Advertisement

Age-Related Changes in Vascular Biology and Implications for Heart Failure Therapy in the Aging Population

  • Michael Sean McMurtryEmail author
Chapter

Abstract

Heart failure is a common cardiovascular disorder that is increasingly prevalent in aging Western populations. While heart failure is more prevalent in elderly populations due in part to increased prevalence of risk factors for heart failure, aging itself can alter the structure and function of the cardiovascular system, including the arterial tree as well as the myocardium, and contribute to heart failure independent of comorbidities or other exposures. This review will discuss the impact of age on the epidemiology of heart failure, age-related changes of the arterial tree and myocardium, age-associated changes in hemodynamics like arterial stiffness and their contribution to heart failure even in the presence of preserved left ventricular function, and putative molecular mechanism of aging in the cardiovascular system and discuss briefly implications of these observations for future efforts to prevent and to treat heart failure in elderly populations.

Keywords

Heart Failure Arterial Stiffness Arterial Tree Left Ventricular Systolic Dysfunction Aortic Stiffness 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Acknowledgments

Dr. O Baclic (Chronic Disease Management Division, PHAC), L Bartlett (The First Nations Information Governance Committee), T Bhatia (Data Coordination and Access Program, PHAC), Dr. M de Groh (Chronic Disease Prevention Division, PHAC), B Foster (Chronic Disease Prevention Division, PHAC), J Francis (Chronic Disease Evidence and Risk Assessment Division, PHAC), M-F Giguere (Strategic Policy Directorate, PHAC), C Gilbert (Chronic Disease Surveillance Division, PHAC), E Jones-McLean (Chronic Disease Prevention Division, PHAC), Dr. J Kahn (Portal Communications), K Lynch, Q Li (Statistics Canada), B Maga (Maga Policy Consultants Ltd.), J MacInnes (Chronic Disease Prevention Division, PHAC), N Martin (Neasa Martin & Associates), Dr. H Morrison (Chronic Disease Science Office, PHAC), B Power (Chronic Disease Management Division, PHAC), R Przybysz (Canadian Institute for Health Information), O Randell (Inuit Tapiriit Kanatami), H Roberge (Strategic Policy Directorate, PHAC), K Roberts (Chronic Disease Surveillance Division, PHAC), P Sales (Douglas Consulting), R Semenciw (Chronic Disease Surveillance Division, PHAC), T Simpson (Chronic Disease Prevention Division, PHAC), J Snider (Tobacco Control Programme, Health Canada), R Susanto (Statistics Canada), S Tanguay (Strategic Policy Directorate, PHAC), E Vanden (Chronic Disease Management Division, PHAC), R Walker (University of Calgary), and F Wang (Chronic Disease Evidence and Risk Assessment Division, PHAC).

We acknowledge Dr. RA Hegele and RL Pollex in the writing of Chapter Three – The Genetic Epidemiology of CVD.

We acknowledge Dr. MP Lindsay, Dr. M Hill, Dr. MK Kapral, Dr. M Sharma, Dr. S Phillips, and Dr. A Hakim, on behalf of the Canadian Stroke Network (www.canadianstrokenetwork.ca), in the writing of Chapter Five – Stroke.”

References

  1. 1.
    Roger VL, Go AS, Lloyd-Jones DM, Benjamin EJ, Berry JD, Borden WB, Bravata DM, Dai S, Ford ES, Fox CS, Fullerton HJ, Gillespie C, Hailpern SM, Heit JA, Howard VJ, Kissela BM, Kittner SJ, Lackland DT, Lichtman JH, Lisabeth LD, Makuc DM, Marcus GM, Marelli A, Matchar DB, Moy CS, Mozaffarian D, Mussolino ME, Nichol G, Paynter NP, Soliman EZ, Sorlie PD, Sotoodehnia N, Turan TN, Virani SS, Wong ND, Woo D, Turner MB. Heart disease and stroke statistics–2012 update: a report from the American heart association. Circulation. 2012;125:e2–220.PubMedGoogle Scholar
  2. 2.
    Levy D, Kenchaiah S, Larson MG, Benjamin EJ, Kupka MJ, Ho KK, Murabito JM, Vasan RS. Long-term trends in the incidence of and survival with heart failure. N Engl J Med. 2002;347:1397–402.PubMedGoogle Scholar
  3. 3.
    Roger VL, Weston SA, Redfield MM, Hellermann-Homan JP, Killian J, Yawn BP, Jacobsen SJ. Trends in heart failure incidence and survival in a community-based population. JAMA. 2004;292:344–50.PubMedGoogle Scholar
  4. 4.
    Barker WH, Mullooly JP, Getchell W. Changing incidence and survival for heart failure in a well-defined older population, 1970–1974 and 1990–1994. Circulation. 2006;113:799–805.PubMedGoogle Scholar
  5. 5.
    Heidenreich PA, Trogdon JG, Khavjou OA, Butler J, Dracup K, Ezekowitz MD, Finkelstein EA, Hong Y, Johnston SC, Khera A, Lloyd-Jones DM, Nelson SA, Nichol G, Orenstein D, Wilson PW, Woo YJ. Forecasting the future of cardiovascular disease in the united states: a policy statement from the American heart association. Circulation. 2011;123:933–44.PubMedGoogle Scholar
  6. 6.
    Tracking heart disease and stroke in Canada. Public Health Agency of Canada. Ottawa: Her Majesty the Queen in Right of Canada; 2009.Google Scholar
  7. 7.
    Lakatta EG, Levy D. Arterial and cardiac aging: major shareholders in cardiovascular disease enterprises: Part II: The aging heart in health: links to heart disease. Circulation. 2003;107:346–54.PubMedGoogle Scholar
  8. 8.
    Lakatta EG, Levy D. Arterial and cardiac aging: major shareholders in cardiovascular disease enterprises: Part I: Aging arteries: a “set up” for vascular disease. Circulation. 2003;107:139–46.PubMedGoogle Scholar
  9. 9.
    Mureddu GF, Agabiti N, Rizzello V, Forastiere F, Latini R, Cesaroni G, Masson S, Cacciatore G, Colivicchi F, Uguccioni M, Perucci CA, Boccanelli A. Prevalence of preclinical and clinical heart failure in the elderly. A population-based study in central Italy. Eur J Heart Fail. 2012;14:718–29.PubMedGoogle Scholar
  10. 10.
    Steinberg BA, Zhao X, Heidenreich PA, Peterson ED, Bhatt DL, Cannon CP, Hernandez AF, Fonarow GC. Trends in patients hospitalized with heart failure and preserved left ventricular ejection fraction: prevalence, therapies, and outcomes. Circulation. 2012;126:65–75.PubMedGoogle Scholar
  11. 11.
    Kawaguchi M, Hay I, Fetics B, Kass DA. Combined ventricular systolic and arterial stiffening in patients with heart failure and preserved ejection fraction: implications for systolic and diastolic reserve limitations. Circulation. 2003;107:714–20.PubMedGoogle Scholar
  12. 12.
    Fleg JL, Aronow WS, Frishman WH. Cardiovascular drug therapy in the elderly: benefits and challenges. Nat Rev Cardiol. 2011;8:13–28.PubMedGoogle Scholar
  13. 13.
    Lloyd-Jones DM, Larson MG, Leip EP, Beiser A, D’Agostino RB, Kannel WB, Murabito JM, Vasan RS, Benjamin EJ, Levy D. Lifetime risk for developing congestive heart failure: the Framingham heart study. Circulation. 2002;106:3068–72.PubMedGoogle Scholar
  14. 14.
    Djousse L, Driver JA, Gaziano JM. Relation between modifiable lifestyle factors and lifetime risk of heart failure. JAMA. 2009;302:394–400.PubMedCentralPubMedGoogle Scholar
  15. 15.
    Kalogeropoulos A, Georgiopoulou V, Kritchevsky SB, Psaty BM, Smith NL, Newman AB, Rodondi N, Satterfield S, Bauer DC, Bibbins-Domingo K, Smith AL, Wilson PW, Vasan RS, Harris TB, Butler J. Epidemiology of incident heart failure in a contemporary elderly cohort: the health, aging, and body composition study. Arch Intern Med. 2009;169:708–15.PubMedCentralPubMedGoogle Scholar
  16. 16.
    Franco OH, Peeters A, Bonneux L, de Laet C. Blood pressure in adulthood and life expectancy with cardiovascular disease in men and women: life course analysis. Hypertension. 2005;46:280–6.PubMedGoogle Scholar
  17. 17.
    Chen G, Hemmelgarn B, Alhaider S, Quan H, Campbell N, Rabi D. Meta-analysis of adverse cardiovascular outcomes associated with antecedent hypertension after myocardial infarction. Am J Cardiol. 2009;104:141–7.PubMedGoogle Scholar
  18. 18.
    Thune JJ, Signorovitch J, Kober L, Velazquez EJ, McMurray JJ, Califf RM, Maggioni AP, Rouleau JL, Howlett J, Zelenkofske S, Pfeffer MA, Solomon SD. Effect of antecedent hypertension and follow-up blood pressure on outcomes after high-risk myocardial infarction. Hypertension. 2008;51:48–54.PubMedGoogle Scholar
  19. 19.
    Andersson C, Gislason GH, Weeke P, Kjaergaard J, Hassager C, Akkan D, Moller JE, Kober L, Torp-Pedersen C. The prognostic importance of a history of hypertension in patients with symptomatic heart failure is substantially worsened by a short mitral inflow deceleration time. BMC Cardiovasc Disord. 2012;12:30.PubMedCentralPubMedGoogle Scholar
  20. 20.
    Harjola VP, Follath F, Nieminen MS, Brutsaert D, Dickstein K, Drexler H, Hochadel M, Komajda M, Lopez-Sendon JL, Ponikowski P, Tavazzi L. Characteristics, outcomes, and predictors of mortality at 3 months and 1 year in patients hospitalized for acute heart failure. Eur J Heart Fail. 2010;12:239–48.PubMedGoogle Scholar
  21. 21.
    Ather S, Chan W, Bozkurt B, Aguilar D, Ramasubbu K, Zachariah AA, Wehrens XH, Deswal A. Impact of noncardiac comorbidities on morbidity and mortality in a predominantly male population with heart failure and preserved versus reduced ejection fraction. J Am Coll Cardiol. 2012;59:998–1005.PubMedGoogle Scholar
  22. 22.
    Sikdar KC, Dowden J, Alaghehbandan R, Macdonald D, Peter P, Gadag V. Adverse drug reactions in elderly hospitalized patients: a 12-year population-based retrospective cohort study. Ann Pharmacother. 2012;46:960–71.PubMedGoogle Scholar
  23. 23.
    Schlatmann TJ, Becker AE. Histologic changes in the normal aging aorta: implications for dissecting aortic aneurysm. Am J Cardiol. 1977;39:13–20.PubMedGoogle Scholar
  24. 24.
    Virmani R, Avolio AP, Mergner WJ, Robinowitz M, Herderick EE, Cornhill JF, Guo SY, Liu TH, Ou DY, O’Rourke M. Effect of aging on aortic morphology in populations with high and low prevalence of hypertension and atherosclerosis. Comparison between occidental and chinese communities. Am J Pathol. 1991;139:1119–29.PubMedGoogle Scholar
  25. 25.
    Sugawara J, Hayashi K, Yokoi T, Tanaka H. Age-associated elongation of the ascending aorta in adults. JACC Cardiovasc Imaging. 2008;1:739–48.PubMedGoogle Scholar
  26. 26.
    Spagnoli LG, Orlandi A, Mauriello A, Santeusanio G, de Angelis C, Lucreziotti R, Ramacci MT. Aging and atherosclerosis in the rabbit. 1. Distribution, prevalence and morphology of atherosclerotic lesions. Atherosclerosis. 1991;89:11–24.PubMedGoogle Scholar
  27. 27.
    Clarkson TB. Nonhuman primate models of atherosclerosis. Lab Anim Sci. 1998;48:569–72.PubMedGoogle Scholar
  28. 28.
    Lorenz MW, Markus HS, Bots ML, Rosvall M, Sitzer M. Prediction of clinical cardiovascular events with carotid intima-media thickness: a systematic review and meta-analysis. Circulation. 2007;115:459–67.PubMedGoogle Scholar
  29. 29.
    Den Ruijter HM, Peters SA, Anderson TJ, Britton AR, Dekker JM, Eijkemans MJ, Engstrom G, Evans GW, de Graaf J, Grobbee DE, Hedblad B, Hofman A, Holewijn S, Ikeda A, Kavousi M, Kitagawa K, Kitamura A, Koffijberg H, Lonn EM, Lorenz MW, Mathiesen EB, Nijpels G, Okazaki S, O’Leary DH, Polak JF, Price JF, Robertson C, Rembold CM, Rosvall M, Rundek T, Salonen JT, Sitzer M, Stehouwer CD, Witteman JC, Moons KG, Bots ML. Common carotid intima-media thickness measurements in cardiovascular risk prediction: a meta-analysis. JAMA. 2012;308:796–803.Google Scholar
  30. 30.
    Elias-Smale SE, Kavousi M, Verwoert GC, Koller MT, Steyerberg EW, Mattace-Raso FU, Hofman A, Hoeks AP, Reneman RS, Witteman JC. Common carotid intima-media thickness in cardiovascular risk stratification of older people: the Rotterdam study. Eur J Prev Cardiol. 2012;19:698–705.PubMedGoogle Scholar
  31. 31.
    Nesi G, Anichini C, Tozzini S, Boddi V, Calamai G, Gori F. Pathology of the thoracic aorta: a morphologic review of 338 surgical specimens over a 7-year period. Cardiovasc Pathol. 2009;18:134–9.PubMedGoogle Scholar
  32. 32.
    Cattell MA, Anderson JC, Hasleton PS. Age-related changes in amounts and concentrations of collagen and elastin in normotensive human thoracic aorta. Clin Chim Acta. 1996;245:73–84.PubMedGoogle Scholar
  33. 33.
    Robert L. Aging of the vascular-wall and atherosclerosis. Exp Gerontol. 1999;34:491–501.PubMedGoogle Scholar
  34. 34.
    Atkinson J. Aging of arterial extracellular matrix elastin: etiology and consequences. Pathol Biol (Paris). 1998;46:555–9.Google Scholar
  35. 35.
    Yildiz O. Vascular smooth muscle and endothelial functions in aging. Ann N Y Acad Sci. 2007;1100:353–60.PubMedGoogle Scholar
  36. 36.
    Brandes RP, Fleming I, Busse R. Endothelial aging. Cardiovasc Res. 2005;66:286–94.PubMedGoogle Scholar
  37. 37.
    Celermajer DS, Sorensen KE, Spiegelhalter DJ, Georgakopoulos D, Robinson J, Deanfield JE. Aging is associated with endothelial dysfunction in healthy men years before the age-related decline in women. J Am Coll Cardiol. 1994;24:471–6.PubMedGoogle Scholar
  38. 38.
    Asai K, Kudej RK, Shen YT, Yang GP, Takagi G, Kudej AB, Geng YJ, Sato N, Nazareno JB, Vatner DE, Natividad F, Bishop SP, Vatner SF. Peripheral vascular endothelial dysfunction and apoptosis in old monkeys. Arterioscler Thromb Vasc Biol. 2000;20:1493–9.PubMedGoogle Scholar
  39. 39.
    Shirasaki Y, Su C, Lee TJ, Kolm P, Cline Jr WH, Nickols GA. Endothelial modulation of vascular relaxation to nitrovasodilators in aging and hypertension. J Pharmacol Exp Ther. 1986;239:861–6.PubMedGoogle Scholar
  40. 40.
    Busse R, Fleming I. Regulation of endothelium-derived vasoactive autacoid production by hemodynamic forces. Trends Pharmacol Sci. 2003;24:24–9.PubMedGoogle Scholar
  41. 41.
    Mantelli L, Amerini S, Ledda F. Roles of nitric oxide and endothelium-derived hyperpolarizing factor in vasorelaxant effect of acetylcholine as influenced by aging and hypertension. J Cardiovasc Pharmacol. 1995;25:595–602.PubMedGoogle Scholar
  42. 42.
    Bussemaker E, Popp R, Fisslthaler B, Larson CM, Fleming I, Busse R, Brandes RP. Aged spontaneously hypertensive rats exhibit a selective loss of EDHF-mediated relaxation in the renal artery. Hypertension. 2003;42:562–8.PubMedGoogle Scholar
  43. 43.
    Dohi Y, Kojima M, Sato K, Luscher TF. Age-related changes in vascular smooth muscle and endothelium. Drugs Aging. 1995;7:278–91.PubMedGoogle Scholar
  44. 44.
    Hamilton CA, Brosnan MJ, McIntyre M, Graham D, Dominiczak AF. Superoxide excess in hypertension and aging: a common cause of endothelial dysfunction. Hypertension. 2001;37:529–34.PubMedGoogle Scholar
  45. 45.
    van der Loo B, Labugger R, Skepper JN, Bachschmid M, Kilo J, Powell JM, Palacios-Callender M, Erusalimsky JD, Quaschning T, Malinski T, Gygi D, Ullrich V, Luscher TF. Enhanced peroxynitrite formation is associated with vascular aging. J Exp Med. 2000;192:1731–44.PubMedCentralPubMedGoogle Scholar
  46. 46.
    Numaguchi Y, Harada M, Osanai H, Hayashi K, Toki Y, Okumura K, Ito T, Hayakawa T. Altered gene expression of prostacyclin synthase and prostacyclin receptor in the thoracic aorta of spontaneously hypertensive rats. Cardiovasc Res. 1999;41:682–8.PubMedGoogle Scholar
  47. 47.
    Tschudi MR, Barton M, Bersinger NA, Moreau P, Cosentino F, Noll G, Malinski T, Luscher TF. Effect of age on kinetics of nitric oxide release in rat aorta and pulmonary artery. J Clin Invest. 1996;98:899–905.PubMedCentralPubMedGoogle Scholar
  48. 48.
    Barton M, Cosentino F, Brandes RP, Moreau P, Shaw S, Luscher TF. Anatomic heterogeneity of vascular aging: role of nitric oxide and endothelin. Hypertension. 1997;30:817–24.PubMedGoogle Scholar
  49. 49.
    Matz RL, Andriantsitohaina R. Age-related endothelial dysfunction: potential implications for pharmacotherapy. Drugs Aging. 2003;20:527–50.PubMedGoogle Scholar
  50. 50.
    Tanabe T, Maeda S, Miyauchi T, Iemitsu M, Takanashi M, Irukayama-Tomobe Y, Yokota T, Ohmori H, Matsuda M. Exercise training improves ageing-induced decrease in eNOS expression of the aorta. Acta Physiol Scand. 2003;178:3–10.PubMedGoogle Scholar
  51. 51.
    Maeda S, Tanabe T, Miyauchi T, Otsuki T, Sugawara J, Iemitsu M, Kuno S, Ajisaka R, Yamaguchi I, Matsuda M. Aerobic exercise training reduces plasma endothelin-1 concentration in older women. J Appl Physiol. 2003;95:336–41.PubMedGoogle Scholar
  52. 52.
    Taddei S, Galetta F, Virdis A, Ghiadoni L, Salvetti G, Franzoni F, Giusti C, Salvetti A. Physical activity prevents age-related impairment in nitric oxide availability in elderly athletes. Circulation. 2000;101:2896–901.PubMedGoogle Scholar
  53. 53.
    Peters SA, den Ruijter HM, Bots ML, Moons KG. Improvements in risk stratification for the occurrence of cardiovascular disease by imaging subclinical atherosclerosis: a systematic review. Heart. 2012;98:177–84.PubMedGoogle Scholar
  54. 54.
    Yeboah J, Folsom AR, Burke GL, Johnson C, Polak JF, Post W, Lima JA, Crouse JR, Herrington DM. Predictive value of brachial flow-mediated dilation for incident cardiovascular events in a population-based study: the multi-ethnic study of atherosclerosis. Circulation. 2009;120:502–9.PubMedCentralPubMedGoogle Scholar
  55. 55.
    Rattazzi M, Bertacco E, Puato M, Faggin E, Pauletto P. Hypertension and vascular calcification: a vicious cycle? J Hypertens. 2012;30:1885–93.PubMedGoogle Scholar
  56. 56.
    Sage AP, Tintut Y, Demer LL. Regulatory mechanisms in vascular calcification. Nat Rev Cardiol. 2010;7:528–36.PubMedCentralPubMedGoogle Scholar
  57. 57.
    Speer MY, Yang HY, Brabb T, Leaf E, Look A, Lin WL, Frutkin A, Dichek D, Giachelli CM. Smooth muscle cells give rise to osteochondrogenic precursors and chondrocytes in calcifying arteries. Circ Res. 2009;104:733–41.PubMedCentralPubMedGoogle Scholar
  58. 58.
    Rattazzi M, Iop L, Faggin E, Bertacco E, Zoppellaro G, Baesso I, Puato M, Torregrossa G, Fadini GP, Agostini C, Gerosa G, Sartore S, Pauletto P. Clones of interstitial cells from bovine aortic valve exhibit different calcifying potential when exposed to endotoxin and phosphate. Arterioscler Thromb Vasc Biol. 2008;28:2165–72.PubMedGoogle Scholar
  59. 59.
    Fadini GP, Albiero M, Menegazzo L, Boscaro E, Vigili de Kreutzenberg S, Agostini C, Cabrelle A, Binotto G, Rattazzi M, Bertacco E, Bertorelle R, Biasini L, Mion M, Plebani M, Ceolotto G, Angelini A, Castellani C, Menegolo M, Grego F, Dimmeler S, Seeger F, Zeiher A, Tiengo A, Avogaro A. Widespread increase in myeloid calcifying cells contributes to ectopic vascular calcification in type 2 diabetes. Circ Res. 2011;108:1112–21.PubMedGoogle Scholar
  60. 60.
    Yeboah J, McClelland RL, Polonsky TS, Burke GL, Sibley CT, O’Leary D, Carr JJ, Goff DC, Greenland P, Herrington DM. Comparison of novel risk markers for improvement in cardiovascular risk assessment in intermediate-risk individuals. JAMA. 2012;308:788–95.PubMedGoogle Scholar
  61. 61.
    Eisen A, Tenenbaum A, Koren-Morag N, Tanne D, Shemesh J, Imazio M, Fisman EZ, Motro M, Schwammenthal E, Adler Y. Calcification of the thoracic aorta as detected by spiral computed tomography among stable angina pectoris patients: association with cardiovascular events and death. Circulation. 2008;118:1328–34.PubMedGoogle Scholar
  62. 62.
    Santos RD, Rumberger JA, Budoff MJ, Shaw LJ, Orakzai SH, Berman D, Raggi P, Blumenthal RS, Nasir K. Thoracic aorta calcification detected by electron beam tomography predicts all-cause mortality. Atherosclerosis. 2010;209:131–5.PubMedGoogle Scholar
  63. 63.
    Allison MA, Hsi S, Wassel CL, Morgan C, Ix JH, Wright CM, Criqui MH. Calcified atherosclerosis in different vascular beds and the risk of mortality. Arterioscler Thromb Vasc Biol. 2012;32:140–6.PubMedGoogle Scholar
  64. 64.
    Izzo Jr JL, Shykoff BE. Arterial stiffness: clinical relevance, measurement, and treatment. Rev Cardiovasc Med. 2001;2(29–34):37–40.Google Scholar
  65. 65.
    Franklin SS, Gustin WT, Wong ND, Larson MG, Weber MA, Kannel WB, Levy D. Hemodynamic patterns of age-related changes in blood pressure. The Framingham heart study. Circulation. 1997;96:308–15.PubMedGoogle Scholar
  66. 66.
    Safar ME, London GM. Therapeutic studies and arterial stiffness in hypertension: recommendations of the European society of hypertension. The clinical committee of arterial structure and function. Working group on vascular structure and function of the european society of hypertension. J Hypertens. 2000;18:1527–35.PubMedGoogle Scholar
  67. 67.
    Blacher J, Asmar R, Djane S, London GM, Safar ME. Aortic pulse wave velocity as a marker of cardiovascular risk in hypertensive patients. Hypertension. 1999;33:1111–7.PubMedGoogle Scholar
  68. 68.
    Redheuil A, Yu WC, Wu CO, Mousseaux E, de Cesare A, Yan R, Kachenoura N, Bluemke D, Lima JA. Reduced ascending aortic strain and distensibility: earliest manifestations of vascular aging in humans. Hypertension. 2010;55:319–26.PubMedCentralPubMedGoogle Scholar
  69. 69.
    Cecelja M, Chowienczyk P. Dissociation of aortic pulse wave velocity with risk factors for cardiovascular disease other than hypertension: a systematic review. Hypertension. 2009;54:1328–36.PubMedGoogle Scholar
  70. 70.
    McEniery CM, Yasmin, Maki-Petaja KM, McDonnell BJ, Munnery M, Hickson SS, Franklin SS, Cockcroft JR, Wilkinson IB. The impact of cardiovascular risk factors on aortic stiffness and wave reflections depends on age: the Anglo-Cardiff collaborative trial (ACCT III). Hypertension 2010;56:591–7.Google Scholar
  71. 71.
    Bhuiyan AR, Srinivasan SR, Chen W, Paul TK, Berenson GS. Correlates of vascular structure and function measures in asymptomatic young adults: the Bogalusa heart study. Atherosclerosis. 2006;189:1–7.PubMedGoogle Scholar
  72. 72.
    O’Rourke MF, Hashimoto J. Mechanical factors in arterial aging: a clinical perspective. J Am Coll Cardiol. 2007;50:1–13.PubMedGoogle Scholar
  73. 73.
    McEniery CM, McDonnell BJ, So A, Aitken S, Bolton CE, Munnery M, Hickson SS, Yasmin, Maki-Petaja KM, Cockcroft JR, Dixon AK, Wilkinson IB. Aortic calcification is associated with aortic stiffness and isolated systolic hypertension in healthy individuals. Hypertension 2009;53:524–31.Google Scholar
  74. 74.
    Vlachopoulos C, Aznaouridis K, Stefanadis C. Prediction of cardiovascular events and all-cause mortality with arterial stiffness: a systematic review and meta-analysis. J Am Coll Cardiol. 2010;55:1318–27.PubMedGoogle Scholar
  75. 75.
    Franklin SS, Khan SA, Wong ND, Larson MG, Levy D. Is pulse pressure useful in predicting risk for coronary heart disease? The Framingham heart study. Circulation. 1999;100:354–60.PubMedGoogle Scholar
  76. 76.
    Millar JA, Lever AF, Burke V. Pulse pressure as a risk factor for cardiovascular events in the MRC mild hypertension trial. J Hypertens. 1999;17:1065–72.PubMedGoogle Scholar
  77. 77.
    Chae CU, Pfeffer MA, Glynn RJ, Mitchell GF, Taylor JO, Hennekens CH. Increased pulse pressure and risk of heart failure in the elderly. JAMA. 1999;281:634–9.PubMedGoogle Scholar
  78. 78.
    Mitchell GF, Parise H, Benjamin EJ, Larson MG, Keyes MJ, Vita JA, Vasan RS, Levy D. Changes in arterial stiffness and wave reflection with advancing age in healthy men and women: the Framingham heart study. Hypertension. 2004;43:1239–45.PubMedGoogle Scholar
  79. 79.
    Olivetti G, Giordano G, Corradi D, Melissari M, Lagrasta C, Gambert SR, Anversa P. Gender differences and aging: effects on the human heart. J Am Coll Cardiol. 1995;26:1068–79.PubMedGoogle Scholar
  80. 80.
    Swinne CJ, Shapiro EP, Lima SD, Fleg JL. Age-associated changes in left ventricular diastolic performance during isometric exercise in normal subjects. Am J Cardiol. 1992;69:823–6.PubMedGoogle Scholar
  81. 81.
    Schulman SP, Lakatta EG, Fleg JL, Lakatta L, Becker LC, Gerstenblith G. Age-related decline in left ventricular filling at rest and exercise. Am J Physiol. 1992;263:H1932–8.PubMedGoogle Scholar
  82. 82.
    Benjamin EJ, Levy D, Anderson KM, Wolf PA, Plehn JF, Evans JC, Comai K, Fuller DL, Sutton MS. Determinants of Doppler indexes of left ventricular diastolic function in normal subjects (the Framingham heart study). Am J Cardiol. 1992;70:508–15.PubMedGoogle Scholar
  83. 83.
    Fleg JL, O’Connor F, Gerstenblith G, Becker LC, Clulow J, Schulman SP, Lakatta EG. Impact of age on the cardiovascular response to dynamic upright exercise in healthy men and women. J Appl Physiol. 1995;78:890–900.PubMedGoogle Scholar
  84. 84.
    Rodeheffer RJ, Gerstenblith G, Beard E, Fleg JL, Becker LC, Weisfeldt ML, Lakatta EG. Postural changes in cardiac volumes in men in relation to adult age. Exp Gerontol. 1986;21:367–78.PubMedGoogle Scholar
  85. 85.
    Yin FC, Raizes GS, Guarnieri T, Spurgeon HA, Lakatta EG, Fortuin NJ, Weisfeldt ML. Age-associated decrease in ventricular response to haemodynamic stress during beta-adrenergic blockade. Br Heart J. 1978;40:1349–55.PubMedCentralPubMedGoogle Scholar
  86. 86.
    Nussbacher A, Gerstenblith G, O’Connor FC, Becker LC, Kass DA, Schulman SP, Fleg JL, Lakatta EG. Hemodynamic effects of unloading the old heart. Am J Physiol. 1999;277:H1863–71.PubMedGoogle Scholar
  87. 87.
    Schulman SP, Fleg JL, Goldberg AP, Busby-Whitehead J, Hagberg JM, O’Connor FC, Gerstenblith G, Becker LC, Katzel LI, Lakatta LE, Lakatta EG. Continuum of cardiovascular performance across a broad range of fitness levels in healthy older men. Circulation. 1996;94:359–67.PubMedGoogle Scholar
  88. 88.
    North BJ, Sinclair DA. The intersection between aging and cardiovascular disease. Circ Res. 2012;110:1097–108.PubMedCentralPubMedGoogle Scholar
  89. 89.
    Drexler H, Hayoz D, Munzel T, Hornig B, Just H, Brunner HR, Zelis R. Endothelial function in chronic congestive heart failure. Am J Cardiol. 1992;69:1596–601.PubMedGoogle Scholar
  90. 90.
    Lam CS, Brutsaert DL. Endothelial dysfunction: a pathophysiologic factor in heart failure with preserved ejection fraction. J Am Coll Cardiol. 2012;60:1787–9.PubMedGoogle Scholar
  91. 91.
    Gomez DE, Armando RG, Farina HG, Menna PL, Cerrudo CS, Ghiringhelli PD, Alonso DF. Telomere structure and telomerase in health and disease (review). Int J Oncol. 2012;41:1561–9.PubMedGoogle Scholar
  92. 92.
    Sahin E, Depinho RA. Linking functional decline of telomeres, mitochondria and stem cells during ageing. Nature. 2010;464:520–8.PubMedCentralPubMedGoogle Scholar
  93. 93.
    Chin L, Artandi SE, Shen Q, Tam A, Lee SL, Gottlieb GJ, Greider CW, DePinho RA. P53 deficiency rescues the adverse effects of telomere loss and cooperates with telomere dysfunction to accelerate carcinogenesis. Cell. 1999;97:527–38.PubMedGoogle Scholar
  94. 94.
    van der Harst P, de Boer RA, Samani NJ, Wong LS, Huzen J, Codd V, Hillege HL, Voors AA, van Gilst WH, Jaarsma T, van Veldhuisen DJ. Telomere length and outcome in heart failure. Ann Med. 2010;42:36–44.PubMedGoogle Scholar
  95. 95.
    Kenyon CJ. The genetics of ageing. Nature. 2010;464:504–12.PubMedGoogle Scholar
  96. 96.
    Greer EL, Brunet A. Signaling networks in aging. J Cell Sci. 2008;121:407–12.PubMedGoogle Scholar
  97. 97.
    Houtkooper RH, Williams RW, Auwerx J. Metabolic networks of longevity. Cell. 2010;142:9–14.PubMedGoogle Scholar
  98. 98.
    Brown EJ, Albers MW, Shin TB, Ichikawa K, Keith CT, Lane WS, Schreiber SL. A mammalian protein targeted by g1-arresting rapamycin-receptor complex. Nature. 1994;369:756–8.PubMedGoogle Scholar
  99. 99.
    Powers III RW, Kaeberlein M, Caldwell SD, Kennedy BK, Fields S. Extension of chronological life span in yeast by decreased tor pathway signaling. Genes Dev. 2006;20:174–84.PubMedGoogle Scholar
  100. 100.
    Spiegelman BM. Transcriptional control of mitochondrial energy metabolism through the pgc1 coactivators. Novartis Found Symp. 2007;287:60–3. discussion 63–69.PubMedGoogle Scholar
  101. 101.
    Collins CJ, Sedivy JM. Involvement of the INK4a/Arf gene locus in senescence. Aging Cell. 2003;2:145–50.PubMedGoogle Scholar
  102. 102.
    Yang DG, Liu L, Zheng XY. Cyclin-dependent kinase inhibitor p16(ink4a) and telomerase may co-modulate endothelial progenitor cells senescence. Ageing Res Rev. 2008;7:137–46.PubMedGoogle Scholar
  103. 103.
    Someya S, Yu W, Hallows WC, Xu J, Vann JM, Leeuwenburgh C, Tanokura M, Denu JM, Prolla TA. Sirt3 mediates reduction of oxidative damage and prevention of age-related hearing loss under caloric restriction. Cell. 2010;143:802–12.PubMedCentralPubMedGoogle Scholar
  104. 104.
    Haigis MC, Guarente LP. Mammalian sirtuins–emerging roles in physiology, aging, and calorie restriction. Genes Dev. 2006;20:2913–21.PubMedGoogle Scholar
  105. 105.
    van den Berg MC, Burgering BM. Integrating opposing signals toward Forkhead box O. Antioxid Redox Signal. 2011;14:607–21.PubMedGoogle Scholar
  106. 106.
    Azevedo PS, Minicucci MF, Santos PP, Paiva SA, Zornoff LA. Energy metabolism in cardiac remodeling and heart failure. Cardiol Rev. 2013;21(3):135–40.PubMedGoogle Scholar
  107. 107.
    Balaban RS, Nemoto S, Finkel T. Mitochondria, oxidants, and aging. Cell. 2005;120:483–95.PubMedGoogle Scholar
  108. 108.
    Dai DF, Rabinovitch PS, Ungvari Z. Mitochondria and cardiovascular aging. Circ Res. 2012;110:1109–24.PubMedGoogle Scholar
  109. 109.
    Osterholt M, Nguyen TD, Schwarzer M, Doenst T. Alterations in mitochondrial function in cardiac hypertrophy and heart failure. Heart Fail Rev. 2013;18(5):645–56.PubMedGoogle Scholar
  110. 110.
    Reed MJ, Edelberg JM. Impaired angiogenesis in the aged. Sci Aging knowledge Environ. 2004;2004:pe7.PubMedGoogle Scholar
  111. 111.
    Rivard A, Berthou-Soulie L, Principe N, Kearney M, Curry C, Branellec D, Semenza GL, Isner JM. Age-dependent defect in vascular endothelial growth factor expression is associated with reduced hypoxia-inducible factor 1 activity. J Biol Chem. 2000;275:29643–7.PubMedGoogle Scholar
  112. 112.
    Ahluwalia A, Narula J, Jones MK, Deng X, Tarnawski AS. Impaired angiogenesis in aging myocardial microvascular endothelial cells is associated with reduced importin alpha and decreased nuclear transport of hif1 alpha: mechanistic implications. J Physiol Pharmacol. 2010;61:133–9.PubMedGoogle Scholar
  113. 113.
    Lim JH, Lee YM, Chun YS, Chen J, Kim JE, Park JW. Sirtuin 1 modulates cellular responses to hypoxia by deacetylating hypoxia-inducible factor 1alpha. Mol Cell. 2010;38:864–78.PubMedGoogle Scholar
  114. 114.
    Paulus WJ, Tschope C, Sanderson JE, Rusconi C, Flachskampf FA, Rademakers FE, Marino P, Smiseth OA, De Keulenaer G, Leite-Moreira AF, Borbely A, Edes I, Handoko ML, Heymans S, Pezzali N, Pieske B, Dickstein K, Fraser AG, Brutsaert DL. How to diagnose diastolic heart failure: a consensus statement on the diagnosis of heart failure with normal left ventricular ejection fraction by the heart failure and echocardiography associations of the European society of cardiology. Eur Heart J. 2007;28:2539–50.PubMedGoogle Scholar
  115. 115.
    Hunt SA, Abraham WT, Chin MH, Feldman AM, Francis GS, Ganiats TG, Jessup M, Konstam MA, Mancini DM, Michl K, Oates JA, Rahko PS, Silver MA, Stevenson LW, Yancy CW, Antman EM, Smith Jr SC, Adams CD, Anderson JL, Faxon DP, Fuster V, Halperin JL, Hiratzka LF, Jacobs AK, Nishimura R, Ornato JP, Page RL, Riegel B, American College of C, American Heart Association Task Force on Practice G, American College of Chest P, International Society for H, Lung T, Heart Rhythm S. ACC/AHA 2005 guideline update for the diagnosis and management of chronic heart failure in the adult: a report of the American college of cardiology/American heart association task force on practice guidelines (writing committee to update the 2001 guidelines for the evaluation and management of heart failure): developed in collaboration with the American college of chest physicians and the international society for heart and lung transplantation: endorsed by the heart rhythm society. Circulation. 2005;112:e154–235.PubMedGoogle Scholar
  116. 116.
    Owan TE, Hodge DO, Herges RM, Jacobsen SJ, Roger VL, Redfield MM. Trends in prevalence and outcome of heart failure with preserved ejection fraction. N Engl J Med. 2006;355:251–9.PubMedGoogle Scholar
  117. 117.
    Senni M, Tribouilloy CM, Rodeheffer RJ, Jacobsen SJ, Evans JM, Bailey KR, Redfield MM. Congestive heart failure in the community: a study of all incident cases in Olmsted county, Minnesota, in 1991. Circulation. 1998;98:2282–9.PubMedGoogle Scholar
  118. 118.
    Lee DS, Gona P, Vasan RS, Larson MG, Benjamin EJ, Wang TJ, Tu JV, Levy D. Relation of disease pathogenesis and risk factors to heart failure with preserved or reduced ejection fraction: insights from the Framingham heart study of the national heart, lung, and blood institute. Circulation. 2009;119:3070–7.PubMedCentralPubMedGoogle Scholar
  119. 119.
    O’Connor CM, Gattis WA, Shaw L, Cuffe MS, Califf RM. Clinical characteristics and long-term outcomes of patients with heart failure and preserved systolic function. Am J Cardiol. 2000;86:863–7.PubMedGoogle Scholar
  120. 120.
    Hunt SA, Abraham WT, Chin MH, Feldman AM, Francis GS, Ganiats TG, Jessup M, Konstam MA, Mancini DM, Michl K, Oates JA, Rahko PS, Silver MA, Stevenson LW, Yancy CW. 2009 focused update incorporated into the ACC/AHA 2005 guidelines for the diagnosis and management of heart failure in adults: a report of the American college of cardiology foundation/American heart association task force on practice guidelines: developed in collaboration with the international society for heart and lung transplantation. Circulation. 2009;119:e391–479.PubMedGoogle Scholar
  121. 121.
    Burkhoff D, Maurer MS, Packer M. Heart failure with a normal ejection fraction: is it really a disorder of diastolic function? Circulation. 2003;107:656–8.PubMedGoogle Scholar
  122. 122.
    Aurigemma GP, Gaasch WH. Clinical practice. Diastolic heart failure. N Engl J Med. 2004;351:1097–105.PubMedGoogle Scholar
  123. 123.
    Yellin EL, Nikolic S, Frater RW. Left ventricular filling dynamics and diastolic function. Prog Cardiovasc Dis. 1990;32:247–71.PubMedGoogle Scholar
  124. 124.
    Zile MR, Brutsaert DL. New concepts in diastolic dysfunction and diastolic heart failure: Part II: Causal mechanisms and treatment. Circulation. 2002;105:1503–8.PubMedGoogle Scholar
  125. 125.
    Chen CH, Nakayama M, Nevo E, Fetics BJ, Maughan WL, Kass DA. Coupled systolic-ventricular and vascular stiffening with age: implications for pressure regulation and cardiac reserve in the elderly. J Am Coll Cardiol. 1998;32:1221–7.PubMedGoogle Scholar
  126. 126.
    Redfield MM, Jacobsen SJ, Borlaug BA, Rodeheffer RJ, Kass DA. Age- and gender-related ventricular-vascular stiffening: a community-based study. Circulation. 2005;112:2254–62.PubMedGoogle Scholar
  127. 127.
    Cotter G, Felker GM, Adams KF, Milo-Cotter O, O’Connor CM. The pathophysiology of acute heart failure–is it all about fluid accumulation? Am Heart J. 2008;155:9–18.PubMedGoogle Scholar
  128. 128.
    Milo-Cotter O, Adams KF, O’Connor CM, Uriel N, Kaluski E, Felker GM, Weatherley B, Vered Z, Cotter G. Acute heart failure associated with high admission blood pressure–a distinct vascular disorder? Eur J Heart Fail. 2007;9:178–83.PubMedGoogle Scholar
  129. 129.
    Cotter G, Moshkovitz Y, Milovanov O, Salah A, Blatt A, Krakover R, Vered Z, Kaluski E. Acute heart failure: a novel approach to its pathogenesis and treatment. Eur J Heart Fail. 2002;4:227–34.PubMedGoogle Scholar
  130. 130.
    Haykowsky MJ, Brubaker PH, John JM, Stewart KP, Morgan TM, Kitzman DW. Determinants of exercise intolerance in elderly heart failure patients with preserved ejection fraction. J Am Coll Cardiol. 2011;58:265–74.PubMedCentralPubMedGoogle Scholar
  131. 131.
    Bejan-Angoulvant T, Saadatian-Elahi M, Wright JM, Schron EB, Lindholm LH, Fagard R, Staessen JA, Gueyffier F. Treatment of hypertension in patients 80 years and older: the lower the better? A meta-analysis of randomized controlled trials. J Hypertens. 2010;28:1366–72.PubMedGoogle Scholar
  132. 132.
    Scott IA, Guyatt GH. Cautionary tales in the interpretation of clinical studies involving older persons. Arch Intern Med. 2010;170:587–95.PubMedGoogle Scholar
  133. 133.
    Talbot LA, Metter EJ, Fleg JL. Leisure-time physical activities and their relationship to cardiorespiratory fitness in healthy men and women 18–95 years old. Med Sci Sports Exerc. 2000;32:417–25.PubMedGoogle Scholar
  134. 134.
    Rywik TM, Blackman MR, Yataco AR, Vaitkevicius PV, Zink RC, Cottrell EH, Wright JG, Katzel LI, Fleg JL. Enhanced endothelial vasoreactivity in endurance-trained older men. J Appl Physiol. 1999;87:2136–42.PubMedGoogle Scholar
  135. 135.
    Haykowsky MJ, Brubaker PH, Stewart KP, Morgan TM, Eggebeen J, Kitzman DW. Effect of endurance training on the determinants of peak exercise oxygen consumption in elderly patients with stable compensated heart failure and preserved ejection fraction. J Am Coll Cardiol. 2012;60:120–8.PubMedCentralPubMedGoogle Scholar
  136. 136.
    Vaitkevicius PV, Fleg JL, Engel JH, O’Connor FC, Wright JG, Lakatta LE, Yin FC, Lakatta EG. Effects of age and aerobic capacity on arterial stiffness in healthy adults. Circulation. 1993;88:1456–62.PubMedGoogle Scholar
  137. 137.
    Lieber A, Millasseau S, Mahmud A, Bourhis L, Mairesse S, Protogerou A, Agnoletti D, Zhang Y, Blacher J, Safar ME. Cardiovascular prevention: relationships between arterial aging and chronic drug treatment. J Hum Hypertens. 2011;25:524–31.PubMedGoogle Scholar
  138. 138.
    Shahin Y, Khan JA, Chetter I. Angiotensin converting enzyme inhibitors effect on arterial stiffness and wave reflections: a meta-analysis and meta-regression of randomised controlled trials. Atherosclerosis. 2012;221:18–33.PubMedGoogle Scholar
  139. 139.
    Boutouyrie P, Lacolley P, Briet M, Regnault V, Stanton A, Laurent S, Mahmud A. Pharmacological modulation of arterial stiffness. Drugs. 2011;71:1689–701.PubMedGoogle Scholar
  140. 140.
    Barnes MM, Dorsch MP, Hummel SL, Koelling TM, Bleske BE. Treatment of heart failure with preserved ejection fraction. Pharmacotherapy. 2011;31:312–31.PubMedGoogle Scholar
  141. 141.
    Benetos A, Levy BI, Lacolley P, Taillard F, Duriez M, Safar ME. Role of angiotensin II and bradykinin on aortic collagen following converting enzyme inhibition in spontaneously hypertensive rats. Arterioscler Thromb Vasc Biol. 1997;17:3196–201.PubMedGoogle Scholar
  142. 142.
    Corman B, Duriez M, Poitevin P, Heudes D, Bruneval P, Tedgui A, Levy BI. Aminoguanidine prevents age-related arterial stiffening and cardiac hypertrophy. Proc Natl Acad Sci USA. 1998;95:1301–6.PubMedGoogle Scholar
  143. 143.
    Corti R, Burnett Jr JC, Rouleau JL, Ruschitzka F, Luscher TF. Vasopeptidase inhibitors: a new therapeutic concept in cardiovascular disease? Circulation. 2001;104:1856–62.PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  1. 1.Division of Cardiology, Department of MedicineUniversity of AlbertaEdmontonCanada

Personalised recommendations