Vascular aging and isolated systolic hypertension: scientific data and personal experience with the use of a fixed combination of amlodipine and indapamide

Arterial hypertension (HTN) remains a global medical and social problem, significantly affecting cardiovascular morbidity and mortality. Detailed study of mechanical and functional changes in the arterial wall associated with age has led to the development of the concepts of Early Vascular Aging (EVA syndrome), Healthy Vascular Aging (HVA) and SUPERNOrmal Vascular Aging (SUPERNOVA). Identification of predictors and pathogenetic mechanisms of the phenotypes formation, as well as determinants of arterial stiffness progression, allows developing preventive and therapeutic strategies to reduce mortality from cardiovascular diseases. At the same time, it is no less important to isolate patients with already formed arterial rigidity and, as a consequence, isolated systolic arterial hypertension (ISAH) into a separate group due to the need to optimize the treatment of this cohort in order to slow down the processes of increasing arterial stiffness and minimize the undesirable effects of hypoperfusion. Thus, the purpose of this literature review was to systematize the accumulated knowledge about the possibilities of slowing down the processes of vascular aging, as well as tools to improve the effectiveness and safety of treatment in the group of patients with ISAH. The article presents a clinical observation of 44 patients with ISAH who were treated at the Omsk Region Budgetary Healthcare Institution “Clinical Cardiology Dispensary” and received a fixed combination of amlodipine/indapamide. By the end of the observation period, high adherence, tolerability and effectiveness of this therapy were observed, as well as a trend towards a decrease in arterial stiffness, assessed by the cardio-ankle vascular index (CAVI). However, there is a need for further studies to stratify patients in order to identify cohorts that can potentially benefit more from the use of preventive interventions.

1. Zharenikova NV, Lopatynskaya NV, Tugova YUT. Hypertension: background and current aspects of therapeutic tactics. Istoriya i Pedagogika Estestvoznaniya = History and Pedagogy of Natural Science. 2018;4:33–39. (In Russ.) https://doi.org/10.24411/2226-2296-2018-10408

2. Balanova YuA, Drapkina OM, Kutsenko VA, Imaeva AE, Kontsevaya AV, Maksimov SA, et al. Hypertension in the Russian population during the COVID-19 pandemic: sex differences in prevalence, treatment and its effectiveness. Data from the ESSE-RF3 study. Kardiovaskulyarnaya Terapiya i Profilaktika = Cardiovascular Therapy and Prevention. 2023;22(8S):3785. (In Russ.) https://doi.org/10.15829/1728-8800-2023-3785

3. Rogoza AN, Kaveshnikov VS, Trubacheva IA, Serebriakova VN, Zairova AR, Zhernakova YuV, et al. The state of the vascular wall in adult population of Tomsk in the framework of the project ESSAY RF. Sistemnye Gipertenzii = Systemic Hypertension. 2014;11(4):42–48. (In Russ.) https://doi.org/10.26442/SG29048

4. Falaschetti E, Mindell J, Knott C, Poulter N. Hypertension management in England: a serial cross-sectional study from 1994 to 2011. Lancet. 2014;383(9932):1912–1919. https://doi.org/10.1016/S0140-6736(14)60688-7

5. Kobalava ZhD, Konradi AO, Nedogoda SV, Shlyakhto EV, Arutyunov GP, Baranova EI, et al. 2024 Clinical practice guidelines for hypertension in adults. Rossijskij Kardiologicheskij Zhurnal = Russian Journal of Cardiology. 2024;29(9):6117. (In Russ.) https://doi.org/10.15829/1560–4071–2024–6117

6. Vlachopoulos Ch, Nichols WW, O’Rourke M. McDonald’s blood flow in arteries: theoretical, experimental and clinical principles. 4th ed. London, UK: Arnold. 1998:54–401. https://doi.org/10.1201/b13568

7. Safar ME, London GM. The arterial system in human hypertension. In: Swales JD, ed. Textbook of Hypertension. London, UK: Blackwell Scientific; 1994: 85–102.

8. London GM, Pannier B. Arterial functions: how to interpret the complex physiology. Nephrol Dial Transplant. 2010;25(12):3815–23. https://doi.org/10.1093/ndt/gfq614

9. Safar ME, Levy BI, Struijker-Boudier H. Current perspectives on arterial stiffness and pulse pressure in hypertension and cardiovascular diseases. Circulation. 2003;107:2864–2869. https://doi.org/10.1161/01.CIR.0000069826.36125.B4

10. Vasan RS, Pan S, Xanthakis V, Beiser A, Larson MG, Seshadri S, et al. Arterial stiffness and long-term risk of health outcomes: The Framingham Heart Study. Hypertension. 2022;79:1045–1056. https://doi.org/10.1161/HYPERTENSIONAHA.121.18776

11. Tąpolska M, Spałek M, Szybowicz U, Domin R, Owsik K, Sochacka K, et al. Arterial stiffness parameters correlate with estimated cardiovascular risk in humans: a clinical study. Int J Environ Res Public Health. 2019;16(14):2547. https://doi.org/10.3390/ijerph16142547

12. Rotar OP, Tolkunova KM. EVA and SUPERNOVA concepts of vascular aging: ongoing research on damaging and protective risk factors. Arterial’naya Gipertenziya = Arterial Hypertension. 2020;26(2):133–145. (In Russ.) https://doi.org/10.18705/1607-419X-2020-26-2-133-145

13. Nilsson PM, Lurbe E, Laurent S. The early life origins of vascular ageing and cardiovascular risk: the EVA syndrome. J Hypertens. 2008;26(6):1049–57. https://doi.org/10.1097/HJH.0b013e3282f82c3e

14. Nilsson PM, Boutouyrie P, Laurent S. Vascular aging: A tale of EVA and ADAM in cardiovascular risk assessment and prevention. Hypertension. 2009;54(1):3–10. https://doi.org/10.1161/HYPERTENSIONAHA.109.129114

15. Laurent S, Boutouyrie P, Cunha PG, Lacolley P, Nilsson PM. Concept of extremes in vascular aging. Hypertension. 2019;74(2): 218–228. https://doi.org/10.1161/HYPERTENSIONAHA.119.12655

16. Nedogoda SV, SalasyukAS, Barykina IN, Lutova VO, Popova EA. Early vascular aging in patients with metabolic syndrome: features of the course and diagnosis. South Russia Journal of Therapeutic Practices. 2021;2(1):50–62. (In Russ.) https://doi.org/10.21886/2712-8156-2021-2-1-50-62

17. 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):267–274. https://doi.org/10.1161/HYPERTENSIONAHA.117.09026

18. Vipler B, Magee C, Douglas K. A Randomized trial of intensive versus standard blood-pressure control. N Engl J Med. 2016;374(23):2290–1. https://doi.org/10.1056/NEJMc1602668

19. Whelton P, Carey R, Aronow W. Casey DEJr, Collins KJ, Dennison Himmelfarb C, et al. 2017 ACC/AHA/AAPA/ABC/ ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA Guideline for the prevention, detection, evaluation, and management of high blood pressure in adults: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. JACC. 2018;71(19):e127-e248. https://doi.org/10.1016/j.jacc.2017.11.006

20. Nowak KL, Rossman MJ, Chonchol M, Seals DR. Strategies for achieving healthy vascular aging. Hypertension. 2018;71(3):389–402. https://doi.org/10.1161/HYPERTENSIONAHA.117.10439

21. De Oliveira Roza TL, Pimentel EB, Sartorio CL, and Mill J. G. Abstract P445: high salt intake increases arterial stiffness measured by pulse wave velocity in spontaneously hypertension rats. Hypertension. 2024;81(Suppl_1). https://doi.org/10.1161/hyp.81.suppl_1.P445

22. Ma H, Xue Q, Wang X, Li X, Franco OH, Li Y, et al. Adding salt to foods and hazard of premature mortality. Eur Heart J. 2022;43(30):2878–2888. https://doi.org/10.1093/eurheartj/ehac208

23. Otero-Luis I, Saz-Lara A, Moreno-Herráiz N, Lever-Megina CG, Bizzozero-Peroni B, Martínez-Ortega IA, et al. Exploring the association between mediterranean diet adherence and arterial stiffness in healthy adults: findings from the EvasCu Study. Nutrients. 2024;16(13):2158. https://doi:10.3390/nu16132158

24. Yang J, Chen X, Chen X, Li L. Physical activity and arterial stiffness: a narrative review. J Clin Hypertens (Greenwich). 2025;27(1): e14941. https://doi:10.1111/jch.14941

25. Saz-Lara A, Lucerón-Lucas-Torres M, Mesas AE, Notario-Pacheco B, López-Gil JF, Cavero-Redondo I. Association between sleep duration and sleep quality with arterial stiffness: A systematic review and meta-analysis. Sleep Health. 2022;8(6):663–670. https://doi:10.1016/j.sleh.2022.07.001

26. Voineskos D, Blumberger DM, Zomorrodi R, Rogasch NC, Farzan F, Foussias G, et al. Altered transcranial magnetic stimulation-electroencephalographic markers of inhibition and excitation in the dorsolateral prefrontal cortex in major depressive disorder. Biol Psychiatry. 2019;85(6):477–486. https://doi:10.1016/j.biopsych.2018.09.032

27. Luo S, Zhao Y, Zhu S, Liu L, Cheng K, Ye B, et al. Flavonifractor plautii protects against elevated arterial stiffness. Circ Res. 2023;132(2):167–181. https://doi:10.1161/CIRCRESAHA.122.321975

28. Rudoi MD. Prevalence of early vascular aging syndrome in men working under noise exposure. Arhiv Vnutrennej Meditsiny = The Russian Archives of Internal Medicine. 2024;14(1):72–80. (In Russ.) https://doi.org/10.20514/2226-6704-2024-14-1-72-80

29. Hamczyk MR, Nevado RM, Barettino A, Fuster V, Andrés V. Biological versus chronological aging: JACC focus seminar. J Am Coll Cardiol. 2020;75(8):919–930. https://doi:10.1016/j.jacc.2019.11.062

30. Solini A, Giannini L, Seghieri M, Vitolo E, Taddei S, Ghiadoni L, et al. Dapagliflozin acutely improves endothelial dysfunction, reduces aortic stiffness and renal resistive index in type 2 diabetic patients: a pilot study. Cardiovasc Diabetol. 2017;16(1):138. https://doi:10.1186/s12933-017-0621-8

31. Radić J, Vučković M, Đogaš H, Gelemanović A, Belančić A, Radić M. Is arterial stiffness interconnected with cardiovascular drug prescription patterns, body composition parameters, and the quality of blood pressure regulation in hypertensive patients? Biomedicines. 2024;12(9):2062. https://doi:10.3390/biomedicines12092062

32. Tolkunova KM, Rotar OP, Erina AM, Boiarinova MA, Alievа AS, Moguchaia EV, et al. Supernormal vascular aging — prevalence and determinants at population level (the ESSE-RF data). Arterial’naya Gipertenziya = Arterial Hypertensioт. 2020;26(2):170–183. (In Russ.) https://doi.org/10.18705/1607-419X-2020-26–2-170-183

33. Bruno RM, Nilsson PM, Engström G, Wadström BN, Empana JP, Boutouyrie P, et al. Early and supernormal vascular aging: clinical characteristics and association with incident cardiovascular events. Hypertension. 2020;76(5):1616–1624. https://doi:10.1161/HYPERTENSIONAHA.120.14971

34. Laurent S, Cunha P. Large vessels in hypertension: central blood pressure. In Lurbe E and Wuhl E, editors. Hypertension in Children and Adolescents. New York, NY: Springer publisher. 2019. https://doi:10.1007/978-3-030-18167-3_5

35. O’Rourke MF, Safar ME. Relationship between aortic stiffening and microvascular disease in brain and kidney: cause and logic of therapy. Hypertension. 2005;46(1):200–4. https://doi:10.1161/01.HYP.0000168052.00426.65

36. Al-Qamari A, Adeleke I, Kretzer A, Hogue CW. Pulse pressure and perioperative stroke. Curr Opin Anaesthesiol. 2019;32(1):57–63. https://doi:10.1097/ACO.0000000000000673

37. Boutouyrie P, Laurent S, Girerd X, Benetos A, Lacolley P, Abergel E, at al. Common carotid artery stiffness and patterns of left ventricular hypertrophy in hypertensive patients. Hypertension. 1995;25(4 Pt 1):651–9. https://doi:10.1161/01.hyp.25.4.651

38. Drapkina OM, Kaburova AN. Vascular stiffness and diastolic heart failure. Terapevticheskij arhiv = Therapeutic archive. 2013;11:75–81. (In Russ.)

39. Tang KS, Medeiros ED, Shah AD. Wide pulse pressure: A clinical review. J Clin Hypertens (Greenwich). 2020;22(11):1960– 1967. https://doi:10.1111/jch.14051

40. Brunström M, Carlberg B, Kjeldsen SE. Effect of antihypertensive treatment in isolated systolic hypertension (ISH) — systematic review and meta-analysis of randomised controlled trials. Blood Press. 2023;32(1):2226757. https://doi:10.1080/08037051.2023.2226757

41. Zhang S, Zhong Y, Wu S, Wu H, Cai J, Zhang W; STEP Study Group. Intensive blood pressure control on arterial stiffness among older patients with hypertension. Chin Med J (Engl). 2024;137(9):1078–1087. https://doi:10.1097/CM9.0000000000002868

42. Somes GW, Pahor M, Shorr RI, Cushman WC, Applegate WB. The role of diastolic blood pressure when treating isolated systolic hypertension. Arch Intern Med. 1999;159(17):2004–9. https://doi:10.1001/archinte.159.17.2004

43. Messerli FH, Mancia G, Conti CR, Hewkin AC, Kupfer S, Champion A, et al. Dogma disputed: can aggressively lowering blood pressure in hypertensive patients with coronary artery disease be dangerous? Ann Intern Med. 2006;144(12):884–93. https://doi:10.7326/0003-4819-144-12-200606200-00005

44. Kobalava ZD, Kolesnik EL, Shavarova EK, Goreva LA, Karapetyan LV. Effectiveness of indapamide/amlodipine single-pill combination in patients with isolated systolic hypertension: posthoc analysis of the ARBALET study. BMC Cardiovasc Disord. 2022;22(1):85. https://doi:10.1186/s12872-022-02514-y

45. Rimoldi SF, Messerli FH, Chavez P, Stefanini GG, Scherrer U. Efficacy and safety of calcium channel blocker/diuretics combination therapy in hypertensive patients: a meta-analysis. J Clin Hypertens (Greenwich). 2015;17(3):193–9. https://doi:10.1111/jch.12462

46. Coca A, Whelton SP, Camafort M, López-López JP, Yang E. Single-pill combination for treatment of hypertension: Just a matter of practicality or is there a real clinical benefit? Eur J Intern Med. 2024;126:16–25. https://doi:10.1016/j.ejim.2024.04.011

47. Kiru G, Roy A, Kondal D, Chandrasekaran AM, Mukherjee S, Mohan B et al; TOPSPIN Investigators. Treatment optimisation for blood pressure with single-pill combinations in India (TOPSPIN) — Protocol design and baseline characteristics. Int J Cardiol Cardiovasc Risk Prev. 2024;23:200346. https://doi:10.1016/j.ijcrp.2024.200346

48. Bäck M, Topouchian J, Labat C, Gautier S, Blacher J, Cwynar M, et al. Cardio-ankle vascular index for predicting cardiovascular morbimortality and determinants for its progression in the prospective advanced approach to arterial stiffness (TRIPLE-A-Stiffness) study. EBioMedicine. 2024;103:105107. https://doi:10.1016/j.ebiom.2024.105107

49. Gaisenok OV, Medvedev PA, Trifonova1 SS, Shatalova1 IV, Martsevich SYu, Sidorenko BA. Application of CAVI index in clinical practice: calculated vascular age as a tool for decision on additional examination of patients with cardiovascular diseases. Kardiologiia. 2015;55(7):51–56. (In Russ.)

50. Dawes J. Do data characteristics change according to the number of scale points used? An experiment using 5-point, 7-point and 10-point scales. Int. J. Mark. Res.2008;50(1):61–104. https://doi:10.1177/147078530805000106

51. Morisky DE, Green LW, Levine DM. Concurrent and predictive validity of a self-reported measure of medication adherence. Med Care. 1986;24(1):67–74. https://doi:10.1097/00005650-198601000-00007

52. Burnier M, Egan BM. Adherence in hypertension. Circ Res. 2019;124(7):1124–1140. https://doi:10.1161/CIRCRESAHA.118.313220