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Decreasing Arterial Stiffness and/or Wave Reflections Independently of Mean Arterial Pressure: Effect of Antihypertensive Drugs (Part 1)

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Blood Pressure and Arterial Wall Mechanics in Cardiovascular Diseases

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Abstract

Change in arterial stiffness with drugs is a major end point in clinical trials, although evidence for arterial stiffness as a therapeutic target still needs to be confirmed. Drugs which affect arterial stiffness include antihypertensive drugs, mostly blockers of the renin–angiotensin–aldosterone system. Other drugs will be addressed in Chap. 40. Whether the reduction in arterial stiffness after antihypertensive treatment is only due to the blood pressure (BP) lowering which unloads the stiff components of the arterial wall such as collagen, or additional BP-independent effects are involved, has been largely debated. Currently, an increasing body of evidence, including theoretical aspects of arterial mechanics, long-term observational studies in humans and recent meta-analyses of double-blind, randomized, controlled trials, suggests that only part of aortic stiffness could be reduced through the normalization of BP by pharmacological treatment, and further reduction of aortic stiffness would require arterial structural changes, including reduction in collagen density and rearrangement of the wall materials. Mechanistic pharmacological studies are required to demonstrate that novel pharmacological classes have true “de-stiffening” properties.

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References

  1. 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. 2010;55:1318–27.

    Article  PubMed  Google Scholar 

  2. Ben-Shlomo Y, Spears M, Boustred C, May M, Anderson SG, Benjamin EJ, Boutouyrie P, Cameron J, Chen CH, Cruickshank JK, Hwang SJ, Lakatta EG, Laurent S, Maldonado J, Mitchell GF, Najjar SS, Newman AB, Ohishi M, Pannier B, Pereira T, Vasan RS, Shokawa T, Sutton-Tyrell K, Verbeke F, Wang KL, Webb DJ, Hansen TW, Zoungas S, McEniery CM, Cockcroft JR, Wilkinson IB. 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. 2014;63(7):636–46.

    Article  PubMed  Google Scholar 

  3. Boutouyrie P, Lacolley P, Briet M, Regnault V, Stanton A, Laurent S, Mahmud A. Pharmacological modulation of arterial stiffness. Drugs. 2011;71:1689–701.

    Article  CAS  PubMed  Google Scholar 

  4. Protogerou AD, Papaioannou TG, Lekakis JP, Blacher J, Safar ME. The effect of antihypertensive drugs on central blood pressure beyond peripheral blood pressure. Part i: (patho)-physiology, rationale and perspective on pulse pressure amplification. Curr Pharm Des. 2009;15:267–71.

    Article  CAS  PubMed  Google Scholar 

  5. Protogerou AD, Stergiou GS, Vlachopoulos C, Blacher J, Achimastos A. The effect of antihypertensive drugs on central blood pressure beyond peripheral blood pressure. Part ii: Evidence for specific class-effects of antihypertensive drugs on pressure amplification. Curr Pharm Des. 2009;15:272–89.

    Article  CAS  PubMed  Google Scholar 

  6. Galmiche G, Labat C, Mericskay M, Aissa KA, Blanc J, Retailleau K, Bourhim M, Coletti D, Loufrani L, Gao-Li J, Feil R, Challande P, Henrion D, Decaux JF, Regnault V, Lacolley P, Li Z. Inactivation of serum response factor contributes to decrease vascular muscular tone and arterial stiffness in mice. Circ Res. 2013;112:1035–45.

    Article  CAS  PubMed  Google Scholar 

  7. Boutouyrie P, Bussy C, Lacolley P, Girerd X, Laloux B, Laurent S. Association between local pulse pressure, mean blood pressure, and large-artery remodeling. Circulation. 1999;100:1387–93.

    Article  CAS  PubMed  Google Scholar 

  8. Boutouyrie P, Laurent S, Benetos A, Girerd XJ, Hoeks AP, Safar ME. Opposing effects of ageing on distal and proximal large arteries in hypertensives. J Hypertens Suppl. 1992;10:S87–91.

    Article  CAS  PubMed  Google Scholar 

  9. Laurent S, Cockcroft J, Van Bortel L, Boutouyrie P, Giannattasio C, Hayoz D, Pannier B, Vlachopoulos C, Wilkinson I, Struijker-Boudier H. Expert consensus document on arterial stiffness: methodological issues and clinical applications. Eur Heart J. 2006;27:2588–605.

    Article  PubMed  Google Scholar 

  10. Laurent S, Boutouyrie P, Lacolley P. Structural and genetic bases of arterial stiffness. Hypertension. 2005;45:1050–5.

    Article  CAS  PubMed  Google Scholar 

  11. Schiffrin EL. Circulatory therapeutics: use of antihypertensive agents and their effects on the vasculature. J Cell Mol Med. 2010;14:1018–29.

    CAS  PubMed  Google Scholar 

  12. Boutouyrie P, Bussy C, Hayoz D, Hengstler J, Dartois N, Laloux B, Brunner H, Laurent S. Local pulse pressure and regression of arterial wall hypertrophy during long-term antihypertensive treatment. Circulation. 2000;101:2601–6.

    Article  CAS  PubMed  Google Scholar 

  13. Van Bortel LM, Kool MJ, Boudier HA, Struijker Boudier HA. Effects of antihypertensive agents on local arterial distensibility and compliance. Hypertension. 1995;26:531–4.

    Article  PubMed  Google Scholar 

  14. Shahin Y, Khan JA, Chetter I. Angiotensin converting enzyme inhibitors effect on arterial stiffness and wave reflections: a meta-analysis and meta-regression of randomised controlled trials. Atherosclerosis. 2012;221:18–33.

    Article  CAS  PubMed  Google Scholar 

  15. Benetos A, Gautier S, Lafleche A, Topouchian J, Frangin G, Girerd X, Sissmann J, Safar ME. Blockade of angiotensin ii type 1 receptors: effect on carotid and radial artery structure and function in hypertensive humans. J Vasc Res. 2000;37:8–15; discussion 68–70.

    Article  CAS  PubMed  Google Scholar 

  16. Davies J, Gavin A, Band M, Morris A, Struthers A. Spironolactone reduces brachial pulse wave velocity and piiinp levels in hypertensive diabetic patients. Br J Clin Pharmacol. 2005;59:520–3.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  17. Benetos A, Vasmant D, Thiery P, Safar M. Effects of ramipril on arterial hemodynamics. J Cardiovasc Pharmacol. 1991;18 Suppl 2:S153–6.

    Article  PubMed  Google Scholar 

  18. Heesen WF, Beltman FW, Smit AJ, May JF, de Graeff PA, Muntinga JH, Havinga TK, Schuurman FH, van der Veur E, Meyboom-de Jong B, Lie KI. Reversal of pathophysiologic changes with long-term lisinopril treatment in isolated systolic hypertension. J Cardiovasc Pharmacol. 2001;37:512–21.

    Article  CAS  PubMed  Google Scholar 

  19. Mitchell GF, Dunlap ME, Warnica W, Ducharme A, Arnold JM, Tardif JC, Solomon SD, Domanski MJ, Jablonski KA, Rice MM, Pfeffer MA, Prevention of Events With Angiotensin-Converting Enzyme Inhibition I. Long-term trandolapril treatment is associated with reduced aortic stiffness: the prevention of events with angiotensin-converting enzyme inhibition hemodynamic substudy. Hypertension. 2007;49:1271–7.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  20. O’Rourke MF, Safar ME, Dzau V. The cardiovascular continuum extended: aging effects on the aorta and microvasculature. Vasc Med. 2010;15:461–8.

    Article  PubMed  Google Scholar 

  21. Topouchian J, El Feghali R, Pannier B, Wang S, Zhao F, Smetana K, Teo K, Asmar R. Arterial stiffness and pharmacological interventions–the transcend arterial stiffness substudy (trans study). Vasc Health Risk Manag. 2007;3:381–7.

    PubMed Central  PubMed  Google Scholar 

  22. Boutouyrie P, Achouba A, Trunet P, Laurent S. Amlodipine-valsartan combination decreases central systolic blood pressure more effectively than the amlodipine-atenolol combination: the explor study. Hypertension. 2010;55:1314–22.

    Article  CAS  PubMed  Google Scholar 

  23. Paulis L, Becker ST, Lucht K, Schwengel K, Slavic S, Kaschina E, Thone-Reineke C, Dahlof B, Baulmann J, Unger T, Steckelings UM. Direct angiotensin ii type 2 receptor stimulation in nomega-nitro-l-arginine-methyl ester-induced hypertension: the effect on pulse wave velocity and aortic remodeling. Hypertension. 2012;59:485–92.

    Article  CAS  PubMed  Google Scholar 

  24. Virdis A, Ghiadoni L, Qasem AA, Lorenzini G, Duranti E, Cartoni G, Bruno RM, Bernini G, Taddei S. Effect of aliskiren treatment on endothelium-dependent vasodilation and aortic stiffness in essential hypertensive patients. Eur Heart J. 2012;33:1530–8.

    Article  CAS  PubMed  Google Scholar 

  25. Ong KT, Delerme S, Pannier B, Safar ME, Benetos A, Laurent S, Boutouyrie P. 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. 2011;29(6):1034–42.

    Article  CAS  PubMed  Google Scholar 

  26. Ait-Oufella H, Collin C, Bozec E, Laloux B, Ong KT, Dufouil C, Boutouyrie P, Laurent S. Long-term reduction in aortic stiffness: a 5.3-year follow-up in routine clinical practice. J Hypertens. 2010;28:2336–41.

    Article  CAS  PubMed  Google Scholar 

  27. Asmar R. Effect of telmisartan on arterial distensibility and central blood pressure in patients with mild to moderate hypertension and type 2 diabetes mellitus. J Renin Angiotensin Aldosterone Syst. 2001;2 Suppl 2:S8–11.

    Article  CAS  PubMed  Google Scholar 

  28. Karalliedde J, Smith A, DeAngelis L, Mirenda V, Kandra A, Botha J, Ferber P, Viberti G. Valsartan improves arterial stiffness in type 2 diabetes independently of blood pressure lowering. Hypertension. 2008;51:1617–23.

    Article  CAS  PubMed  Google Scholar 

  29. Tropeano AI, Boutouyrie P, Pannier B, Joannides R, Balkestein E, Katsahian S, Laloux B, Thuillez C, Struijker-Boudier H, Laurent S. Brachial pressure-independent reduction in carotid stiffness after long-term angiotensin-converting enzyme inhibition in diabetic hypertensives. Hypertension. 2006;48:80–6.

    Article  CAS  PubMed  Google Scholar 

  30. Spoelstra-de Man AM, van Ittersum FJ, Schram MT, Kamp O, van Dijk RA, Ijzerman RG, Twisk JW, Brouwer CB, Stehouwer CD. Aggressive antihypertensive strategies based on hydrochlorothiazide, candesartan or lisinopril decrease left ventricular mass and improve arterial compliance in patients with type ii diabetes mellitus and hypertension. J Hum Hypertens. 2006;20:599–611.

    Article  CAS  PubMed  Google Scholar 

  31. Jensen-Urstad KJ, Reichard PG, Rosfors JS, Lindblad LE, Jensen-Urstad MT. Early atherosclerosis is retarded by improved long-term blood glucose control in patients with iddm. Diabetes. 1996;45:1253–8.

    Article  CAS  PubMed  Google Scholar 

  32. Williams B, Lacy PS, Thom SM, Cruickshank K, Stanton A, Collier D, Hughes AD, Thurston H, O’Rourke M. 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. 2006;113:1213–25.

    Article  CAS  PubMed  Google Scholar 

  33. Matsui Y, Eguchi K, O’Rourke MF, Ishikawa J, Miyashita H, Shimada K, Kario K. 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. 2009;54:716–23.

    Article  CAS  PubMed  Google Scholar 

  34. Gates PE, Tanaka H, Hiatt WR, Seals DR. Dietary sodium restriction rapidly improves large elastic artery compliance in older adults with systolic hypertension. Hypertension. 2004;44:35–41.

    Article  CAS  PubMed  Google Scholar 

  35. Asmar RG, Benetos A, Chaouche-Teyara K, Raveau-Landon CM, Safar ME. Comparison of effects of felodipine versus hydrochlorothiazide on arterial diameter and pulse-wave velocity in essential hypertension. Am J Cardiol. 1993;72:794–8.

    Article  CAS  PubMed  Google Scholar 

  36. Benetos A, Lafleche A, Asmar R, Gautier S, Safar A, Safar ME. Arterial stiffness, hydrochlorothiazide and converting enzyme inhibition in essential hypertension. J Hum Hypertens. 1996;10:77–82.

    CAS  PubMed  Google Scholar 

  37. Ishimitsu T, Numabe A, Masuda T, Akabane T, Okamura A, Minami J, Matsuoka H. Angiotensin-ii receptor antagonist combined with calcium channel blocker or diuretic for essential hypertension. Hypertens Res. 2009;32:962–8.

    Article  CAS  PubMed  Google Scholar 

  38. Kool MJ, Lustermans FA, Breed JG, Struyker Boudier HA, Hoeks AP, Reneman RS, Van Bortel LM. The influence of perindopril and the diuretic combination amiloride + hydrochlorothiazide on the vessel wall properties of large arteries in hypertensive patients. J Hypertens. 1995;13:839–48.

    Article  CAS  PubMed  Google Scholar 

  39. Mahmud A, Feely J. Effect of angiotensin ii receptor blockade on arterial stiffness: beyond blood pressure reduction. Am J Hypertens. 2002;15:1092–5.

    Article  CAS  PubMed  Google Scholar 

  40. Mahmud A, Feely J. Aldosterone-to-renin ratio, arterial stiffness, and the response to aldosterone antagonism in essential hypertension. Am J Hypertens. 2005;18:50–5.

    Article  CAS  PubMed  Google Scholar 

  41. Safar ME. Can antihypertensive treatment reverse large-artery stiffening? Curr Hypertens Rep. 2010;12:47–51.

    Article  PubMed  Google Scholar 

  42. Matsui Y, Eguchi K, O’Rourke MF, Ishikawa J, Shimada K, Kario K. Association between aldosterone induced by antihypertensive medication and arterial stiffness reduction: the j-core study. Atherosclerosis. 2011;215:184–8.

    Article  CAS  PubMed  Google Scholar 

  43. London GM, Asmar RG, O’Rourke MF, Safar ME. 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. 2004;43:92–9.

    Article  CAS  PubMed  Google Scholar 

  44. Protogerou A, Blacher J, Stergiou GS, Achimastos A, Safar ME. 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. 2009;53:445–51.

    Article  CAS  PubMed  Google Scholar 

  45. Ong KT, Perdu J, De BJ, Bozec E, Collignon P, Emmerich J, Fauret al, Fiessinger JN, Germain DP, Georgesco G, Hulot JS, De PA, Plauchu H, Jeunemaitre X, Laurent S, Boutouyrie P. Effect of celiprolol on prevention of cardiovascular events in vascular ehlers-danlos syndrome: a prospective randomised, open, blinded-endpoints trial. Lancet. 2010;376:1476–84.

    Google Scholar 

  46. Dhakam Z, Yasmin, McEniery CM, Burton T, Brown MJ, Wilkinson IB. A comparison of atenolol and nebivolol in isolated systolic hypertension. J Hypertens. 2008;26:351–6.

    Article  CAS  PubMed  Google Scholar 

  47. Mahmud A, Feely J. Beta-blockers reduce aortic stiffness in hypertension but nebivolol, not atenolol, reduces wave reflection. Am J Hypertens. 2008;21:663–7.

    Article  CAS  PubMed  Google Scholar 

  48. McEniery CM, Schmitt M, Qasem A, Webb DJ, Avolio AP, Wilkinson IB, Cockcroft JR. Nebivolol increases arterial distensibility in vivo. Hypertension. 2004;44:305–10.

    Article  CAS  PubMed  Google Scholar 

  49. Boutouyrie P, Beaussier H, Achouba A, Laurent S. Destiffening effect of valsartan and atenolol: influence of heart rate and blood pressure. J Hypertens. 2014;32(1):108–14.

    Article  CAS  PubMed  Google Scholar 

  50. Casey DP, Curry TB, Joyner MJ, Charkoudian N, Hart EC. Acute beta-adrenergic blockade increases aortic wave reflection in young men and women: differing mechanisms between sexes. Hypertension. 2012;59:145–50.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  51. Casey DP, Curry TB, Charkoudian N, Joyner MJ, Hart EC. The effects of acute beta-adrenergic blockade on aortic wave reflection in postmenopausal women. Am J Hypertens. 2013;26:503–10.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  52. Westling H, Jansson L, Jonson B, Nilsen R. Vasoactive drugs and elastic properties of human arteries in vivo, with special reference to the action of nitroglycerine. Eur Heart J. 1984;5:609–16.

    CAS  PubMed  Google Scholar 

  53. Laurent S, Arcaro G, Benetos A, Lafleche A, Hoeks A, Safar M. Mechanism of nitrate-induced improvement on arterial compliance depends on vascular territory. J Cardiovasc Pharmacol. 1992;19:641–9.

    Article  CAS  PubMed  Google Scholar 

  54. Kool MJ, Spek JJ, Struyker Boudier HA, Hoeks AP, Reneman RS, van Herwaarden RH, Van Bortel LM. Acute and subacute effects of nicorandil and isosorbide dinitrate on vessel wall properties of large arteries and hemodynamics in healthy volunteers. Cardiovasc Drugs Ther. 1995;9:331–7.

    Article  CAS  PubMed  Google Scholar 

  55. Van Bortel LM, Spek JJ, Balkestein EJ, Sardina M, Struijker Boudier HA. Is it possible to develop drugs that act more selectively on large arteries? J Hypertens. 1999;17:701–5.

    Article  PubMed  Google Scholar 

  56. Fok H, Jiang B, Clapp B, Chowienczyk P. Regulation of vascular tone and pulse wave velocity in human muscular conduit arteries: selective effects of nitric oxide donors to dilate muscular arteries relative to resistance vessels. Hypertension. 2012;60:1220–5.

    Article  CAS  PubMed  Google Scholar 

  57. Laurent S, Schlaich M, Esler M. New drugs, procedures, and devices for hypertension. Lancet. 2012;380:591–600.

    Article  CAS  PubMed  Google Scholar 

  58. Corti R, Burnett Jr JC, Rouleau JL, Ruschitzka F, Luscher TF. Vasopeptidase inhibitors: a new therapeutic concept in cardiovascular disease? Circulation. 2001;104:1856–62.

    Article  CAS  PubMed  Google Scholar 

  59. Dive V, Chang CF, Yiotakis A, Sturrock ED. Inhibition of zinc metallopeptidases in cardiovascular disease–from unity to trinity, or duality? Curr Pharm Des. 2009;15:3606–21.

    Article  CAS  PubMed  Google Scholar 

  60. Daull P, Jeng AY, Battistini B. Towards triple vasopeptidase inhibitors for the treatment of cardiovascular diseases. J Cardiovasc Pharmacol. 2007;50:247–56.

    Article  CAS  PubMed  Google Scholar 

  61. Kalk P, Sharkovska Y, Kashina E, von Websky K, Relle K, Pfab T, Alter M, Guillaume P, Provost D, Hoffmann K, Fischer Y, Hocher B. Endothelin-converting enzyme/neutral endopeptidase inhibitor slv338 prevents hypertensive cardiac remodeling in a blood pressure-independent manner. Hypertension. 2011;57:755–63.

    Article  CAS  PubMed  Google Scholar 

  62. Gu J, Noe A, Chandra P, Al-Fayoumi S, Ligueros-Saylan M, Sarangapani R, Maahs S, Ksander G, Rigel DF, Jeng AY, Lin TH, Zheng W, Dole WP. Pharmacokinetics and pharmacodynamics of lcz696, a novel dual-acting angiotensin receptor-neprilysin inhibitor (arni). J Clin Pharmacol. 2010;50:401–14.

    Article  CAS  PubMed  Google Scholar 

  63. Arcaro G, Laurent S, Jondeau G, Hoeks AP, Safar ME. Stiffness of the common carotid artery in treated hypertensive patients. J Hypertens. 1991;9:947–54.

    CAS  PubMed  Google Scholar 

  64. Guerin AP, Blacher J, Pannier B, Marchais SJ, Safar ME, London GM. Impact of aortic stiffness attenuation on survival of patients in end-stage renal failure. Circulation. 2001;103:987–92.

    Article  CAS  PubMed  Google Scholar 

  65. Laurent S, Briet M, Boutouyrie P. Arterial stiffness as surrogate end point: needed clinical trials. Hypertension. 2012;60:518–22.

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Clinical Research Unit and Pharmacy, Fondation Hôpital Saint Joseph, Paris, France

    Hélène Beaussier

  2. Hopital Europeen Georges Pompidou, Assistance Publique Hôpitaux de Paris, Université Paris Descartes, Paris, France

    Hélène Beaussier

  3. Department of Pharmacology and Institut National de la Santé et de la Recherche Médicale U970(Eq7)-PARCC, Hôpital Européen Georges Pompidou, Assistance Publique-Hôpitaux de Paris, Université Paris-Descartes, 20, rue Leblanc, 75015, Paris, France

    Stéphane Laurent & Pierre Boutouyrie

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  1. Hélène Beaussier
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  2. Stéphane Laurent
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  3. Pierre Boutouyrie
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Editors and Affiliations

  1. Hôtel-Dieu Hospital Diagnosis and Therapeutics Center, Paris Descartes University, Paris, Paris, France

    Michel E. Safar

  2. St Vincent Clinic and Hospital, University of New South Wales, Victor Chang Cardiac Research Institute, Darlinghurst, Sydney, New South Wales, Australia

    Michael F. O'Rourke

  3. Department of Cardiology, Ochsner Clinic Foundation, New Orleans, Louisiana, USA

    Edward D. Frohlich

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Beaussier, H., Laurent, S., Boutouyrie, P. (2014). Decreasing Arterial Stiffness and/or Wave Reflections Independently of Mean Arterial Pressure: Effect of Antihypertensive Drugs (Part 1). In: Safar, M., O'Rourke, M., Frohlich, E. (eds) Blood Pressure and Arterial Wall Mechanics in Cardiovascular Diseases. Springer, London. https://doi.org/10.1007/978-1-4471-5198-2_39

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