacement in Patients With Aortic Stenosis Stroke, October 1, 2002; 33(10): 2446 - 2450. [Abstract] [Full Text] [PDF]
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C. R. L. Boot, Jan. T. Groothuis, H. van Langen, and M. T. E. Hopman Shear stress levels in paralyzed legs of spinal cord-injured individuals with and without nerve degeneration J Appl Physiol, June 1, 2002; 92(6): 2335 - 2340. [Abstract] [Full Text] [PDF]
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 A. Scuteri, C.-H. Chen, F. C.P. Yin, T. Chih-Tai, H. A. Spurgeon, and E. G. Lakatta Functional Correlates of Central Arterial Geometric Phenotypes Hypertension, December 1, 2001; 38(6): 1471 - 1475. [Abstract] [Full Text] [PDF]
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 J.J Piek, E Boersma, M Voskuil, C di Mario, E Schroeder, C Vrints, P Probst, B de Bruyne, C Hanet, E Fleck, et al. The immediate and long-term effect of optimal balloon angioplasty on the absolute coronary blood flow velocity reserve. A subanalysis of the DEBATE study Eur. Heart J., September 2, 2001; 22(18): 1725 - 1732. [Abstract] [PDF]
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A. Schmidt-Trucksass, A. Schmid, C. Brunner, N. Scherer, G. Zach, J. Keul, and M. Huonker Arterial properties of the carotid and femoral artery in endurance-trained and paraplegic subjects J Appl Physiol, November 1, 2000; 89(5): 1956 - 1963. [Abstract] [Full Text] [PDF]
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Y. Jiang, K. Kohara, and K. Hiwada Association Between Risk Factors for Atherosclerosis and Mechanical Forces in Carotid Artery Stroke, October 1, 2000; 31(10): 2319 - 2324. [Abstract] [Full Text] [PDF]
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A. Gnasso, C. Motti, C. Irace, C. Carallo, L. Liberatoscioli, S. Bernardini, R. Massoud, P. L. Mattioli, G. Federici, and C. Cortese Genetic Variation in Human Stromelysin Gene Promoter and Common Carotid Geometry in Healthy Male Subjects Arterioscler. Thromb. Vasc. Biol., June 1, 2000; 20(6): 1600 - 1605. [Abstract] [Full Text] [PDF]
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M. Zureik, P. Ducimetiere, P.-J. Touboul, D. Courbon, C. Bonithon-Kopp, C. Berr, and C. Magne Common Carotid Intima-Media Thickness Predicts Occurrence of Carotid Atherosclerotic Plaques : Longitudinal Results From the Aging Vascular Study (EVA) Study Arterioscler. Thromb. Vasc. Biol., June 1, 2000; 20(6): 1622 - 1629. [Abstract] [Full Text] [PDF]
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 A. M. Shaaban and A. J. Duerinckx Wall Shear Stress and Early Atherosclerosis: A Review Am. J. Roentgenol., June 1, 2000; 174(6): 1657 - 1665. [Full Text]
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 A. M. Malek, S. L. Alper, and S. Izumo Hemodynamic Shear Stress and Its Role in Atherosclerosis JAMA, December 1, 1999; 282(21): 2035 - 2042. [Abstract] [Full Text] [PDF]
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L. Kornet, A. P. G. Hoeks, J. Lambregts, and R. S. Reneman In the Femoral Artery Bifurcation, Differences in Mean Wall Shear Stress Within Subjects Are Associated With Different Intima-Media Thicknesses Arterioscler. Thromb. Vasc. Biol., December 1, 1999; 19(12): 2933 - 2939. [Abstract] [Full Text] [PDF]
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C. Carallo, C. Irace, A. Pujia, M. S. De Franceschi, A. Crescenzo, C. Motti, C. Cortese, P. L. Mattioli, and A. Gnasso Evaluation of Common Carotid Hemodynamic Forces : Relations With Wall Thickening Hypertension, August 1, 1999; 34(2): 217 - 221. [Abstract] [Full Text] [PDF]
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P. Pauletto, P. Palatini, S. Da Ros, V. Pagliara, N. Santipolo, S. Baccillieri, E. Casiglia, P. Mormino, and A. C. Pessina Factors Underlying the Increase in Carotid Intima-Media Thickness in Borderline Hypertensives Arterioscler. Thromb. Vasc. Biol., May 1, 1999; 19(5): 1231 - 1237. [Abstract] [Full Text] [PDF]
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A. Schmidt-Trucksass, D. Grathwohl, A. Schmid, R. Boragk, C. Upmeier, J. Keul, and M. Huonker Structural, Functional, and Hemodynamic Changes of the Common Carotid Artery With Age in Male Subjects Arterioscler. Thromb. Vasc. Biol., April 1, 1999; 19(4): 1091 - 1097. [Abstract] [Full Text] [PDF]
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L. Kornet, J. Lambregts, A. P. G. Hoeks, and R. S. Reneman Differences in Near-Wall Shear Rate in the Carotid Artery Within Subjects Are Associated With Different Intima-Media Thicknesses Arterioscler. Thromb. Vasc. Biol., December 1, 1998; 18(12): 1877 - 1884. [Abstract] [Full Text] [PDF]
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 S.K. Samijo, J.M. Willigers, R. Barkhuysen, P.J.E.H.M. Kitslaar, R.S. Reneman, P.J. Brands, and A.P.G. Hoeks Wall shear stress in the human common carotid artery as function of age and gender Cardiovasc Res, August 1, 1998; 39(2): 515 - 522. [Abstract] [Full Text] [PDF]
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S. Oyre, S. Ringgaard, S. Kozerke, W. P. Paaske, M. Erlandsen, P. Boesiger, and E. M. Pedersen Accurate noninvasive quantitation of blood flow, cross-sectional lumen vessel area and wall shear stress by three-dimensional paraboloid modeling of magnetic resonance imaging velocity data J. Am. Coll. Cardiol., July 1, 1998; 32(1): 128 - 134. [Abstract] [Full Text] [PDF]
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