Rational Pharmacotherapy in Cardiology

Advanced search

The Concept of Early Vascular Aging

Full Text:


The age is one of the main non-modified factors which reduces the elasticity of vessels and increases the appearance of atherosclerotic plaques. A number of studies have revealed that in some people, vascular changes occur at a younger age, while the presence of only classical risk factors does not explain the development of cardiovascular events in young people. This phenomenon is described as a syndrome of early, or accelerated, vascular aging (EVA). Aspects of this premature process include endothelial dysfunction, increased arterial stiffness, thickening of the intima-media complex and impaired dilatation of the central arteries, an increase of the reflected wave, hypertrophy of small vessels with a decrease in their lumen. Accelerated aging of the vascular wall increases the frequency of complications, therefore, recently "vascular age” is considered as an important predictor of individual risk of cardiovascular events. The review describes factors and mechanisms that trigger the process of EVA, genetic aspects of vascular damage and the biology of telomeres. Changes in hemodynamics and structural and functional properties of arteries during physiological and accelerated aging are presented. Currently, several indicators have been proposed that indicate arterial wall damaging and progression of vascular aging. The carotid-femoral pulse wave velocity is included in the list of indicators of subclinical target organs damage in ESH-ESC Guidelines for the management of arterial hypertension. The results of studies on the developing the new diagnostic markers for identifying individuals with "normal" or "early" ("accelerated") vascular aging are presented. Therapeutic strategies are aimed at decreasing the influence of factors that provoke EVA and include a non-pharmacological approach and medical intervention. The paper describes methods of therapeutic correction of the EVA syndrome.

About the Authors

N. V. Burko
Penza State University
Russian Federation

MD, PhD, Associate Professor, Chair of Therapy,

Krasnaya ul., 40, Penza, 440026

I. V. Avdeeva
Penza State University
Russian Federation

MD, PhD, Associate Professor, Chair of Therapy,

Krasnaya ul., 40, Penza, 440026

V. E. Oleynikov
Penza State University
Russian Federation

MD, PhD, Professor, Head of Chair of Therapy,

Krasnaya ul., 40, Penza, 440026

S. A. Boytsov
National Medical Research Center of Cardiology
Russian Federation

MD, PhD, Professor, Corresponding Member of the Russian Academy of Sciences, General Director of National Medical Research Center of Cardiology,

Tretya Cherepkovskaya ul. 15a, Moscow, 121552


1. Nilsson P.M. Early vascular ageing – a concept in development. European Endocrinology. 2015;11(1):26-31. DOI:10.17925/EE.2015.11.01.26.

2. Lakatta E.G., Levy D. Arterial and cardiac aging: major shareholders in cardiovascular disease enterprises (part I). Circulation. 2003;107:139-46. DOI:10.1161/01.CIR.0000048893.62841.F7.

3. Canto J.G., Kiefe С.I., Rogers W.J., et al. Number of coronary heart disease risk factors and mortality in patients with first myocardial infarction. JAMA. 2011;306(19):2120-7. DOI:10.1001/jama.2011.1654.

4. Nilsson P.M. Early vascular aging (EVA): consequences and prevention. Vasc Health Risk Manag. 2008;4:547-52.

5. Leonard A. The theories of Thomas Sydenham (1624-1689). J R Coll Physicians. 1990;24:141-3.

6. Arutyunov A.G., Nozdrin A.V., Shavgulidze K.B., et al. Differences between passport and biological (actual) age in the population of Russian patients suffering from arterial hypertension (analysis of the HYPERION register). Ter Arckhiv. 2018;4:21-8 (In Russ) DOI:10.26442/terarkh201890421-28.

7. Milei J., Ottaviani G., Lavezzi A.M., et al. Perinatal and infant early atherosclerotic coronary lesions. Can J Cardiol. 2008;24(2):137-41. DOI:10.1016/S0828-282X(08)70570-1.

8. Bouissou C., Lacolley P., Dabire H., et al. Increased stiffness and cell-matrix interactions of abdominal aorta in two experimental nonhypertensive models: long-term chemically sympathectomized and sinoaortic denervated rats.JHypertens. 2014;32(3):652-8.DOI:10.1097/HJH.0000000000000073.

9. DoyonA., KrachtD., BayazitA.K., et al. Carotid artery intima-media thickness and distensibility in children and adolescents. Hypertension. 2013; 62:550-6. DOI:10.1161/HYPERTENSIONAHA. 113.01297.

10. Nilsson P., Boutouyrie P., Laurent S. Vascular aging a tale of EVA and ADAM in cardiovascular risk assessment and prevention. Hypertension. 2009; 54:3-10. DOI:10.1161/HYPERTENSIONAHA. 109.129114.

11. Lee S.J., Park S.H. Arterial ageing. Korean Circ J. 2013;43(2):73-9. DOI:10.4070/kcj.2013.43.2.73.

12. Triantafyllidis H., Trivilou P., Ikonomidis I., et al. Is arterial hypertension control enough to improve aortic stiffness in untreated patients with hypertension? A 3-year follow-up study. Angiology. 2015;66(10):904-10. DOI:10.1177/0003319714552811.

13. Napoli C., D’Armiento F.P., Mancini F.P., et al. Fatty streak formation occurs in human fetal aortas and is greatly enhanced by maternal hypercholesterolemia. Intimal accumulation of low density lipoprotein and its oxidation precede monocyte recruitment into early atherosclerotic lesions. J Clin Invest. 1997;100(11):2680-90. DOI:10.1172/JCI119813.

14. Nilsson P., Boutouyrie P., Cunha P., et al. Early vascular ageing in translation: from laboratory investigations to clinical applications in cardiovascular prevention. J Hypertens. 2013;(31):1517-26. DOI:10.1097/HJH.0b013e328361e4bd.

15. Iurciuc S., Cimpean A.M., Mitu F., et al. Vascular aging and subclinical atherosclerosis: why such a “never ending” and challenging story in cardiology? Clinical Interventions in Aging. 2017;12:1339- 45. DOI:10.2147/CIA.S141265.

16. KotsisV.,Antza C., Stabouli S. Pathophysiology of early vascular ageing-opportunities fortreatment. The OpenHypertension Journal. 2013;5(Suppl 1:M2):58-62.DOI:10.2174/1876526201305010058.

17. Pitale S., Sahasrabuddhe A. Fetal origin of vascular aging. Indian J Endocrinol Metabol. 2011;15(Suppl 4):289-97. DOI:10.4103/2230-8210.86971.

18. Coimbra B.M., Carvalho C.M., Moretti P.N., et al. Stress-related telomere length in children: a systematic review. J Psychiatr Res. 2017;92:47-54. DOI:10.1016/j.jpsychires.2017.03.023.

19. Steven G., Chrysant S.G., Chrysant G.S. The age-related hemodynamic changes of blood pressure and their impact on the incidence of cardiovascular disease and stroke: new evidence. J Clin Hypertens. 2014;16(2):87-90. DOI:10.1111/jch.12253.

20. Ungvari Z., Kaley G., de Cabo R., et al. Mechanisms of vascular aging: new perspectives. J Gerontol Biol Sci Med Sci. 2010;65(10):1028-41. DOI:10.1093/gerona/glq113.

21. Le J., Zhang D., Menees S., et al. “Vascular age” is advanced in children with atherosclerosis-promoting risk factors. Circulation. 2010;3:8-14. DOI:10.1161/CIRCIMAGING.109.880070.

22. Kruglikova A. S., Strazhesko I. D., Tkacheva O. N., et al. Relationship of cardiovascular risk factors and biology of telomeres with signs of vascular aging. Cardiovascular Therapy and Prevention. 2014; 13(3):11-7. (In Russ.)

23. Denil S.L., Rietzschel E.R, De Buyzere M.L., et al. On cross-sectional associations of leukocyte telomere length with cardiac systolic, diastolic and vascular function: the Asklepios study. PLoS One. 2014;9:e115071. DOI:10.1371/journal.pone.0115071.

24. Logan J.G., Engler M.B., Kim H. Genetic determinants of arterial stiffness. J Cardiovasc Transl Res. 2015;8:23-43. DOI:10.1007/s12265-014-9597-x.

25. Yiannoutsos A, Levy B.I., Safar M.E., et al. Pathophysiology of hypertension: interactions between macro and microvascular alterations through endothelial dysfunction. J Hypertens. 2014;32(2):216- 24. DOI:10.1097/HJH.0000000000000021.

26. Anwar M.A., Shalhoub J., Lim C.S. The effect of pressure-induced mechanical stretch on vascular wall differential gene expression. J Vasc Res. 2012;49:463-78. DOI:10.1159/000339151.

27. Redheuil A., Yu W.C., Mousseaux E., et al. Age-related changes in aortic arch geometry: relationship with proximal aortic function and left ventricular mass and remodeling. J Am Coll Cardiol. 2011;58(12):1262-70. DOI:10.1016/j.jacc.2011.06.012.

28. Safar M.E., O’Rourke M.F., Frohlich E.D. Blood pressure and arterial wall mechanics in cardiovascular disease. London: Springer-Verlag; 2014. DOI:10.1007/978-1-4471-5198-2.

29. Berry J.D., Dyer A.D., Cai X., et al. Lifetime risks of cardiovascular disease. N Engl J Med. 2012;366:321-9. DOI:10.1056/NEJMoa1012848.

30. Engelen L., Ferreira I., Stehouwer C.D., et al. Reference intervals for common carotid intima-media thickness measured with echotracking: relation with risk factors. Eur Heart J. 2013;34(30):2368- 80. DOI:10.1093/eurheartj/ehs380.

31. Parati G., Ochoa J.E., Salvi P., Schillaci G. Arterial stiffness and blood pressure variability. In: Nilsson PM, ed. Early vascular aging. New directions in cardiovascular protections. London: Elsevier Inc; 2015.

32. Boutouyrie P., Laurent S., Benetos A., et al. Opposing effects of ageing on distal and proximal large arteries in hypertensives. J Hypertens Suppl. 1992;10(6):S87-91.

33. Briet M., Collin C., Karras A., et al. Arterial remodeling associates with CKD progression. J Am Soc Nephrol. 2011;22(5):967-74. DOI:10.1681/ASN.2010080863.

34. Olejnik A., Franczak A., Krzywonos-Zawadzka A., et al. The Biological Role of Klotho Protein in the Development of Cardiovascular Diseases. Biomed Res Int. 2018;5171945. DOI:10.1155/2018/ 5171945.

35. Laurent S., Cockkroft J., Van Bortel L., et al. Expert consensus document on arterial stiffness: methodological issues and clinical applications. Eur Heart J. 2006;27:2588-605. DOI:10.1093/eurheartj/ehl254.

36. Vlachopoulos С., Aznaouridis K., O'Rourke M.F., et al. Prediction of cardiovascular events and allcause mortality with central haemodynamics: a systematic review and meta-analysis. Eur Heart J. 2010;31(15):1865-71. DOI:10.1093/eurheartj/ehq024.

37. Mattace-Raso F., Hofman A., Verwoert G.C., et al. 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. DOI:10.1093/eurheartj/ehq165.

38. The Task Force for the management of arterial hypertension of the European Society of Cardiology (ESC) and the European Society of Hypertension (ESH). 2018 ESC/ESH Guidelines for the management of arterial hypertension. Journal of Hypertension. 2018;36:1953-2041. DOI:10.1093/eurheartj/ehy339.

39. Hald E.M., Lijfering W.M., Mathiesen E.B., et al. Carotid atherosclerosis predicts future myocardial infarction but not venous thromboembolism: the Tromso study. Arterioscler Thromb Vasc Biol. 2014;34(1):226-30. DOI:10.1161/ATVBAHA.113.302162.

40. Polak J.F., Sacco R.L., Post W.S., et al. Incident stroke is associated with common carotid artery diameter and not common carotid artery intima-media thickness. Stroke. 2014;45(5):1442-6. DOI:10.1016/j.jacc.2015.08.888.

41. Makris G.C., Lavida A., Griffin M., et al. Three-dimensional ultrasound imaging for the evaluation of carotid atherosclerosis. Atherosclerosis. 2011;219(2):377-83. DOI:10.1016/j.atherosclerosis.2011.05.006.

42. Teynor A., Caviezel S., Dratva J., et al. An automated, interactive analysis system for ultrasound sequences of the common carotid artery. Ultrasound Med Biol. 2012;38(8):1440-50. DOI:10.1016/j.ultrasmedbio.2012.03.015.

43. Alametsä J., Palomäki A. Comparison of local pulse wave velocity values acquired with EMFi sensor. Fin Je He W. 2012;4(2):89-98.

44. Williams B., Lacy P.S. Impact of heart rate on central aortic pressures and hemodynamics: analysis from the CAFE (Conduit Artery Function Evaluation) study: CAFE-Heart Rate. J Am Coll Cardiol. 2009;54(8):705-13. DOI:10.1016/j.jacc.2009.02.088.

45. Buljan K., Butković-Soldo B., Jančuljak D., et al. Relationship between age and thickness of carotid arteries in a population without risk factors for atherosclerosis. Coll Antr. 2015;39(3):779-84.

46. Grillo A., Lonati A.M., Guida V., Parati G. Cardio-ankle vascular stiffness index (CAVI) and 24-h blood pressure profiles. European Heart Journal Suppl. 2017; 19(Suppl B):17-23.

47. Fortier C., Sidibé A., Desjardins M.P., et al. Aortic-Brachial Pulse Wave Velocity Ratio: A Blood Pressure-Independent Index of Vascular Aging. Hypertension. 2017;69(1):96-101. DOI:10.1161/hypertensionaha.116.08409.

48. Mackenzie I.S., Wilkinson I.B., Cockcroft J. Assessment of arterial stiffness in clinical practice. QJM. 2002; 95:67-74.

49. Stabouli S., Papakatsika S., Kotronis G., et al. Arterial stiffness and SBP variability in children and adolescents. J Hypertens. 2015;33(1):88-95. DOI:10.1097/HJH.0000000000000369.

50. Recio-Rodriguez J.A., Gómez-Marcos M.A., Agudo-Conde C., et al. EVIDENT 3 Study: A randomized, controlled clinical trial to reduce inactivity and caloric intake in sedentary and overweight or obese people using a smartphone application. Medicine (Baltimore). 2018;97(2):e9633. DOI:10.1097/MD.0000000000009633.

51. Karpov Yu.A. How to prevent early vascular aging in patients with arterial hypertension? Atmosphere. Cardiology News. 2016;3:2-10. (In Russ.)

52. Nedogoda S.V., Palashkin R.V., Ledyaeva A.A., et al. Prevention of early vascular aging in obesity during therapy with angiotensin-converting enzyme inhibitors. Doctor.Ru. 2016;11(128):5-9. (In Russ.)

53. Nedogoda S.V., Chumachek E.V., Ledyaeva A.A., et al. Optimization of blood pressure control, organoprotection and metabolic disorders using a fixed combination of lisinopril+amlodipine+rosuvastatin in patients with arterial hypertension. Russian Cardiology Journal. 2018;4(156):131-42. (In Russ.) DOI:10.15829/1560- 4071-2018-4.

54. Kobalava Z.D., Kotovskaya Yu.V., Semagina I.M. Markers of cardiovascular aging: the effects of multicomponent therapy. Clinical Pharmacology and Therapy. 2016;25(3):46-52 (In Russ.)

55. Ong K.T., Delerme S., Pannier B., et al. 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;29:1034-42. DOI:10.1097/HJH.0b013e328346a583.

56. Laurent S., Mousseaux E., Boutouyrie P. Arterial stiffness as an imaging biomarker: are all pathways equal? Hypertension. 2013;62:10-2. DOI:10.1161/HYPERTENSIONAHA.113.01372.

57. Chow B.S.M., Koulis C., Krishnaswamy P., et al. The angiotensin II type 2 receptor agonist Compound 21 is protective in experimental diabetes-associated atherosclerosis. Diabetologia. 2016;59:1778. DOI:10.1007/s00125-016-3977-5.

58. Paulis L., Becker S.T., Lucht K., et al. Direct angiotensin II type 2 receptor stimulation in Nω-nitro-Larginine-methyl ester-induced hypertension: the effect on pulse wave velocity and aortic remodeling. Hypertension. 2012; 59:485-92. DOI:10.1161/HYPERTENSIONAHA.111.185496.

59. Guo Y., Li P., Gao L., et al. Kallistatin reduces vascular senescence and aging by regulating microRNA34a-SIRT1 pathway. Aging Cell. 2017;16(4):837-46. DOI:10.1111/acel.12615.

60. da Silva M.L., Chiappa G.R., da Silva V.M., et al. Effect of transcutaneous electrical nerve stimulation on peripheral to central blood pressure ratio in healthy subjects. Clin Physiol Funct Imaging. 2016;36(4):293-7. DOI:10.1111/cpf.12227.


For citations:

Burko N.V., Avdeeva I.V., Oleynikov V.E., Boytsov S.A. The Concept of Early Vascular Aging. Rational Pharmacotherapy in Cardiology. 2019;15(5):742-749. (In Russ.)

Views: 759

Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.

ISSN 1819-6446 (Print)
ISSN 2225-3653 (Online)