Skip to main content

Reversing Arterial Stiffening and Calcification: A Pipe Dream?

  • Chapter
  • First Online:
Cardio-Renal Clinical Challenges

Abstract

The development of technical means to non-invasively investigate the cardiovascular system on other features than pulse and blood pressure, slowly led to the recognition that additional characteristics of the heart and vasculature play a crucial role in the pathogenesis of cardiovascular disease. Possibly the most prominent feature is arterial stiffness. Although being an inevitable consequence of aging and inseparable phenomenon with hypertension, it is clear that it predicts cardiovascular risk independently form these two factors. The variability of arterial stiffness is explained by a large range of endocrine, metabolic, haemodynamic, structural and functional properties, that all frequently occur together in chronic kidney disease. Although calcification of the tunica media in the arterial wall, a hallmark of chronic kidney disease, appears difficult to improve, several other components that contribute to arterial stiffness are likely more accessible for modification. Although it is not proven that specifically targeting arterial stiffness translates into improved clinical outcome, this pathological feature of the arterial system is likely neglected clinically and has a sound basis for rational intervention, preferably preceded by interventional trials with clinically important endpoints. In this chapter modifiable and hardly-modifiable factors that likely contribute to arterial stiffness in the setting of chronic kidney disease are addressed. Although areas of uncertainty exist and are underlined, raising awareness of the relevance of this neglected feature of the cardiovascular system, holds the promise of improving the unacceptably high prevalence of complications in chronic kidney disease.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 159.00
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 109.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. O’Hare AM, Choi AI, Bertenthal D, Bacchetti P, Garg AX, Kaufman JS, Walter LC, Mehta KM, Steinman MA, Allon M, McClellan WM, Landefeld CS. Age affects outcomes in chronic kidney disease. J Am Soc Nephrol. 2007;18:2758–65.

    Article  PubMed  Google Scholar 

  2. Okin PM, Devereux RB, Jern S, Kjeldsen SE, Julius S, Nieminen MS, Snapinn S, Harris KE, Aurup P, Edelman JM, Wedel H, Lindholm LH, Dahlof B. Regression of electrocardiographic left ventricular hypertrophy during antihypertensive treatment and the prediction of major cardiovascular events. JAMA. 2004;292:2343–9.

    Article  CAS  PubMed  Google Scholar 

  3. Suzuki T, Hirata K, Elkind MS, Jin Z, Rundek T, Miyake Y, Boden-Albala B, Di Tullio MR, Sacco R, Homma S. Metabolic syndrome, endothelial dysfunction, and risk of cardiovascular events: the Northern Manhattan Study (NOMAS). Am Heart J. 2008;156:405–10.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  4. 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 

  5. Blacher J, Guerin AP, Pannier B, Marchais SJ, Safar ME, London GM. Impact of aortic stiffness on survival in end-stage renal disease. Circulation. 1999;99:2434–9.

    Article  CAS  PubMed  Google Scholar 

  6. Safar ME, London GM, Plante GE. Arterial stiffness and kidney function. Hypertension. 2004;43:163–8.

    Article  CAS  PubMed  Google Scholar 

  7. Safar ME. Peripheral pulse pressure, large arteries, and microvessels. Hypertension. 2004;44:121–2.

    Article  CAS  PubMed  Google Scholar 

  8. Boutouyrie P, Fliser D, Goldsmith D, Covic A, Wiecek A, Ortiz A, Martinez-Castelao A, Lindholm B, Massy ZA, Suleymanlar G, Sicari R, Gargani L, Parati G, Mallamaci F, Zoccali C, London GM. Assessment of arterial stiffness for clinical and epidemiological studies: methodological considerations for validation and entry into the European Renal and Cardiovascular Medicine registry. Nephrol Dial Transplant. 2014;29:232–9.

    Article  PubMed  Google Scholar 

  9. Kelly RP, Tunin R, Kass DA. Effect of reduced aortic compliance on cardiac efficiency and contractile function of in situ canine left ventricle. Circ Res. 1992;71:490–502.

    Article  CAS  PubMed  Google Scholar 

  10. Pahlevan NM, Gharib M. Aortic wave dynamics and its influence on left ventricular workload. PLoS One. 2011;6:e23106.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  11. Nobari S, Mongrain R, Gaillard E, Leask R, Cartier R. Therapeutic vascular compliance change may cause significant variation in coronary perfusion: a numerical study. Comput Math Methods Med. 2012;2012:791686.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  12. Toyota E, Ogasawara Y, Hiramatsu O, Tachibana H, Kajiya F, Yamamori S, Chilian WM. Dynamics of flow velocities in endocardial and epicardial coronary arterioles. Am J Physiol Heart Circ Physiol. 2005;288:H1598–603.

    Article  CAS  PubMed  Google Scholar 

  13. Mitchell GF, Hwang SJ, Vasan RS, Larson MG, Pencina MJ, Hamburg NM, Vita JA, Levy D, Benjamin EJ. Arterial stiffness and cardiovascular events: the Framingham Heart Study. Circulation. 2010;121:505–11.

    Article  PubMed Central  PubMed  Google Scholar 

  14. 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. 2010;31:2338–50.

    Article  Google Scholar 

  15. Rhee EJ, Seo MH, Kim JD, Jeon WS, Park SE, Park CY, Oh KW, Park SW, Lee WY. Metabolic health is more closely associated with coronary artery calcification than obesity. PLoS One. 2013;8:e74564.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  16. Shroff R, Long DA, Shanahan C. Mechanistic insights into vascular calcification in CKD. J Am Soc Nephrol. 2013;24:179–89.

    Article  CAS  PubMed  Google Scholar 

  17. Leonard O, Spaak J, Goldsmith D. Regression of vascular calcification in chronic kidney disease – feasible or fantasy? A review of the clinical evidence. Br J Clin Pharmacol. 2013;76:560–72.

    CAS  PubMed Central  PubMed  Google Scholar 

  18. Aoshima Y, Mizobuchi M, Ogata H, Kumata C, Nakazawa A, Kondo F, Ono N, Koiwa F, Kinugasa E, Akizawa T. Vitamin D receptor activators inhibit vascular smooth muscle cell mineralization induced by phosphate and TNF-alpha. Nephrol Dial Transplant. 2012;27:1800–6.

    Article  CAS  PubMed  Google Scholar 

  19. Richart T, Li Y, Staessen JA. Renal versus extrarenal activation of vitamin D in relation to atherosclerosis, arterial stiffening, and hypertension. Am J Hypertens. 2007;20:1007–15.

    Article  CAS  PubMed  Google Scholar 

  20. Charitaki E, Davenport A. Aortic pulse wave velocity in haemodialysis patients is associated with the prescription of active vitamin D analogues. J Nephrol. 2014 jan 29 [Epub ahead of print].

    Google Scholar 

  21. Norman PE, Powell JT. Vitamin D, shedding light on the development of disease in peripheral arteries. Arterioscler Thromb Vasc Biol. 2005;25:39–46.

    CAS  PubMed  Google Scholar 

  22. Seifert ME, de las FL, Rothstein M, Dietzen DJ, Bierhals AJ, Cheng SC, Ross W, Windus D, vila-Roman VG, Hruska KA. Effects of phosphate binder therapy on vascular stiffness in early-stage chronic kidney disease. Am J Nephrol. 2013;38:158–67.

    CAS  PubMed  Google Scholar 

  23. Block GA, Wheeler DC, Persky MS, Kestenbaum B, Ketteler M, Spiegel DM, Allison MA, Asplin J, Smits G, Hoofnagle AN, Kooienga L, Thadhani R, Mannstadt M, Wolf M, Chertow GM. Effects of phosphate binders in moderate CKD. J Am Soc Nephrol. 2012;23:1407–15.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  24. Frazao JM, Adragao T. Non-calcium-containing phosphate binders: comparing efficacy, safety, and other clinical effects. Nephron Clin Pract. 2012;120:c108–19.

    Article  CAS  PubMed  Google Scholar 

  25. Motro M, Shemesh J. Calcium channel blocker nifedipine slows down progression of coronary calcification in hypertensive patients compared with diuretics. Hypertension. 2001;37:1410–3.

    Article  CAS  PubMed  Google Scholar 

  26. Raggi P, Chertow GM, Torres PU, Csiky B, Naso A, Nossuli K, Moustafa M, Goodman WG, Lopez N, Downey G, Dehmel B, Floege J. The ADVANCE study: a randomized study to evaluate the effects of cinacalcet plus low-dose vitamin D on vascular calcification in patients on hemodialysis. Nephrol Dial Transplant. 2011;26:1327–39.

    Article  CAS  PubMed  Google Scholar 

  27. Schurgers LJ. Vitamin K: key vitamin in controlling vascular calcification in chronic kidney disease. Kidney Int. 2013;83:782–4.

    Article  CAS  PubMed  Google Scholar 

  28. McCabe KM, Booth SL, Fu X, Shobeiri N, Pang JJ, Adams MA, Holden RM. Dietary vitamin K and therapeutic warfarin alter the susceptibility to vascular calcification in experimental chronic kidney disease. Kidney Int. 2013;83:835–44.

    Article  CAS  PubMed  Google Scholar 

  29. Jahnen-Dechent W, Heiss A, Schafer C, Ketteler M. Fetuin-A regulation of calcified matrix metabolism. Circ Res. 2011;108:1494–509.

    Article  CAS  PubMed  Google Scholar 

  30. Elmariah S, Delaney JA, O’Brien KD, Budoff MJ, Vogel-Claussen J, Fuster V, Kronmal RA, Halperin JL. Bisphosphonate use and prevalence of valvular and vascular calcification in women MESA (The Multi-Ethnic Study of Atherosclerosis). J Am Coll Cardiol. 2010;56:1752–9.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  31. Samelson EJ, Miller PD, Christiansen C, Daizadeh NS, Grazette L, Anthony MS, Egbuna O, Wang A, Siddhanti SR, Cheung AM, Franchimont N, Kiel DP. RANKL inhibition with denosumab does not influence 3-year progression of aortic calcification or incidence of adverse cardiovascular events in postmenopausal women with osteoporosis and high cardiovascular risk. J Bone Miner Res. 2014;29:450–7.

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  33. Manisty CH, Hughes AD. Meta-analysis of the comparative effects of different classes of antihypertensive agents on brachial and central systolic blood pressure, and augmentation index. Br J Clin Pharmacol. 2013;75:79–92.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  34. Dhakam Z, McEniery CM, Yasmin, Cockcroft JR, Brown MJ, Wilkinson IB. Atenolol and eprosartan: differential effects on central blood pressure and aortic pulse wave velocity. Am J Hypertens. 2006;19:214–9.

    Article  CAS  PubMed  Google Scholar 

  35. Ishii H, Tsukada T, Yoshida M. Angiotensin II type-I receptor blocker, candesartan, improves brachial-ankle pulse wave velocity independent of its blood pressure lowering effects in type 2 diabetes patients. Intern Med. 2008;47:2013–8.

    Article  PubMed  Google Scholar 

  36. 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 

  37. Dudenbostel T, Glasser SP. Effects of antihypertensive drugs on arterial stiffness. Cardiol Rev. 2012;20:259–63.

    Article  PubMed  Google Scholar 

  38. Rabkin SW, Chan SH. Correlation of pulse wave velocity with left ventricular mass in patients with hypertension once blood pressure has been normalized. Heart Int. 2012;7:e5.

    Article  PubMed Central  PubMed  Google Scholar 

  39. Girerd X, Giannattasio C, Moulin C, Safar M, Mancia G, Laurent S. Regression of radial artery wall hypertrophy and improvement of carotid artery compliance after long-term antihypertensive treatment in elderly patients. J Am Coll Cardiol. 1998;31:1064–73.

    Article  CAS  PubMed  Google Scholar 

  40. Savoia C, Touyz RM, Amiri F, Schiffrin EL. Selective mineralocorticoid receptor blocker eplerenone reduces resistance artery stiffness in hypertensive patients. Hypertension. 2008;51:432–9.

    Article  CAS  PubMed  Google Scholar 

  41. He FJ, Marciniak M, Visagie E, Markandu ND, Anand V, Dalton RN, MacGregor GA. Effect of modest salt reduction on blood pressure, urinary albumin, and pulse wave velocity in white, black, and Asian mild hypertensives. Hypertension. 2009;54:482–8.

    Article  CAS  PubMed  Google Scholar 

  42. Fukuoka Y, Nuruki N, Amiya S, Tofuku K, Aosaki S, Tsubouchi H. Effects of a fish-based diet and administration of pure eicosapentaenoic acid on brachial-ankle pulse wave velocity in patients with cardiovascular risk factors. J Cardiol. 2014;63(3):211–7.

    Article  PubMed  Google Scholar 

  43. Wallace SM, Yasmin, McEniery CM, Maki-Petaja KM, Booth AD, Cockcroft JR, Wilkinson IB. Isolated systolic hypertension is characterized by increased aortic stiffness and endothelial dysfunction. Hypertension. 2007;50:228–33.

    Article  CAS  PubMed  Google Scholar 

  44. Dhaun N, Melville V, Blackwell S, Talwar DK, Johnston NR, Goddard J, Webb DJ. Endothelin-A receptor antagonism modifies cardiovascular risk factors in CKD. J Am Soc Nephrol. 2013;24:31–6.

    Article  CAS  PubMed  Google Scholar 

  45. Kanaki AI, Sarafidis PA, Georgianos PI, Kanavos K, Tziolas IM, Zebekakis PE, Lasaridis AN. Effects of low-dose atorvastatin on arterial stiffness and central aortic pressure augmentation in patients with hypertension and hypercholesterolemia. Am J Hypertens. 2013;26:608–16.

    Article  CAS  PubMed  Google Scholar 

  46. Fassett RG, Robertson IK, Ball MJ, Geraghty DP, Sharman JE, Coombes JS. Effects of atorvastatin on arterial stiffness in chronic kidney disease: a randomised controlled trial. J Atheroscler Thromb. 2010;17:235–41.

    Article  CAS  PubMed  Google Scholar 

  47. Han SH, Kang EW, Yoon SJ, Yoon HS, Lee HC, Yoo TH, Choi KH, Han DS, Kang SW. Combined vascular effects of HMG-CoA reductase inhibitor and angiotensin receptor blocker in non-diabetic patients undergoing peritoneal dialysis. Nephrol Dial Transplant. 2011;26:3722–8.

    Article  CAS  PubMed  Google Scholar 

  48. Liu J, Cao TS, Duan YY, Yang YL, Yuan LJ. Effects of cold pressor-induced sympathetic stimulation on the mechanical properties of common carotid and femoral arteries in healthy males. Heart Vessels. 2011;26:214–21.

    Article  CAS  PubMed  Google Scholar 

  49. Swierblewska E, Hering D, Kara T, Kunicka K, Kruszewski P, Bieniaszewski L, Boutouyrie P, Somers VK, Narkiewicz K. An independent relationship between muscle sympathetic nerve activity and pulse wave velocity in normal humans. J Hypertens. 2010;28:979–84.

    Article  CAS  PubMed  Google Scholar 

  50. Hering D, Lambert EA, Marusic P, Ika-Sari C, Walton AS, Krum H, Sobotka PA, Mahfoud F, Bohm M, Lambert GW, Esler MD, Schlaich MP. Renal nerve ablation reduces augmentation index in patients with resistant hypertension. J Hypertens. 2013;31:1893–900.

    Article  CAS  PubMed  Google Scholar 

  51. Hering D, Mahfoud F, Walton AS, Krum H, Lambert GW, Lambert EA, Sobotka PA, Bohm M, Cremers B, Esler MD, Schlaich MP. Renal denervation in moderate to severe CKD. J Am Soc Nephrol. 2012;23:1250–7.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  52. Jatoi NA, Jerrard-Dunne P, Feely J, Mahmud A. Impact of smoking and smoking cessation on arterial stiffness and aortic wave reflection in hypertension. Hypertension. 2007;49:981–5.

    Article  CAS  PubMed  Google Scholar 

  53. Giallauria F, Milaneschi Y, Tanaka T, Maggio M, Canepa M, Elango P, Vigorito C, Lakatta EG, Ferrucci L, Strait J. Arterial stiffness and vitamin D levels: the Baltimore longitudinal study of aging. J Clin Endocrinol Metab. 2012;97:3717–23.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  54. Witham MD, Price RJ, Struthers AD, Donnan PT, Messow CM, Ford I, McMurdo ME. Cholecalciferol treatment to reduce blood pressure in older patients with isolated systolic hypertension: the VitDISH randomized controlled trial. JAMA Intern Med. 2013;173:1672–9.

    CAS  PubMed  Google Scholar 

  55. Gepner AD, Ramamurthy R, Krueger DC, Korcarz CE, Binkley N, Stein JH. A prospective randomized controlled trial of the effects of vitamin D supplementation on cardiovascular disease risk. PLoS One. 2012;7:e36617.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  56. Yue WS, Lau KK, Siu CW, Wang M, Yan GH, Yiu KH, Tse HF. Impact of glycemic control on circulating endothelial progenitor cells and arterial stiffness in patients with type 2 diabetes mellitus. Cardiovasc Diabetol. 2011;10:113.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Marc G. Vervloet MD, PhD, FERA .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2015 Springer International Publishing Switzerland

About this chapter

Cite this chapter

Vervloet, M.G. (2015). Reversing Arterial Stiffening and Calcification: A Pipe Dream?. In: Goldsmith, D., Covic, A., Spaak, J. (eds) Cardio-Renal Clinical Challenges. Springer, Cham. https://doi.org/10.1007/978-3-319-09162-4_13

Download citation

  • DOI: https://doi.org/10.1007/978-3-319-09162-4_13

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-319-09161-7

  • Online ISBN: 978-3-319-09162-4

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics