Skip to main content

Reducing arterial stiffness and wave reflection — Quest for the Holy Grail?

Summary

Arterial stiffness and wave reflection are fast emerging as therapeutic targets in their own right. While thiazide diuretics have little or no effect on either arterial stiffness or wave reflection, vasodilators including nitrates and phosphodiesterase type-5 inhibitors e.g., sildenafil, reduce wave reflections and aortic pressures but not aortic stiffness. β-blockers have the opposite effect; they reduce aortic stiffness but increase aortic pulse pressure and wave reflections while calcium antagonists and α-blockers show varying effects on the vascular wall. Drugs targeting the renin—angiotensin—aldosterone system, namely angiotensin-converting enzyme inhibitors (ACEI), angiotensin receptor blockers (ARBs) and aldosterone antagonists have been shown as the most effective in reducing both arterial stiffness and wave reflection, and in some cases, to a greater extent than predicted from the extent of blood pressure (BP) reduction. Also, there is evidence of an additive effect on arterial stiffness with combined ACEI and ARBs. Exploring further the synergistic effects of anti-hypertensive drugs on arterial stiffness, a polypill containing a low-dose combination of a thiazide diuretic, calcium antagonist, β-blocker and an ACEI, decreased arterial stiffness more than the individual drugs in standard doses. However, beyond the dynamic effects of anti-hypertensive drugs, future therapies may directly target vascular structural alterations including collagen degradation, advanced glycation end-products, the matrix-metalloproteinases and vascular inflammation. Finally, one can speculate about the role of pharmacogenomics which may help tailor ‘de-stiffening therapy’ in individuals with stiff arteries.

References

  1. Nichols WW, O’Rourke MF. Theoretical experimental and clinical principles. McDonald’s blood flow in arteries. London: Edward Arnold; 1998. p. 54–113.

    Google Scholar 

  2. Mahmud A, Feely J. Antihypertensive drugs and arterial stiffness. Expert Rev Cardiovasc Ther 2003; 1(1): 89–102.

    Google Scholar 

  3. Mahmud A, Feely J. Augmentation index and pulse wave velocity: do both measure arterial stiffness? Am J Hypertens 2006; 18(5):17A.

    Google Scholar 

  4. Mahmud A, Feely J. Doxazocin reduces augmentation index but not pulse wave velocity in essential hypertension. Br J Clin Pharmacol 2006;61(5):628.

    Google Scholar 

  5. O’Rourke MF, Adji A. An updated clinical primer on large artery mechanics: implications of pulse waveform analysis and arterial tonometry. Curr Opin Cardiol 2005;20:275–81.

    Google Scholar 

  6. Mahmud A, Feely J. Effect of angiotensin II receptor blockade on arterial stiffness: beyond blood pressure reduction. Am J Hypertens 2002; 15(12): 1092–5.

    Google Scholar 

  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;46:269–76.

    Google Scholar 

  8. 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.

    Google Scholar 

  9. Chen CH, Ting C-T, Lin SJ, Hsu TL, Yin ICP, Siu CO. Different effects of fosinopril and atenolol on wave reflection in hypertension patients. Hypertension 1995;25:1034–41.

    Google Scholar 

  10. Asmar RG, London GM, O’Rourke ME, Safar ME, REASON Project Co-ordinators and Investigators. 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 2001; 38(4): 922–6.

    Google Scholar 

  11. Kelly RP, Daley J, Avolio A, O’Rourke MF. Arterial dilatation and reduced wave reflection: benefit of dilevalol in hypertension. Hypertension 1989;14:14–21.

    Google Scholar 

  12. Mahmud A, Feely J. Beta-blockers, nebivolol and atenolol favourable reduce arterial stiffness. J Hypertens 2002;20(Suppl. 4):S376.

    Google Scholar 

  13. Fitchett D, Simkus GJ, Beaudry J, Marpole D. Reflected pressure waves on the ascending aorta: effect of glyceryl trinitrate. Cardiovasc Res 1988;22:494–500.

    Google Scholar 

  14. Jiang XJ, O’Rourke MF, Jin WQ, Liu LS, Li CW, Tai PC, et al. Quantification of glyceryl trinitrate effect through analysis of the synthesised ascending aortic pressure waveform. Heart 2002; 88(2): 143–8.

    Google Scholar 

  15. Mahmud A, Hennessy M, Feely J. Effect of sildenafil on blood pressure and arterial wave reflection in treated hypertensive men. J Hum Hypertens 2001; 15(10): 707–13.

    Google Scholar 

  16. Zieman SJ, Melenovsky V, Kass DA. Mechanisms, pathophysiol-ogy and therapy of arterial stiffness. Arterioscler Thromb Vasc Biol 2005;25:932–43.

    Google Scholar 

  17. Mahmud A, Feely J. Vascular effects of amlodipine in essential hypertension. Br J Clin Pharmacol 2004;57:684–5.

    Google Scholar 

  18. Morgan T, Lauri JI, Bertram D, Anderson A. Effect of different antihypertensive drug classes on central aortic pressure. Am J Hypertens 2004;17:118–23.

    Google Scholar 

  19. Komai N, Ohishi M, Moriguchi A, Yanagitani Y, Jinno T, Matsumoto K, et al. Low-dose doxazosin improved aortic stiffness and endothelial dysfunction as measured by noninvasive evaluation. Hypertens Res 2002; 25(1): 5–10.

    Google Scholar 

  20. Rehman A, Rahman AR, Rasool AH, Naing NN. The effects of an-giotensin II on pulse wave velocity in healthy humans. Int J Clin Pharmacol Ther 2001; 39(10): 423–30.

    Google Scholar 

  21. Wilkinson I, MacCallum H, Hupperetz PC, van Thoor CJ, Cockcroft JR, Webb DJ. Changes in the derived central pressure waveform and pulse pressure in response to angiotensin II and noradrenaline in man. J Physiol 2001;530:541–50.

    Google Scholar 

  22. Vingerhoedt NM, Gilles R, Howes JB, Griffin M, Howes LG. Hae-modynamic and pulse wave responses to intravenous infusions of angiotensin II during chronic telmisartan therapy in normal volunteers. J Renin Angiotensin Aldosterone Syst 2003; 4(4): 244–8.

    Google Scholar 

  23. Mahmud A, Feely J. Arterial stiffness and the renin–angioten-sin–aldosterone system. J Renin Angiotensin Aldosterone Syst 2004; 5(3): 102–8.

    Google Scholar 

  24. Schmidt BM, Oehmer S, Delles C, Bratke R, Schneider MP, Klingbeil A, et al. Rapid non-genomic effects of aldosterone on human forearm vasculature. Hypertension 2003; 42(2): 156–60.

    Google Scholar 

  25. Schmidt BM, Schmieder RE. Aldosterone-induced cardiac damage: focus on blood pressure independent effects. Am J Hyper-tens 2003; 16(1): 80–6.

    Google Scholar 

  26. Lacolley P, Labat C, Pujol A, Delcayre C, Benefit A, Safar M. Increased carotid wall elastic modulus and fibronectin in aldos-terone–salt-treated rats: effects of eplerenone. Circulation 2002; 106(22): 2848–53.

    Google Scholar 

  27. Blacher J, Amah G, Girerd X, Kheder A, Ben Mais H, London GM, et al. Association between increased plasma levels of aldoste-rone and decreased systemic arterial compliance in subjects with essential hypertension. Am J Hypertens 1997;10: 1326–34.

    Google Scholar 

  28. Resnick LM, Catanzaro D, Sealey JE, Laragh JH. Acute vascular effects of the angiotensin II receptor antagonist olmesartan in normal subjects: relation to the renin–aldosterone system. Am J Hypertens 2004;17:203–8.

    Google Scholar 

  29. 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.

    Google Scholar 

  30. Mahmud A, Feely J. Favourable effects on arterial wave reflection and pulse pressure amplification of adding angiotensin II receptor blockade in resistant hypertension. J Hum Hypertens 2000;14:54–6.

    Google Scholar 

  31. Mahmud A, Feely J. Reduction in arterial stiffness with angio-tensin II antagonist is comparable with and additive to ACE inhibition. Am J Hypertens 2002;15:321–5.

    Google Scholar 

  32. White WB, Duprez D, St. Hillaire R, Krause S, Roniker B, Kuse-Hamilton J, et al. Effects of the selective aldosterone antagonist eplerenone versus the calcium antagonist amlodipine in systolic hypertension. Hypertension 2003; 41(5):1021–6.

    Google Scholar 

  33. Mahmud A, Feely J. Greater reduction in arterial stiffness with low-dose polypill compared with monotherapy in hypertension. Br J Clin Pharmacol 2005;59:631.

    Google Scholar 

  34. 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(7):987–92.

    Google Scholar 

  35. Williams B, Lacy PS, Thom SM, Cruickshank K, Stanton A, Collier D, et al. Anglo-Scandinavian Cardiac Outcomes Trial Investigators, CAFE Steering Committee and Writing Committee. 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.

    Google Scholar 

  36. Vlachopoulos C, Dima I, Aznaouridis K, Vasiliadou C, Ioakeimidis N, Aggeli C, et al. Acute systemic inflammation increases arterial stiffness and decreases wave reflections in healthy individuals. Circulation 2005; 112(14): 2193–200.

    Google Scholar 

  37. Mahmud A, Feely J. Arterial stiffness is related to systemic inflammation in essential hypertension. Hypertension 2005; 46(5):1118–21.

    Google Scholar 

  38. Mahmud A, Feely J. Adiponectin and arterial stiffness. Am J Hypertens 2005;18:1543–8.

    Google Scholar 

  39. McNulty M, Mahmud A, Spiers J, Feely J. Collagen type-I degradation is related to arterial stiffness in hypertensive and nor-motensive subjects. J Hum Hypertens 2006;20:867–73.

    Google Scholar 

  40. McNulty M, Mahmud A, Feely J. Advanced glycation end products and arterial stiffness in hypertension. Am J Hypertens 2007; 20(3): 242–7.

    Google Scholar 

  41. Zhou S, Mahmud A, Spiers JP, Feely J. Matrix metalloprotei-nase-9 polymorphism contributes to blood pressure and large arterial stiffness in essential hypertension. Br J Clin Pharmacol 2006; 61(5): 629–30.

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Azra Mahmud.

Rights and permissions

This is an open access article distributed under the CC BY-NC license. https://doi.org/creativecommons.org/licenses/by/4.0/

Reprints and permissions

About this article

Cite this article

Mahmud, A. Reducing arterial stiffness and wave reflection — Quest for the Holy Grail?. Artery Res 1, 13–19 (2007). https://doi.org/10.1016/j.artres.2007.03.001

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1016/j.artres.2007.03.001

Keywords