Seminars in Nuclear Medicine
Volume 37, Issue 2 , Pages 120-143 , March 2007

The Aging of the Heart and Blood Vessels: A Consideration of Anatomy and Physiology in the Era of Computed Tomography, Magnetic Resonance Imaging, and Positron Emission Tomographic Imaging Methods With Special Consideration of Atherogenesis

References 

  1. Tolson GC, Barnes JM, Gay GA, et al. The 1989 revision of the U.S. Standard Certificates and Reports. Vital Health Stat. 1991;4:1–34
  2. In:  Kannel W,  Wolf P,  Garrison R editor. The Framingham Study: An Epidemiological Investigation of Cardiovascular Disease. Bethesda, MD: NHLBI, NIH; 1988;
  3. Fleg JL, Gerstenblith G, Zonderman AB, et al. Prevalence and prognostic significance of exercise-induced silent myocardial ischemia detected by thallium scintigraphy and electrocardiography in asymptomatic volunteers. Circulation. 1990;81:428–436
  4. Ferrari AU, Radaelli A, Centola M. Invited review: aging and the cardiovascular system. J Appl Physiol. 2003;95:2591–2597
  5. U.S. Census Bureau DaIDB. World Health Organization Report. Geneva: WHO; 2004;
  6. Best B. Mechanism of aging. Volume 2006. Available at: http://www.benbest.com/lifeext/aging.html. Accessed November 14, 2006.
  7. Rohde D. Afghanistan, symbol for change becomes symbol for failure. New York Times 2006 9/05/2006
  8. Gerstenblith G, Frederiksen J, Yin FC, et al. Echocardiographic assessment of a normal adult aging population. Circulation. 1977;56:273–278
  9. Goor D, Lillehei CW, Edwards JE. The “sigmoid septum.” Variation in the contour of the left ventricular outlet. Am J Roentgenol Radium Ther Nucl Med. 1969;107:366–376
  10. Miller TR, Grossman SJ, Schectman KB, et al. Left ventricular diastolic filling and its association with age. Am J Cardiol. 1986;58:531–535
  11. Lakatta EG, Gerstenblith G, Angell CS, et al. Prolonged contraction duration in aged myocardium. J Clin Invest. 1975;55:61–68
  12. Kitzman DW, Gardin JM, Gottdiener JS, et al. CHS Research Group Importance of heart failure with preserved systolic function in patients > or = 65 years of age. Cardiovascular Health Study Am J Cardiol. 2001;87:413–419
  13. Levy D, Garrison RJ, Savage DD, et al. Prognostic implications of echocardiographically determined left ventricular mass in the Framingham Heart Study. N Engl J Med. 1990;322:1561–1566
  14. Sigwart UGM, Payot M, et al. Ischemic events during coronary artery balloon obstruction. In:  Rutishauser W,  Roskamm H editor. Silent Myocardial Ischemia. Berlin: Springer-Verlag; 1984;p. 29–36
  15. Wolf PA, Abbott RD, Kannel WB. Atrial fibrillation as an independent risk factor for stroke: The Framingham Study. Stroke. 1991;22:983–988
  16. Brand FN, Abbott RD, Kannel WB, et al. Characteristics and prognosis of lone atrial fibrillation (30-year follow-up in the Framingham Study). JAMA. 1985;254:3449–3453
  17. Lakatta EG. Cardiovascular regulatory mechanisms in advanced age. Physiol Rev. 1993;73:413–467
  18. Virmani R, Avolio AP, Mergner WJ, et al. 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;139:1119–1129
  19. O’Leary DH, Polak JF, Kronmal RA, et al. Cardiovascular Health Study Collaborative Research Group Carotid-artery intima and media thickness as a risk factor for myocardial infarction and stroke in older adults. N Engl J Med. 1999;340:14–22
  20. Challah M, Nadaud S, Philippe M, et al. Circulating and cellular markers of endothelial dysfunction with aging in rats. Am J Physiol. 1997;273:H1941–H1948
  21. Li Z, Froehlich J, Galis ZS, Lakatta EG. Increased expression of matrix metalloproteinase-2 in the thickened intima of aged rats. Hypertension. 1999;33:116–123
  22. Vaitkevicius PV, Lane M, Spurgeon H, et al. A cross-link breaker has sustained effects on arterial and ventricular properties in older rhesus monkeys. Proc Natl Acad Sci USA. 2001;98:1171–1175
  23. 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;107:139–146
  24. Roach MR, Burton AC. The effect of age on the elasticity of human iliac arteries. Can J Biochem Physiol. 1959;37:557–570
  25. Taddei S, Virdis A, Mattei P, et al. Aging and endothelial function in normotensive subjects and patients with essential hypertension. Circulation. 1995;91:1981–1987
  26. Elliott HL, Sumner DJ, McLean K, et al. Effect of age on the responsiveness of vascular alpha-adrenoceptors in man. J Cardiovasc Pharmacol. 1982;4:388–392
  27. Gimbrone MA. Vascular endothelium, hemodynamic forces, and atherogenesis. Am J Pathol. 1999;155:1–5
  28. Fleg JL, O’Connor F, Gerstenblith G, et al. Impact of age on the cardiovascular response to dynamic upright exercise in healthy men and women. J Appl Physiol. 1995;78:890–900
  29. Julius S, Amery A, Whitlock LS, et al. Influence of age on the hemodynamic response to exercise. Circulation. 1967;36:222–230
  30. Gribbin B, Pickering TG, Sleight P, et al. Effect of age and high blood pressure on baroreflex sensitivity in man. Circ Res. 1971;29:424–431
  31. Ferrari AU, Daffonchio A, Albergati F, et al. Differential effects of aging on the heart rate and blood pressure influences of arterial baroreceptors in awake rats. J Hypertens. 1991;9:615–621
  32. Dae MW, O’Connell JW, Botvinick EH, et al. Scintigraphic assessment of regional cardiac adrenergic innervation. Circulation. 1989;79:634–644
  33. Dae MW, Botvinick EH. Imaging of the heart using metaiodobenzylguanidine. J Thorac Imaging. 1990;5:31–36
  34. Dae MW, Chin MC, Botvinick EH, et al. Scintigraphic assessment of postnatal maturation of myocardial sympathetic nerves. Circulation. 1988;76:455
  35. Dae MW, De Marco T, Botvinick EH, et al. Scintigraphic assessment of MIBG uptake in globally denervated human and canine hearts–implications for clinical studies. J Nucl Med. 1992;33:1444–1450
  36. Hunt BE, Farquhar WB, Taylor JA. Does reduced vascular stiffening fully explain preserved cardiovagal baroreflex function in older, physically active men?. Circulation. 2001;103:2424–2427
  37. Tanabe S, Bunag RD. Aging escalates baroreceptor reflex suppression by the posterior hypothalamus in rats. Hypertension. 1991;17:80–90
  38. Chapleau MW, Cunningham JT, Sullivan MJ, et al. Structural versus functional modulation of the arterial baroreflex. Hypertension. 1995;26:341–347
  39. Ziegler MG, Lake CR, Kopin IJ. Plasma noradrenaline increases with age. Nature. 1976;261:333–335
  40. Mangoni AA, Mircoli L, Giannattasio C, et al. Effect of sympathectomy on mechanical properties of common carotid and femoral arteries. Hypertension. 1997;30:1085–1088
  41. McLean MR, Goldberg PB, Roberts J. An ultrastructural study of the effects of age on sympathetic innervation and atrial tissue in the rat. J Mol Cell Cardiol. 1983;15:75–92
  42. Rodeheffer RJ, Gerstenblith G, Becker LC, et al. Exercise cardiac output is maintained with advancing age in healthy human subjects: cardiac dilatation and increased stroke volume compensate for a diminished heart rate. Circulation. 1984;69:203–213
  43. Rywik TM, Blackman MR, Yataco AR, et al. Enhanced endothelial vasoreactivity in endurance-trained older men. J Appl Physiol. 1999;87:2136–2142
  44. Cleroux J, Giannattasio C, Bolla G, et al. Decreased cardiopulmonary reflexes with aging in normotensive humans. Am J Physiol. 1989;257:H961–H968
  45. Davy KP, Seals DR, Tanaka H. Augmented cardiopulmonary and integrative sympathetic baroreflexes but attenuated peripheral vasoconstriction with age. Hypertension. 1998;32:298–304
  46. Levy BI, Michel JB, Salzmann JL, et al. Remodeling of heart and arteries by chronic converting enzyme inhibition in spontaneously hypertensive rats. Am J Hypertens. 1991;4:240S–245S
  47. Haberl R, Becker A, Leber A, et al. Correlation of coronary calcification and angiographically documented stenoses in patients with suspected coronary artery disease: Results of 1,764 patients. J Am Coll Cardiol. 2001;37:451–457
  48. Fuster V, Corti R, Fayad ZA, Schwitter J, Badimon JJ. Integration of vascular biology and magnetic resonance imaging in the understanding of atherothrombosis and acute coronary syndromes. J Thromb Haemost. 2003;1:1410–1421
  49. Toussaint JF, Southern JF, Fuster V, et al. T2-weighted contrast for NMR characterization of human atherosclerosis. Arterioscler Thromb Vasc Biol. 1995;15:1533–1542
  50. Yuan C, Mitsumori LM, Beach KW, et al. Carotid atherosclerotic plaque: noninvasive MR characterization and identification of vulnerable lesions. Radiology. 2001;221:285–299
  51. Wilensky RL, Song HK, Ferrari VA. Role of magnetic resonance and intravascular magnetic resonance in the detection of vulnerable plaques. J Am Coll Cardiol. 2006;47(suppl 8):C48–C56
  52. Martin AJ, Gotlieb AI, Henkelman RM. High-resolution MR imaging of human arteries. J Magn Reson Imaging. 1995;5:93–100
  53. Corti R, Fuster V, Fayad ZA, et al. Lipid lowering by simvastatin induces regression of human atherosclerotic lesions: Two years’ follow-up by high-resolution noninvasive magnetic resonance imaging. Circulation. 2002;106:2884–2887
  54. Lima JA, Desai MY, Steen H, et al. Statin-induced cholesterol lowering and plaque regression after 6 months of magnetic resonance imaging-monitored therapy. Circulation. 2004;110:2336–2341
  55. Yuan C, Kerwin WS, Ferguson MS, et al. Contrast-enhanced high resolution MRI for atherosclerotic carotid artery tissue characterization. J Magn Reson Imaging. 2002;15:62–67
  56. Li H, Gray BD, Corbin I, et al. MR and fluorescent imaging of low-density lipoprotein receptors. Acad Radiol. 2004;11:1251–1259
  57. Frias JC, Williams KJ, Fisher EA, et al. Recombinant HDL-like nanoparticles: a specific contrast agent for MRI of atherosclerotic plaques. J Am Chem Soc. 2004;126:16316–16317
  58. Kooi ME, Cappendijk VC, Cleutjens KB, et al. Accumulation of ultrasmall superparamagnetic particles of iron oxide in human atherosclerotic plaques can be detected by in vivo magnetic resonance imaging. Circulation. 2003;107:2453–2458
  59. Natori S, Lai S, Finn JP, et al. Cardiovascular function in multi-ethnic study of atherosclerosis: normal values by age, sex, and ethnicity. AJR Am J Roentgenol. 2006;186(suppl 2):S357–S365
  60. Rudd JH, Warburton EA, Fryer TD, et al. Imaging atherosclerotic plaque inflammation with [18F]-fluorodeoxyglucose positron emission tomography. Circulation. 2002;105:2708–2711
  61. Ogawa M, Ishino S, Mukai T, et al. (18)F-FDG accumulation in atherosclerotic plaques: Immunohistochemical and PET imaging study. J Nucl Med. 2004;45:1245–1250
  62. Bural GG, Torigian DA, Chamroonrat W, et al. Quantitative assessment of atherosclerotic burden of the aorta by combined FDG-PET and CT image analysis: A new concept. Nucl Med Biol. 2006;33:1037–1043
  63. Little WC, Constantinescu M, Applegate RJ, et al. Can coronary angiography predict the site of a subsequent myocardial infarction in patients with mild-to-moderate coronary artery disease?. Circulation. 1988;78:1157–1166
  64. Ambrose JA, Fuster V. Can we predict future acute coronary events in patients with stable coronary artery disease?. JAMA. 1997;277:343–344
  65. Naghavi M, Falk E, Hecht HS, et al. From vulnerable plaque to vulnerable patient—Part III: Executive summary of the Screening for Heart Attack Prevention and Education (SHAPE) Task Force report. Am J Cardiol. 2006;98:2H–15H
  66. Alderman EL, Corley SD, Fisher LD, et al. CASS Participating Investigators and Staff Five-year angiographic follow-up of factors associated with progression of coronary artery disease in the Coronary Artery Surgery Study (CASS). J Am Coll Cardiol. 1993;22:1141–1154
  67. Naghavi M, Libby P, Falk E, et al. From vulnerable plaque to vulnerable patient: a call for new definitions and risk assessment strategies: Part I. Circulation. 2003;108:1664–1672
  68. Davies MJ, Woolf N, Rowles P, et al. Lipid and cellular constituents of unstable human aortic plaques. Basic Res Cardiol. 1994;89(suppl 1):33–39
  69. Davies JR, Rudd JH, Weissberg PL. Molecular and metabolic imaging of atherosclerosis. J Nucl Med. 2004;45:1898–1907
  70. O’Malley PG, Taylor AJ, Jackson JL, et al. Prognostic value of coronary electron-beam computed tomography for coronary heart disease events in asymptomatic populations. Am J Cardiol. 2000;85:945–948
  71. Poredos P. Endothelial dysfunction and cardiovascular disease. Pathophysiol Haemost Thromb. 2002;32:274–277
  72. Osterud B, Bjorklid E. Role of monocytes in atherogenesis. Physiol Rev. 2003;83:1069–1112
  73. Galis ZS, Khatri JJ. Matrix metalloproteinases in vascular remodeling and atherogenesis: The good, the bad, and the ugly. Circ Res. 2002;90:251–262
  74. Davies MJ. Stability and instability: Two faces of coronary atherosclerosis (The Paul Dudley White Lecture 1995). Circulation. 1996;94:2013–2020
  75. Davies JR, Rudd JF, Fryer TD, et al. Targeting the vulnerable plaque: The evolving role of nuclear imaging. J Nucl Cardiol. 2005;12:234–246
  76. Davies JR, Rudd JH, Weissberg PL, et al. Radionuclide imaging for the detection of inflammation in vulnerable plaques. J Am Coll Cardiol. 2006;47(suppl 8):C57–C68
  77. Casscells W, Hathorn B, David M, et al. Thermal detection of cellular infiltrates in living atherosclerotic plaques: possible implications for plaque rupture and thrombosis. Lancet. 1996;347:1447–1451
  78. Verheye S, De Meyer GR, Van Langenhove G, et al. In vivo temperature heterogeneity of atherosclerotic plaques is determined by plaque composition. Circulation. 2002;105:1596–1601
  79. Nissen SE, Nicholls SJ, Sipahi I, et al. Effect of very high-intensity statin therapy on regression of coronary atherosclerosis: the ASTEROID trial. JAMA. 2006;295:1556–1565
  80. Corot C, Petry KG, Trivedi R, et al. Macrophage imaging in central nervous system and in carotid atherosclerotic plaque using ultrasmall superparamagnetic iron oxide in magnetic resonance imaging. Invest Radiol. 2004;39:619–625
  81. Steffens S, Mach F. Inflammation and atherosclerosis. Herz. 2004;29:741–748
  82. Falk E. Pathogenesis of atherosclerosis. J Am Coll Cardiol. 2006;47(suppl 8):C7–C12
  83. Naghavi M, Libby P, Falk E, et al. From vulnerable plaque to vulnerable patient: A call for new definitions and risk assessment strategies: Part II. Circulation. 2003;108:1772–1778
  84. Virgolini I, Rauscha F, Lupattelli G, et al. Autologous low-density lipoprotein labeling allows characterization of human atherosclerotic lesions in vivo as to presence of foam cells and endothelial coverage. Eur J Nucl Med. 1991;18:948–951
  85. Lees AM, Lees RS, Schoen FJ, et al. Imaging human atherosclerosis with 99mTc-labeled low density lipoproteins. Arteriosclerosis. 1988;8:461–470
  86. Virgolini I, Muller C, Fitscha P, et al. Radio labeling autologous monocytes with 111-indium-oxine for reinjection in patients with atherosclerosis. Prog Clin Biol Res. 1990;355:271–280
  87. Rosenfeld ME. Leukocyte recruitment into developing atherosclerotic lesions: The complex interaction between multiple molecules keeps getting more complex. Arterioscler Thromb Vasc Biol. 2002;22:361–363
  88. Kopka K, Breyholz HJ, Wagner S, et al. Synthesis and preliminary biological evaluation of new radioiodinated MMP inhibitors for imaging MMP activity in vivo. Nucl Med Biol. 2004;31:257–267
  89. Kietselaer BL, Reutelingsperger CP, Heidendal GA, et al. Noninvasive detection of plaque instability with use of radiolabeled annexin A5 in patients with carotid-artery atherosclerosis. N Engl J Med. 2004;350:1472–1473
  90. Kolodgie FD, Petrov A, Virmani R, et al. Targeting of apoptotic macrophages and experimental atheroma with radiolabeled annexin V: A technique with potential for noninvasive imaging of vulnerable plaque. Circulation. 2003;108:3134–3139
  91. Johnstrom P, Rudd JH, Richards HK, et al. Imaging endothelin ET(B) receptors using [18F]-BQ3020: In vitro characterization and positron emission tomography (microPET). Exp Biol Med (Maywood). 2006;231:736–740
  92. Zhang Z, Machac J, Helft G, et al. Non-invasive imaging of atherosclerotic plaque macrophage in a rabbit model with F-18 FDG PET: A histopathological correlation. BMC Nucl Med. 2006;6:3
  93. Tatsumi M, Cohade C, Nakamoto Y, et al. Fluorodeoxyglucose uptake in the aortic wall at PET/CT: Possible finding for active atherosclerosis. Radiology. 2003;229:831–837
  94. Yun M, Jang S, Cucchiara A, et al. 18F FDG uptake in the large arteries: Acorrelation study with the atherogenic risk factors. Semin Nucl Med. 2002;32:70–76
  95. Dunphy MP, Freiman A, Larson SM, et al. Association of vascular 18F-FDG uptake with vascular calcification. J Nucl Med. 2005;46:1278–1284
  96. Rothwell PM, Eliasziw M, Gutnikov SA, et al. Analysis of pooled data from the randomized controlled trials of endarterectomy for symptomatic carotid stenosis. Lancet. 2003;361:107–116
  97. Jander S, Sitzer M, Schumann R, et al. Inflammation in high-grade carotid stenosis: A possible role for macrophages and T cells in plaque destabilization. Stroke. 1998;29:1625–1630
  98. Galis ZS, Sukhova GK, Lark MW, et al. Increased expression of matrix metalloproteinases and matrix degrading activity in vulnerable regions of human atherosclerotic plaques. J Clin Invest. 1994;94:2493–2503
  99. Boyle JJ, Bowyer DE, Weissberg PL, et al. Human blood-derived macrophages induce apoptosis in human plaque-derived vascular smooth muscle cells by Fas-ligand/Fas interactions. Arterioscler Thromb Vasc Biol. 2001;21:1402–1407
  100. Falk E. Why do plaques rupture?. Circulation. 1992;86(suppl 6):III30–III42
  101. Libby P, Geng YJ, Sukhova GK, et al. Molecular determinants of atherosclerotic plaque vulnerability. Ann N Y Acad Sci. 1997;811:134–142discussion 142-135
  102. Davies JR, Rudd JH, Fryer TD, et al. Identification of culprit lesions after transient ischemic attack by combined 18F fluorodeoxyglucose positron-emission tomography and high-resolution magnetic resonance imaging. Stroke. 2005;36:2642–2647
  103. Matsunari I, Sauraki M, Chen W, et al. Relationship between serum markers of atherosclerosis and vascular FDG uptake in asymptomatic subjects. J Nucl Med. 2006;47:127
  104. Bural G, Alkhawaldeh K, Houseni M, et al. Differences in FDG uptake in the large arteries of diabetic and age matched normal subject may indicate early atherosclerosis. J Nucl Med. 2006;47:126
  105. Chamroonrat W, Houseni M, Bural G, et al. Correlation of hyperlipidemia with high degree of FDG uptake in human aorta. J Nucl Med. 2006;47:127
  106. Chamroonrat W, Bural G, Houseni M, et al. Obesity correlated with high degree of FDG uptake in the aorta in populations with normal lipid profile of same age group. J Nucl Med. 2006;47:262
  107. Bural G, Chamroonrat M, Houseni M, et al. Degree of FDG uptake and MDP uptake in femoral arteries: changes with age. J Nucl Med. 2006;47:128
  108. Lee S, Lee K, Lee E, et al. Evaluation of arterial FDG uptake and calcification in healthy subjects with serial FDG PET/CT. J Nucl Med. 2006;47:127
  109. McMillin JB, Taffet GE, Taegtmeyer H, et al. Mitochondrial metabolism and substrate competition in the aging Fischer rat heart. Cardiovasc Res. 1993;27:2222–2228
  110. Abu-Erreish GM, Neely JR, Whitmer JT, et al. Fatty acid oxidation by isolated perfused working hearts of aged rats. Am J Physiol. 1977;232:E258–E262
  111. Kates AM, Herrero P, Dence C, et al. Impact of aging on substrate metabolism by the human heart. J Am Coll Cardiol. 2003;41:293–299
  112. Acikgoz G, Bural G, Houseni M, et al. Does intense myocardial uptake of fasting FDG-PET scan indicate cardiac disease?. J Nucl Med. 2006;47:274
  113. Kaneta T, Hakamatsuka T, Takanami K, et al. Evaluation of the relationship between physiological FDG uptake in the heart and age, blood glucose level, fasting period, and hospitalization. Ann Nucl Med. 2006;20:203–208
  114. de Groot M, Meeuwis AP, Kok PJ, et al. Influence of blood glucose level, age and fasting period on non-pathological FDG uptake in heart and gut. Eur J Nucl Med Mol Imaging. 2005;32:98–101
  115. Patlak CS, Blasberg RG. Graphical evaluation of blood-to-brain transfer constants from multiple-time uptake data (Generalizations). J Cereb Blood Flow Metab. 1985;5:584–590

 This article was written while E.H.B. was on professional leave from the University of California San Francisco, San Francisco, CA.

PII: S0001-2998(06)00082-1

doi: 10.1053/j.semnuclmed.2006.10.005

Seminars in Nuclear Medicine
Volume 37, Issue 2 , Pages 120-143 , March 2007