Abstract
Arterial aging can be attributed to two different pathophysiological changes—increase in arterial stiffness and disturbed wave reflections. The capacity of the aorta to absorb the force exerted by the left ventricular ejection and dampen pulsatile flow becomes diminished with advancing age, owing to the progressive hardening of the arterial wall. These changes contribute to increase blood pressure, mainly systolic blood pressure and pulse pressure, which can trigger cardiovascular events. Understanding the pulsatile arterial hemodynamics that elevate cardiovascular risk has led to the use of pharmacological therapies, which prevent arterial stiffness and reduce wave reflections, and improve cardiovascular morbidity and mortality. Antifibrotic agents, such as those that block the renin–angiotensin–aldosterone pathway, are often given in association with diuretics, calcium-channel blockers, or both, but not with standard β-blockers. Consistent reductions in cardiovascular outcomes obtained using these agents can be predicted through noninvasive measurements of central systolic blood pressure and pulse pressure.
Key Points
-
Changes in the vasculature occur with advancing age, especially in the large arteries, which affect the function of the heart and other organs
-
Arterial stiffness and increased pulse wave velocity are important predictors of cardiovascular disease, particularly in the elderly
-
Systolic hypertension is the most common type of hypertension in the elderly, and occurs as a result of age-related structural and functional changes in the vasculature
-
Antifibrotic agents, mainly those that block the renin–angiotensin–aldosterone system, are the primary basis of treatment to prevent arterial stiffening and lower blood pressure
-
The use of diuretics, calcium-channel inhibitors, or both may also be required to reduce cardiovascular outcomes, but standard β-blockers should be avoided
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 12 print issues and online access
$209.00 per year
only $17.42 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Staessen, J. E., Li, Y., Thijs, L. & Wang, J. G. in Handbook of Hypertension: Arterial Stiffness in Hypertension Vol. 23 Ch. 29 (eds Safar, M. E. & O'Rourke, M. F.) 459–484 (Elsevier, Edinburgh, 2006).
Nichols, W. W. & O'Rourke, M. F. McDonald's Blood Flow in Arteries: Theoretical, Experimental and Clinical Principles, 5th edn (Hodder Arnold, London, 2005).
Safar, M. E. & O'Rourke, M. F. (eds) Handbook of Hypertension: Arterial Stiffness in Hypertension Vol. 23 (Elsevier, Edinburgh, 2006).
Black, H. R. The paradigm has shifted, to systolic blood pressure. Hypertension 34, 386–387 (1999).
Langille, B. L. Remodeling of developing and mature arteries: endothelium, smooth muscle, and matrix. J. Cardiovasc. Pharmacol. 21 (Suppl. 1), S11–S17 (1993).
Levy, B. I., Ambrosio, G., Pries, A. R. & Struijker-Boudier, H. A. Microcirculation in hypertension: a new target for treatment? Circulation 104, 735–740 (2001).
Gibbons, G. H. & Dzau, V. J. The emerging concept of vascular remodeling. N. Engl. J. Med. 330, 1431–1438 (1994).
Levy, B. I. et al. Effects of chronic inhibition of converting enzyme on mechanical and structural properties of arteries in rat renovascular hypertension. Circ. Res. 63, 227–239 (1988).
Levy, B. I., Benessiano, J., Poitevin, P. & Safar, M. E. Endothelium-dependent mechanical properties of the carotid artery in WKY and SHR. Role of angiotensin converting enzyme inhibition. Circ. Res. 66, 321–328 (1990).
Schiffrin, E. L. Remodeling of resistance arteries in essential hypertension and effects of antihypertensive treatment. Am. J. Hypertens. 17, 1192–1200 (2004).
London, G. M., Asmar, R. G., O'Rourke, M. F. & Safar, M. E. Mechanism(s) of selective systolic blood pressure reduction after a low-dose combination of perindopril/indapamide in hypertensive subjects: comparison with atenolol. J. Am. Coll. Cardiol. 43, 92–99 (2004).
Safar, M. E., Rizzoni, D., Blacher, J., Muiesan, M. L. & Agabiti-Rosei, E. Macro and microvasculature in hypertension: therapeutic aspects. J. Hum. Hypertens. 22, 590–595 (2008).
Williams, B. Mechanical influences on vascular smooth muscle cell function. J. Hypertens. 16, 1921–1929 (1998).
Agabiti-Rosei, E., Heagerty, A. M. & Rizzoni, D. Effects of antihypertensive treatment on small artery remodelling. J. Hypertens. 27, 1107–1114 (2009).
Franklin, S. S. et al. Hemodynamic patterns of age-related changes in blood pressure. The Framingham Heart Study. Circulation 96, 308–315 (1997).
Safar, M. E. et al. The Data from an Epidemiologic Study on the Insulin Resistance Syndrome Study: the change and the rate of change of the age-blood pressure relationship. J. Hypertens. 26, 1903–1911 (2008).
Baksi, A. J. et al. A meta-analysis of the mechanism of blood pressure change with aging. J. Am. Coll. Cardiol. 54, 2087–2092 (2009).
Lieber, A. et al. Aortic wave reflection in women and men. Am. J. Physiol. Heart Circ. Physiol. doi:10.1152/ajpheart.00985.2009.
Darne, B., Girerd, X., Safar, M., Cambien, F. & Guize, L. Pulsatile versus steady component of blood pressure: a cross-sectional analysis and a prospective analysis on cardiovascular mortality. Hypertension 13, 392–400 (1989).
Madhavan, S., Ooi, W. L., Cohen, H. & Alderman, M. H. Relation of pulse pressure and blood pressure reduction to the incidence of myocardial infarction. Hypertension 23, 395–401 (1994).
Blacher, J., Asmar, R., Djane, S., London, G. M. & Safar, M. E. Aortic pulse wave velocity as a marker of cardiovascular risk in hypertensive patients. Hypertension 33, 1111–1117 (1999).
Meaume, S., Benetos, A., Henry, O. F., Rudnichi, A. & Safar, M. E. Aortic pulse wave velocity predicts cardiovascular mortality in subjects >70 years of age. Arterioscler. Thromb. Vasc. Biol. 21, 2046–2050 (2001).
Avolio, A. P. et al. Role of pulse pressure amplification in arterial hypertension: experts' opinion and review of the data. Hypertension 54, 375–383 (2009).
Westerhof, N., Stergiopulos, N. & Noble, M. I. M. Snapshots of Hemodynamics. An Aid for Clinical Research and Graduate Education (Springer, New York, 2005).
London, G. M. et al. Arterial wave reflections and survival in end-stage renal failure. Hypertension 38, 434–438 (2001).
Westerbacka, J., Seppälä-Lindroos, A. & Yki-Järvinen, H. Resistance to acute insulin induced decreases in large artery stiffness accompanies the insulin resistance syndrome. J. Clin. Endocrinol. Metab. 86, 5262–5268 (2001).
Lacolley, P., Safar, M. E., Regnault, V. & Frohlich, E. D. Angiotensin II, mechanotransduction, and pulsatile arterial hemodynamics in hypertension. Am. J. Physiol. Heart Circ. Physiol. 297, H1567–H1575 (2009).
Hirai, T., Sasayama, S., Kawasaki, T. & Yagi, S. Stiffness of systemic arteries in patients with myocardial infarction. A noninvasive method to predict severity of coronary atherosclerosis. Circulation 80, 78–86 (1989).
Gatzka, C. D., Cameron, J. D., Kingwell, B. A. & Dart, A. M. Relation between coronary artery disease, aortic stiffness, and left ventricular structure in a population sample. Hypertension 32, 575–578 (1998).
Stefanadis, C., Wooley, C. F., Bush, C. A., Kolibash, A. J. & Boudoulas, H. Aortic distensibility abnormalities in coronary artery disease. Am. J. Cardiol. 59, 1300–1304 (1987).
Jankowski, P. et al. Pulsatile but not steady component of blood pressure predicts cardiovascular events in coronary patients. Hypertension 51, 848–855 (2008).
Agabiti-Rosei, E. et al. Central blood pressure measurements and antihypertensive therapy: a consensus document. Hypertension 50, 154–160 (2007).
Weber, T. et al. Arterial stiffness, wave reflections, and the risk of coronary artery disease. Circulation 109, 184–189 (2004).
Safar, M. E. et al. Central pulse pressure and mortality in end-stage renal disease. Hypertension 39, 735–738 (2002).
Roman, M. J. et al. Central pressure more strongly relates to vascular disease and outcome than does brachial pressure: the Strong Heart Study. Hypertension 50, 197–203 (2007).
Van Bortel, L. M., Struijker-Boudier, H. A. & Safar, M. E. Pulse pressure, arterial stiffness, and drug treatment of hypertension. Hypertension 38, 914–921 (2001).
Ingber, D. Integrins as mechanochemical transducers. Curr. Opin. Cell Biol. 3, 841–848 (1991).
Wilson, E., Sudhir, K. & Ives, H. E. Mechanical strain of rat vascular smooth muscle cells is sensed by specific extracellular matrix/integrin interactions. J. Clin. Invest. 96, 2364–2372 (1995).
Louis, H. et al. Role of alpha1beta1-integrin in arterial stiffness and angiotensin-induced arterial wall hypertrophy in mice. Am. J. Physiol. Heart Circ. Physiol. 293, H2597–H2604 (2007).
Bézie, Y. et al. Fibronectin expression and aortic wall elastic modulus in spontaneously hypertensive rats. Arterioscler. Thromb. Vasc. Biol. 18, 1027–1034 (1998).
Kakou, A. et al. Selective reduction of central pulse pressure under angiotensin blockage in SHR: role of the fibronectin-alpha5beta1 integrin complex. Am. J. Hypertens. 22, 711–717 (2009).
Labat, C. et al. Effects of valsartan on mechanical properties of the carotid artery in spontaneously hypertensive rats under high-salt diet. Hypertension 38, 439–443 (2001).
Lacolley, P. et al. Increased carotid wall elastic modulus and fibronectin in aldosterone-salt-treated rats: effects of eplerenone. Circulation 106, 2848–2853 (2002).
Bezie, Y., Lacolley, P., Laurent, S. & Gabella, G. Connection of smooth muscle cells to elastic lamellae in aorta of spontaneously hypertensive rats. Hypertension 32, 166–169 (1998).
Koffi, I. et al. Prevention of arterial structural alterations with verapamil and trandolapril and consequences for mechanical properties in spontaneously hypertensive rats. Eur. J. Pharmacol. 361, 51–60 (1998).
Safar, M. E. et al. Peripheral arterial disease and isolated systolic hypertension: the ATTEST study. J. Hum. Hypertens. 23, 182–187 (2009).
de Luca, N., Asmar, R. G., London, G. M., O'Rourke, M. F. & Safar, M. E. Selective reduction of cardiac mass and central blood pressure on low-dose combination perindopril/indapamide in hypertensive subjects. J. Hypertens. 22, 1623–1630 (2004).
Protogerou, A., Blacher, J., Stergiou, G. S., Achimastos, A. & Safar, M. E. Blood pressure response under chronic antihypertensive drug therapy: the role of aortic stiffness in the REASON (Preterax in Regression of Arterial Stiffness in a Controlled Double-Blind) study. J. Am. Coll. Cardiol. 53, 445–451 (2009).
Dhakam, Z. et al. A comparison of atenolol and nebivolol in isolated systolic hypertension. J. Hypertens. 26, 351–356 (2008).
Guerin, A. P. et al. Impact of aortic stiffness attenuation on survival of patients in end-stage renal failure. Circulation 103, 987–992 (2001).
Kengne, A. P. et al. Blood pressure variables and cardiovascular risk: new findings from ADVANCE. Hypertension 54, 399–404 (2009).
Williams, B. et al. Differential impact of blood pressure-lowering drugs on central aortic pressure and clinical outcomes: principal results of the Conduit Artery Function Evaluation (CAFE) study. Circulation 113, 1213–1225 (2006).
Matsui, Y. et al. Differential effects between a calcium channel blocker and a diuretic when used in combination with angiotensin II receptor blocker on central aortic pressure in hypertensive patients. Hypertension 54, 716–723 (2009).
Dengo, A. L. et al. Arterial destiffening with weight loss in overweight and obese middle-aged and older adults. Hypertension 55, 855–861 (2010).
Ferrario, C. M., Trask, A. J. & Jessup, J. A. Advances in biochemical and functional roles of angiotensin-converting enzyme 2 and angiotensin-(1–7) in regulation of cardiovascular function. Am. J. Physiol. Heart Circ. Physiol. 289, H2281–H2290 (2005).
Gueyffier, F. et al. Antihypertensive drugs in very old people: a subgroup meta-analysis of randomised controlled trials. INDANA Group. Lancet 353, 793–796 (1999).
Asmar, R. G., London, G. M., O'Rourke, M. E. & Safar, M. E. Improvement in blood pressure, arterial stiffness and wave reflections with a very-low-dose perindopril/indapamide combination in hypertensive patient: a comparison with atenolol. Hypertension 38, 922–926 (2001).
Acknowledgements
This work was performed with the help of INSERM (Institut National de la Santé et de la Recherche Médicale) and GPH-CV (Groupe de Pharmacologie et d'Hémodynamique Cardiovasculaire). The author thanks Dr. Anne Safar for helpful and stimulating discussions.
Charles P. Vega, University of California, Irvine, CA, is the author of and is solely responsible for the content of the learning objectives, questions and answers of the MedscapeCME-accredited continuing medical education activity associated with this article.
Author information
Authors and Affiliations
Ethics declarations
Competing interests
The author declares no competing financial interests.
Rights and permissions
About this article
Cite this article
Safar, M. Arterial aging—hemodynamic changes and therapeutic options. Nat Rev Cardiol 7, 442–449 (2010). https://doi.org/10.1038/nrcardio.2010.96
Issue Date:
DOI: https://doi.org/10.1038/nrcardio.2010.96
This article is cited by
-
Correlation between TyG index and coronary atherosclerosis assessed by CCTA in elderly male patients: a cross-sectional study
Diabetology & Metabolic Syndrome (2023)
-
Hyperlipidemia and hypertension have synergistic interaction on ischemic stroke: insights from a general population survey in China
BMC Cardiovascular Disorders (2022)
-
Microskeletal stiffness promotes aortic aneurysm by sustaining pathological vascular smooth muscle cell mechanosensation via Piezo1
Nature Communications (2022)
-
Small-Vessel Vasculopathy Due to Aberrant Autophagy in LAMP-2 Deficiency
Scientific Reports (2018)
-
Quantification of aortic stiffness in stroke patients using 4D flow MRI in comparison with transesophageal echocardiography
The International Journal of Cardiovascular Imaging (2018)