Growth hormone and the cardiovascular system

Cardiology in Review

Volumn 20, Issue 4, 2012, Pages 197-207

  Palmeiro, Christopher R ^a   Anand, Rishi ^a   Dardi, Inderpreet Kaur ^a   Balasubramaniyam, Nivas ^a   Schwarcz, Monica D ^a   Weiss, Irene A ^a  

^a NEW YORK MEDICAL COLLEGE   (United States)

Author keywords

anabolic hormone abuse; cardiovascular disease; growth hormone; IGF 1

Indexed keywords

ALDOSTERONE; ANGIOPEPTIN; APOLIPOPROTEIN B; BROMOCRIPTINE; C REACTIVE PROTEIN; CATECHOLAMINE; DOPAMINE RECEPTOR STIMULATING AGENT; GROWTH HORMONE; INTERLEUKIN 6; LOW DENSITY LIPOPROTEIN; MESSENGER RNA; OCTREOTIDE; PEGVISOMANT; SOMATOMEDIN BINDING PROTEIN 4; SOMATOMEDIN C; SOMATOSTATIN DERIVATIVE; VERY LOW DENSITY LIPOPROTEIN;

ACROMEGALY; APOPTOSIS; ATHEROSCLEROSIS; BLOOD FLOW; BLOOD PRESSURE; BODY COMPOSITION; CARDIOMEGALY; CARDIOMYOPATHY; CARDIOVASCULAR DISEASE; CONGESTIVE HEART FAILURE; DISEASE ASSOCIATION; DISEASE DURATION; DRUG MEGADOSE; DYSLIPIDEMIA; ECHOCARDIOGRAPHY; ENDOTHELIUM; GLUCOSE INTOLERANCE; GROWTH HORMONE DEFICIENCY; HEART ARRHYTHMIA; HEART CATHETERIZATION; HEART EJECTION FRACTION; HEART HYPERTROPHY; HEART MUSCLE; HUMAN; HYPERKINESIA; HYPERTENSION; INSULIN RESISTANCE; INSULIN SENSITIVITY; LIPOPROTEIN METABOLISM; LOW DRUG DOSE; MUSCLE WEAKNESS; NONHUMAN; OBESITY; PROTEIN EXPRESSION; RENIN ANGIOTENSIN ALDOSTERONE SYSTEM; REVIEW; SHEAR STRESS; SODIUM ABSORPTION; TACHYCARDIA; TOTAL BODY WATER; TRANSSPHENOIDAL SURGERY; VALVULAR HEART DISEASE;

BIOLOGICAL MARKERS; BODY COMPOSITION; CARDIOMEGALY; CARDIOMYOPATHIES; CARDIOVASCULAR DISEASES; DYSLIPIDEMIAS; GROWTH HORMONE; HEART DISEASES; HEART VALVE DISEASES; HUMAN GROWTH HORMONE; HUMANS; HYPERTENSION; INSULIN RESISTANCE; INSULIN-LIKE GROWTH FACTOR I; RECOMBINANT PROTEINS; SOMATOSTATIN;

EID: 84862200855     PISSN: 10615377     EISSN: 15384683     Source Type: Journal    
DOI: 10.1097/CRD.0b013e318248a3e1     Document Type: Review

References (172)

1. Tomlinson JW, Holden N, Hills RK, et al. Association between premature mortality and hypopituitarism. West Midlands Prospective Hypopituitary Study Group. Lancet. 2001;357:425-431.
2. Holdaway IM. Excess mortality in acromegaly. Horm Res. 2007;68(suppl 5):166-172.
3. Rajasoorya C, Holdaway IM, Wrightson P, et al. Determinants of clinical outcome and survival in acromegaly. Clin Endocrinol (Oxf). 1994;41:95-102.
4. Han Y, Leaman DW, Watling D, et al. Participation of JAK and STAT proteins in growth hormone-induced signaling. J Biol Chem. 1996;271:5947-5952.
5. Reiss K, Kajstura J, Zhang X, et al. Acute myocardial infarction leads to upregulation of the IGF-1 autocrine system, DNA replication, and nuclear mitotic division in the remaining viable cardiac myocytes. Exp Cell Res. 1994;213:463-472.
6. McGuffin WL Jr, Sherman BM, Roth F, et al. Acromegaly and cardiovascular disorders. A prospective study. Ann Intern Med. 1974;81:11-18.
7. Colao A, Vitale G, Pivonello R, et al. The heart: An end-organ of GH action. Eur J Endocrinol. 2004;151(suppl 1):S93-S101.
8. Verhelst J, Abs R. Cardiovascular risk factors in hypopituitary GH-deficient adults. Eur J Endocrinol. 2009;161(suppl 1):S41-S49.
9. Møller N, Jørgensen JO. Effects of growth hormone on glucose, lipid, and protein metabolism in human subjects. Endocr Rev. 2009;30:152-177.
10. Delafontaine P. Insulin-like growth factor I and its binding proteins in the cardiovascular system. Cardiovasc Res. 1995;30:825-834.
11. Mason VR, Corville C. The heart in acromegaly. Arch Intern Med. 1938;61:704-713.
12. de Herder WW. Acromegaly and gigantism in the medical literature. Case descriptions in the era before and the early years after the initial publication of Pierre Marie (1886). Pituitary. 2009;12:236-244.
13. Cushing H, Davidoff LM. The Pathological Findings in Four Autopsied Cases of Acromegaly, with a Discussion of Their Significance. Monograph of the Rockefeller Institute for Medical Research. 1927;22:1-126.
14. Clayton RN. Cardiovascular function in acromegaly. Endocr Rev. 2003;24:272-277.
15. Han VK, D'Ercole AJ, Lund PK. Cellular localization of somatomedin (insulin-like growth factor) messenger RNA in the human fetus. Science. 1987;236:193-197.
16. Freestone NS, Ribaric S, Mason WT. The effect of insulin-like growth factor-1 on adult rat cardiac contractility. Mol Cell Biochem. 1996;163-164:223-229.
17. Ito H, Hiroe M, Hirata Y, et al. Insulin-like growth factor-I induces hypertrophy with enhanced expression of muscle specific genes in cultured rat cardiomyocytes. Circulation. 1993;87:1715-1721.
18. Thomas MR, Miell JP, Taylor AM, et al. Endocrine and cardiac paracrine actions of insulin-like growth factor-I (IGF-I) during thyroid dysfunction in the rat: Is IGF-I implicated in the mechanism of heart weight/body weight change during abnormal thyroid function? J Mol Endocrinol. 1993;10:313-323.
19. Lu C, Schwartzbauer G, Sperling MA, et al. Demonstration of direct effects of growth hormone on neonatal cardiomyocytes. J Biol Chem. 2001;276:22892-22900.
20. Lei LQ, Rubin SA, Fishbein MC. Cardiac architectural changes with hypertrophy induced by excess growth hormone in rats. Lab Invest. 1988;59:357-362.
21. Chen DB, Wang L, Wang PH. Insulin-like growth factor I retards apoptotic signaling induced by ethanol in cardiomyocytes. Life Sci. 2000;67:1683-1693.
22. Frustaci A, Chimenti C, Setoguchi M, et al. Cell death in acromegalic cardiomyopathy. Circulation. 1999;99:1426-1434.
23. Colao A. 5 Long-term acromegaly and associated cardiovascular complications: A case-based review. Best Pract Res Clin Endocrinol Metab. 2009;23(suppl 1):S31-S38.
24. Lie JT. Pathology of the heart in acromegaly: Anatomic findings in 27 autopsied patients. Am Heart J. 1980;100:41-52.
25. Colao A, Marzullo P, Di Somma C, et al. Growth hormone and the heart. Clin Endocrinol (Oxf). 2001;54:137-154.
26. Colao A, Marzullo P, Lombardi G. Effect of a six-month treatment with lanreotide on cardiovascular risk factors and arterial intima-media thickness in patients with acromegaly. Eur J Endocrinol. 2002;146:303-309.
27. Minniti G, Jaffrain-Rea ML, Moroni C, et al. Echocardiographic evidence for a direct effect of GH/IGF-I hypersecretion on cardiac mass and function in young acromegalics. Clin Endocrinol (Oxf). 1998;49:101-106.
28. Colao A, Ferone D, Marzullo P, et al. Systemic complications of acromegaly: Epidemiology, pathogenesis, and management. Endocr Rev. 2004;25:102-152.
29. Colao A, Di Somma C, Cuocolo A, et al. The severity of growth hormone deficiency correlates with the severity of cardiac impairment in 100 adult patients with hypopituitarism: An observational, case-control study. J Clin Endocrinol Metab. 2004;89:5998-6004.
30. Morvan D, Komajda M, Grimaldi A, et al. Cardiac hypertrophy and function in asymptomatic acromegaly. Eur Heart J. 1991;12:666-672.
31. Fazio S, Palmieri EA, Affuso F, et al. Effects of growth hormone on exercise capacity and cardiopulmonary performance in patients with chronic heart failure. J Clin Endocrinol Metab. 2007;92:4218-4223.
32. Fazio S, Cittadini A, Sabatini D, et al. Evidence for biventricular involvement in acromegaly: A Doppler echocardiographic study. Eur Heart J. 1993;14:26-33.
33. Colao A, Baldelli R, Marzullo P, et al. Systemic hypertension and impaired glucose tolerance are independently correlated to the severity of the acromegalic cardiomyopathy. J Clin Endocrinol Metab. 2000;85:193-199.
34. Colao A. The GH-IGF-I axis and the cardiovascular system: Clinical implications. Clin Endocrinol (Oxf). 2008;69:347-358.
35. Fazio S, Cittadini A, Cuocolo A, et al. Impaired cardiac performance is a distinct feature of uncomplicated acromegaly. J Clin Endocrinol Metab. 1994;79:441-446.
36. Vitale G, Pivonello R, Auriemma RS, et al. Hypertension in acromegaly and in the normal population: Prevalence and determinants. Clin Endocrinol (Oxf). 2005;63:470-476.
37. Ikkos D, Luft R, Sjogren B. Body water and sodium in patients with acromegaly. J Clin Invest. 1954;33:989-994.
38. Johannsson G, Sverrisdóttir YB, Ellegard L, et al. GH increases extracellular volume by stimulating sodium reabsorption in the distal nephron and preventing pressure natriuresis. J Clin Endocrinol Metab. 2002;87:1743-1749.
39. Møller J, Jørgensen JO, Marqversen J, et al. Insulin-like growth factor I administration induces fluid and sodium retention in healthy adults: Pos-sible involvement of renin and atrial natriuretic factor. Clin Endocrinol (Oxf). 2000;52:181-186.
40. Deray G, Chanson P, Maistre G, et al. Atrial natriuretic factor in patients with acromegaly. Eur J Clin Pharmacol. 1990;38:409-413.
41. Chanson P, Megnien JL, del Pino M, et al. Decreased regional blood flow in patients with acromegaly. Clin Endocrinol (Oxf). 1998;49:725-731.
42. Evans LM, Davies JS. Heterogeneous haemodynamics in acromegaly: Evidence of endothelial dysfunction? Clin Endocrinol (Oxf). 1998;49:711-712.
43. Maison P, Démolis P, Young J, et al. Vascular reactivity in acromegalic patients: Preliminary evidence for regional endothelial dysfunction and increased sympathetic vasoconstriction. Clin Endocrinol (Oxf). 2000;53:445-451.
44. Brevetti G, Marzullo P, Silvestro A, et al. Early vascular alterations in acromegaly. J Clin Endocrinol Metab. 2002;87:3174-3179.
45. Colao A, Spiezia S, Cerbone G, et al. Increased arterial intima-media thickness by B-M mode echodoppler ultrasonography in acromegaly. Clin Endocrinol (Oxf). 2001;54:515-524.
46. Otsuki M, Kasayama S, Yamamoto H, et al. Characterization of premature atherosclerosis of carotid arteries in acromegalic patients. Clin Endocrinol (Oxf). 2001;54:791-796.
47. Colao A, di Somma C, Cuocolo A, et al. Improved cardiovascular risk factors and cardiac performance after 12 months of growth hormone (GH) replacement in young adult patients with GH deficiency. J Clin Endocrinol Metab. 2001;86:1874-1881.
48. Rodrigues EA, Caruana MP, Lahiri A, et al. Subclinical cardiac dysfunction in acromegaly: Evidence for a specific disease of heart muscle. Br Heart J. 1989;62:185-194.
49. Kahaly G, Olshausen KV, Mohr-Kahaly S, et al. Arrhythmia profile in acromegaly. Eur Heart J. 1992;13:51-56.
50. Colao A, Spinelli L, Marzullo P, et al. High prevalence of cardiac valve disease in acromegaly: An observational, analytical, case-control study. J Clin Endocrinol Metab. 2003;88:3196-3201.
51. van der Klaauw AA, Bax JJ, Roelfsema F, et al. Uncontrolled acromegaly is associated with progressive mitral valvular regurgitation. Growth Horm IGF Res. 2006;16:101-107.
52. Bates AS, Van't Hoff W, Jones JM, et al. An audit of outcome of treatment in acromegaly. Q J Med. 1993;86:293-299.
53. Swearingen B, Barker FG 2nd, Katznelson L, et al. Long-term mortality after transsphenoidal surgery and adjunctive therapy for acromegaly. J Clin Endocrinol Metab. 1998;83:3419-3426.
54. Baldwin A, Cundy T, Butler J, et al. Progression of cardiovascular disease in acromegalic patients treated by external pituitary irradiation. Acta Endocrinol. 1985;108:26-30.
55. Colao A, Ferone D, Marzullo P, et al. Effect of different dopaminergic agents in the treatment of acromegaly. J Clin Endocrinol Metab. 1997;82:518-523.
56. Luboshitzky R, Barzilai D. Bromocriptine for an acromegalic patient. Improvement in cardiac function and carpal tunnel syndrome. JAMA. 1980;244:1825-1827.
57. Colao A, Pivonello R, Galderisi M, et al. Impact of treating acromegaly first with surgery or somatostatin analogs on cardiomyopathy. J Clin Endocrinol Metab. 2008;93:2639-2646.
58. Tokgözoglu SL, Erbas T, Aytemir K, et al. Effects of octreotide on left ventricular mass in acromegaly. Am J Cardiol. 1994;74:1072-1074.
59. Thuesen L, Christensen SE, Weeke J, et al. The cardiovascular effects of octreotide treatment in acromegaly: An echocardiographic study. Clin Endocrinol (Oxf). 1989;30:619-625.
60. Lombardi G, Colao A, Marzullo P, et al. Multicenter Italian Study Group on Lanreotide. Improvement of left ventricular hypertrophy and arrhythmias after lanreotide-induced GH and IGF-I decrease in acromegaly. A prospective multi-center study. J Endocrinol Invest. 2002;25:971-976.
61. Merola B, Cittadini A, Colao A, et al. Chronic treatment with the somatostatin analog octreotide improves cardiac abnormalities in acromegaly. J Clin Endocrinol Metab. 1993;77:790-793.
62. Chanson P, Timsit J, Masquet C, et al. Cardiovascular effects of the somatostatin analog octreotide in acromegaly. Ann Intern Med. 1990;113:921-925.
63. Colao A, Cuocolo A, Marzullo P, et al. Effects of 1-year treatment with octreotide on cardiac performance in patients with acromegaly. J Clin Endocrinol Metab. 1999;84:17-23.
64. Colao A, Auriemma RS, Galdiero M, et al. Effects of initial therapy for five years with somatostatin analogs for acromegaly on growth hormone and insulin-like growth factor-I levels, tumor shrinkage, and cardiovascular disease: A prospective study. J Clin Endocrinol Metab. 2009;94:3746-3756.
65. Maison P, Tropeano AI, Macquin-Mavier I, et al. Impact of somatostatin analogs on the heart in acromegaly: A metaanalysis. J Clin Endocrinol Metab. 2007;92:1743-1747.
66. Fatti LM, Scacchi M, Lavezzi E, et al. Effects of treatment with somatostatin analogues on QT interval duration in acromegalic patients. Clin Endocrinol (Oxf). 2006;65:626-630.
67. Bubinski R, Kus W, Goch J. [Effect of somatostatin on the conduction system of the heart]. Kardiol Pol. 1993;38:258-262.
68. Cook DM, Ezzat S, Katznelson L, et al.; AACE Acromegaly Guidelines Task Force. AACE Medical Guidelines for Clinical Practice for the diagnosis and treatment of acromegaly. Endocr Pract. 2004;10:213-225.
69. Pivonello R, Galderisi M, Auriemma RS, et al. Treatment with growth hormone receptor antagonist in acromegaly: Effect on cardiac structure and performance. J Clin Endocrinol Metab. 2007;92:476-482.
70. Colao A, Pivonello R, Auriemma RS, et al. Efficacy of 12-month treatment with the GH receptor antagonist pegvisomant in patients with acromegaly resistant to long-term, high-dose somatostatin analog treatment: Effect on IGF-I levels, tumor mass, hypertension and glucose tolerance. Eur J Endocrinol. 2006;154:467-477.
71. Mitchell G. Office of the Commissioner of Baseball, Major League Baseball. Report to the commissioner of baseball of an independent investigation into the illegal use of steriods and other performance enhancing substances by players in major league baseball. Available at: Http://files.mlb.com/mitchrpt. pdf. Accessed December 13, 2011.
72. Liu H, Bravata DM, Olkin I, et al. Systematic review: The effects of growth hormone on athletic performance. Ann Intern Med. 2008;148:747-758.
73. Holt RI, Sönksen PH. Growth hormone, IGF-I and insulin and their abuse in sport. Br J Pharmacol. 2008;154:542-556.
74. Graham MR, Baker JS, Evans P, et al. Evidence for a decrease in cardiovascular risk factors following recombinant growth hormone administration in abstinent anabolic-androgenic steroid users. Growth Horm IGF Res. 2007;17:201-209.
75. Irving BA, Patrie JT, Anderson SM, et al. The effects of time following acute growth hormone administration on metabolic and power output measures during acute exercise. J Clin Endocrinol Metab. 2004;89:4298-4305.
76. Lange KH, Larsson B, Flyvbjerg A, et al. Acute growth hormone administration causes exaggerated increases in plasma lactate and glycerol during moderate to high intensity bicycling in trained young men. J Clin Endocrinol Metab. 2002;87:4966-4975.
77. Hansen TK, Møller J, Thomsen K, et al. Effects of growth hormone on renal tubular handling of sodium in healthy humans. Am J Physiol Endocrinol Metab. 2001;281:E1326-E1332.
78. Berggren A, Ehrnborg C, Rosén T, et al. Short-term administration of supraphysiological recombinant human growth hormone (GH) does not increase maximum endurance exercise capacity in healthy, active young men and women with normal GH-insulin-like growth factor I axes. J Clin Endocrinol Metab. 2005;90:3268-3273.
79. Hansen M, Morthorst R, Larsson B, et al. No effect of growth hormone administration on substrate oxidation during exercise in young, lean men. J Physiol (Lond). 2005;567(Pt 3):1035-1045.
80. Graham MR, Evans P, Thomas NE, et al. Changes in endothelial dysfunction and associated cardiovascular disease morbidity markers in GH-IGF axis pathology. Am J Cardiovasc Drugs. 2009;9:371-381.
81. Cittadini A, Strömer H, Katz SE, et al. Differential cardiac effects of growth hormone and insulin-like growth factor-1 in the rat. A combined in vivo and in vitro evaluation. Circulation. 1996;93:800-809.
82. Thuesen L, Christiansen JS, Sørensen KE, et al. Increased myocardial contractility following growth hormone administration in normal man. An echocardiographic study. Dan Med Bull. 1988;35:193-196.
83. Hoffman JR, Kraemer WJ, Bhasin S, et al. Position stand on androgen and human growth hormone use. J Strength Cond Res. 2009;23(5 suppl):S1-S59.
84. Karila TA, Karjalainen JE, Mäntysaari MJ, et al. Anabolic androgenic steroids produce dose-dependant increase in left ventricular mass in power atheletes, and this effect is potentiated by concomitant use of growth hormone. Int J Sports Med. 2003;24:337-343.
85. Rosén T, Bengtsson BA. Premature mortality due to cardiovascular disease in hypopituitarism. Lancet. 1990;336:285-288.
86. Bates AS, Van't Hoff W, Jones PJ, et al. The effect of hypopituitarism on life expectancy. J Clin Endocrinol Metab. 1996;81:1169-1172.
87. Juul A, Scheike T, Davidsen M, et al. Low serum insulin-like growth factor I is associated with increased risk of ischemic heart disease: A population-based case-control study. Circulation. 2002;106:939-944.
88. Vasan RS, Sullivan LM, D'Agostino RB, et al. Serum insulin-like growth factor I and risk for heart failure in elderly individuals without a previous myocardial infarction: The Framingham Heart Study. Ann Intern Med. 2003;139:642-648.
89. Laughlin GA, Barrett-Connor E, Criqui MH, et al. The prospective association of serum insulin-like growth factor I (IGF-I) and IGF-binding protein-1 levels with all cause and cardiovascular disease mortality in older adults: The Rancho Bernardo Study. J Clin Endocrinol Metab. 2004;89:114-120.
90. Colao A, Di Somma C, Filippella M, et al. Insulin-like growth factor-1 deficiency determines increased intima-media thickness at common carotid arteries in adult patients with growth hormone deficiency. Clin Endocrinol (Oxf). 2004;61:360-366.
91. Colao A, Di Somma C, Savanelli MC, et al. Beginning to end: Cardiovascular implications of growth hormone (GH) deficiency and GH therapy. Growth Horm IGF Res. 2006;16(suppl A):S41-S48.
92. Colao A, Di Somma C, Spiezia S, et al. Growth hormone treatment on atherosclerosis: Results of a 5-year open, prospective, controlled study in male patients with severe growth hormone deficiency. J Clin Endocrinol Metab. 2008;93:3416-3424.
93. Colao A, Di Somma C, Spiezia S, et al. The natural history of partial growth hormone deficiency in adults: A prospective study on the cardiovascular risk and atherosclerosis. J Clin Endocrinol Metab. 2006;91:2191-2200.
94. Snel YE, Brummer RJ, Doerga ME, et al. Energy and macronutrient intake in growth hormone-deficient adults: The effect of growth hormone replacement. Eur J Clin Nutr. 1995;49:492-500.
95. Johansson JO, Fowelin J, Landin K, et al. Growth hormone-deficient adults are insulin-resistant. Metab Clin Exp. 1995;44:1126-1129.
96. Sesmilo G, Biller BM, Llevadot J, et al. Effects of growth hormone administration on inflammatory and other cardiovascular risk markers in men with growth hormone deficiency. A randomized, controlled clinical trial. Ann Intern Med. 2000;133:111-122.
97. Molitch ME, Clemmons DR, Malozowski S, et al. Endocrine Society's Clinical Guidelines Subcommittee. Evaluation and treatment of adult growth hormone deficiency: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2006;91:1621-1634.
98. Giustina A, Barkan A, Chanson P, et al.; Pituitary Society; European Neuroendocrine Association. Guidelines for the treatment of growth hormone excess and growth hormone deficiency in adults. J Endocrinol Invest. 2008;31:820-838.
99. Verhelst J, Kendall-Taylor P, Erfurth EM, et al. Baseline characteristics and response to 2 years of growth hormone (GH) replacement of hypopituitary patients with GH deficiency due to adult-onset craniopharyngioma in comparison with patients with nonfunctioning pituitary adenoma: Data from KIMS (Pfizer International Metabolic Database). J Clin Endocrinol Metab. 2005;90:4636-4643.
100. Lamberts SW. Hypopituitary control and complications study (HypoCCS): A decade of an outcomes assessment observational study. J Endocrinol Invest. 2008;31(9 suppl):2-5.
101. Bidlingmaier M, Freda PU. Measurement of human growth hormone by immunoassays: Current status, unsolved problems and clinical consequences. Growth Horm IGF Res. 2010;20:19-25.
102. Colao A, Di Somma C, Rota F, et al. Short-term effects of growth hormone (GH) treatment or deprivation on cardiovascular risk parameters and intima-media thickness at carotid arteries in patients with severe GH deficiency. J Clin Endocrinol Metab. 2005;90:2056-2062.
103. Colao A, Di Somma C, Rota F, et al. Common carotid intima-media thickness in growth hormone (GH)-deficient adolescents: A prospective study after GH withdrawal and restarting GH replacement. J Clin Endocrinol Metab. 2005;90:2659-2665.
104. Anwar A, Gaspoz JM, Pampallona S, et al. Effect of congestive heart failure on the insulin-like growth factor-1 system. Am J Cardiol. 2002;90:1402-1405.
105. Okura Y, Brink M, Zahid AA, et al. Decreased expression of insulin-like growth factor-1 and apoptosis of vascular smooth muscle cells in human atherosclerotic plaque. J Mol Cell Cardiol. 2001;33:1777-1789.
106. Patel VA, Zhang QJ, Siddle K, et al. Defect in insulin-like growth factor-1 survival mechanism in atherosclerotic plaque-derived vascular smooth muscle cells is mediated by reduced surface binding and signaling. Circ Res. 2001;88:895-902.
107. Colao A, Spiezia S, Di Somma C, et al. Circulating insulin-like growth factor-I levels are correlated with the atherosclerotic profile in healthy subjects independently of age. J Endocrinol Invest. 2005;28:440-448.
108. Makimura H, Stanley T, Mun D, et al. Reduced growth hormone secretion is associated with increased carotid intima-media thickness in obesity. J Clin Endocrinol Metab. 2009;94:5131-5138.
109. Markussis V, Beshyah SA, Fisher C, et al. Detection of premature atherosclerosis by high-resolution ultrasonography in symptom-free hypopituitary adults. Lancet. 1992;340:1188-1192.
110. Capaldo B, Patti L, Oliviero U, et al. Increased arterial intima-media thickness in childhood-onset growth hormone deficiency. J Clin Endocrinol Metab. 1997;82:1378-1381.
111. Capaldo B, Guardasole V, Pardo F, et al. Abnormal vascular reactivity in growth hormone deficiency. Circulation. 2001;103:520-524.
112. Lanes R, Soros A, Flores K, et al. Endothelial function, carotid artery intima-media thickness, epicardial adipose tissue, and left ventricular mass and function in growth hormone-deficient adolescents: Apparent effects of growth hormone treatment on these parameters. J Clin Endocrinol Metab. 2005;90:3978-3982.
113. Evans LM, Davies JS, Goodfellow J, et al. Endothelial dysfunction in hypopituitary adults with growth hormone deficiency. Clin Endocrinol (Oxf). 1999;50:457-464.
114. Merola B, Cittadini A, Colao A, et al. Cardiac structural and functional abnormalities in adult patients with growth hormone deficiency. J Clin Endocrinol Metab. 1993;77:1658-1661.
115. Longobardi S, Cuocolo A, Merola B, et al. Left ventricular function in young adults with childhood and adulthood onset growth hormone deficiency. Clin Endocrinol (Oxf). 1998;48:137-143.
116. Amato G, Carella C, Fazio S, et al. Body composition, bone metabolism, and heart structure and function in growth hormone (GH)-deficient adults before and after GH replacement therapy at low doses. J Clin Endocrinol Metab. 1993;77:1671-1676.
117. Nass R, Huber RM, Klauss V, et al. Effect of growth hormone (hGH) replacement therapy on physical work capacity and cardiac and pulmonary function in patients with hGH deficiency acquired in adulthood. J Clin Endocrinol Metab. 1995;80:552-557.
118. Valcavi R, Gaddi O, Zini M, et al. Cardiac performance and mass in adults with hypopituitarism: Effects of one year of growth hormone treatment. J Clin Endocrinol Metab. 1995;80:659-666.
119. Borson-Chazot F, Serusclat A, Kalfallah Y, et al. Decrease in carotid intima-media thickness after one year growth hormone (GH) treatment in adults with GH deficiency. J Clin Endocrinol Metab. 1999;84:1329-1333.
120. van der Klaauw AA, Pereira AM, Rabelink TJ, et al. Recombinant human GH replacement increases CD34+ cells and improves endothelial function in adults with GH deficiency. Eur J Endocrinol. 2008;159:105-111.
121. Mauras N, Pescovitz OH, Allada V, et al.; Transition Study Group. Limited efficacy of growth hormone (GH) during transition of GH-deficient patients from adolescence to adulthood: A phase III multicenter, double-blind, randomized two-year trial. J Clin Endocrinol Metab. 2005;90:3946-3955.
122. Sneppen SB, Steensgaard-Hansen F, Feldt-Rasmussen U. Cardiac effects of low-dose growth hormone replacement therapy in growth hormone-deficient adults. An 18-month randomised, placebo-controlled, double-blind study. Horm Res. 2002;58:21-29.
123. Oliveira JL, Aguiar-Oliveira MH, D'Oliveira A Jr, et al. Congenital growth hormone (GH) deficiency and atherosclerosis: Effects of GH replacement in GH-naive adults. J Clin Endocrinol Metab. 2007;92:4664-4670.
124. Colao A, Di Somma C, Cuocolo A, et al. Does a gender-related effect of growth hormone (GH) replacement exist on cardiovascular risk factors, cardiac morphology, and performance and atherosclerosis? Results of a two-year open, prospective study in young adult men and women with severe GH deficiency. J Clin Endocrinol Metab. 2005;90:5146-5155.
125. Joaquin C, Aguilera E, Granada ML, et al. Effects of GH treatment in GH-deficient adults on adiponectin, leptin and pregnancy-associated plasma protein-A. Eur J Endocrinol. 2008;158:483-490.
126. Crea F, Andreotti F. Pregnancy associated plasma protein-A and coronary atherosclerosis: Marker, friend, or foe? Eur Heart J. 2005;26:2075-2076.
127. Hansen TK, Fisker S, Dall R, et al. Growth hormone increases vascular cell adhesion molecule 1 expression: In vivo and in vitro evidence. J Clin Endocrinol Metab. 2004;89:909-916.
128. Heliövaara MK, Teppo AM, Karonen SL, et al. Plasma IL-6 concentration is inversely related to insulin sensitivity, and acute-phase proteins associate with glucose and lipid metabolism in healthy subjects. Diabetes Obes Metab. 2005;7:729-736.
129. Beauregard C, Utz AL, Schaub AE, et al. Growth hormone decreases visceral fat and improves cardiovascular risk markers in women with hypopituitarism: A randomized, placebo-controlled study. J Clin Endocrinol Metab. 2008;93:2063-2071.
130. Christ ER, Cummings MH, Jackson N, et al. Effects of growth hormone (GH) replacement therapy on low-density lipoprotein apolipoprotein B100 kinetics in adult patients with GH deficiency: A stable isotope study. J Clin Endocrinol Metab. 2004;89:1801-1807.
131. Rudling M, Parini P, Angelin B. Growth hormone and bile acid synthesis. Key role for the activity of hepatic microsomal cholesterol 7alpha-hydroxylase in the rat. J Clin Invest. 1997;99:2239-2245.
132. Colao A, Cerbone G, Pivonello R, et al. The growth hormone (GH) response to the arginine plus GH-releasing hormone test is correlated to the severity of lipid profile abnormalities in adult patients with GH deficiency. J Clin Endocrinol Metab. 1999;84:1277-1282.
133. Sanmartí A, Lucas A, Hawkins F, et al. Observational study in adult hypopituitary patients with untreated growth hormone deficiency (ODA study). Socio-economic impact and health status. Collaborative ODA (Observational GH Deficiency in Adults) Group. Eur J Endocrinol. 1999;141:481-489.
134. Abs R, Feldt-Rasmussen U, Mattsson AF, et al. Determinants of cardiovascular risk in 2589 hypopituitary GH-deficient adults - a KIMS database analysis. Eur J Endocrinol. 2006;155:79-90.
135. de Boer H, Blok GJ, Voerman HJ, et al. Serum lipid levels in growth hormone-deficient men. Metab Clin Exp. 1994;43:199-203.
136. Deepak D, Daousi C, Javadpour M, et al. The influence of growth hormone replacement on peripheral inflammatory and cardiovascular risk markers in adults with severe growth hormone deficiency. Growth Horm IGF Res. 2010;20:220-225.
137. Beshyah SA, Freemantle C, Thomas E, et al. Abnormal body composition and reduced bone mass in growth hormone deficient hypopituitary adults. Clin Endocrinol (Oxf). 1995;42:179-189.
138. Binnerts A, Deurenberg P, Swart GR, et al. Body composition in growth hormone-deficient adults. Am J Clin Nutr. 1992;55:918-923.
139. Salomon F, Cuneo RC, Hesp R, et al. The effects of treatment with recombinant human growth hormone on body composition and metabolism in adults with growth hormone deficiency. N Engl J Med. 1989;321:1797-1803.
140. Rosén T, Edén S, Larson G, et al. Cardiovascular risk factors in adult patients with growth hormone deficiency. Acta Endocrinol. 1993;129:195-200.
141. Shi J, Sekhar RV, Balasubramanyam A, et al. Short- and long-term effects of growth hormone (GH) replacement on protein metabolism in GH-deficient adults. J Clin Endocrinol Metab. 2003;88:5827-5833.
142. Maison P, Chanson P. Cardiac effects of growth hormone in adults with growth hormone deficiency: A meta-analysis. Circulation. 2003;108:2648-2652.
143. Bramnert M, Segerlantz M, Laurila E, et al. Growth hormone replacement therapy induces insulin resistance by activating the glucose-fatty acid cycle. J Clin Endocrinol Metab. 2003;88:1455-1463.
144. Svensson J, Herlitz H, Lundberg PA, et al. Adiponectin, leptin, and erythrocyte sodium/lithium countertransport activity, but not resistin, are related to glucose metabolism in growth hormone-deficient adults. J Clin Endocrinol Metab. 2005;90:2290-2296.
145. Valle D, Di Minno MN, Palmieri V, et al. Changes in insulin levels following 6-month treatment with recombinant human growth hormone in growth hormone-deficient adults. J Endocrinol Invest. 2009;32:908-912.
146. Yuen KC, Frystyk J, White DK, et al. Improvement in insulin sensitivity without concomitant changes in body composition and cardiovascular risk markers following fixed administration of a very low growth hormone (GH) dose in adults with severe GH deficiency. Clin Endocrinol (Oxf). 2005;63:428-436.
147. Brasil RR, Soares DV, Spina LD, et al. Association of insulin resistance and nocturnal fall of blood pressure in GH-deficient adults during GH replacement. J Endocrinol Invest. 2007;30:306-312.
148. Fideleff HL, Boquete HR, Stalldecker G, et al. Comparative results of a 4-year study on cardiovascular parameters, lipid metabolism, body composition and bone mass between untreated and treated adult growth hormone deficient patients. Growth Horm IGF Res. 2008;18:318-324.
149. Beshyah SA, Johnston DG. Cardiovascular disease and risk factors in adults with hypopituitarism. Clin Endocrinol (Oxf). 1999;50:1-15.
150. Sverrisdóttir YB, Elam M, Herlitz H, et al. Intense sympathetic nerve activity in adults with hypopituitarism and untreated growth hormone deficiency. J Clin Endocrinol Metab. 1998;83:1881-1885.
151. Conceiçao FL, de Rooij Mansur VA, Brasil RR, et al. Ambulatory monitoring of blood pressure in growth hormone-deficient adults. Blood Press Monit. 2002;7:89-94.
152. Ahmad AM, Hopkins MT, Weston PJ, et al. Effects of GH replacement on 24-h ambulatory blood pressure and its circadian rhythm in adult GH deficiency. Clin Endocrinol (Oxf). 2002;56:431-437.
153. Fazio S, Cittadini A, Sabatini D, et al. Growth hormone and heart performance. A novel mechanism of cardiac wall stress regulation in humans. Eur Heart J. 1997;18:340-347.
154. Fazio S, Sabatini D, Capaldo B, et al. A preliminary study of growth hormone in the treatment of dilated cardiomyopathy. N Engl J Med. 1996;334:809-814.
155. Castellano G, Affuso F, Conza PD, et al. The GH/IGF-1 Axis and Heart Failure. Curr Cardiol Rev. 2009;5:203-215.
156. Houck WV, Pan LC, Kribbs SB, et al. Effects of growth hormone supplementation on left ventricular morphology and myocyte function with the development of congestive heart failure. Circulation. 1999;100:2003-2009.
157. Castagnino HE, Toranzos FA, Milei J, et al. Preservation of the myocardial collagen framework by human growth hormone in experimental infarctions and reduction in the incidence of ventricular aneurysms. Int J Cardiol. 1992;35:101-114.
158. Yang R, Bunting S, Gillett N, et al. Growth hormone improves cardiac performance in experimental heart failure. Circulation. 1995;92:262-267.
159. Grimm D, Cameron D, Griese DP, et al. Differential effects of growth hormone on cardiomyocyte and extracellular matrix protein remodeling following experimental myocardial infarction. Cardiovasc Res. 1998;40:297-306.
160. Kinugawa S, Tsutsui H, Ide T, et al. Positive inotropic effect of insulin-like growth factor-1 on normal and failing cardiac myocytes. Cardiovasc Res. 1999;43:157-164.
161. von Lewinski D, Voss K, Hülsmann S, et al. Insulin-like growth factor-1 exerts Ca2+-dependent positive inotropic effects in failing human myocardium. Circ Res. 2003;92:169-176.
162. Kang PM, Izumo S. Apoptosis and heart failure: A critical review of the literature. Circ Res. 2000;86:1107-1113.
163. Baixeras E, Jeay S, Kelly PA, et al. The proliferative and antiapoptotic actions of growth hormone and insulin-like growth factor-1 are mediated through distinct signaling pathways in the Pro-B Ba/F3 cell line. Endocrinology. 2001;142:2968-2977.
164. Jeay S, Sonenshein GE, Kelly PA, et al. Growth hormone exerts antiapoptotic and proliferative effects through two different pathways involving nuclear factor-kappaB and phosphatidylinositol 3-kinase. Endocrinology. 2001;142:147-156.
165. Le Corvoisier P, Hittinger L, Chanson P, et al. Cardiac effects of growth hormone treatment in chronic heart failure: A meta-analysis. J Clin Endocrinol Metab. 2007;92:180-185.
166. Genth-Zotz S, Zotz R, Geil S, et al. Recombinant growth hormone therapy
167. Perrot A, Ranke MB, Dietz R, et al. Growth hormone treatment in dilated cardiomyopathy. J Card Surg. 2001;16:127-131.
168. Osterziel KJ, Strohm O, Schuler J, et al. Randomised, double-blind, placebo-controlled trial of human recombinant growth hormone in patients with chronic heart failure due to dilated cardiomyopathy. Lancet. 1998;351:1233-1237.
169. Isgaard J, Kujacic V, Jennische E, et al. Growth hormone improves cardiac function in rats with experimental myocardial infarction. Eur J Clin Invest. 1997;27:517-525.
170. Cittadini A, Ines Comi L, Longobardi S, et al. A preliminary randomized study of growth hormone administration in Becker and Duchenne muscular dystrophies. Eur Heart J. 2003;24:664-672.
171. Adamopoulos S, Parissis JT, Paraskevaidis I, et al. Effects of growth hormone on circulating cytokine network, and left ventricular contractile performance and geometry in patients with idiopathic dilated cardiomyopathy. Eur Heart J. 2003;24:2186-2196.
172. Adamopoulos S, Parissis JT, Georgiadis M, et al. Growth hormone administration reduces circulating proinflammatory cytokines and soluble Fas/soluble Fas ligand system in patients with chronic heart failure secondary to idiopathic dilated cardiomyopathy. Am Heart J. 2002;144:359-364.