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Natural pathophysiological processes of heart aging as a factor in the development of cardiovascular diseases

Authors: Stepanova N.M., Serguladze S.Yu.

Company: Bakoulev National Medical Research Center for Cardiovascular Surgery, Moscow, 121552, Russian Federation

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Type:  Reviews


DOI: https://doi.org/10.24022/1997-3187-2021-15-1-72-86

For citation: Stepanova N.M., Serguladze S.Yu. Natural pathophysiological processes of heart aging as a factor in the development of cardiovascular diseases. Creative Cardiology. 2021; 15 (1): 72–86 (in Russ.). DOI: 10.24022/1997-3187-2021-15-1-72-86

Received / Accepted:  19.03.2021 / 26.03.2021

Keywords: heart pathophysiology of aging atrial fibrillation heart failure frailty

Full text:  

 

Abstract

An increase in the incidence of cardiovascular diseases (CVD) is directly associated with a patient's age. CVD occur as a result of various modifiable (lifestyle) and non-modifiable (age and heredity) risk factors. An increase in the life expectancy as well as in the percentage of the elderly population in the developed countries has attract-ed the attention of researchers to the role of unmodifiable risk factors in the development of CVD. During the process of aging, changes affect micro- and macroscopic levels of the cardiovascular system, calcium homeostasis, regulation of the adrenergic and the renin-angiotensin-aldosterone systems, and normal functioning of intracellular structures. They lead to the age-related myocardial remodeling, disruption of the cardiac conduction system, and changes in the systolic and diastolic functions of the heart. Structural and functional alterations of vessels accumulate throughout life, culminating in increased risk of developing CVD. The average age of the world's population is increasing at an unprecedented rate and this increase is changing the world. This "silver tsunami" emphasizes the need to provide advanced training in epidemiology and increase the cadre of experts in the study of aging. This review analyses studies performed to investigate the mechanisms of the pathophysiological processes of natural heart aging and their role in the development of CVD.

References

  1. Eurostat Statistics Explained. https://ec.europa.eu/eurostat/statistics-explained (Available at March 26, 2021)
  2. Sidney S., Quesenberry C.P. Jr, Jaffe M.G., Sorel M., Nguyen-Huynh M.N., Kushi L.H. et al. Recent trends in cardiovascular mortality in the United States and public health goals. JAMA Cardiol. 2016; 1 (5): 594–9. DOI: 10.1001/jamacardio.2016.1326. PMID: 27438477
  3. Sidney S., Go A.S., Jaffe M.G., Solomon M.D., Ambrosy A.P., Rana J.S. Association between aging of the US population and heart disease mortality from 2011 to 2017. JAMA Cardiol. 2019; 4 (12): 1280–6. DOI: 10.1001/jamacardio.2019.4187
  4. Ehrlich P.R., Ehrlich A.H. Can a collapse of global civilization be avoided? Proc. Biol. Sci. 2013; 280 (1754): 20122845. DOI: 10.1098/rspb.2012.2845
  5. United Nations. Department of Economic and Social Affairs. http://www.un.org/en/development/desa/news/population/2015-report.html (Available at 26.03.2021).
  6. Centers for Disease Control and Prevention. National Diabetes Statistics Report, 2020. Atlanta, GA: Centers for Disease Control and Prevention, U.S. Dept of Health and Human Services. http://wonder.cdc.gov/ucd-icd10.html (Available at 26.03.2021).
  7. Fryar C.D., Ostchega Y., Hales C.M., Zhang G., Kruszon-Moran D. Hypertension prevalence and control among adults: United States, 2015–2016. NCHS Data Brief. 2017; (289): 1–8. PMID: 29155682
  8. Wright S.P., Doughty R.N., Pearl A., Gamble G.D., Whalley G.A., Walsh H.J. et al. Plasma amino-terminal pro-brain natriuretic peptide and accuracy of heart-failure diagnosis in primary care: a randomized, controlled trial. J. Am. Coll. Cardiol. 2003; 42 (10): 1793–800. DOI: 10.1016/j.jacc.2003.05.011
  9. Oudejans I., Mosterd A., Bloemen J.A., Valk M.J., van Velzen E., Wielders J.P. et al. Clinical evaluation of geriatric outpatients with suspected heart failure: value of symptoms, signs, and additional tests. Eur. J. Heart Fail. 2011; 13 (5): 518–27. DOI: 10.1093/eurjhf/hfr021
  10. Goodnough L.T., Schrier S.L. Evaluation and management of anemia in the elderly. Am. J. Hematol. 2014; 89 (1): 88–96. DOI: 10.1002/ajh.23598
  11. Anker S.D., Kirwan B.A., van Veldhuisen D.J., Filippatos G., Comin-Colet J., Ruschitzka F. et al. Effects of ferric carboxymaltose on hospitalisations and mortality rates in iron-deficient heart failure patients: an individual patient data meta-analysis. Eur. J. Heart Fail. 2018; 20 (1): 125–33. DOI: 10.1002/ejhf.823
  12. Bansal N., Katz R., Robinson-Cohen C., Odden M.C., Dalrymple L, Shlipak M.G. et al. Absolute rates of heart failure, coronary heart disease, and stroke in chronic kidney disease: An analysis of 3 community-based cohort studies. JAMA Cardiol. 2017; 2 (3): 314–8. DOI: 10.1001/jamacardio.2016.4652
  13. Thadhani R., Appelbaum E., Pritchett Y., Chang Y., Wenger J., Tamez H. et al. Vitamin D therapy and cardiac structure and function in patients with chronic kidney disease: the PRIMO randomized controlled trial. JAMA. 2012; 307 (7): 674–84. DOI: 10.1001/jama.2012.120
  14. Evans M., Methven S., Gasparini A., Barany P., Birnie K., MacNeill S. et al. Cinacalcet use and the risk of cardiovascular events, fractures and mortality in chronic kidney disease patients with secondary hyperparathyroidism. Sci. Rep. 2018; 8 (1): 2103. DOI: 10.1038/s41598-018-20552-5
  15. Antonicelli R., Spazzafumo L., Scalvini S., Olivieri F., Matassini M.V., Parati G. et al. Exercise: a "new drug" for elderly patients with chronic heart failure. Aging (Albany NY). 2016; 8 (5): 860–72. DOI: 10.18632/aging.100901
  16. Dokainish H., Nguyen J.S., Bobek J., Goswami R., Lakkis N.M. Assessment of the American Society of Echocardiography – European Association of Echocardiography guidelines for diastolic function in patients with depressed ejection fraction: An echocardiographic and invasive haemodynamic study. Eur. J. Echocardiogr. 2011; 12 (11): 857–64. DOI: 10.1093/ejechocard/jer157
  17. Ponikowski P., Voors A.A., Anker S.D., Bueno H., Cleland J.G., Coats A.J. et al.; Authors/Task Force Members; Document Reviewers. 2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: The Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC). Developed with the special contribution of the Heart Failure Association (HFA) of the ESC. Eur. J. Heart Fail. 2016; 18 (8): 891–975. DOI: 10.1002/ejhf.592
  18. Redfield M.M. Heart failure with preserved ejection fraction. N. Engl. J. Med. 2016; 375 (19): 1868–77. DOI: 10.1056/NEJMcp1511175
  19. Bozkurt B., Khalaf S. Heart failure in women. Methodist DeBakey Cardiovasc J. 2017; 13 (4): 216–23. DOI: 10.14797/mdcj-13-4-216 20. Smulyan H., Mookherjee S., Safar M.E. The two faces of hypertension: role of aortic stiffness. J. Am. Soc. Hypertens. 2016; 10 (2): 175–83. DOI: 10.1016/j.jash.2015.11.012
  20. Angeli F., Reboldi G., Verdecchia P. Heart failure, pulse pressure and heart rate: Refining risk stratification. Int. J. Cardiol. 2018; 271: 206–8. DOI: 10.1016/j.ijcard.2018.07.072
  21. Tunbridge M., Holdaas H., Jardine A.G. Pulse pressure: A risk factor for renal transplant failure or a useful therapeutic target? Transplantation. 2019; 103 (4): 662–3. DOI: 10.1097/TP.0000000000002441
  22. Böckmann I., Lischka J., Richter B., Deppe J., Rahn A., Fischer D.C. et al. FGF23-Mediated Activation of Local RAAS Promotes Cardiac Hypertrophy and Fibrosis. Int. J. Mol. Sci. 2019; 20 (18): 4634. DOI: 10.3390/ijms20184634
  23. Travers J.G., Kamal F.A., Robbins J., Yutzey K.E., Blaxall B.C. Cardiac fibrosis: The fibroblast awakens. Circ. Res. 2016; 118 (6): 1021–40. DOI: 10.1161/CIRCRESAHA.115.306565
  24. Tesauro M., Mauriello A., Rovella V., Annicchiarico-Petruzzelli M., Cardillo C., Melino G., Di Daniele N. Arterial ageing: From endothelial dysfunction to vascular calcification. J. Intern. Med. 2017; 281 (5): 471–82. DOI: 10.1111/joim.12605
  25. Staessen J.A., Gasowski J., Wang J.G., Thijs L., Den Hond E., Boissel J.P. et al. Risks of untreated and treated isolated systolic hypertension in the elderly: Meta-analysis of outcome trials. Lancet. 2000; 355 (9207): 865–72. DOI: 10.1016/s0140-6736(99)07330-4
  26. Cook N.R., Appel L.J., Whelton P.K. Sodium intake and all-cause mortality over 20 years in the trials of hypertension prevention. J. Am. Coll. Cardiol. 2016; 68 (15): 1609–17. DOI: 10.1016/j.jacc.2016.07.745
  27. Bhatt D.L. Troponin and the J-curve of diastolic blood pressure: When lower is not better. J. Am. Coll. Cardiol. 2016; 68 (16): 1723–6. DOI: 10.1016/j.jacc.2016.08.007
  28. Beckett N.S., Peters R., Fletcher A.E., Staessen J.A., Liu L., Dumitrascu D. et al.; HYVET Study Group. Treatment of hypertension in patients 80 years of age or older. N. Engl. J. Med. 2008; 358 (18): 1887–98. DOI: 10.1056/NEJMoa0801369
  29. Khan N.A., Rabkin S.W., Zhao Y., McAlister F.A., Park J.E., Guan M. et al. Effect of lowering diastolic pressure in patients with and without cardiovascular disease: Analysis of the SPRINT (Systolic Blood Pressure Intervention Trial). Hypertension. 2018; 71 (5): 840–7. DOI: 10.1161/HYPERTENSIONAHA.117.10177
  30. Fuster V. No such thing as ideal blood pressure: A case for personalized medicine. J. Am. Coll. Cardiol. 2016; 67 (25): 3014–5. DOI: 10.1016/j.jacc.2016.05.005
  31. Konukoglu D., Uzun H. Endothelial dysfunction and hypertension. Adv. Exp. Med. Biol. 2017; 956: 511–40. DOI: 10.1007/5584_2016_90
  32. Durrant J.R., Seals D.R., Connell M.L., Russell M.J., Lawson B.R., Folian B.J. et al. Voluntary wheel running restores endothelial function in conduit arteries of old mice: direct evidence for reduced oxidative stress, increased superoxide dismutase activity and down-regulation of NADPH oxidase. J. Physiol. 2009; 587 (Pt 13): 3271–85. DOI: 10.1113/jphysiol.2009.169771
  33. Zhao Y., Vanhoutte P.M., Leung S.W. Vascular nitric oxide: Beyond eNOS. J. Pharmacol. Sci. 2015; 129 (2): 83–94. DOI: 10.1016/j.jphs.2015.09.002
  34. Wang H., Hartnett M.E. Roles of Nicotinamide Adenine Dinucleotide Phosphate (NADPH) Oxidase in angiogenesis: isoform-specific effects. Antioxidants (Basel). 2017; 6 (2): 40. DOI: 10.3390/antiox6020040
  35. Te Riet L., van Esch J.H., Roks A.J., van den Meiracker A.H., Danser A.H. Hypertension: renin-angiotensin-aldosterone system alterations. Circ. Res. 2015; 116 (6): 960–75. DOI: 10.1161/CIRCRESAHA.116.303587
  36. Gureev A.P., Shaforostova E.A., Popov V.N. Regulation of Mitochondrial Biogenesis as a Way for Active Longevity: Interaction Between the Nrf2 and PGC-1α Signaling Pathways. Front. Genet. 2019; 10: 435. DOI: 10.3389/fgene.2019.00435
  37. Saxena T., Ali A.O., Saxena M. Pathophysiology of essential hypertension: an update. Expert. Rev. Cardiovasc. Ther. 2018; 16 (12): 879–87. DOI: 10.1080/14779072.2018.1540301
  38. Paneni F., Diaz Cañestro C., Libby P., Lüscher T.F., Camici G.G. The Aging Cardiovascular System: Understanding It at the Cellular and Clinical Levels. J. Am. Coll. Cardiol. 2017; 69 (15): 1952–67. DOI: 10.1016/j.jacc.2017.01.064
  39. Niiranen T.J., Kalesan B., Hamburg N.M., Benjamin E.J., Mitchell G.F., Vasan R.S. Relative contributions of arterial stiffness and hypertension to cardiovascular disease: The Framingham Heart Study. J. Am. Heart. Assoc. 2016; 5 (11): e004271. DOI: 10.1161/JAHA.116.004271
  40. Fleg J.L., Strait J. Age-associated changes in cardiovascular structure and function: a fertile milieu for future disease. Heart Fail. Rev. 2012; 17: 545–54. DOI: 10.1007/s10741-011-9270-2
  41. Vorob'eva N.M., Tkacheva O.N. An elderly patient with atrial fibrillation: ways to enhance safety of anticoagulant therapy. Doctor.Ru. 2019; 10 (165): 16–22. DOI: 10.31550/1727-2378-2019-165-10- 16-22 (in Russ.).
  42. Zholbaeva A.Z., Tabina A.E., Golukhova E.Z. Molecular mechanisms of atrial fibrillation: “ideal” marker searching. Creative Cardiology. 2015; 2: 40–53. DOI: 10.15275/kreatkard.2015. 02.04 (in Russ.).
  43. Dun W., Boyden P.A. Aged atria: Electrical remodeling conducive to atrial fibrillation. J. Interv. Card. Electrophysiol. 2009; 25: 9–18. DOI: 10.1007/s10840-008-9358-3
  44. Bockeria L.A., Shengeliya L.D. Changes in the heart associated with atrial fibrillation. Part I. Cardiopathy of atrial fibrillation: new dilemmas and old problems. Annals of Arrhythmology. 2016; 13 (3): 138–47. DOI: 10.15275/annaritmol.2016. 3.2 (in Russ.).
  45. Packer M., McMurray J.J.V. Importance of endogenous compensatory vasoactive peptides in broadening the effects of inhibitors of the reninangiotensin system for the treatment of heart failure. Lancet. 2017; 389 (10081): 1831–40. DOI: 10.1016/S0140-6736(16)30969-2
  46. Pfeffer M.A., Claggett B., Assmann S.F., Boineau R., Anand I.S., Clausell N. et al. Regional variation in patients and outcomes in the Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist (TOPCAT) trial. Circulation. 2015; 131 (1): 34–42. DOI: 10.1161/CIRCULATIONAHA.114.013255
  47. Solomon S.D., Zile M., Pieske B., Voors A., Shah A., Kraigher-Krainer E. et al.; Prospective comparison of ARNI with ARB on Management of heart failure with preserved ejection fraction (PARAMOUNT) Investigators. The angiotensin receptor neprilysin inhibitor LCZ696 in heart failure with preserved ejection fraction: A phase 2 double-blind randomised controlled trial. Lancet. 2012; 380 (9851): 1387–95. DOI: 10.1016/S0140- 6736(12)61227-6
  48. Butler J., Hamo C.E., Filippatos G., Pocock S.J., Bernstein R.A., Brueckmann M. et al.; EMPEROR Trials Program. The potential role and rationale for treatment of heart failure with sodiumglucose co-transporter 2 inhibitors. Eur. J. Heart. Fail. 2017; 19 (11): 1390–400. DOI: 10.1002/ejhf.933
  49. Dekkers C.C.J., Sjöström C.D., Greasley P.J., Cain V., Boulton D.W., Heerspink H.J.L. Effects of the sodium-glucose co-transporter-2 inhibitor dapagliflozin on estimated plasma volume in patients with type 2 diabetes. Diabetes Obes Metab. 2019; 21 (12): 2667–73. DOI: 10.1111/dom.13855
  50. Matsutani D., Sakamoto M., Kayama Y., Takeda N., Horiuchi R., Utsunomiya K. Effect of canagliflozin on left ventricular diastolic function in patients with type 2 diabetes. Cardiovasc. Diabetol. 2018; 17 (1): 73. DOI: 10.1186/s12933-018-0717-9
  51. Mudaliar S., Alloju S., Henry R.R. Can a Shift in Fuel Energetics Explain the Beneficial Cardiorenal Outcomes in the EMPA-REG OUTCOME Study? A Unifying Hypothesis. Diabetes Care. 2016; 39 (7): 1115–22. DOI: 10.2337/dc16-0542
  52. Crawford P.A. Refueling the Failing Heart: A Case for Sodium-Glucose Cotransporter 2 Inhibition in Cardiac Energy Homeostasis. JACC Basic Transl. Sci. 2018; 3 (5): 588–90. DOI: 10.1016/j.jacbts. 2018.08.002
  53. Packer M. SGLT2 Inhibitors Produce Cardiorenal Benefits by Promoting Adaptive Cellular Reprog-ramming to Induce a State of Fasting Mimicry: A Paradigm Shift in Understanding Their Mecha-nism of Action. Diabetes Care. 2020; 43 (3): 508–11. DOI: 10.2337/dci19-0074. PMID: 32079684
  54. Shigiyama F., Kumashiro N., Miyagi M., Ikehara K., Kanda E, Uchino H., Hirose T. Effectiveness of dapagliflozin on vascular endothelial function and glycemic control in patients with early-stage type 2 diabetes mellitus: DEFENCE study. Cardiovasc. Diabetol. 2017; 16 (1): 84. DOI: 10.1186/s12933-017-0564-0
  55. Lambadiari V., Pavlidis G., Kousathana F., Maratou E., Georgiou D., Andreadou I. et al. Effects of different antidiabetic medications on endothelial glycocalyx, myocardial function, and vascular function in type 2 diabetic patients: One year follow-up study. J. Clin. Med. 2019; 8 (7): 983. DOI: 10.3390/jcm8070983
  56. Lee T.M., Chang N.C., Lin S.Z. Dapagliflozin, a selective SGLT2 Inhibitor, attenuated cardiac fibrosis by regulating the macrophage polarization via STAT3 signaling in infarcted rat hearts. Free Radic. Biol. Med. 2017; 104: 298–310. DOI: 10.1016/j.freeradbiomed.2017.01.035
  57. Habibi J., Aroor A.R., Sowers J.R., Jia G., Hayden M.R., Garro M. et al. Sodium glucose transporter 2 (SGLT2) inhibition with empagliflozin improves cardiac diastolic function in a female rodent model of diabetes. Cardiovasc. Diabetol. 2017; 16 (1): 9. DOI: 10.1186/s12933-016-0489-z

About Authors

  • Nadezhda M. Stepanova, Postgraduate, ORCID
  • Sergey Yu. Serguladze, Dr. Med. Sc., Senior Researcher, Head of Department, ORCID

Chief Editor

Leo A. Bockeria, MD, PhD, DSc, Professor, Academician of Russian Academy of Sciences, President of Bakoulev National Medical Research Center for Cardiovascular Surgery


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