Arterial Stiffness Aging Arteriosclerosis and Atherosclerosis

As described earlier, age is the major determinant of increased arterial stiffness. The CV risk factors mentioned earlier contribute greatly to arterial wall stiffening, even independently of MAP level. However, the most important connection of increased arterial stiffness is atherosclerosis.

Aging, Loss of Elastin and Fatigue [2]

Central artery elasticity is critically dependent on normal content and function of the matrix protein elastin, which with a half-life of 40 years, is one of the most stable proteins in the body. Despite this stability, fatigue of elastin fibers and lamellae can occur by the sixth decade of life from the accumulated cyclic stress of more than 2 billion aorta expansions during ventricular contraction. Long-standing cyclic stress in the media of elastic-containing arteries produces fatigue and eventual fracturing of elastin along with structural changes of the ECM that include proliferation of collagen and deposition of calcium [2]. Humoral factors, cytokines, and oxidative metabolites may also play a role. This degenerative process, classically termed arteriosclerosis, is the pathologic process that results in increased central arterial stiffness. In untreated, and even long-term treated hypertensive subjects, an acceleration of the rate of development of conduit artery stiffness is observed. This process in turn may perpetuate a vicious cycle of accelerated hypertension and further increase in aortic rigidity, particularly through the associated development of vascular calcifications.

Atherosclerosis versus Arteriosclerosis

Disease processes such as diabetes, chronic renal failure and generalized atherosclerosis can accelerate aging of the aorta and central arteries with earlier development of arterial stiffness. Arteriosclerosis is often confused with atherosclerosis, but these two disease states are independent, but frequently in overlapping, conditions (table 2) [1-4]. Atherosclerosis is primarily focal, starts in the intima, and tends to be occlusive. Arteriosclerosis tends to be diffuse, starts in the media, and frequently results in a dilated and tortuous aorta. Moreover, the pathophysiology of atherosclerosis is that of inflammatory disease with lipid-containing plaques and predominantly downstream ischemic disease, which results in increased thoracic aortic stiffness and elevated left ventricle workload.

Finally, the purpose of this book is not only to give some insight into the relationship between arterial stiffness and atherosclerosis, but also to establish the possible interactions with age and high BP, and therefore to define new therapeutic perspectives for CV prevention.

Table 2. Differential features of atherosclerosis and arteriosclerosis [2]





Focal Intima


Media, adventitia Dilatory fElastin, dcollagen, Ca2+ Large artery stiffness dLeft ventricular workload

Location Geometry Pathology Physiology

Occlusive Plaque

Inflammation Ischemia

Hemodynamics f = Decrease; Î = increase.


This study was performed with the help of INSERM and GPH- CV (groupe de Pharmacologie et d'Hémodynamique Cardiovasculaire), Paris. We thank Dr. Anne Safar for helpful and stimulating discussions.


1 Caro CG, Pedley TJ, Schroter RC, Seed WA: The Mechanics of the Circulation. New York, Oxford University Press, 1978, pp 243-349.

2 Nichols WW, O'Rourke M: McDonald's Blood Flow in Arteries. Theoretical, Experimental and Clinical Principles, ed 4. London, Arnold, 1998, pp 54-401.

3 Safar ME, Levy BI, Struijker-Boudier H: Current perspectives on arterial stiffness and pulse pressure in hypertension and cardiovascular diseases. Circulation 2003; 107:2864-2869.

4 Glagov S: Hemodynamic risk factors: mechanical stress, mural architecture, medial nutrition and vulnerability of arteries to atherosclerosis; in Wissler RW, Geer JC (eds): The Pathogenesis of Atherosclerosis. Baltimore, Williams & Wilkins, 1972, pp 164-199.

5 Li DY, Brooke B, Davis EC, Mecham RP, Sorensen LK, Boak BB, Eichwald E, Keating MT: Elastin is an essential determinant of arterial morphogenesis. Nature 1998;393:276-280.

6 Fleischmayer R, Perlish JS, Burgeson RE, Shaikh-Bahai F: Type I and type III collagen interactions during fibrillogenesis. Ann NY Acad Sci 1990;580:161-175.

7 Safar ME, Thuilliez C, Richard V, Benetos A: Pressure-independent contribution of sodium to large artery structure and function in hypertension. Cardiovasc Res 2000;46:269-276.

8 Ko YS, Coppen SR, Dupont E, Rothery S, Severs NJ: Regional differentiation of desmin, con-nexin43, and connexin45 expression patterns in rat aortic smooth muscle. Arterioscler Thromb Vasc Biol 2001;21:355-364.

9 Lacolley P, Challande P, Boumaza S, Cohuet G, Laurent S, Boutouyrie P, Grimaud JA, Paulin D, Lamaziere JM, Li Z: Mechanical properties and structure of carotid arteries in mice lacking des-min. Cardiovasc Res 2001;51:178-187.

10 Hamet P: Proliferation and apoptosis of vascular smooth muscle in hypertension. Curr Opin Nephrol Hypertens 1995;4:1-7.

11 Davies PF: Flow-mediated endothelial mechanotransduction. Physiol Rev 1995;75:519-560.

12 Levy BI, Ambrosio G, Pries AR, Struijker-Boudier HAJ: Microcirculation in hypertension. A new target for treatment? Circulation 2001;104:735-740.

13 Cohn JN, Finkelstein S, McVeigh G: Non-invasive pulse wave analysis for the early detection of vascular disease. Hypertension 1995;26:503-508.

14 Langille BL: Remodeling of developing and mature arteries: endothelium, smooth muscles, and matrix. J Cardiovasc Pharmacol 1993;21(suppl I):S11-S17.

15 Kamiya A, Togawa T: Adaptative regulation of wall shear stress to flow change in the carotid artery. Am J Physiol 1980;239:H14-H21.

16 Gibbons GH, Dzau VJ: The emerging concept of vascular remodeling. N Eng J Med 1994;330: 1431-1438.

17 Williams B: Mechanical influences on vascular smooth muscle cell function. J Hypertens 1998; 16:1921-1929.

18 Folkow B: Physiological aspects of primary hypertension. Physiol Rev 1982;62:347-504.

19 Pohl U, Holtz J, Busse R, Bassenge E: Crucial role of endothelium in the vasodilator response to the increased flow in vivo. Hypertension 1986;8:37-44.

20 Girerd X, London G, Boutouyrie P, Mourad JJ, Safar M, Laurent S: Remodeling of radial artery in response to a chronic increase in shear stress. Hypertension 1996;27:799-803.

21 Safar ME, Blacher J, Mourad JJ, London GM: Stiffness of carotid artery wall material and blood pressure in humans. Stroke 2000;31:782-790.

22 Balkenstein EJ, Staessen JA, Wang JG, van der Heijden-Spek JJ, van Bortel LM, Barlassina C, Bi-anchi G, Brand E, Herrmann SM, Struijker Boudier HA: Carotid and femoral artery stiffness in relation to three candidate genes in a white population. Hypertension 2001;38:1190-1197.

23 Safar ME, Lajemi M, Rudnichi A, Asmar R, Benetos A: Angiotensin-converting enzyme D/I gene polymorphism and age-related changes in pulse pressure in subjects with hypertension. Arterio-scler Thromb Vasc Biol 2004;24:782-786.

Prof. Michel Safar

Centre de Diagnostic Hôtel-Dieu, 1, place du Parvis Notre-Dame FR-75181 Paris Cedex 04 (France)

Tel. +33 1 4234 8025, Fax +33 1 4234 8632, E-Mail [email protected]

Blood Pressure Health

Blood Pressure Health

Your heart pumps blood throughout your body using a network of tubing called arteries and capillaries which return the blood back to your heart via your veins. Blood pressure is the force of the blood pushing against the walls of your arteries as your heart beats.Learn more...

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