Heart and Arterial Aging

Chapter
Part of the Advances in Biochemistry in Health and Disease book series (ABHD, volume 4)

Abstract

Aging is the dominant risk factor for cardiovascular disease, and is linked to the age-associated changes to the structure and function of the heart and arteries. Age-associated changes occur in everyone but not necessarily at the same rate or to the same extent, and this may account for the difference noted in the development of cardiovascular disease between individuals of the same chronological age. Age-associated changes in cardiovascular physiology must be differentiated from the effects of pathology, such as coronary artery disease, which occur with increasing frequency as age increases to gain an understanding of normative aging. Prominent age-associated changes in the cardiovascular system include arterial remodeling, an increase in arterial stiffness, and an impaired endothelial vasoreactivity. This results in an increased afterload (including an increase in aortic and brachial pressures) on the left ventricle resulting in left ventricular wall thickening, and prolonged relaxation of the left ventricle in diastole. During stress there is also a decreased responsiveness to β-adrenergic receptor stimulation in the context of increased circulating catecholamines. These changes not only ultimately impair the ability of the cardiovascular system to respond to times of stress (exercise, illness, and mental stress) in older individuals, but also set the stage for the development of cardiovascular diseases in the elderly. Those individuals who maintain an physically active lifestyle, or who partake in exercise training later in life, however, can either ameliorate or delay some, but not all, of the cardiovascular alterations that accompany advancing age.

Keywords

Aging Cardiac Arteries Exercise 

Notes

Acknowledgments

This research was supported in part by the Intramural Research Program of the NIH, National Institute on Aging.

References

  1. 1.
    Arbab-Zadeh A, Dijk E, Prasad A, Fu Q, Torres P, Zhang R, Thomas JD, Palmer D, Levine BD (2004) Effect of aging and physical activity on left ventricular compliance. Circulation 110:1799–1805PubMedCrossRefGoogle Scholar
  2. 2.
    Gerstenblith G, Frederiksen J, Yin FC, Fortuin NJ, Lakatta EG, Weisfeldt ML (1977) Echocardiographic assessment of a normal adult aging population. Circulation 56:273–278PubMedCrossRefGoogle Scholar
  3. 3.
    Lam CS, Xanthakis V, Sullivan LM, Lieb W, Aragam J, Redfield MM, Mitchell GF, Benjamin EJ, Vasan RS (2010) Aortic root remodeling over the adult life course: longitudinal data from the Framingham Heart Study. Circulation 122:884–890PubMedCrossRefGoogle Scholar
  4. 4.
    Redheuil A, Yu WC, Mousseaux E, Harouni AA, Kachenoura N, Wu CO, Bluemke D, Lima JA (2011) Age-related changes in aortic arch geometry: relationship with proximal aortic function and left ventricular mass and remodeling. J Am Coll Cardiol 58:1262–1270PubMedCrossRefGoogle Scholar
  5. 5.
    Farasat SM, Morrell CH, Scuteri A, Ting CT, Yin FC, Spurgeon HA, Chen CH, Lakatta EG, Najjar SS (2008) Pulse pressure is inversely related to aortic root diameter implications for the pathogenesis of systolic hypertension. Hypertension 51:196–202PubMedCrossRefGoogle Scholar
  6. 6.
    Nagai Y, Metter EJ, Earley CJ, Kemper MK, Becker LC, Lakatta EG, Fleg JL (1998) Increased carotid artery intimal-medial thickness in asymptomatic older subjects with exercise-induced myocardial ischemia. Circulation 98:1504–1509PubMedCrossRefGoogle Scholar
  7. 7.
    Virmani R, Avolio AP, Mergner WJ, Robinowitz M, Herderick EE, Cornhill JF, Guo SY, Liu TH, Ou DY, O’Rourke M (1991) 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 139:1119–1129PubMedGoogle Scholar
  8. 8.
    Woo KS, Chook P, Raitakari OT, McQuillan B, Feng JZ, Celermajer DS (1999) Westernization of Chinese adults and increased subclinical atherosclerosis. Arterioscler Thromb Vasc Biol 19:2487–2493PubMedCrossRefGoogle Scholar
  9. 9.
    Adams MR, Nakagomi A, Keech A, Robinson J, McCredie R, Bailey BP, Freedman SB, Celermajer DS (1995) Carotid intima-media thickness is only weakly correlated with the extent and severity of coronary artery disease. Circulation 92:2127–2134PubMedCrossRefGoogle Scholar
  10. 10.
    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 (2000) Peripheral vascular endothelial dysfunction and apoptosis in old monkeys. Arterioscler Thromb Vasc Biol 20:1493–1499PubMedCrossRefGoogle Scholar
  11. 11.
    Najjar SS, Scuteri A, Lakatta EG (2005) Arterial aging: is it an immutable cardiovascular risk factor? Hypertension 46:454–462PubMedCrossRefGoogle Scholar
  12. 12.
    Wang M, Lakatta EG (2009) The salted artery and angiotensin II signaling: a deadly duo in arterial disease. J Hypertens 27:19–21PubMedCrossRefGoogle Scholar
  13. 13.
    Lorenz MW, Markus HS, Bots ML, Rosvall M, Sitzer M (2007) Prediction of clinical cardiovascular events with carotid intima-media thickness. Circulation 115:459–467PubMedCrossRefGoogle Scholar
  14. 14.
    Li Z, Froehlich J, Galis ZS, Lakatta EG (1999) Increased expression of matrix metalloproteinase-2 in the thickened intima of aged rats. Hypertension 33:116–123PubMedCrossRefGoogle Scholar
  15. 15.
    Orlandi A, Marcellini M, Spagnoli LG (2000) Aging influences development and progression of early aortic atherosclerotic lesions in cholesterol-fed rabbits. Arterioscler Thromb Vasc Biol 20:1123–1136PubMedCrossRefGoogle Scholar
  16. 16.
    Spinetti G, Wang M, Monticone R, Zhang J, Zhao D, Lakatta EG (2004) Rat aortic MCP-1 and its receptor CCR2 increase with age and alter vascular smooth muscle cell function. Arterioscler Thromb Vasc Biol 24:1397–1402PubMedCrossRefGoogle Scholar
  17. 17.
    Sporn MB, Roberts AB (1992) Transforming growth factor-beta: recent progress and new challenges. J Cell Biol 119:1017–1021PubMedCrossRefGoogle Scholar
  18. 18.
    Wang M, Lakatta EG (2002) Altered regulation of matrix metalloproteinase-2 in aortic remodeling during aging. Hypertension 39:865–873PubMedCrossRefGoogle Scholar
  19. 19.
    Wang M, Zhang J, Jiang LQ, Spinetti G, Pintus G, Monticone R, Kolodgie FD, Virmani R, Lakatta EG (2007) Proinflammatory profile within the grossly normal aged human aortic wall. Hypertension 50:219–227PubMedCrossRefGoogle Scholar
  20. 20.
    Wang M, Takagi G, Asai K, Resuello RG, Natividad FF, Vatner DE, Vatner SF, Lakatta EG (2003) Aging increases aortic MMP-2 activity and angiotensin II in nonhuman primates. Hypertension 41:1308–1316PubMedCrossRefGoogle Scholar
  21. 21.
    Pauly RR, Passaniti A, Crow M, Kinsella JL, Papadopoulos N, Monticone R, Lakatta EG, and Martin GR (1992) Experimental models that mimic the differentiation and dedifferentiation of vascular cells. Circulation 86:III68–73Google Scholar
  22. 22.
    Li Z, Cheng H, Lederer WJ, Froehlich J, Lakatta EG (1997) Enhanced proliferation and migration and altered cytoskeletal proteins in early passage smooth muscle cells from young and old rat aortic explants. Exp Mol Pathol 64:1–11PubMedCrossRefGoogle Scholar
  23. 23.
    Celermajer DS, Sorensen KE, Spiegelhalter DJ, Georgakopoulos D, Robinson J, Deanfield JE (1994) Aging is associated with endothelial dysfunction in healthy men years before the age-related decline in women. J Am Coll Cardiol 24:471–476PubMedCrossRefGoogle Scholar
  24. 24.
    Taddei S, Virdis A, Ghiadoni L, Mattei P, Sudano I, Bernini G, Pinto S, Salvetti A (1996) Menopause is associated with endothelial dysfunction in women. Hypertension 28:576–582PubMedCrossRefGoogle Scholar
  25. 25.
    Bush DE, Jones CE, Bass KM, Walters GK, Bruza JM, Ouyang P (1998) Estrogen replacement reverses endothelial dysfunction in postmenopausal women. Am J Med 104:552–558PubMedCrossRefGoogle Scholar
  26. 26.
    Lieberman EH, Gerhard MD, Uehata A, Walsh BW, Selwyn AP, Ganz P, Yeung AC, Creager MA (1994) Estrogen improves endothelium-dependent, flow-mediated vasodilation in postmenopausal women. Ann Intern Med 121:936–941PubMedGoogle Scholar
  27. 27.
    Tagawa H, Shimokawa H, Tagawa T, Kuroiwa-Matsumoto M, Hirooka Y, Takeshita A (1997) Short-term estrogen augments both nitric oxide-mediated and non-nitric oxide-mediated endothelium-dependent forearm vasodilation in postmenopausal women. J Cardiovasc Pharmacol 30:481–488PubMedCrossRefGoogle Scholar
  28. 28.
    Celermajer DS, Sorensen KE, Bull C, Robinson J, Deanfield JE (1994) Endothelium-dependent dilation in the systemic arteries of asymptomatic subjects relates to coronary risk factors and their interaction. J Am Coll Cardiol 24:1468–1474PubMedCrossRefGoogle Scholar
  29. 29.
    Taddei S, Virdis A, Mattei P, Ghiadoni L, Gennari A, Fasolo CB, Sudano I, Salvetti A (1995) Aging and endothelial function in normotensive subjects and patients with essential hypertension. Circulation 91:1981–1987PubMedCrossRefGoogle Scholar
  30. 30.
    Fichtlscherer S, Breuer S, Zeiher AM (2004) Prognostic value of systemic endothelial dysfunction in patients with acute coronary syndromes. Circulation 110:1926–1932PubMedCrossRefGoogle Scholar
  31. 31.
    Perticone F, Ceravolo R, Pujia A, Ventura G, Iacopino S, Scozzafava A, Ferraro A, Chello M, Mastroroberto P, Verdecchia P, Schillaci G (2001) Prognostic significance of endothelial dysfunction in hypertensive patients. Circulation 104:191–196PubMedCrossRefGoogle Scholar
  32. 32.
    Taddei S, Virdis A, Ghiadoni L, Salvetti G, Bernini G, Magagna A, Salvetti A (2001) Age-related reduction of NO availability and oxidative stress in humans. Hypertension 38:274–279PubMedCrossRefGoogle Scholar
  33. 33.
    Shi Q, Aida K, Vandeberg JL, Wang XL (2004) Passage-dependent changes in baboon endothelial cells–relevance to in vitro aging. DNA Cell Biol 23:502–509PubMedCrossRefGoogle Scholar
  34. 34.
    Comi P, Chiaramonte R, Maier JA (1995) Senescence-dependent regulation of type 1 plasminogen activator inhibitor in human vascular endothelial cells. Exp Cell Res 219:304–308PubMedCrossRefGoogle Scholar
  35. 35.
    Csiszar A, Ungvari Z, Edwards JG, Kaminski P, Wolin MS, Koller A, Kaley G (2002) Aging-induced phenotypic changes and oxidative stress impair coronary arteriolar function. Circ Res 90:1159–1166PubMedCrossRefGoogle Scholar
  36. 36.
    Matz RL, Andriantsitohaina R (2003) Age-related endothelial dysfunction : potential implications for pharmacotherapy. Drugs Aging 20:527–550PubMedCrossRefGoogle Scholar
  37. 37.
    Chang E, Harley CB (1995) Telomere length and replicative aging in human vascular tissues. Proc Natl Acad Sci U S A 92:11190–11194PubMedCrossRefGoogle Scholar
  38. 38.
    Iwama H, Ohyashiki K, Ohyashiki JH, Hayashi S, Yahata N, Ando K, Toyama K, Hoshika A, Takasaki M, Mori M, Shay JW (1998) Telomeric length and telomerase activity vary with age in peripheral blood cells obtained from normal individuals. Hum Genet 102:397–402PubMedCrossRefGoogle Scholar
  39. 39.
    Csiszar A, Wang M, Lakatta EG, Ungvari Z (2008) Inflammation and endothelial dysfunction during aging: role of NF-kappaB. J Appl Physiol 105:1333–1341PubMedCrossRefGoogle Scholar
  40. 40.
    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 (2000) Enhanced peroxynitrite formation is associated with vascular aging. J Exp Med 192:1731–1744PubMedCrossRefGoogle Scholar
  41. 41.
    Rauscher FM, Goldschmidt-Clermont PJ, Davis BH, Wang T, Gregg D, Ramaswami P, Pippen AM, Annex BH, Dong C, Taylor DA (2003) Aging, progenitor cell exhaustion, and atherosclerosis. Circulation 108:457–463PubMedCrossRefGoogle Scholar
  42. 42.
    Conboy IM, Conboy MJ, Wagers AJ, Girma ER, Weissman IL, Rando TA (2005) Rejuvenation of aged progenitor cells by exposure to a young systemic environment. Nature 433:760–764PubMedCrossRefGoogle Scholar
  43. 43.
    Vaitkevicius PV, Fleg JL, Engel JH, O’Connor FC, Wright JG, Lakatta LE, Yin FC, Lakatta EG (1993) Effects of age and aerobic capacity on arterial stiffness in healthy adults. Circulation 88:1456–1462PubMedCrossRefGoogle Scholar
  44. 44.
    O’Rourke MF, Staessen JA, Vlachopoulos C, Duprez D, Plante GeE (2002) Clinical applications of arterial stiffness; definitions and reference values. Am J Hypertens 15:426–444Google Scholar
  45. 45.
    O’Rourke MF, Nichols WW (2005) Aortic diameter, aortic stiffness, and wave reflection increase with age and isolated systolic hypertension. Hypertension 45:652–658PubMedCrossRefGoogle Scholar
  46. 46.
    Safar ME, Temmar M, Kakou A, Lacolley P, Thornton SN (2009) Sodium intake and vascular stiffness in hypertension. Hypertension 54:203–209PubMedCrossRefGoogle Scholar
  47. 47.
    Wildman RP, Farhat GN, Patel AS, Mackey RH, Brockwell S, Thompson T, Sutton-Tyrrell K (2005) Weight change is associated with change in arterial stiffness among healthy young adults. Hypertension 45:187–192PubMedCrossRefGoogle Scholar
  48. 48.
    Wilkinson IB, Franklin SS, Cockcroft JR (2004) Nitric oxide and the regulation of large artery stiffness: from physiology to pharmacology. Hypertension 44:112–116PubMedCrossRefGoogle Scholar
  49. 49.
    Tarasov KV, Sanna S, Scuteri A, Strait JB, Orru M, Parsa A, Lin PI, Maschio A, Lai S, Piras MG, Masala M, Tanaka T, Post W, O’Connell JR, Schlessinger D, Cao A, Nagaraja R, Mitchell BD, Abecasis GR, Shuldiner AR, Uda M, Lakatta EG, Najjar SS (2009) COL4A1 is associated with arterial stiffness by genome-wide association scan. Circ Cardiovasc Genet 2:151–158PubMedCrossRefGoogle Scholar
  50. 50.
    Avolio A (1995) Genetic and environmental factors in the function and structure of the arterial wall. Hypertension 26:34–37PubMedCrossRefGoogle Scholar
  51. 51.
    Blacher J, Asmar R, Djane S, London GM, Safar ME (1999) Aortic pulse wave velocity as a marker of cardiovascular risk in hypertensive patients. Hypertension 33:1111–1117PubMedCrossRefGoogle Scholar
  52. 52.
    Dart AM, Kingwell BA (2001) Pulse pressure–a review of mechanisms and clinical relevance. J Am Coll Cardiol 37:975–984PubMedCrossRefGoogle Scholar
  53. 53.
    Vaitkevicius PV, Lane M, Spurgeon H, Ingram DK, Roth GS, Egan JJ, Vasan S, Wagle DR, Ulrich P, Brines M, Wuerth JP, Cerami A, Lakatta EG (2001) A cross-link breaker has sustained effects on arterial and ventricular properties in older rhesus monkeys. Proc Nat Acad Sci 98:1171–1175PubMedCrossRefGoogle Scholar
  54. 54.
    Safar ME, Toto-Moukouo JJ, Bouthier JA, Asmar RE, Levenson JA, Simon AC, London GM (1987) Arterial dynamics, cardiac hypertrophy, and antihypertensive treatment. Circulation 75:I156–I161PubMedCrossRefGoogle Scholar
  55. 55.
    Simon AC, Levenson JA, Bouthier JL, Safar ME (1984) Captopril-induced changes in large arteries in essential hypertension. Am J Med 76:71–75PubMedCrossRefGoogle Scholar
  56. 56.
    Ting CT, Brin KP, Lin SJ, Wang SP, Chang MS, Chiang BN, Yin FC (1986) Arterial hemodynamics in human hypertension. J Clin Invest 78:1462–1471PubMedCrossRefGoogle Scholar
  57. 57.
    Vlachopoulos C, Aznaouridis K, Stefanadis C (2010) Prediction of cardiovascular events and all-cause mortality with arterial stiffness: a systematic review and meta-analysis. J Am Coll Cardiol 55:1318–1327PubMedCrossRefGoogle Scholar
  58. 58.
    Mitchell GF (2008) Effects of central arterial aging on the structure and function of the peripheral vasculature: implications for end-organ damage. J Appl Physiol 105:1652–1660PubMedCrossRefGoogle Scholar
  59. 59.
    Mitchell GF, Pfeffer MA, Finn PV, Pfeffer JM (1996) Equipotent antihypertensive agents variously affect pulsatile hemodynamics and regression of cardiac hypertrophy in spontaneously hypertensive rats. Circulation 94:2923–2929PubMedCrossRefGoogle Scholar
  60. 60.
    Mitchell GF, Gudnason V, Launer LJ, Aspelund T, Harris TB (2008) Hemodynamics of increased pulse pressure in older women in the community-based Age, Gene/Environment Susceptibility-Reykjavik Study. Hypertension 51:1123–1128PubMedCrossRefGoogle Scholar
  61. 61.
    Nichols WW, O’Rourke MF (eds) McDonalds blood flow in arteries: theoretical, experimental and clinical principles. Hodder Arnold, New York, p 616Google Scholar
  62. 62.
    Kelly R, Hayward C, Avolio A, O’Rourke M (1989) Noninvasive determination of age-related changes in the human arterial pulse. Circulation 80:1652–1659PubMedCrossRefGoogle Scholar
  63. 63.
    McEniery CM, Yasmin, Hall IR, Qasem A, Wilkinson IB, Cockcroft JR, on behalf of the ACCT Investigators (2005). Normal vascular aging: differential effects on wave reflection and aortic pulse wave velocity: The Anglo-Cardiff Collaborative Trial (ACCT). J Am Coll Cardiol 46:1753–1760Google Scholar
  64. 64.
    Mitchell GF, Parise H, Benjamin EJ, Larson MG, Keyes MJ, Vita JA, Vasan RS, Levy D (2004) Changes in arterial stiffness and wave reflection with advancing age in healthy men and women: the Framingham heart study. Hypertension 43:1239–1245PubMedCrossRefGoogle Scholar
  65. 65.
    Kawamoto A, Shimada K, Matsubayashi K, Chikamori T, Kuzume O, Ogura H, Ozawa T (1989) Cardiovascular regulatory functions in elderly patients with hypertension. Hypertension 13:401–407PubMedCrossRefGoogle Scholar
  66. 66.
    Lund-Johansen P (1991) Twenty-year follow-up of hemodynamics in essential hypertension during rest and exercise. Hypertension 18: III54–61Google Scholar
  67. 67.
    Messerli FH, Frohlich ED, Suarez DH, Reisin E, Dreslinski GR, Dunn FG, Cole FE (1981) Borderline hypertension: relationship between age, hemodynamics and circulating catecholamines. Circulation 64:760–764PubMedCrossRefGoogle Scholar
  68. 68.
    Nussbacher A, Gerstenblith G, O’Connor FC, Becker LC, Kass DA, Schulman SP, Fleg JL, Lakatta EG (1999) Hemodynamic effects of unloading the old heart. Am J Physiol 277:H1863–H1871PubMedGoogle Scholar
  69. 69.
    Franklin SS, Gustin W IV, Wong ND, Larson MG, Weber MA, Kannel WB, Levy D (1997) Hemodynamic patterns of age-related changes in blood pressure: the framingham heart study. Circulation 96:308–315PubMedCrossRefGoogle Scholar
  70. 70.
    Mitchell GF (2009) Arterial stiffness and wave reflection: biomarkers of cardiovascular risk. Artery Res 3:56–64PubMedCrossRefGoogle Scholar
  71. 71.
    Protogerou AD, Papaioannou TG, Lekakis JP, Blacher J, Safar ME (2009) The effect of antihypertensive drugs on central blood pressure beyond peripheral blood pressure. Part I: (Patho)-physiology, rationale and perspective on pulse pressure amplification. Curr Pharm Des 15:267–271PubMedCrossRefGoogle Scholar
  72. 72.
    Roman MJ, Devereux RB, Kizer JR, Lee ET, Galloway JM, Ali T, Umans JG, Howard BV (2007) Central pressure more strongly relates to vascular disease and outcome than does brachial pressure: the strong heart study. Hypertension 50:197–203PubMedCrossRefGoogle Scholar
  73. 73.
    Williams B, Lacy PS, Thom SM, Cruickshank K, Stanton A, Collier D, Hughes AD, Thurston H, O’Rourke M (2006) Differential impact of blood pressure-lowering drugs on central aortic pressure and clinical outcomes: principal results of the Conduit Artery Function Evaluation (CAFE) study. Circulation 113:1213–1225PubMedCrossRefGoogle Scholar
  74. 74.
    Li Y, Staessen JA, Sheng CS, Huang QF, O’Rourke M, Wang JG (2012) Age dependency of peripheral and central systolic blood pressures: cross-sectional and longitudinal observations in a Chinese population. Hypertens Res 35:115–122PubMedCrossRefGoogle Scholar
  75. 75.
    Smulyan H, Asmar RG, Rudnicki A, London GM, Safar ME (2001) Comparative effects of aging in men and women on the properties of the arterial tree. J Am Coll Cardiol 37:1374–1380PubMedCrossRefGoogle Scholar
  76. 76.
    Sunagawa K, Maughan WL, Burkhoff D, Sagawa K (1983) Left ventricular interaction with arterial load studied in isolated canine ventricle. Am J Physiol 245:H773–H780PubMedGoogle Scholar
  77. 77.
    Chen CH, Nakayama M, Nevo E, Fetics BJ, Maughan WL, Kass DA (1998) Coupled systolic-ventricular and vascular stiffening with age: implications for pressure regulation and cardiac reserve in the elderly. J Am Coll Cardiol 32:1221–1227PubMedCrossRefGoogle Scholar
  78. 78.
    Cohen-Solal A, Caviezel B, Laperche T, Gourgon R (1996) Effects of aging on left ventricular-arterial coupling in man: assessment by means of arterial effective and left ventricular elastances. J Hum Hypertens 10:111–116PubMedGoogle Scholar
  79. 79.
    Redfield MM, Jacobsen SJ, Borlaug BA, Rodeheffer RJ, Kass DA (2005) Age- and gender-related ventricular-vascular stiffening: a community-based study. Circulation 112:2254–2262PubMedCrossRefGoogle Scholar
  80. 80.
    Eghbali M, Robinson TF, Seifter S, Blumenfeld OO (1989) Collagen accumulation in heart ventricles as a function of growth and aging. Cardiovasc Res 23:723–729PubMedCrossRefGoogle Scholar
  81. 81.
    Lakatta EG, Levy D (2003) Arterial and cardiac aging: major shareholders in cardiovascular disease enterprises: Part II: the aging heart in health: links to heart disease. Circulation 107:346–354PubMedCrossRefGoogle Scholar
  82. 82.
    Lakatta EG, Yin FC (1982) Myocardial aging: functional alterations and related cellular mechanisms. Am J Physiol 242:H927–H941PubMedGoogle Scholar
  83. 83.
    Olivetti G, Giordano G, Corradi D, Melissari M, Lagrasta C, Gambert SR, Anversa P (1995) Gender differences and aging: effects on the human heart. J Am Coll Cardiol 26:1068–1079PubMedCrossRefGoogle Scholar
  84. 84.
    Schulman SP, Lakatta EG, Fleg JL, Lakatta L, Becker LC, Gerstenblith G (1992) Age-related decline in left ventricular filling at rest and exercise. Am J Physiol 263:H1932–H1938PubMedGoogle Scholar
  85. 85.
    Froehlich JP, Lakatta EG, Beard E, Spurgeon HA, Weisfeldt ML, Gerstenblith G (1978) Studies of sarcoplasmic reticulum function and contraction duration in young adult and aged rat myocardium. J Mol Cell Cardiol 10:427–438PubMedCrossRefGoogle Scholar
  86. 86.
    Prasad A, Popovic ZB, Arbab-Zadeh A, Fu Q, Palmer D, Dijk E, Greenberg NL, Garcia MJ, Thomas JD, Levine BD (2007) The effects of aging and physical activity on Doppler measures of diastolic function. Am J Cardiol 99:1629–1636PubMedCrossRefGoogle Scholar
  87. 87.
    Swinne CJ, Shapiro EP, Lima SD, Fleg JL (1992) Age-associated changes in left ventricular diastolic performance during isometric exercise in normal subjects. Am J Cardiol 69:823–826PubMedCrossRefGoogle Scholar
  88. 88.
    Spirito P, Maron BJ (1988) Influence of aging on Doppler echocardiographic indices of left ventricular diastolic function. Br Heart J 59:672–679PubMedCrossRefGoogle Scholar
  89. 89.
    Fleg JL, O’Connor F, Gerstenblith G, Becker LC, Clulow J, Schulman SP, Lakatta EG (1995) Impact of age on the cardiovascular response to dynamic upright exercise in healthy men and women. J Appl Physiol 78:890–900PubMedGoogle Scholar
  90. 90.
    Fleg JL, Gerstenblith G, Zonderman AB, Becker LC, Weisfeldt ML, Costa PT Jr, Lakatta EG (1990) Prevalence and prognostic significance of exercise-induced silent myocardial ischemia detected by thallium scintigraphy and electrocardiography in asymptomatic volunteers. Circulation 81:428–436PubMedCrossRefGoogle Scholar
  91. 91.
    Lakatta EG (2003) Arterial and cardiac aging: major shareholders in cardiovascular disease enterprises: Part III: cellular and molecular clues to heart and arterial aging. Circulation 107:490–497PubMedCrossRefGoogle Scholar
  92. 92.
    Capasso JM, Malhotra A, Remily RM, Scheuer J, Sonnenblick EH (1983) Effects of age on mechanical and electrical performance of rat myocardium. Am J Physiol 245:H72–H81PubMedGoogle Scholar
  93. 93.
    Sagawa K (1978) The ventricular pressure-volume diagram revisited. Circ Res 43:677–687PubMedCrossRefGoogle Scholar
  94. 94.
    Borlaug BA, Kass DA (2008) Ventricular-vascular interaction in heart failure. Heart Fail Clin 4:23–36PubMedCrossRefGoogle Scholar
  95. 95.
    Fleg JL, Morrell CH, Bos AG, Brant LJ, Talbot LA, Wright JG, Lakatta EG (2005) Accelerated longitudinal decline of aerobic capacity in healthy older adults. Circulation 12:674–682Google Scholar
  96. 96.
    Coggan AR, Spina RJ, King DS, Rogers MA, Brown M, Nemeth PM, Holloszy JO (1992) Histochemical and enzymatic comparison of the gastrocnemius muscle of young and elderly men and women. J Gerontol 47:B71–B76PubMedGoogle Scholar
  97. 97.
    Short KR, Bigelow ML, Kahl J, Singh R, Coenen-Schimke J, Raghavakaimal S, Nair KS (2005) Decline in skeletal muscle mitochondrial function with aging in humans. Proc Natl Acad Sci U S A 102:5618–5623PubMedCrossRefGoogle Scholar
  98. 98.
    Yin FC, Weisfeldt ML, Milnor WR (1981) Role of aortic input impedance in the decreased cardiovascular response to exercise with aging in dogs. J Clin Invest 68:28–38PubMedCrossRefGoogle Scholar
  99. 99.
    Yin FC, Spurgeon HA, Kallman CH (1983) Age-associated alterations in viscoelastic properties of canine aortic strips. Circ Res 53:464–472PubMedCrossRefGoogle Scholar
  100. 100.
    Goldspink DF, George KP, Chantler PD, Clements RE, Sharp L, Hodges G, Stephenson C, Reilly TP, Patwala A, Szakmany T, Tan LB, Cable NT (2009) A study of presbycardia, with gender differences favoring ageing women. Int J Cardiol 137:236–245PubMedCrossRefGoogle Scholar
  101. 101.
    Ogawa T, Spina RJ, Martin WH 3rd, Kohrt WM, Schechtman KB, Holloszy JO, Ehsani AA (1992) Effects of aging, sex, and physical training on cardiovascular responses to exercise. Circulation 86:494–503PubMedCrossRefGoogle Scholar
  102. 102.
    Rowell LB (1991) Blood pressure regulation during exercise. Ann Med 23:329–333PubMedCrossRefGoogle Scholar
  103. 103.
    Casey DP, Nichols WW, Braith RW (2008) Impact of aging on central pressure wave reflection characteristics during exercise. Am J Hypertens 21:419–424PubMedCrossRefGoogle Scholar
  104. 104.
    Sharman JE, McEniery CM, Dhakam ZR, Coombes JS, Wilkinson IB, Cockcroft JR (2007) Pulse pressure amplification during exercise is significantly reduced with age and hypercholesterolemia. J Hypertens 25:1249–1254PubMedCrossRefGoogle Scholar
  105. 105.
    Fleg JL, Schulman S, O’Connor F, Becker LC, Gerstenblith G, Clulow JF, Renlund DG, Lakatta EG (1994) Effects of acute beta-adrenergic receptor blockade on age-associated changes in cardiovascular performance during dynamic exercise. Circulation 90:2333–2341PubMedCrossRefGoogle Scholar
  106. 106.
    Fleg JL, Tzankoff SP, Lakatta EG (1985) Age-related augmentation of plasma catecholamines during dynamic exercise in healthy males. J Appl Physiol 59:1033–1039PubMedGoogle Scholar
  107. 107.
    White M, Roden R, Minobe W, Khan MF, Larrabee P, Wollmering M, Port JD, Anderson F, Campbell D, Feldman AM et al (1994) Age-related changes in beta-adrenergic neuroeffector systems in the human heart. Circulation 90:1225–1238PubMedCrossRefGoogle Scholar
  108. 108.
    Najjar SS, Schulman SP, Gerstenblith G, Fleg JL, Kass DA, O’Connor F, Becker LC, Lakatta EG (2004) Age and gender affect ventricular-vascular coupling during aerobic exercise. J Am Coll Cardiol 44:611–617PubMedCrossRefGoogle Scholar
  109. 109.
    Chantler PD, Nussbacher A, Gerstenblith G, Schulman SP, Becker LC, Ferrucci L, Fleg JL, Lakatta EG, Najjar SS (2011) Abnormalities in arterial-ventricular coupling in older healthy persons are attenuated by sodium nitroprusside. Am J o Physiol—Heart Circ Physiol 300:H1914–H1922CrossRefGoogle Scholar
  110. 110.
    Otsuki T, Maeda S, Iemitsu M, Saito Y, Tanimura Y, Ajisaka R, Miyauchi T (2006) Contribution of systemic arterial compliance and systemic vascular resistance to effective arterial elastance changes during exercise in humans. Acta Physiol 188:15–20CrossRefGoogle Scholar
  111. 111.
    Asanoi H, Kameyama T, Ishizaka S, Miyagi K, Sasayama S (1992) Ventriculoarterial coupling during exercise in normal human subjects. Int J Cardiol 36:177–186PubMedCrossRefGoogle Scholar
  112. 112.
    Cohen-Solal A, Faraggi M, Czitrom D, Le Guludec D, Delahaye N, Gourgon R (1998) Left ventricular-arterial system coupling at peak exercise in dilated nonischemic cardiomyopathy. Chest 113:870–877PubMedCrossRefGoogle Scholar
  113. 113.
    Chantler PD, Melenovsky V, Schulman SP, Gerstenblith G, Becker LC, Ferrucci L, Fleg JL, Lakatta EG, Najjar SS (2011) Use of the frank-starling mechanism during exercise is linked to exercise-induced changes in arterial load. Am J Physiol Heart Circ Physiol 408(5):863–878Google Scholar
  114. 114.
    Chemla D, Antony I, Lecarpentier Y, Nitenberg A (2003) Contribution of systemic vascular resistance and total arterial compliance to effective arterial elastance in humans. Am J Physiol Heart Circ Physiol 285:H614–H620PubMedGoogle Scholar
  115. 115.
    Segers P, Stergiopulos N, Westerhof N (2002) Relation of effective arterial elastance to arterial system properties. Am J Physiol Heart Circ Physiol 282:H1041–H1046PubMedGoogle Scholar
  116. 116.
    Lakatta EG (1993) Cardiovascular regulatory mechanisms in advanced age. Physiol Rev 73:413–467PubMedGoogle Scholar
  117. 117.
    Tanaka H, Seals DR (2003) Invited review: dynamic exercise performance in masters athletes: insight into the effects of primary human aging on physiological functional capacity. J Appl Physiol 95:2152–2162PubMedGoogle Scholar
  118. 118.
    Seals DR, Stevenson ET, Jones PP, DeSouza CA, Tanaka H (1999) Lack of age-associated elevations in 24-h systolic and pulse pressures in women who exercise regularly. Am J Physiol 277:H947–H955PubMedGoogle Scholar
  119. 119.
    Taddei S, Galetta F, Virdis A, Ghiadoni L, Salvetti G, Franzoni F, Giusti C, Salvetti A (2000) Physical activity prevents age-related impairment in nitric oxide availability in elderly athletes. Circulation 101:2896–2901PubMedCrossRefGoogle Scholar
  120. 120.
    Tanaka H, DeSouza CA, Seals DR (1998) Absence of age-related increase in central arterial stiffness in physically active women. Arterioscler Thromb Vasc Biol 18:127–132PubMedCrossRefGoogle Scholar
  121. 121.
    Moreau KL, Donato AJ, Seals DR, Dinenno FA, Blackett SD, Hoetzer GL, Desouza CA, Tanaka H (2002) Arterial intima-media thickness: site-specific associations with HRT and habitual exercise. Am J Physiol Heart Circ Physiol 283:H1409–H1417PubMedGoogle Scholar
  122. 122.
    Tanaka H, Seals DR, Monahan KD, Clevenger CM, DeSouza CA, Dinenno FA (2002) Regular aerobic exercise and the age-related increase in carotid artery intima-media thickness in healthy men. J Appl Physiol 92:1458–1464PubMedCrossRefGoogle Scholar
  123. 123.
    Boutouyrie P, Bussy C, Hayoz D, Hengstler J, Dartois N, Laloux B, Brunner H, Laurent S (2000) Local pulse pressure and regression of arterial wall hypertrophy during long-term antihypertensive treatment. Circulation 101:2601–2606PubMedCrossRefGoogle Scholar
  124. 124.
    Moreau KL, Donato AJ, Seals DR, DeSouza CA, Tanaka H (2003) Regular exercise, hormone replacement therapy and the age-related decline in carotid arterial compliance in healthy women. Cardiovasc Res 57:861–868PubMedCrossRefGoogle Scholar
  125. 125.
    Tanaka H, Dinenno FA, Monahan KD, Clevenger CM, DeSouza CA, Seals DR (2000) Aging, habitual exercise, and dynamic arterial compliance. Circulation 102:1270–1275PubMedCrossRefGoogle Scholar
  126. 126.
    Ferrier KE, Waddell TK, Gatzka CD, Cameron JD, Dart AM, Kingwell BA (2001) Aerobic exercise training does not modify large-artery compliance in isolated systolic hypertension. Hypertension 38:222–226PubMedCrossRefGoogle Scholar
  127. 127.
    Seals DR, Tanaka H, Clevenger CM, Monahan KD, Reiling MJ, Hiatt WR, Davy KP, DeSouza CA (2001) Blood pressure reductions with exercise and sodium restriction in postmenopausal women with elevated systolic pressure: role of arterial stiffness. J Am Coll Cardiol 38:506–513PubMedCrossRefGoogle Scholar
  128. 128.
    Spina RJ, Meyer TE, Peterson LR, Villareal DT, Rinder MR, Ehsani AA (2004) Absence of left ventricular and arterial adaptations to exercise in octogenarians. J Appl Physiol 97:1654–1659PubMedCrossRefGoogle Scholar
  129. 129.
    DeSouza CA, Shapiro LF, Clevenger CM, Dinenno FA, Monahan KD, Tanaka H, Seals DR (2000) Regular aerobic exercise prevents and restores age-related declines in endothelium-dependent vasodilation in healthy men. Circulation 102:1351–1357PubMedCrossRefGoogle Scholar
  130. 130.
    Durrant JR, Seals DR, Connell ML, Russell MJ, Lawson BR, Folian BJ, Donato AJ, Lesniewski LA (2009) 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 587:3271–3285PubMedCrossRefGoogle Scholar
  131. 131.
    Spier SA, Delp MD, Meininger CJ, Donato AJ, Ramsey MW, Muller-Delp JM (2004) Effects of ageing and exercise training on endothelium-dependent vasodilatation and structure of rat skeletal muscle arterioles. J Physiol 556:947–958PubMedCrossRefGoogle Scholar
  132. 132.
    Spier SA, Delp MD, Stallone JN, Dominguez JM, Muller-Delp JM (2007) Exercise training enhances flow-induced vasodilation in skeletal muscle resistance arteries of aged rats: role of PGI2 and nitric oxide. Am J Physiol—Heart Circ Physiol 292:H3119–H3127PubMedCrossRefGoogle Scholar
  133. 133.
    Thijssen DHJ, De Groot PCE, Smits P, Hopman MTE (2007) Vascular adaptations to 8-week cycling training in older men. Acta Physiol 190:221–228CrossRefGoogle Scholar
  134. 134.
    Dinenno FA, Tanaka H, Monahan KD, Clevenger CM, Eskurza I, DeSouza CA, Seals DR (2001) Regular endurance exercise induces expansive arterial remodelling in the trained limbs of healthy men. J Physiol 534:287–295PubMedCrossRefGoogle Scholar
  135. 135.
    Green DJ, Swart A, Exterkate A, Naylor LH, Black MA, Cable NT, Thijssen DHJ (2010) Impact of age, sex and exercise on brachial and popliteal artery remodelling in humans. Atherosclerosis 210:525–530PubMedCrossRefGoogle Scholar
  136. 136.
    Goto C, Higashi Y, Kimura M, Noma K, Hara K, Nakagawa K, Kawamura M, Chayama K, Yoshizumi M, Nara I (2003) Effect of different intensities of exercise on endothelium-dependent vasodilation in humans. Circulation 108:530–535PubMedCrossRefGoogle Scholar
  137. 137.
    Baynard T, Carhart R, Weinstock R, Ploutz-Snyder L, Kanaley J (2009) Short-term exercise training improves aerobic capacity with no change in arterial function in obesity. Eur J Appl Physiol 107:299–308PubMedCrossRefGoogle Scholar
  138. 138.
    Clarkson P, Montgomery HE, Mullen MJ, Donald AE, Powe AJ, Bull T, Jubb M, World M, Deanfield JE (1999) Exercise training enhances endothelial function in young men. J Am Coll Cardiol 33:1379–1385PubMedCrossRefGoogle Scholar
  139. 139.
    Kingwell BA, Sherrard B, Jennings GL, Dart AM (1997) Four weeks of cycle training increases basal production of nitric oxide from the forearm. Am J Physiol—Heart Circ Physiol 272:H1070–H1077Google Scholar
  140. 140.
    Rivilis I, Milkiewicz M, Boyd P, Goldstein J, Brown MD, Egginton S, Hansen FM, Hudlicka O, Haas TL (2002) Differential involvement of MMP-2 and VEGF during muscle stretch- versus shear stress-induced angiogenesis. Am J Physiol Heart Circ Physiol 283:H1430–H1438PubMedGoogle Scholar
  141. 141.
    Urso M, Pierce J, Alemany J, Harman E, Nindl B (2009) Effects of exercise training on the matrix metalloprotease response to acute exercise. Eur J Appl Physiol 106:655–663PubMedCrossRefGoogle Scholar
  142. 142.
    Gatta L, Armani A, Iellamo F, Consoli C, Molinari F, Caminiti G, Volterrani M, Rosano GM (2010). Effects of a short-term exercise training on serum factors involved in ventricular remodelling in chronic heart failure patients. Int J Cardiol 142(1):50–55Google Scholar
  143. 143.
    Green DJ, Maiorana A, O’Driscoll G, Taylor R (2004) Effect of exercise training on endothelium-derived nitric oxide function in humans. J Physiol 561:1–25PubMedCrossRefGoogle Scholar
  144. 144.
    Hambrecht R, Adams V, Erbs S, Linke A, Krankel N, Shu Y, Baither Y, Gielen S, Thiele H, Gummert JF, Mohr FW, Schuler G (2003) Regular physical activity improves endothelial function in patients with coronary artery disease by increasing phosphorylation of endothelial nitric oxide synthase. Circulation 107:3152–3158PubMedCrossRefGoogle Scholar
  145. 145.
    Sessa WC, Pritchard K, Seyedi N, Wang J, Hintze TH (1994) Chronic exercise in dogs increases coronary vascular nitric oxide production and endothelial cell nitric oxide synthase gene expression. Circ Res 74:349–353PubMedCrossRefGoogle Scholar
  146. 146.
    Fukai T, Siegfried MR, Ushio-Fukai M, Cheng Y, Kojda G, Harrison DG (2000) Regulation of the vascular extracellular superoxide dismutase by nitric oxide and exercise training. J Clin Invest 105:1631–1639PubMedCrossRefGoogle Scholar
  147. 147.
    Douglas PS, O’Toole M (1992) Aging and physical activity determine cardiac structure and function in the older athlete. J Appl Physiol 72:1969–1973PubMedGoogle Scholar
  148. 148.
    Heath GW, Hagberg JM, Ehsani AA, Holloszy JO (1981) A physiological comparison of young and older endurance athletes. J Appl Physiol 51:634–640PubMedGoogle Scholar
  149. 149.
    Schulman SP, Fleg JL, Goldberg AP, Busby-Whitehead J, Hagberg JM, O’Connor FC, Gerstenblith G, Becker LC, Katzel LI, Lakatta LE, Lakatta EG (1996) Continuum of cardiovascular performance across a broad range of fitness levels in healthy older men. Circulation 94:359–367PubMedCrossRefGoogle Scholar
  150. 150.
    Seals D, Hagberg J, Spina R, Rogers M, Schechtman K, Ehsani A (1994) Enhanced left ventricular performance in endurance trained older men. Circulation 89:198–205PubMedCrossRefGoogle Scholar
  151. 151.
    Baggish AL, Wang F, Weiner RB, Elinoff JM, Tournoux F, Boland A, Picard MH, Hutter AM, Wood MJ (2008) Training-specific changes in cardiac structure and function: a prospective and longitudinal assessment of competitive athletes. J Appl Physiol 104:1121–1128PubMedCrossRefGoogle Scholar
  152. 152.
    Fujimoto N, Prasad A, Hastings JL, Arbab-Zadeh A, Bhella PS, Shibata S, Palmer D, Levine BD (2010) Cardiovascular effects of 1 year of progressive and vigorous exercise training in previously sedentary individuals older than 65 years of age. Circulation 122(18):1797–1805Google Scholar
  153. 153.
    Rodrigues ACT, de Melo Costa J, Alves GB, Ferreira da Silva D, Picard MH, Andrade JL, Mathias Jr W, Negrão CE (2006) Left ventricular function after exercise training in young men. Am J Cardiol 97:1089–1092Google Scholar
  154. 154.
    Spina RJ, Turner MJ, Ehsani AA (1998) β-Adrenergic-mediated improvement in left ventricular function by exercise training in older men. Am J Physiol—Heart Circ Physiol 274:H397–H404Google Scholar
  155. 155.
    Beere PA, Russell SD, Morey MC, Kitzman DW, Higginbotham MB (1999) Aerobic exercise training can reverse age-related peripheral circulatory changes in healthy older men. Circulation 100:1085–1094PubMedCrossRefGoogle Scholar
  156. 156.
    Ehsani A, Ogawa T, Miller T, Spina R, Jilka S (1991) Exercise training improves left ventricular systolic function in older men. Circulation 83:96–103PubMedCrossRefGoogle Scholar
  157. 157.
    Spina RJ, Turner MJ, Ehsani AA (1997) Exercise training enhances cardiac function in response to an afterload stress in older men. Am J Physiol— Heart Circ Physiol 272:H995–H1000Google Scholar
  158. 158.
    Stratton J, Levy W, Cerqueira M, Schwartz R, Abrass I (1994) Cardiovascular responses to exercise. Effects of aging and exercise training in healthy men. Circulation 89:1648–1655PubMedCrossRefGoogle Scholar
  159. 159.
    Aronson D (2003) Cross-linking of glycated collagen in the pathogenesis of arterial and myocardial stiffening of aging and diabetes. J Hypertens 21:3–12PubMedCrossRefGoogle Scholar
  160. 160.
    Hartley LH, Grimby G, Kilbom Å, Nilsson NJ, Åstrand I, Bjure J, Ekblom B, Saltin B (1969) Physical training in sedentary middle-aged and older men III. Cardiac output and gas exchange at submaximal and maximal exercise. Scand J Clin Lab Invest 24:335–344PubMedCrossRefGoogle Scholar
  161. 161.
    Seals DR, Hagberg JM, Hurley BF, Ehsani AA, Holloszy JO (1984) Endurance training in older men and women. I. Cardiovascular responses to exercise. J Appl Physiol 57:1024–1029PubMedGoogle Scholar
  162. 162.
    Stratton JR, Cerqueira MD, Schwartz RS, Levy WC, Veith RC, Kahn SE, Abrass IB (1992) Differences in cardiovascular responses to isoproterenol in relation to age and exercise training in healthy men. Circulation 86:504–512PubMedCrossRefGoogle Scholar
  163. 163.
    Najjar S, Lakatta, EG, Gerstenblith, G (2011) Cardiovascular Aging : The next Frontier in cardiovascular prevention. Elsevier Saunders, PennsylvaniaGoogle Scholar
  164. 164.
    Strait JB, Lakatta EG (2012) Aging-associated cardiovascular changes and their relationship to heart failure. Heart Fail Clin 8(1):143–164PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  1. 1.Division of Exercise Physiology, School of MedicineWest Virginia UniversityMorgantownUSA
  2. 2.Laboratory of Cardiovascular Science, Intramural Research Program, National Institute on AgingNational Institutes of HealthBaltimoreUSA

Personalised recommendations