Healthy Vascular Ageing and Early Vascular Ageing

  • Gemma CurrieEmail author
  • Peter M. Nilsson


Chronological age is an important independent predictor of cardiovascular events. Although the cumulative effect of cardiovascular risk factors over time partly explains this relationship, accumulating evidence suggests this is a simplistic interpretation of a more complex concept. With advancing age slowly progressive changes can be seen affecting the structure and function of large and small vessels as well as the phenotype of various cell lines. It is important to note that these changes occur at different rates depending on the clinical context and can be detected much earlier in individuals affected by chronic metabolic or vascular diseases. Determining ‘vascular age’ may therefore be an important tool for cardiovascular risk stratification. This chapter will review the cellular, functional and structural effects of ageing on the vasculature, clinical and research tools for assessing aspects of vascular age, the concept of ‘early vascular ageing’ and associated clinical conditions and pathways to achieve healthy vascular ageing.


Ageing Aortic distensibility Cardiovascular risk Carotid intima-media thickness Early vascular ageing Pulse wave velocity Vascular stiffness 


  1. 1.
    Mahmood SS, Levy D, Vasan RS, Wang TJ. The Framingham Heart Study and the epidemiology of cardiovascular disease: a historical perspective. Lancet. 2014;383(9921):999–1008.PubMedCrossRefGoogle Scholar
  2. 2.
    Savji N, Rockman CB, Skolnick AH, Guo Y, Adelman MA, Riles T, et al. Association between advanced age and vascular disease in different arterial territories: a population database of over 3.6 million subjects. J Am Coll Cardiol. 2013;61(16):1736–43.PubMedCrossRefGoogle Scholar
  3. 3.
    Nilsson PM. Early vascular aging (EVA): consequences and prevention. Vasc Health Risk Manag. 2008;4(3):547–52.PubMedPubMedCentralCrossRefGoogle Scholar
  4. 4.
    Kovacic JC, Moreno P, Hachinski V, Nabel EG, Fuster V. Cellular senescence, vascular disease, and aging: part 1 of a 2-part review. Circulation. 2011;123(15):1650–60.PubMedCrossRefGoogle Scholar
  5. 5.
    Haycock PC, Heydon EE, Kaptoge S, Butterworth AS, Thompson A, Willeit P. Leucocyte telomere length and risk of cardiovascular disease: systematic review and meta-analysis. BMJ. 2014;349:g4227.PubMedPubMedCentralCrossRefGoogle Scholar
  6. 6.
    Fyhrquist F, Saijonmaa O, Strandberg T. The roles of senescence and telomere shortening in cardiovascular disease. Nat Rev Cardiol. 2013;10(5):274–83.PubMedCrossRefGoogle Scholar
  7. 7.
    Camici GG, Savarese G, Akhmedov A, Luscher TF. Molecular mechanism of endothelial and vascular aging: implications for cardiovascular disease. Eur Heart J. 2015;36(48):3392–403.PubMedCrossRefGoogle Scholar
  8. 8.
    Wang JC, Bennett M. Aging and atherosclerosis: mechanisms, functional consequences, and potential therapeutics for cellular senescence. Circ Res. 2012;111(2):245–59.PubMedPubMedCentralCrossRefGoogle Scholar
  9. 9.
    Laina A, Stellos K, Stamatelopoulos K. Vascular ageing: Underlying mechanisms and clinical implications. Exp Gerontol. 2017;109:16–30.PubMedCrossRefGoogle Scholar
  10. 10.
    Besler C, Heinrich K, Rohrer L, Doerries C, Riwanto M, Shih DM, et al. Mechanisms underlying adverse effects of HDL on eNOS-activating pathways in patients with coronary artery disease. J Clin Invest. 2011;121(7):2693–708.PubMedPubMedCentralCrossRefGoogle Scholar
  11. 11.
    Kuningas M, Putters M, Westendorp RG, Slagboom PE, van Heemst D. SIRT1 gene, age-related diseases, and mortality: the Leiden 85-plus study. J Gerontol A Biol Sci Med Sci. 2007;62(9):960–5.PubMedCrossRefGoogle Scholar
  12. 12.
    Franzeck FC, Hof D, Spescha RD, Hasun M, Akhmedov A, Steffel J, et al. Expression of the aging gene p66Shc is increased in peripheral blood monocytes of patients with acute coronary syndrome but not with stable coronary artery disease. Atherosclerosis. 2012;220(1):282–6.PubMedCrossRefGoogle Scholar
  13. 13.
    Mitchell GF, Verwoert GC, Tarasov KV, Isaacs A, Smith AV, Yasmin, et al. Common genetic variation in the 3′-BCL11B gene desert is associated with carotid-femoral pulse wave velocity and excess cardiovascular disease risk: the AortaGen Consortium. Circ Cardiovasc Genet. 2012;5(1):81–90.PubMedCrossRefGoogle Scholar
  14. 14.
    Wenzel P, Schuhmacher S, Kienhofer J, Muller J, Hortmann M, Oelze M, et al. Manganese superoxide dismutase and aldehyde dehydrogenase deficiency increase mitochondrial oxidative stress and aggravate age-dependent vascular dysfunction. Cardiovasc Res. 2008;80(2):280–9.PubMedPubMedCentralCrossRefGoogle Scholar
  15. 15.
    Feng X, Wang L, Li Y. Change of telomere length in angiotensin II-induced human glomerular mesangial cell senescence and the protective role of losartan. Mol Med Rep. 2011;4(2):255–60.PubMedGoogle Scholar
  16. 16.
    Laurent S, Cockcroft J, Van Bortel L, Boutouyrie P, Giannattasio C, Hayoz D, et al. Expert consensus document on arterial stiffness: methodological issues and clinical applications. Eur Heart J. 2006;27(21):2588–605.PubMedCrossRefGoogle Scholar
  17. 17.
    O’Rourke MF, Safar ME, Dzau V. The Cardiovascular Continuum extended: aging effects on the aorta and microvasculature. Vasc Med. 2010;15(6):461–8.PubMedCrossRefGoogle Scholar
  18. 18.
    O’Rourke MF, Nichols WW. Aortic diameter, aortic stiffness, and wave reflection increase with age and isolated systolic hypertension. Hypertension. 2005;45(4):652–8.PubMedCrossRefGoogle Scholar
  19. 19.
    Laurent S, Boutouyrie P. The structural factor of hypertension: large and small artery alterations. Circ Res. 2015;116(6):1007–21.PubMedCrossRefGoogle Scholar
  20. 20.
    Mancia G, Fagard R, Narkiewicz K, Redon J, Zanchetti A, Bohm M, 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. 2013;34(28):2159–219.PubMedPubMedCentralCrossRefGoogle Scholar
  21. 21.
    Reference Values for Arterial Stiffness C. 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(19):2338–50.CrossRefGoogle Scholar
  22. 22.
    Ben-Shlomo Y, Spears M, Boustred C, May M, Anderson SG, Benjamin EJ, 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. 2014;63(7):636–46.PubMedPubMedCentralCrossRefGoogle Scholar
  23. 23.
    Laurent S, Boutouyrie P, Asmar R, Gautier I, Laloux B, Guize L, et al. Aortic stiffness is an independent predictor of all-cause and cardiovascular mortality in hypertensive patients. Hypertension. 2001;37(5):1236–41.PubMedCrossRefGoogle Scholar
  24. 24.
    Vlachopoulos C, Aznaouridis K, O’Rourke MF, Safar ME, Baou K, Stefanadis C. Prediction of cardiovascular events and all-cause mortality with central haemodynamics: a systematic review and meta-analysis. Eur Heart J. 2010;31(15):1865–71.PubMedPubMedCentralCrossRefGoogle Scholar
  25. 25.
    Redheuil A, Wu CO, Kachenoura N, Ohyama Y, Yan RT, Bertoni AG, et al. Proximal aortic distensibility is an independent predictor of all-cause mortality and incident CV events: the MESA study. J Am Coll Cardiol. 2014;64(24):2619–29.PubMedPubMedCentralCrossRefGoogle Scholar
  26. 26.
    Lorenz MW, Polak JF, Kavousi M, Mathiesen EB, Volzke H, Tuomainen TP, et al. Carotid intima-media thickness progression to predict cardiovascular events in the general population (the PROG-IMT collaborative project): a meta-analysis of individual participant data. Lancet. 2012;379(9831):2053–62.PubMedPubMedCentralCrossRefGoogle Scholar
  27. 27.
    Laurent S, Marais L, Boutouyrie P. The noninvasive assessment of vascular aging. Can J Cardiol. 2016;32(5):669–79.PubMedCrossRefGoogle Scholar
  28. 28.
    Garcia-Ortiz L, Recio-Rodriguez JI, Agudo-Conde C, Patino-Alonso MC, Rodriguez-Sanchez E, Maderuelo-Fernandez JA, et al. The role of retinal vessels caliber as a marker of vascular aging in large arteries. J Hypertens. 2015;33(4):818–26.. discussion 26PubMedCrossRefGoogle Scholar
  29. 29.
    Mitchell GF, van Buchem MA, Sigurdsson S, Gotal JD, Jonsdottir MK, Kjartansson O, et al. Arterial stiffness, pressure and flow pulsatility and brain structure and function: the age, gene/environment susceptibility – Reykjavik study. Brain. 2011;134(Pt 11):3398–407.PubMedPubMedCentralCrossRefGoogle Scholar
  30. 30.
    Maillard P, Seshadri S, Beiser A, Himali JJ, Au R, Fletcher E, et al. Effects of systolic blood pressure on white-matter integrity in young adults in the Framingham Heart Study: a cross-sectional study. Lancet Neurol. 2012;11(12):1039–47.PubMedPubMedCentralCrossRefGoogle Scholar
  31. 31.
    Terentes-Printzios D, Vlachopoulos C, Xaplanteris P, Ioakeimidis N, Aznaouridis K, Baou K, et al. Cardiovascular risk factors accelerate progression of vascular aging in the general population: results from the CRAVE study (Cardiovascular Risk Factors Affecting Vascular Age). Hypertension. 2017;70(5):1057–64.PubMedCrossRefGoogle Scholar
  32. 32.
    Botto F, Obregon S, Rubinstein F, Scuteri A, Nilsson PM, Kotliar C. Frequency of early vascular aging and associated risk factors among an adult population in Latin America: the OPTIMO study. J Hum Hypertens. 2018;32(3):219–27.PubMedCrossRefGoogle Scholar
  33. 33.
    Cunha PG, Boutouyrie P, Nilsson PM, Laurent S. Early Vascular Ageing (EVA): definitions and clinical applicability. Curr Hypertens Rev. 2017;13(1):8–15.PubMedCrossRefGoogle Scholar
  34. 34.
    Koivistoinen T, Lyytikainen LP, Aatola H, Luukkaala T, Juonala M, Viikari J, et al. Pulse wave velocity predicts the progression of blood pressure and development of hypertension in young adults. Hypertension. 2018;71(3):451–6.PubMedCrossRefGoogle Scholar
  35. 35.
    Karras A, Haymann JP, Bozec E, Metzger M, Jacquot C, Maruani G, et al. Large artery stiffening and remodeling are independently associated with all-cause mortality and cardiovascular events in chronic kidney disease. Hypertension. 2012;60(6):1451–7.PubMedCrossRefGoogle Scholar
  36. 36.
    Smith A, Karalliedde J, De Angelis L, Goldsmith D, Viberti G. Aortic pulse wave velocity and albuminuria in patients with type 2 diabetes. J Am Soc Nephrol: JASN. 2005;16(4):1069–75.PubMedCrossRefGoogle Scholar
  37. 37.
    Muhammad IF, Borne Y, Ostling G, Kennback C, Gottsater M, Persson M, et al. Arterial stiffness and incidence of diabetes: a population-based cohort study. Diabetes Care. 2017;40(12):1739–45.PubMedCrossRefGoogle Scholar
  38. 38.
    Elias MF, Robbins MA, Budge MM, Abhayaratna WP, Dore GA, Elias PK. Arterial pulse wave velocity and cognition with advancing age. Hypertension. 2009;53(4):668–73.PubMedPubMedCentralCrossRefGoogle Scholar
  39. 39.
    Wendell CR, Zonderman AB, Metter EJ, Najjar SS, Waldstein SR. Carotid intimal medial thickness predicts cognitive decline among adults without clinical vascular disease. Stroke. 2009;40(10):3180–5.PubMedPubMedCentralCrossRefGoogle Scholar
  40. 40.
    Nilsson PM, Laurent S, Cunha PG, Olsen MH, Rietzschel E, Franco OH, Ryliškytė L, Strazhesko I, Vlachopoulos C, Chen CH, Boutouyrie P, Cucca F, Lakatta EG, Scuteri A; Metabolic syndrome, Arteries REsearch (MARE) Consortium. Characteristics of healthy vascular ageing in pooled population-based cohort studies: the global Metabolic syndrome and Artery REsearch Consortium. J Hypertens. 2018;36(12):2340–9.PubMedPubMedCentralCrossRefGoogle Scholar
  41. 41.
    Bain SC, Gill GV, Dyer PH, Jones AF, Murphy M, Jones KE, et al. Characteristics of type 1 diabetes of over 50 years duration (the Golden Years Cohort). Diabet Med. 2003;20(10):808–11.PubMedCrossRefGoogle Scholar
  42. 42.
    Niiranen TJ, Lyass A, Larson MG, Hamburg NM, Benjamin EJ, Mitchell GF, et al. Prevalence, correlates, and prognosis of healthy vascular aging in a western community-dwelling cohort: the Framingham Heart Study. Hypertension. 2017;70(2):267–74.PubMedPubMedCentralCrossRefGoogle Scholar
  43. 43.
    Nowak KL, Rossman MJ, Chonchol M, Seals DR. Strategies for achieving healthy vascular aging. Hypertension. 2018;71(3):389–402.PubMedPubMedCentralCrossRefGoogle Scholar
  44. 44.
    Lemogoum D, Ngatchou W, Janssen C, Leeman M, Van Bortel L, Boutouyrie P, et al. Effects of hunter-gatherer subsistence mode on arterial distensibility in Cameroonian pygmies. Hypertension. 2012;60(1):123–8.PubMedCrossRefGoogle Scholar
  45. 45.
    Timio M, Lippi G, Venanzi S, Gentili S, Quintaliani G, Verdura C, et al. Blood pressure trend and cardiovascular events in nuns in a secluded order: a 30-year follow-up study. Blood Press. 1997;6(2):81–7.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.Institute of Cardiovascular and Medical Sciences, University of GlasgowGlasgowUK
  2. 2.Department of Clinical Sciences, Skane University HospitalLund UniversityMalmoSweden

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