Heart Failure Reviews

, Volume 17, Issue 4–5, pp 545–554 | Cite as

Age-associated changes in cardiovascular structure and function: a fertile milieu for future disease

  • Jerome L. Fleg
  • James Strait


Important changes occur in the cardiovascular system with advancing age, even in apparently healthy individuals. Thickening and stiffening of the large arteries develop due to collagen and calcium deposition and loss of elastic fibers in the medial layer. These arterial changes cause systolic blood pressure to rise with age, while diastolic blood pressure generally declines after the sixth decade. In the left ventricle, modest concentric wall thickening occurs due to cellular hypertrophy, but cavity size does not change. Although left ventricular systolic function is preserved across the age span, early diastolic filling rate declines 30–50% between the third and ninth decades. Conversely, an age-associated increase in late diastolic filling due to atrial contraction preserves end-diastolic volume. Aerobic exercise capacity declines approximately 10% per decade in cross-sectional studies; in longitudinal studies, however, this decline is accelerated in the elderly. Reductions in peak heart rate and peripheral oxygen utilization but not stroke volume appear to mediate the age-associated decline in aerobic capacity. Deficits in both cardiac β-adrenergic receptor density and in the efficiency of postsynaptic β-adrenergic signaling contribute significantly to the reduced cardiovascular performance during exercise in older adults. Although these cardiovascular aging changes are considered “normative”, they lower the threshold for the development of cardiovascular disease, which affects the majority of older adults.


Cardiovascular Aging Arterial Ventricular function Exercise β adrenergic 


  1. 1.
    U. S. Census Bureau. National population projections link:
  2. 2.
    Lakatta E, Wang M, Najjar SS (2009) Arterial aging and subclinical arterial disease are fundamentally intertwined at macroscopic and molecular levels. Med Clin North Am 93:583–604PubMedCrossRefGoogle Scholar
  3. 3.
    Gerstenblith G, Frederiksen J, Yin FC et al (1977) Echocardiographic assessment of a normal adult aging population. Circulation 56:273–278PubMedGoogle Scholar
  4. 4.
    Lam CSP, Xanthakis V, Sullivan LM et al (2010) Aortic root remodeling over the adult life course. Longitudinal data from the Framingham heart study. Circulation 122:884–890PubMedCrossRefGoogle Scholar
  5. 5.
    Nagai Y, Metter EJ, Earley CJ et al (1998) Increased carotid artery intimal-medial thickness in asymptomatic older subjects with exercise-induced myocardial ischemia. Circulation 98:1504–1509PubMedGoogle Scholar
  6. 6.
    Ungvari Z, Kaley G, de Cabo R, Sonntag WE, Csiszar A (2010) Mechanisms of vascular aging: new perspectives. J Gerontol A Biol Sci Med Sci 65:1028–1041PubMedCrossRefGoogle Scholar
  7. 7.
    Zieman SJ, Melenovsky V, Kass DA (2005) Mechanisms, pathophysiology, and therapy of arterial stiffness. Arterioscler Thromb Vasc Biol 25:932–943PubMedCrossRefGoogle Scholar
  8. 8.
    Lakatta E, Levy D (2003) Arterial and cardiac aging: major shareholders in cardiovascular disease enterprises: part I: aging arteries: a “set up” for vascular disease. Circulation 107:139–146PubMedCrossRefGoogle Scholar
  9. 9.
    Semba RD, Najjar SS, Sun K, Lakatta E, Ferrucci L (2009) Serum carboxymethyl-lysine, an advanced glycation end product, is associated with increased aortic pulse wave velocity in adults. Am J Hypertens 22:74–79PubMedCrossRefGoogle Scholar
  10. 10.
    Cernadas MR et al (1998) Expression of constitutive and inducible nitric oxide synthases in the vascular wall of young and aging rats. Circ Res 83:279–286PubMedGoogle Scholar
  11. 11.
    Wang M, Monticone R, Lakatta E (2010) Arterial aging: a journey into subclinical arterial disease. Curr Opin Nephrol Hypertens 19:201–207PubMedCrossRefGoogle Scholar
  12. 12.
    Pearson JD, Morrell CH, Brant LJ, Landis PK, Fleg JL (1997) Age-associated changes in blood pressure in a longitudinal study of healthy men and women. J Gerontol A Biol Sci Med Sci 52:M177–M183PubMedCrossRefGoogle Scholar
  13. 13.
    Roman MJ et al (2009) High central pulse pressure is independently associated with adverse cardiovascular outcome the strong heart study. J Am Coll Cardiol 54:1730–1734PubMedCrossRefGoogle Scholar
  14. 14.
    Vaitkevicius PV, Fleg JL, Engel JH et al (1993) Effects of age and aerobic capacity on arterial stiffness in healthy adults. Circulation 88:1456–1462PubMedGoogle Scholar
  15. 15.
    Mitchell GF et al (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
  16. 16.
    Willum-Hansen T, Staessen JA, Torp-Pedersen C et al (2006) Prognostic value of aortic pulse wave velocity as index of arterial stiffness in the general population. Circulation 113:664–670PubMedCrossRefGoogle Scholar
  17. 17.
    Weber T et al (2005) Increased arterial wave reflections predict severe cardiovascular events in patients undergoing percutaneous coronary interventions. Eur Heart J 26:2657–2663PubMedCrossRefGoogle Scholar
  18. 18.
    Lam CSP, Borlaug BA, Kane GC et al (2009) Age-associated increases in pulmonary artery systolic pressure in the general population. Circulation 119:2663–2670PubMedCrossRefGoogle Scholar
  19. 19.
    Kovacs G, Berghold A, Scheidl S, Olschewski H (2009) Pulmonary arterial pressure during rest and exercise in healthy subjects: a systematic review. Eur Respir J 34:888–894PubMedCrossRefGoogle Scholar
  20. 20.
    Linzbach AJ, Akuamoa-Boateng E (1973) Changes in the aging human heart. I. Heart weight in the aged. Klin Wochenschr 51:156–163PubMedCrossRefGoogle Scholar
  21. 21.
    Kitzman DW, Scholz DG, Hagen PT, Ilstrup DM, Edwards WD (1988) Age-related changes in normal human hearts during the first 10 decades of life. Part II (Maturity): a quantitative anatomic study of 765 specimens from subjects 20–99 years old. Mayo Clin Proc 63:137–146PubMedGoogle Scholar
  22. 22.
    Olivetti G, Giordano G, Corridi D et al (1995) Gender differences and aging: effects in the human heart. J Am Coll Cardiol 26:1068–1079PubMedCrossRefGoogle Scholar
  23. 23.
    Hees PS, Fleg JL, Lakatta EG, Shapiro EP (2002) Left ventricular remodeling with age in normal men versus women: novel insights using three-dimensional magnetic resonance imaging. Am J Cardiol 90:1231–1236PubMedCrossRefGoogle Scholar
  24. 24.
    Cheng S, Fernandes VRS, Bluemke DA et al (2009) Age-related left ventricular remodeling and associated risk for cardiovascular outcomes. The multi-ethnic study of atherosclerosis. Circulation Cardiovasc Imaging 2:191–198CrossRefGoogle Scholar
  25. 25.
    Burgess ML, McCrea JC, Hedrick HL (2001) Age-associated changes in cardiac matrix and integrins. Mech Ageing Dev 122:1739–1756PubMedCrossRefGoogle Scholar
  26. 26.
    Bergmann O et al (2009) Evidence for cardiomyocyte renewal in humans. Science 324:98–102PubMedCrossRefGoogle Scholar
  27. 27.
    Eghbali M, 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
  28. 28.
    Lakatta EG, Yin FC (1982) Myocardial aging: functional alterations and related cellular mechanisms. Am J Physiol 242:H927–H941PubMedGoogle Scholar
  29. 29.
    Lakatta EG (1993) Cardiovascular regulatory mechanisms in advanced age. Physiol Rev 73:413–467PubMedGoogle Scholar
  30. 30.
    Fleg JL, O’Connor FC, Gerstenblith G et al (1995) Impact of age on the cardiovascular response to dynamic upright exercise in healthy men and women. J Appl Physiol 78:890–900PubMedGoogle Scholar
  31. 31.
    Lakatta EG, Gerstenblith G, Angell CS et al (1975) Prolonged contraction duration in aged myocardium. J Clin Invest 55:61–68PubMedCrossRefGoogle Scholar
  32. 32.
    Fleg JL, Lakatta EG (2008) Normal aging of the cardiovascular system. In: Aronow WS, Fleg JL (eds) Cardiovascular disease in the elderly, 4th edn. Informa Healthcare USA, Inc., New York, pp 1–43Google Scholar
  33. 33.
    Downes TR, Nomeir AM, Smith KM, Stewart KP, Little WC (1989) Mechanism of altered pattern of left ventricular filling with aging in subjects without cardiac disease. Am J Cardiol 64:523–527PubMedCrossRefGoogle Scholar
  34. 34.
    Schulman SP, Lakatta EG, Fleg JL et al (1992) Age-related decline in left ventricular filling at rest and exercise. Am J Physiol 263:H1932–H1938PubMedGoogle Scholar
  35. 35.
    Boyd AC, Schiller NB, Leung D, Ross DL, Thomas L (2011) Atrial dilation and altered function are mediated by age and diastolic function but not before the eighth decade. J Am Coll Cardiol Img 4:234–242Google Scholar
  36. 36.
    Hees PS, Fleg JL, Dong S-J et al (2004) MRI and echocardiographic assessment of the diastolic dysfunction of normal aging: altered LV pressure decline or load? Am J Physiol Heart Circ Physiol 286:H782–H788PubMedCrossRefGoogle Scholar
  37. 37.
    Froehlich JP, Lakatta EG, Beard E et al (1978) Studies of sarcoplasmic reticulum function and contraction duration in young and aged rat myocardium. J Mol Cell Cardiol 10:427–438PubMedCrossRefGoogle Scholar
  38. 38.
    Oh JK, Hatle L, Tajik AJ, Little WC (2006) Diastolic heart failure can be diagnosed by comprehensive two-dimensional and Doppler echocardiography. J Am Coll Cardiol 47:500–506PubMedCrossRefGoogle Scholar
  39. 39.
    Tsang TSM, Gersh BJ, Appleton CP et al (2002) Left ventricular diastolic dysfunction as a predictor of the first nonvalvular atrial fibrillation in 840 elderly men and women. J Am Coll Cardiol 40:1636–1644PubMedCrossRefGoogle Scholar
  40. 40.
    Hachamovitch R, Wicker P, Capasso JM, Anversa P (1989) Alterations of coronary blood flow and reserve with aging in Fischer 344 rats. Am J Physiol 256:H66–H73PubMedGoogle Scholar
  41. 41.
    Talbot LA, Metter EJ, Fleg JL (2000) Leisure-time physical activities and their relationship to cardiorespiratory fitness in healthy men and women 18–95 years old. Med Sci Sports Exer 32:417–425CrossRefGoogle Scholar
  42. 42.
    Fleg JL, Morrell CH, Bos AG et al (2005) Accelerated longitudinal decline of aerobic capacity in healthy older adults. Circulation 112:674–682PubMedCrossRefGoogle Scholar
  43. 43.
    Fried LP, Taugen CM, Walston J, For the CHS Collaborative Research Group et al (2001) Frailty in older adults: evidence for a phenotype. J Gerontol 56A:M158–M166Google Scholar
  44. 44.
    Huang G, Gibson CA, Tran ZV et al (2005) Controlled endurance exercise training and VO2max changes in older adults: a meta-analysis. Prev Cardiol 8:217–225PubMedCrossRefGoogle Scholar
  45. 45.
    Schulman SP, Fleg JL, Goldberg AP et al (1996) Continuum of cardiovascular performance across a broad range of fitness levels in healthy older men. Circulation 94:359–367PubMedGoogle Scholar
  46. 46.
    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
  47. 47.
    Woo JS, Derleth C, Stratton JR et al (2006) The influence of age, gender, and training on exercise efficiency. J Am Coll Cardiol 47:1049–1057PubMedCrossRefGoogle Scholar
  48. 48.
    Fleg JL, Schulman SP, Gerstenblith G et al (1993) Additive effects of age and silent myocardial ischemia on the left ventricular response to upright cycle exercise. J Appl Physiol 75:499–504PubMedGoogle Scholar
  49. 49.
    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
  50. 50.
    White M, Roden R, Minobe W et al (1994) Age-related changes in beta- adrenergic neuroeffector systems in the human heart. Circulation 90:1225–1238PubMedGoogle Scholar
  51. 51.
    Correia LCL, Lakatta EG, O’Connor FC et al (2002) Attenuated cardiovascular reserve during prolonged submaximal exercise in healthy older subjects. J Am Coll Cardiol 40:1290–1297PubMedCrossRefGoogle Scholar
  52. 52.
    Fleg JL, Schulman S, O’Connor F et al (1994) Effects of acute β-adrenergic receptor blockade on age-associated changes in cardiovascular performance during dynamic exercise. Circulation 90:2333–2341PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC (outside the USA) 2011

Authors and Affiliations

  1. 1.Division of Cardiovascular SciencesNational Heart, Lung, and Blood InstituteBethesdaUSA
  2. 2.Laboratory of Cardiovascular ScienceNational Institute on AgingBaltimoreUSA

Personalised recommendations