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Vascular Aging and Disease of the Small Vessels

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Abstract

Cardiovascular events are the consequence of vascular damage at both the macro and microcirculatory level. The relationship between large stiffening artery and microvascular disease may be bidirectional, since wave reflection from microvascular sites could increase systolic blood pressure and pulse pressure, while transmission of increased arterial pulsatility to microvessels could represent a mechanism of damage. Hypertension and aging share similar mechanisms of vascular dysfunction. In fact, vascular remodelling, endothelial dysfunction and vascular stiffness are common features in hypertension and aging. Structural and functional changes in small arteries occur during normal and accelerated aging, possibly triggered by hypertension. A cross-talk may be present between large and small artery changes, interacting with pressure wave transmission and reflection, exaggerating cardiac, brain and kidney damage, and finally leading to cardiovascular and renal complications.

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References

  1. Nilsson PM, Boutouyrie P, Laurent S. Vascular aging: a tale of EVA and ADAM in cardiovascular risk assessment and prevention. Hypertension. 2009;54:3–10.

    Article  CAS  PubMed  Google Scholar 

  2. Weber T, Segers P. Changes in central hemodynamics, wave reflection, and heart-vessel coupling with normal and accelerated aging. In: Nilsson P, Olsen MH, Laurent S (eds) Early vascular aging (EVA): new directions in cardiovascular protection. pp 83–95, 2015.

  3. Laurent S, Agabiti-Rosei E. The cross-talk between the macro- and the microcirculation. In: Nilsson P, Olsen MH, Laurent S (eds) Early vascular aging (EVA): new directions in cardiovascular protection. pp 105–118, 2015.

  4. Laurent S, Rizzoni D. Targeting central blood pressure through the micro-and macrocirculation cross-talk. In: Nilsson P, Olsen MH, Laurent S (eds) Early vascular aging (EVA): new directions in cardiovascular protection. pp 297–306, 2015.

  5. 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 

  6. Mulvany MJ, Aalkjaer C. Structure and function of small arteries. Physiol Rev. 1990;70:921–71.

    Article  CAS  PubMed  Google Scholar 

  7. Rizzoni D, Castellano M, Porteri E, Bettoni G, Muiesan ML, Agabiti Rosei E. Delayed development of hypertension after short-term nitrendipine treatment. Hypertension. 1994;24:131–9.

    Article  CAS  PubMed  Google Scholar 

  8. Aalkjaer C, Eiskjaer H, Mulvany MJ, Jespersen B, Kjaer T, Sorensen SS, Pedersen EB. Abnormal structure and function of isolated subcutaneous resistance vessels from essential hypertensive patients despite antihypertensive treatment. J Hypertens. 1989;7:305–10.

    CAS  PubMed  Google Scholar 

  9. Heagerty AM, Aalkjaaer C, Bund SJ, Korsgaard N, Mulvany MJ. Small artery structure in hypertension. Dual process of remodeling and growth. Hypertension. 1993;21:391–7.

    Article  CAS  PubMed  Google Scholar 

  10. Rizzoni D, Porteri E, Castellano M, Bettoni G, Muiesan ML, Muiesan P, Giulini SM, Agabiti Rosei E. Vascular hypertrophy and remodeling in secondary hypertension. Hypertension. 1996;28:785–90.

    Article  CAS  PubMed  Google Scholar 

  11. Rizzoni D, Porteri E, Guelfi D, Muiesan ML, Valentini U, Cimino A, Girelli A, Rodella L, Bianchi R, Sleiman I, Agabiti Rosei E. Structural alterations in subcutaneous small arteries of normotensive and hypertensive patients with non insulin dependent diabetes mellitus. Circulation. 2001;103:1238–44.

    Article  CAS  PubMed  Google Scholar 

  12. Boutouyrie P, Laurent S, Briet M. Importance of arterial stiffness as cardiovascular risk factor for future development of new type of drugs. Fundam Clin Pharmacol. 2008;22:241–6.

    Article  CAS  PubMed  Google Scholar 

  13. Mahmud A, Feely J. Spurious systolic hypertension of youth: fit young men with elastic arteries. Am J Hypertens. 2003;16(3):229–32.

    Article  PubMed  Google Scholar 

  14. Laurent S, Cockcroft J, Van Bortel L, Boutouyrie P, Giannattasio C, Hayoz D, Pannier B, Vlachopoulos C, Wilkinson I, Struijker-Boudier H, On behalf of the European Network for Non-invasive Investigation of Large Arteries. Expert consensus document on arterial stiffness: methodological issues and clinical applications. Eur Heart J. 2006;27:2588–605.

    Article  PubMed  Google Scholar 

  15. Agabiti-Rosei E, Mancia G, O’Rourke MF, Roman MJ, Safar ME, Smulyan H, Wang JG, Wilkinson IB, Williams B, Vlachopoulos C. Central blood pressure measurements and antihypertensive therapy: a consensus document. Hypertension. 2007;50:154–60.

    Article  CAS  PubMed  Google Scholar 

  16. McEniery CM, Yasmin A, Hall IR, Qasem A, Wilkinson IB, Cockcroft JR, ACCT Investigators. Normal vascular aging: differential effects on wave reflection and aortic pulse wave velocity: the Anglo-Cardiff Collaborative Trial (ACCT). Am Coll Cardiol. 2005;46(9):1753–60.

    Article  Google Scholar 

  17. Weber T, Wassertheurer S, Schmidt-Trucksäss A, Rodilla E, Ablasser C, Jankowski P, Lorenza Muiesan M, Giannattasio C, Mang C, Wilkinson I, Kellermair J, Hametner B, Pascual JM, Zweiker R, Czarnecka D, Paini A, Salvetti M, Maloberti A, McEniery C. Relationship between 24-h ambulatory central systolic blood pressure and left ventricular mass: a prospective multicenter study. Hypertension. 2017;70:1157–64.

    Article  CAS  PubMed  Google Scholar 

  18. Safar ME, Rizzoni D, Blacher J, Muiesan ML, Agabiti-Rosei E. Macro and microvasculature in hypertension: therapeutic aspects. J Hum Hypertens. 2008;22(9):590–5.

    Article  CAS  PubMed  Google Scholar 

  19. Westerhof BE, van den Wijngaard JP, Murgo JP, Westerhof N. Location of a reflection site is elusive: consequences for the calculation of aortic pulse wave velocity. Hypertension. 2008;52(3):478–83.

    Article  CAS  PubMed  Google Scholar 

  20. Rehman A, Schiffrin EL. Vascular effects of antihypertensive drug therapy. Curr Hypertens Rep. 2010;12:226–32.

    Article  CAS  PubMed  Google Scholar 

  21. Rizzoni D, Porteri E, Boari GEM, De Ciuceis C, Sleiman I, Muiesan ML, Castellano M, Miclini M, Agabiti-Rosei E. Prognostic significance of small artery structure in hypertension. Circulation. 2003;108:2230–5.

    Article  PubMed  Google Scholar 

  22. Boari GE, Rizzardi N, de Ciuceis C, Platto C, Paiardi S, Porteri E, Paini A, Salvetti M, Muiesan ML, Rizzoni D, Agabiti-Rosei E. Determinants of the structure of resistance-sized arteries in hypertensive patients. Blood Press. 2008;17(4):204–11.

    Article  PubMed  Google Scholar 

  23. Muiesan ML, Salvetti M, Rizzoni D, Paini A, Agabiti-Rosei C, Aggiusti C, Bertacchini F, Stassaldi D, Gavazzi A, Porteri E, De Ciuceis C, Agabiti-Rosei E. Pulsatile hemodynamics and microcirculation: evidence for a close relationship in hypertensive patients. Hypertension. 2013;61:130–6.

    Article  CAS  PubMed  Google Scholar 

  24. Harazny JM, Ritt M, Baleanu D, Ott C, Heckmann J, Schlaich MP, Michelson G, Schmieder RE. Increased wall:lumen ratio of retinal arterioles in male patients with a history of a cerebrovascular event. Hypertension. 2007;50(4):623–829.

    Article  CAS  PubMed  Google Scholar 

  25. Rizzoni D, Porteri E, Duse S, De Ciuceis C, Agabiti Rosei C, La Boria E, Semeraro F, Costagliola C, Sebastiani A, Danzi P, Tiberio GA, Giulini SM, Docchio F, Sansoni G, Sarkar A, Agabiti Rosei E. J Hypertens. 2012;30:1169–75.

    Article  CAS  PubMed  Google Scholar 

  26. Ott C, Raff U, Harazny JM, Michelson G, Schmieder RE. Central pulse pressure is an independent determinant of vascular remodeling in the retinal circulation. Hypertension. 2013;61:1340–5.

    Article  CAS  PubMed  Google Scholar 

  27. Salvetti M, Agabiti Rosei C, Paini A, Aggiusti C, Cancarini A, Duse S, Semeraro F, Rizzoni D, Agabiti Rosei E, Muiesan ML. Relationship of wall-to-lumen ratio of retinal arterioles with clinic and 24-hour blood pressure. Hypertension. 2014;63:1110–5.

    Article  CAS  PubMed  Google Scholar 

  28. Paini A, Muiesan ML, Agabiti-Rosei C, Aggiusti C, De Ciuceis C, Bertacchini F, Duse S, Semeraro F, Rizzoni D, Agabiti-Rosei E, Salvetti M. Carotid stiffness is significantly correlated with wall-to-lumen ratio of retinal arterioles. J Hypertens. 2018;36:580–6.

    Article  CAS  PubMed  Google Scholar 

  29. Laurent S, Briet M, Boutouyrie P. Large and small artery cross-talk and recent morbidity-mortality trials in hypertension. Hypertension. 2009;54:388–92.

    Article  CAS  PubMed  Google Scholar 

  30. Hashimoto J, Aikawa T, Imai Y. Large artery stiffening as a link between cerebral lacunar infarction and renal albuminuria. Am J Hypertens. 2008;21(12):1304–9.

    Article  CAS  PubMed  Google Scholar 

  31. Brisset M, Boutouyrie P, Pico F, Zhu Y, Zureik M, Schilling S, Dufouil C, Mazoyer B, Laurent S, Tzourio C, Debette S. Large-vessel correlates of cerebral small-vessel disease. Neurology. 2013;80:662–9.

    Article  PubMed  PubMed Central  Google Scholar 

  32. Wåhlin A, Ambarki K, Birgander R, Malm J, Eklund A. Intracranial pulsatility is associated with regional brain volume in elderly individuals. Neurobiol Aging. 2014;35:365–72.

    Article  PubMed  Google Scholar 

  33. Lamballais S, Sajjad A, Leening MJG, Gaillard R, Franco OH, Mattace-Raso FUS, Jaddoe VWV, Roza SJ, Tiemeier H, Ikram MA. Association of blood pressure and arterial stiffness with cognition in 2 population-based child and adult cohorts. J Am Heart Assoc. 2018;7:e009847.

    Article  PubMed  PubMed Central  Google Scholar 

  34. Waldstein SR, Rice SC, Thayer JF, Najjar SS, Scuteri A, Zonderman AB. Pulse pressure and pulse wave velocity are related to cognitive decline in the Baltimore Longitudinal Study of Aging. Hypertension. 2008;51:99–104.

    Article  CAS  PubMed  Google Scholar 

  35. SPRINT MIND Investigators for the SPRINT Research Group, Williamson JD, Pajewski NM, Auchus AP, Bryan RN, Chelune G, Cheung AK, Cleveland ML, Coker LH, Crowe MG, Cushman WC, Cutler JA, Davatzikos C, Desiderio L, Erus G, Fine LJ, Gaussoin SA, Harris D, Hsieh MK, Johnson KC, Kimmel PL, Tamura MK, Launer LJ, Lerner AJ, Lewis CE, Martindale-Adams J, Moy CS, Nasrallah IM, Nichols LO, Oparil S, Ogrocki PK, Rahman M, Rapp SR, Reboussin DM, Rocco MV, Sachs BC, Sink KM, Still CH, Supiano MA, Snyder JK, Wadley VG, Walker J, Weiner DE, Whelton PK, Wilson VM, Woolard N, Wright JT Jr, Wright CB. Effect of intensive vs standard blood pressure control on probable dementia: a randomized clinical trial. JAMA. 2019;321:553–61.

    Article  Google Scholar 

  36. Mitchell GF, van Buchem MA, Sigurdsson S, Gotal JD, Jonsdottir MK, Kjartansson Ó, Garcia M, Aspelund T, Harris TB, Gudnason V, Launer LJ. 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.

    Article  PubMed  PubMed Central  Google Scholar 

  37. Webb AJ, Simoni M, Mazzucco S, Kuker W, Schulz U, Rothwell PM. Increased cerebral arterial pulsatility in patients with leukoaraiosis: arterial stiffness enhances transmission of aortic pulsatility. Stroke. 2012;43:2631–6.

    Article  PubMed  Google Scholar 

  38. O’Rourke MF, Safar ME. Relationship between aortic stiffening and microvascular disease in brain and kidney: cause and logic of therapy. Hypertension. 2005;46:200–4.

    Article  CAS  PubMed  Google Scholar 

  39. Scuteri A, Nilsson PM, Tzourio C, Redon J, Laurent S. Microvascular brain damage with aging and hypertension: pathophysiological consideration and clinical implications. J Hypertens. 2011;29:1469–77.

    Article  CAS  PubMed  Google Scholar 

  40. Taddei S, Virdis A, Mattei P, Ghiadoni L, Fasolo CB, Sudano I, Salvetti A. Hypertension causes premature aging of endothelial function in humans. Hypertension. 1997;29:736–43.

    Article  CAS  PubMed  Google Scholar 

  41. De Ciuceis C, Rossini C, Agabiti Rosei C, Sarkar A, Porteri E, La Boria E, Gavazzi A, Petroboni B, Pileri P, Agabiti Rosei E, Rizzoni D. Relationship between age and structural alterations in subcutaneous small resistance arteries in hypertensive patients. In: 25th European meeting on Hypertension and cardiovascular protection (ESH) 2015, Milan, 12–15 June, e100 (7D.03), 2015.

  42. Bruno RM, Duranti E, Ippolito C, Segnani C, Bernardini N, Di Candio G, Chiarugi M, Taddei S, Virdis A. Different impact of essential hypertension on structural and functional age-related vascular changes. Hypertension. 2017;69:71–8.

    Article  CAS  PubMed  Google Scholar 

  43. Bruno RM, Grassi G, Seravalle G, Savoia C, Rizzoni D, Virdis A, Study Group on Micro- and Macrocirculation of the Italian Society of Hypertension (SIIA). Age- and sex-specific reference values for media/lumen ratio in small arteries and relationship with risk factors. Hypertension. 2018;71:1193–200.

    Article  CAS  PubMed  Google Scholar 

  44. Savoia C, Battistoni A, Calvez V, Cesario V, Montefusco G, Filippini A. Microvascular alterations in hypertension and vascular aging. Curr Hypertens Rev. 2017;13:16–23.

    Article  CAS  PubMed  Google Scholar 

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Correspondence to Damiano Rizzoni.

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Rizzoni, D., Rizzoni, M., Nardin, M. et al. Vascular Aging and Disease of the Small Vessels. High Blood Press Cardiovasc Prev 26, 183–189 (2019). https://doi.org/10.1007/s40292-019-00320-w

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