Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review Article
  • Published:

Arterial aging—hemodynamic changes and therapeutic options

Nature Reviews Cardiology volume 7, pages 442–449 (2010)Cite this article

Subjects

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

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Changes in arterial diameter in patients with arteriosclerosis or atherosclerosis.
Figure 2: Relationship between age and blood pressure from the DESIR study.16
Figure 3: Schematic representation of blood pressure in different topographies of the arterial tree.
Figure 4: Pressure wave traveling from the heart to the periphery.
Figure 5: Representative BP curves for young and old individuals with the same MAP.
Figure 6: Meta-analysis of the effects of antihypertensive therapy in patients >80 years.56
Figure 7: Central and brachial blood pressure variation in the REASON study before and after 1 year of treatment.

Similar content being viewed by others

References

  1. 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).

    Google Scholar 

  2. Nichols, W. W. & O'Rourke, M. F. McDonald's Blood Flow in Arteries: Theoretical, Experimental and Clinical Principles, 5th edn (Hodder Arnold, London, 2005).

    Google Scholar 

  3. Safar, M. E. & O'Rourke, M. F. (eds) Handbook of Hypertension: Arterial Stiffness in Hypertension Vol. 23 (Elsevier, Edinburgh, 2006).

    Google Scholar 

  4. Black, H. R. The paradigm has shifted, to systolic blood pressure. Hypertension 34, 386–387 (1999).

    Article  CAS  Google Scholar 

  5. Langille, B. L. Remodeling of developing and mature arteries: endothelium, smooth muscle, and matrix. J. Cardiovasc. Pharmacol. 21 (Suppl. 1), S11–S17 (1993).

    Article  Google Scholar 

  6. 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).

    Article  CAS  Google Scholar 

  7. Gibbons, G. H. & Dzau, V. J. The emerging concept of vascular remodeling. N. Engl. J. Med. 330, 1431–1438 (1994).

    Article  CAS  Google Scholar 

  8. 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).

    Article  CAS  Google Scholar 

  9. 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).

    Article  CAS  Google Scholar 

  10. Schiffrin, E. L. Remodeling of resistance arteries in essential hypertension and effects of antihypertensive treatment. Am. J. Hypertens. 17, 1192–1200 (2004).

    Article  CAS  Google Scholar 

  11. 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).

    Article  CAS  Google Scholar 

  12. 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).

    Article  CAS  Google Scholar 

  13. Williams, B. Mechanical influences on vascular smooth muscle cell function. J. Hypertens. 16, 1921–1929 (1998).

    Article  CAS  Google Scholar 

  14. Agabiti-Rosei, E., Heagerty, A. M. & Rizzoni, D. Effects of antihypertensive treatment on small artery remodelling. J. Hypertens. 27, 1107–1114 (2009).

    Article  CAS  Google Scholar 

  15. Franklin, S. S. et al. Hemodynamic patterns of age-related changes in blood pressure. The Framingham Heart Study. Circulation 96, 308–315 (1997).

    Article  CAS  Google Scholar 

  16. 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).

    Article  CAS  Google Scholar 

  17. 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).

    Article  Google Scholar 

  18. Lieber, A. et al. Aortic wave reflection in women and men. Am. J. Physiol. Heart Circ. Physiol. doi:10.1152/ajpheart.00985.2009.

    Article  CAS  Google Scholar 

  19. 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).

    Article  CAS  Google Scholar 

  20. 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).

    Article  CAS  Google Scholar 

  21. 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).

    Article  CAS  Google Scholar 

  22. 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).

    Article  CAS  Google Scholar 

  23. 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).

    Article  CAS  Google Scholar 

  24. Westerhof, N., Stergiopulos, N. & Noble, M. I. M. Snapshots of Hemodynamics. An Aid for Clinical Research and Graduate Education (Springer, New York, 2005).

    Google Scholar 

  25. London, G. M. et al. Arterial wave reflections and survival in end-stage renal failure. Hypertension 38, 434–438 (2001).

    Article  CAS  Google Scholar 

  26. 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).

    Article  CAS  Google Scholar 

  27. 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).

    Article  CAS  Google Scholar 

  28. 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).

    Article  CAS  Google Scholar 

  29. 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).

    Article  CAS  Google Scholar 

  30. 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).

    Article  CAS  Google Scholar 

  31. Jankowski, P. et al. Pulsatile but not steady component of blood pressure predicts cardiovascular events in coronary patients. Hypertension 51, 848–855 (2008).

    Article  CAS  Google Scholar 

  32. Agabiti-Rosei, E. et al. Central blood pressure measurements and antihypertensive therapy: a consensus document. Hypertension 50, 154–160 (2007).

    Article  CAS  Google Scholar 

  33. Weber, T. et al. Arterial stiffness, wave reflections, and the risk of coronary artery disease. Circulation 109, 184–189 (2004).

    Article  Google Scholar 

  34. Safar, M. E. et al. Central pulse pressure and mortality in end-stage renal disease. Hypertension 39, 735–738 (2002).

    Article  CAS  Google Scholar 

  35. 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).

    Article  CAS  Google Scholar 

  36. 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).

    Article  CAS  Google Scholar 

  37. Ingber, D. Integrins as mechanochemical transducers. Curr. Opin. Cell Biol. 3, 841–848 (1991).

    Article  CAS  Google Scholar 

  38. 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).

    Article  CAS  Google Scholar 

  39. 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).

    Article  CAS  Google Scholar 

  40. Bézie, Y. et al. Fibronectin expression and aortic wall elastic modulus in spontaneously hypertensive rats. Arterioscler. Thromb. Vasc. Biol. 18, 1027–1034 (1998).

    Article  Google Scholar 

  41. 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).

    Article  CAS  Google Scholar 

  42. 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).

    Article  CAS  Google Scholar 

  43. Lacolley, P. et al. Increased carotid wall elastic modulus and fibronectin in aldosterone-salt-treated rats: effects of eplerenone. Circulation 106, 2848–2853 (2002).

    Article  CAS  Google Scholar 

  44. 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).

    Article  CAS  Google Scholar 

  45. 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).

    Article  CAS  Google Scholar 

  46. Safar, M. E. et al. Peripheral arterial disease and isolated systolic hypertension: the ATTEST study. J. Hum. Hypertens. 23, 182–187 (2009).

    Article  CAS  Google Scholar 

  47. 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).

    Article  CAS  Google Scholar 

  48. 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).

    Article  CAS  Google Scholar 

  49. Dhakam, Z. et al. A comparison of atenolol and nebivolol in isolated systolic hypertension. J. Hypertens. 26, 351–356 (2008).

    Article  CAS  Google Scholar 

  50. Guerin, A. P. et al. Impact of aortic stiffness attenuation on survival of patients in end-stage renal failure. Circulation 103, 987–992 (2001).

    Article  CAS  Google Scholar 

  51. Kengne, A. P. et al. Blood pressure variables and cardiovascular risk: new findings from ADVANCE. Hypertension 54, 399–404 (2009).

    Article  CAS  Google Scholar 

  52. 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).

    Article  CAS  Google Scholar 

  53. 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).

    Article  CAS  Google Scholar 

  54. Dengo, A. L. et al. Arterial destiffening with weight loss in overweight and obese middle-aged and older adults. Hypertension 55, 855–861 (2010).

    Article  CAS  Google Scholar 

  55. 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).

    Article  CAS  Google Scholar 

  56. 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).

    Article  CAS  Google Scholar 

  57. 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).

    Article  CAS  Google Scholar 

Download references

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

  1. Diagnosis Center, Hôpital Hôtel-Dieu, 1 Place du Parvis Notre-Dame, Paris Cedex 04, 75181, France

    Michel E. Safar

Authors
  1. Michel E. Safar
    View author publications

    You can also search for this author in PubMed Google Scholar

Ethics declarations

Competing interests

The author declares no competing financial interests.

Rights and permissions

Reprints 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

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1038/nrcardio.2010.96

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing