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  • Review Article
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Arterial stiffness as a risk factor for clinical hypertension

Key Points

  • In uncomplicated essential hypertension, cardiac output remains normal, whereas mean circulatory pressure is increased; vascular resistance is thus augmented, and the viscoelastic properties of the cardiovascular system are markedly impaired

  • Carotid–femoral arterial stiffness, wave reflections, and the ensuing structural vascular changes and endothelial dysfunction are fundamental aspects of the vessel damage observed in chronic hypertension

  • Pulse pressure (PP; the difference between systolic and diastolic blood-pressure (BP) levels) is influenced by arterial stiffness, which also negatively influences wave reflections, kidney function, and cardiovascular risk

  • The stiffness-induced increase in PP is an independent predictor of cardiovascular risk

  • Drug therapies should not only reduce elevated BP levels, but also target arterial stiffness, wave reflections, and PP

  • Effective drug strategies to reduce cardiovascular risk should take individual patient profiles into consideration, including age, sex, and ethnic factors

Abstract

In patients with uncomplicated essential hypertension, cardiac output remains within normal ranges and intravascular volume is normal or low, assuming the presence of a sufficient Windkessel effect and usual resistance and compliance calculations. However, mean circulatory pressure is elevated in these patients. In addition, vascular resistance is augmented, and most importantly, the viscoelasticity of the cardiovascular system is substantially impaired. Such considerations are essential to understanding the mechanisms behind carotid–femoral arterial stiffness, a major risk factor in individuals with hypertension. Arterial stiffness, measured from pulse wave velocity, is substantially increased in hypertension even independently of blood pressure levels. Structural vascular changes and endothelial dysfunction are consistently associated with vessel impairments in animal models of hypertension. Increased arterial stiffness has a major effect on pulse pressure (the difference between systolic and diastolic blood pressure), wave reflections, kidney function, and above all, cardiovascular risk. This increased cardiovascular risk is particularly deleterious in patients with hypertension and/or type 2 diabetes mellitus, who are at risk of both renal and cardiovascular events. In this Review, we discuss the importance of arterial stiffness in the diagnosis and management of hypertension and the need for new approaches for the treatment of hypertension in patients with or without diabetes and/or renal impairment.

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Figure 1: Schematic measurements of arterial stiffness and distensibility in hypertensive and normotensive settings.
Figure 2: Mean pulse wave velocity (PWV) values according to age.
Figure 3: Representation of the transition between pulsatile and steady pressure.

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References

  1. London, G. M. et al. Volume-dependent parameters in essential hypertension. Kidney Int. 11, 204–208 (1977).

    CAS  PubMed  Google Scholar 

  2. Caro, C. G., Pedley, T. J., Schroter R. C. & Seed W. A. The Mechanics of the Circulation 243–349 (Oxford Univ. Press, 1978).

    Google Scholar 

  3. Nichols, W. W., O'Rourke, M. McDonald's Blood Flow in Arteries. Theoretical, Experimental and Clinical Principals 4th edn 54–401 (Edward Arnold, 1998).

    Google Scholar 

  4. Safar, M. E., Levy, B. I. & Struijker-Boudier, H. Current perspectives on arterial stiffness and pulse pressure in hypertension and cardiovascular diseases. Circulation 107, 2864–2869 (2003).

    PubMed  Google Scholar 

  5. Weiss, Y. A. et al. Repeat hemodynamic determinations in borderline hypertension. Am. J. Med. 64, 382–387 (1978).

    CAS  PubMed  Google Scholar 

  6. Chau, N. P., Safar, M. E., London, G. M. & Weiss, Y. A. Essential hypertension: an approach to clinical data by the use of models. Hypertension 1, 86–97 (1979).

    CAS  PubMed  Google Scholar 

  7. Chau, N. P., Coleman, T. G., London, G. M. & Safar, M. E. Meaning of the cardiac output-blood volume relationship in essential hypertension. Am. J. Physiol. 243, R318–R328 (1982).

    CAS  PubMed  Google Scholar 

  8. 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).

    CAS  PubMed  Google Scholar 

  9. Lichtenstein, O., Safar, M. E., Mathieu, E., Poitevin, P. & Levy, B. I. Static and dynamic mechanical properties of the carotid artery from normotensive and hypertensive rats. Hypertension 32, 346–350 (1998).

    CAS  PubMed  Google Scholar 

  10. Safar, M., Plante, G. E. & London, G. M. in Vascular Compliance and Blood Volume in Essential Hypertension (eds Laragh, J. & Brenner, B.) 377–388 (Raven press, 1995).

    Google Scholar 

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

    CAS  PubMed  Google Scholar 

  12. London, G. M., Guerin, A. P., Pannier, B., Marchais, S. J. & Safar, M. E. Large artery structure and function in hypertension and end-stage renal disease. J. Hypertens. 16, 1931–1938 (1998).

    CAS  PubMed  Google Scholar 

  13. Safar, M. E. et al. Metabolic syndrome and age-related progression of aortic stiffness. J. Am. Coll. Cardiol. 47, 72–75 (2006).

    PubMed  Google Scholar 

  14. Schiffrin, E. L. Reactivity of small blood vessels in hypertension: relation with structural changes. State of the art lecture. Hypertension 19 (Suppl. 2), II1–II9 (1992).

    CAS  PubMed  Google Scholar 

  15. Dzau, V. J. & Safar, M. E. Large conduit arteries in hypertension: role of the vascular renin-angiotensin system. Circulation 77, 947–954 (1988).

    CAS  PubMed  Google Scholar 

  16. 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).

    CAS  PubMed  Google Scholar 

  17. Mancia, G. et al. 2013 ESH/ESC guidelines for the management of arterial hypertension. The task force for the management of arterial hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC). Eur. Heart. J. 34, 2159–2219 (2013).

    PubMed  Google Scholar 

  18. Nichols, W. W. & O'Rourke, M. F. McDonald's Blood Flow in Arteries. Theoretical, Experimental and Clinical Principals 5 th edn. 49–94; 193–233; 339–402; 435–502 (Hodder Arnold, 2005).

    Google Scholar 

  19. Protogerou, A. D. et al. Central blood pressures: do we need them in the management of cardiovascular disease? Is it a feasible therapeutic target? J. Hypertens. 25, 265–272 (2007).

    CAS  PubMed  Google Scholar 

  20. Blacher, J. et al. Pulse pressure not mean pressure determines cardiovascular risk in older hypertensive patients. Arch. Intern. Med. 160, 1085–1089 (2000).

    CAS  PubMed  Google Scholar 

  21. Moens, A. I. Die Pulskurve (EJ Brill, 1878).

    Google Scholar 

  22. Korteweg, D. J. Ueber die Fortpflanzungsgeschwindigkeit des Schalles in elastischen Röhren [German]. Ann. Phys. 241, 525–542 (1878).

    Google Scholar 

  23. Pannier, B., Guerin, A. P., Marchais, S. J., Safar, M. E. & London, G. M. Stiffness of capacitive and conduit arteries: prognostic significance for end-stage renal disease patients. Hypertension 45, 592–596 (2005).

    CAS  PubMed  Google Scholar 

  24. Safar, M. E., Peronneau, P. A., Levenson, J. A., Toto-Moukouo, J. A. & Simon, A. C. Pulsed Doppler: diameter, blood flow velocity and volumic flow of the brachial artery in sustained essential hypertension. Circulation 63, 393–400 (1981).

    CAS  PubMed  Google Scholar 

  25. Benetos, A., Laurent, S., Hoeks, A. P., Boutouyrie, P. H. & Safar, M. E. Arterial alterations with aging and high blood pressure. A noninvasive study of carotid and femoral arteries. Arterioscler. Thromb. 13, 90–97 (1993).

    CAS  PubMed  Google Scholar 

  26. Safar, M. E., Girerd, X. & Laurent, S. Structural changes of large conduit arteries in hypertension. J. Hypertens. 14, 545–555 (1996).

    CAS  PubMed  Google Scholar 

  27. Safar, M. E. & O'Rourke, M. E. Handbook of Hypertension: Arterial Stiffness in Hypertension Vol. 23, 3–6; 75–136; 459–501 (Elsevier, 2006).

    Google Scholar 

  28. Reference Values for Arterial Stiffness' Collaboration. Determinants of pulse wave velocity in healthy people and in the presence of cardiovascular risk factors: 'establishing normal and reference values'. Eur. Heart J. 31, 2338–2350 (2010).

  29. Regnault, V. et al. Sex difference in cardiovascular risk: role of pulse pressure amplification. J. Am. Coll. Cardiol. 59, 1771–1777 (2012).

    PubMed  PubMed Central  Google Scholar 

  30. Safar, M. E. & Lacolley, P. Disturbance of macro- and microcirculation: relations with pulse pressure and cardiac organ damage. Am. J. Physiol. Heart. Circ. Physiol. 293, H1–H7 (2007).

    CAS  PubMed  Google Scholar 

  31. Koller, A. Signaling pathways of mechanotransduction in arteriolar endothelium and smooth muscle cells in hypertension. Microcirculation 9, 277–294 (2002).

    CAS  PubMed  Google Scholar 

  32. Sehgel, N. L. et al. Augmented vascular smooth muscle cell stiffness and adhesion when hypertension is superimposed on aging. Hypertension 65, 370–377 (2015).

    CAS  PubMed  Google Scholar 

  33. Lacolley, P., Li, Z., Challande, P. & Regnault, V. SRF/myocardin: a novel molecular axis regulating vascular smooth muscle cell stiffening in hypertension. Cardiovasc. Res. 113, 120–122 (2017).

    CAS  PubMed  Google Scholar 

  34. Protogerou, A. et al. Longitudinal changes in mean and pulse pressure with all cause mortality: data from 71,629 normotensive untreated individuals. Am. J. Hypertens. http://dx.doi.org/10.1093/ajh/hpx110 (2017).

  35. 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).

    CAS  PubMed  Google Scholar 

  36. 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).

    CAS  PubMed  Google Scholar 

  37. 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).

    CAS  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  39. Millar, J. A., Lever, A. F. & Burke, V. Pulse pressure as a risk factor for cardiovascular events in the MRC mild hypertension trial. J. Hypertens. 17, 1065–1072 (1999).

    CAS  PubMed  Google Scholar 

  40. Safar, M. E. Systolic blood pressure, pulse pressure and arterial stiffness as cardiovascular risk factors. Curr. Opin. Nephrol. Hypertens. 10, 257–261 (2001).

    CAS  PubMed  Google Scholar 

  41. Benetos, A. et al. A decrease in diastolic blood pressure combined with an increase in systolic blood pressure is associated with a higher cardiovascular mortality in men. J. Am. Coll. Cardiol. 35, 673–680 (2000).

    CAS  PubMed  Google Scholar 

  42. Benetos, A. et al. Pulse pressure: a predictor of long-term cardiovascular mortality in a French male population. Hypertension 30, 1410–1415 (1997).

    CAS  PubMed  Google Scholar 

  43. Benetos, A., Rudnichi, A., Safar, M. & Guize, L. Pulse pressure and cardiovascular mortality in normotensive and hypertensive subjects. Hypertension 32, 560–564 (1998).

    CAS  PubMed  Google Scholar 

  44. Blacher, J. et al. Impact of aortic stiffness on survival in end-stage renal disease. Circulation 99, 2434–2439 (1999).

    CAS  PubMed  Google Scholar 

  45. Vlachopoulos, C., Aznaouridis, K. & Stefanadis, C. Prediction of cardiovascular events and all-cause mortality with arterial stiffness. A systematic review and meta-analysis. J. Am. Coll. Cardiol. 55, 1318–1327 (2010).

    PubMed  Google Scholar 

  46. Ben-Shlomo, Y. et al. Aortic pulse wave velocity improves cardiovascular event prediction: an individual participant meta-analysis of prospective observational data from 17,635 subjects. J. Am. Coll. Cardiol. 63, 636–646 (2014).

    PubMed  Google Scholar 

  47. 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).

    CAS  PubMed  Google Scholar 

  48. Laurent, S. et al. Aortic stiffness is an independent predictor of all-cause and cardiovascular mortality in hypertensive patients. Hypertension 37, 1236–1241 (2001).

    CAS  PubMed  Google Scholar 

  49. 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).

    CAS  PubMed  Google Scholar 

  50. Benetos, A. et al. Polypharmacy in the aging patient: management of hypertension in octogenarians. JAMA 314, 170–180 (2015).

    CAS  PubMed  Google Scholar 

  51. Kollias, A., Lagou, S., Zeniodi, M. E., Boubouchairopoulou, N. & Stergiou, G. S. Association of central versus brachial blood pressure with target-organ damage. Systematic review and meta-analysis. Hypertension 67, 183–190 (2016).

    CAS  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  54. Protogerou, A. D. et al. Diastolic blood pressure and mortality in the elderly with cardiovascular disease. Hypertension 50, 172–180 (2007).

    CAS  PubMed  Google Scholar 

  55. O'Rourke, M. F. & Safar, M. E. Relationship between aortic stiffening and microvascular disease in brain and kidney: cause and logic of therapy. Hypertension 46, 200–204 (2005).

    CAS  PubMed  Google Scholar 

  56. Safar, M. E., London, G. M. & Plante, G. E. Arterial stiffness and kidney function. Hypertension 43, 163–168 (2004).

    CAS  PubMed  Google Scholar 

  57. Bidani, A. K. & Griffin, K. A. Pathophysiology of hypertensive renal damage: implications for therapy. Hypertension 44, 595–601 (2004).

    CAS  PubMed  Google Scholar 

  58. Lariviere, R. et al. Endothelin type A receptor blockade reduces vascular calcification and inflammation in rats with chronic kidney disease. J. Hypertens. 35, 376–384 (2017).

    CAS  PubMed  Google Scholar 

  59. Das, S. K., McIntyre, H. D. & Mamun, A. A. An early life course association of pulse pressure with adulthood estimated glomerular filtration rate: evidence from a large community-based birth cohort study. J. Hypertens. 35, 392–400 (2017).

    CAS  PubMed  Google Scholar 

  60. Hashimoto, J. & Ito, S. Pulse pressure amplification, arterial stiffness, and peripheral wave reflection determine pulsatile flow waveform of the femoral artery. Hypertension 56, 926–933 (2010).

    CAS  PubMed  Google Scholar 

  61. Guerin, A., Pannier, B., Metivier, F., Marchais, S. J. & London, G. M. Assessment and significance of arterial stiffness in patients with chronic kidney disease. Curr. Opin. Nephrol. Hypertens. 17, 635–641 (2008).

    PubMed  Google Scholar 

  62. Temmar, M. et al. Intraaortic pulse pressure amplification in subjects at high coronary risk. Hypertension 55, 327–332 (2010).

    CAS  PubMed  Google Scholar 

  63. Boutouyrie, P. et al. Aortic stiffness is an independent predictor of primary coronary events in hypertensive patients: a longitudinal study. Hypertension 39, 10–15 (2002).

    CAS  PubMed  Google Scholar 

  64. Bahous, S. A. et al. Renal function decline in recipients and donors of kidney grafts: role of aortic stiffness. Am. J. Nephrol. 41, 57–65 (2015).

    CAS  PubMed  Google Scholar 

  65. Georgianos, P. I., Sarafidis, P. A. & Liakopoulos, V. Arterial stiffness: a novel risk factor for kidney injury progression? Am. J. Hypertens. 28, 958–965 (2015).

    CAS  PubMed  Google Scholar 

  66. Laurent, S. et al. Aortic stiffness is an independent predictor of fatal stroke in essential hypertension. Stroke 34, 1203–1206 (2003).

    PubMed  Google Scholar 

  67. Yannoutsos, A. et al. Hemodynamic parameters in hypertensive diabetic patients. J. Hypertens. 34, 1123–1131 (2016).

    CAS  PubMed  Google Scholar 

  68. 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).

    CAS  PubMed  Google Scholar 

  69. Albaladejo, P. et al. Angiotensin converting enzyme inhibition prevents the increase in aortic collagen in rats. Hypertension 23, 74–82 (1994).

    CAS  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  71. Safar, M. E., Thuilliez, C., Richard, V. & Benetos, A. Pressure-independent contribution of sodium to large artery structure and function in hypertension. Cardiovasc. Res. 46, 269–276 (2000).

    CAS  PubMed  Google Scholar 

  72. Safar, M. E., Simon, A. C., Levenson, J. A. & Cazor, J. L. Hemodynamic effects of diltiazem in hypertension. Circ. Res. 52, I169–173 (1983).

    CAS  PubMed  Google Scholar 

  73. Asmar, R. G. et al. Reversion of cardiac hypertrophy and reduced arterial compliance after converting enzyme inhibition in essential hypertension. Circulation 78, 941–950 (1988).

    CAS  PubMed  Google Scholar 

  74. London, G. M., Asmar, R. G., O'Rourke, M. F. Safar, M. E. & REASON Project Investigators. 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).

    CAS  PubMed  Google Scholar 

  75. Williams, B., et al. Anglo-scandinavian cardiac outcomes trial investigators. 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).

    CAS  PubMed  Google Scholar 

  76. Safar, M. E. et al. Hypertension and vascular dynamics in men and women with metabolic syndrome. J. Am. Coll. Cardiol. 61, 12–19 (2013).

    PubMed  Google Scholar 

  77. Franklin, S. S. et al. Does low diastolic blood pressure contribute to the risk of recurrent hypertensive cardiovascular disease events? The Framingham Heart Study. Hypertension. 65, 299–305 (2015).

    CAS  PubMed  Google Scholar 

  78. Ong, K. T. et al. Aortic stiffness is reduced beyond blood pressure lowering by short-term and long-term antihypertensive treatment: a meta-analysis of individual data in 294 patients. J. Hypertens. 29, 1034–1042 (2011).

    CAS  PubMed  Google Scholar 

  79. Mitchell, G. F. et al. Arterial stiffness and cardiovascular events: the Framingham Heart Study. Circulation 121, 505–511 (2010).

    PubMed  PubMed Central  Google Scholar 

  80. Mansour, A. S. et al. Aortic stiffness and cardiovascular risk in type 2 diabetes. J. Hypertens. 31, 1584–1592 (2013).

    CAS  PubMed  Google Scholar 

  81. Stewart, A. D., Jiang, B., Millasseau, S. C., Ritter, J. M. & Chowienczyk, P. J. Acute reduction of blood pressure by nitroglycerin does not normalize large artery stiffness in essential hypertension. Hypertension 48, 404–410 (2006).

    CAS  PubMed  Google Scholar 

  82. Edwards, N. C., Steeds, R. P., Stewart, P. M., Ferro, C. J. & Townend, J. N. Effect of spironolactone on left ventricular mass and aortic stiffness in early-stage chronic kidney disease: a randomized controlled trial. J. Am. Coll. Cardiol. 54, 505–512 (2009).

    CAS  PubMed  Google Scholar 

  83. Benetos, A., Lacolley, P. & Safar, M. E. Prevention of aortic fibrosis by spironolactone in spontaneously hypertensive rats. Arterioscler. Thromb. Vasc. Biol. 17, 1152–1156 (1997).

    CAS  PubMed  Google Scholar 

  84. Mitchell, G. F. et al. Omapatrilat reduces pulse pressure and proximal aortic stiffness in patients with systolic hypertension: results of the conduit hemodynamics of omapatrilat international research study. Circulation 105, 2955–2961 (2002).

    CAS  PubMed  Google Scholar 

  85. Wang, M. et al. Chronic matrix metalloproteinase inhibition retards age-associated arterial proinflammation and increase in blood pressure. Hypertension 60, 459–466 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  86. Ruilope, L. M. et al. Blood-pressure reduction with LCZ696, a novel dual-acting inhibitor of the angiotensin II receptor and neprilysin: a randomised, double-blind, placebo-controlled, active comparator study. Lancet 375, 1255–1266 (2010).

    CAS  PubMed  Google Scholar 

  87. Williams, B. et al. Rationale and study design of the prospective comparison of angiotensin receptor neprilysin inhibitor with angiotensin receptor blocker measuring arterial stiffness in the elderly (PARAMETER) study. BMJ Open. 4, e004254 (2014).

    PubMed  PubMed Central  Google Scholar 

  88. Belz, G. G. Elastic properties and Windkessel function of the human aorta. Cardiovasc. Drugs. Ther. 9, 73–83 (1995).

    CAS  PubMed  Google Scholar 

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Acknowledgements

This Review was written in collaboration with the GPH-CV (Groupe de Pharmacologie et d'Hémodynamique Cardiovasculaire), Paris, France. The author thanks M. Barbier for stimulating discussions and editorial assistance. I dedicate this manuscript to my wife, Anne Safar, and my children, Marie-Claude, Hélène, and Pierre.

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Safar, M. Arterial stiffness as a risk factor for clinical hypertension. Nat Rev Cardiol 15, 97–105 (2018). https://doi.org/10.1038/nrcardio.2017.155

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