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Published in: Pediatric Cardiology 4/2018

01-04-2018 | Original Article

Determinants of Increased Aortic Diameters in Young Normotensive Patients With Turner Syndrome Without Structural Heart Disease

Authors: A. Uçar, Melike Tuğrul, Bülent Oğuz Erol, Ensar Yekeler, Banu Aydın, Seher Yıldız, Kemal Nişli, Firdevs Baş, Şükran Poyrazoğlu, Feyza Darendeliler, Nurçin Saka, Aylin Yetim Şahin, Yasin Yılmaz, Rüveyde Bundak

Published in: Pediatric Cardiology | Issue 4/2018

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Abstract

Factors associated with aortic dilation and dissection in patients with Turner syndrome (TS) remain unclear. We assessed magnetic resonance imaging-based aortic diameters at nine predefined anatomic positions and examined associations of increased aortic diameters with B-type natriuretic peptide (BNP), A-type NP (ANP), growth hormone treatment, insulin-like growth factor 1 (IGF1), and estrogen status. Forty-seven patients with TS aged 7.3–21 years and 34 healthy peers were enrolled in this study. Aortic diameters were higher in patients with TS at three positions than in controls (p < 0.05). History of GH treatment, pubertal status, and serum estradiol levels were not associated with increased aortic diameters. Patients with TS had higher plasma BNP and ANP levels than controls. BNP and IGF1 were independently associated with the increase in aortic diameters in TS at three positions of the ascending aorta (R2 = 0.361–0.458, p < 0.05 for all). At two positions of the descending aorta, only BNP emerged as an independent variable (R2 = 0.130–0.139, p < 0.05). We conclude that young, normotensive patients with TS had greater aortic diameters at several positions than healthy controls. BNP and IGF1 were independently associated with increased aortic diameters in TS.
Literature
1.
go back to reference Stochholm K, Juul S, Juel K, Naeraa RW, Gravholt CH (2006) Prevalence, incidence, diagnostic delay, and mortality in Turner syndrome. J Clin Endocrinol Metab 91:3897–3902CrossRefPubMed Stochholm K, Juul S, Juel K, Naeraa RW, Gravholt CH (2006) Prevalence, incidence, diagnostic delay, and mortality in Turner syndrome. J Clin Endocrinol Metab 91:3897–3902CrossRefPubMed
2.
go back to reference Natwani NC, Unwin R, Brook CG, Hindmarsh PC (2000) The influence of renal and cardiovascular abnormalities on blood pressure in Turner syndrome. Clin Endocrinol 52:371–377CrossRef Natwani NC, Unwin R, Brook CG, Hindmarsh PC (2000) The influence of renal and cardiovascular abnormalities on blood pressure in Turner syndrome. Clin Endocrinol 52:371–377CrossRef
3.
go back to reference Gravholt CH, Hansen KW, Erlandsen M, Ebbehøj E, Christiansen JS (2006) Nocturnal hypertension and impaired sympathovagal tone in Turner syndrome. J Hypertens 24:353–360CrossRefPubMed Gravholt CH, Hansen KW, Erlandsen M, Ebbehøj E, Christiansen JS (2006) Nocturnal hypertension and impaired sympathovagal tone in Turner syndrome. J Hypertens 24:353–360CrossRefPubMed
4.
go back to reference Ross JL, Feuillan P, Long LM, Kowal K, Kushner H, Cutler GB Jr (1995) Lipid abnormalities in Turner syndrome. J Pediatr 126:242–245CrossRefPubMed Ross JL, Feuillan P, Long LM, Kowal K, Kushner H, Cutler GB Jr (1995) Lipid abnormalities in Turner syndrome. J Pediatr 126:242–245CrossRefPubMed
5.
go back to reference Mortensen KH, Andersen NH, Gravholt CH (2012) Cardiovascular phenotype in Turner syndrome—integrating cardiology, genetics, and endocrinology. Endocr Rev 33:677–714CrossRefPubMed Mortensen KH, Andersen NH, Gravholt CH (2012) Cardiovascular phenotype in Turner syndrome—integrating cardiology, genetics, and endocrinology. Endocr Rev 33:677–714CrossRefPubMed
7.
go back to reference Mortensen KH, Erlandsen M, Andersen NH, Gravholt CH (2013) Prediction of aortic dilation in Turner syndrome—the use of serial cardiovascular magnetic resonance. J Cardiovasc Magn Reson 15:47CrossRefPubMedPubMedCentral Mortensen KH, Erlandsen M, Andersen NH, Gravholt CH (2013) Prediction of aortic dilation in Turner syndrome—the use of serial cardiovascular magnetic resonance. J Cardiovasc Magn Reson 15:47CrossRefPubMedPubMedCentral
9.
go back to reference Quezada E, Lapidus J, Shaughnessy R, Chen Z, Silberbach M (2015) Aortic dimensions in Turner syndrome. Am J Med Genet Part A 167A:2527–2532CrossRefPubMed Quezada E, Lapidus J, Shaughnessy R, Chen Z, Silberbach M (2015) Aortic dimensions in Turner syndrome. Am J Med Genet Part A 167A:2527–2532CrossRefPubMed
10.
go back to reference Gutin LS, Bakalov VK, Douglas R, Rosing DR, Arai AE, Gharib AM, Bondy CA (2012) N-terminal pro-brain natriuretic peptide levels and aortic diameters. Am Heart J 164:419–424CrossRefPubMedPubMedCentral Gutin LS, Bakalov VK, Douglas R, Rosing DR, Arai AE, Gharib AM, Bondy CA (2012) N-terminal pro-brain natriuretic peptide levels and aortic diameters. Am Heart J 164:419–424CrossRefPubMedPubMedCentral
11.
go back to reference Castillo C, Cruzado M, Ariznavarreta C, Gil-Loyzaga P, Lahera V, Cachofeiro V, Tresguerres JA (2005) Effect of recombinant growth hormone administration on body composition and vascular function and structure in old male Wistar rats. Biogerontology 6:303–312CrossRefPubMed Castillo C, Cruzado M, Ariznavarreta C, Gil-Loyzaga P, Lahera V, Cachofeiro V, Tresguerres JA (2005) Effect of recombinant growth hormone administration on body composition and vascular function and structure in old male Wistar rats. Biogerontology 6:303–312CrossRefPubMed
12.
go back to reference Stochholm K, Laursen T, Green A, Laurberg P, Andersen M, Kristensen L, Feldt-Rasmussen U, Christiansen JS, Frydenberg M, Gravholt CH (2008) Morbidity and GH deficiency: a nationwide study. Eur J Endocrinol 158:447–457CrossRefPubMed Stochholm K, Laursen T, Green A, Laurberg P, Andersen M, Kristensen L, Feldt-Rasmussen U, Christiansen JS, Frydenberg M, Gravholt CH (2008) Morbidity and GH deficiency: a nationwide study. Eur J Endocrinol 158:447–457CrossRefPubMed
13.
go back to reference Bengtsson BA, Edén S, Ernest I, Odén A, Sjögren B (1988) Epidemiology and long-term survival in acromegaly. A study of 166 cases diagnosed between 1955 and 1984. Acta Med Scand 223:327–335CrossRefPubMed Bengtsson BA, Edén S, Ernest I, Odén A, Sjögren B (1988) Epidemiology and long-term survival in acromegaly. A study of 166 cases diagnosed between 1955 and 1984. Acta Med Scand 223:327–335CrossRefPubMed
14.
go back to reference Matura LA, Sachdev V, Bakalov VK, Rosing DR, Bondy CA (2007) Growth hormone treatment and left ventricular dimensions in Turner syndrome. J Pediatr 150:587–591CrossRefPubMedPubMedCentral Matura LA, Sachdev V, Bakalov VK, Rosing DR, Bondy CA (2007) Growth hormone treatment and left ventricular dimensions in Turner syndrome. J Pediatr 150:587–591CrossRefPubMedPubMedCentral
15.
go back to reference Van den Berg J, Bannink EM, Wielopolski PA, Hop WC, van Osch-Gevers L, Pattynama PM, de M Keizer-Schrama, Helbing SM WA (2008) Cardiac status after childhood growth hormone treatment of Turner syndrome. J Clin Endocrinol Metab 93:2553–2558CrossRefPubMed Van den Berg J, Bannink EM, Wielopolski PA, Hop WC, van Osch-Gevers L, Pattynama PM, de M Keizer-Schrama, Helbing SM WA (2008) Cardiac status after childhood growth hormone treatment of Turner syndrome. J Clin Endocrinol Metab 93:2553–2558CrossRefPubMed
16.
go back to reference Uçar A, Oz F, Bas F, Oflaz H, Nişli K, Tuğrul M, Yetim A, Darendeliler F, Saka N, Poyrazoğlu Ş, Bundak R (2015) Increased arterial stiffness in young normotensive patients with Turner syndrome: associations with vascular biomarkers. Clin Endocrinol 82:719–727CrossRef Uçar A, Oz F, Bas F, Oflaz H, Nişli K, Tuğrul M, Yetim A, Darendeliler F, Saka N, Poyrazoğlu Ş, Bundak R (2015) Increased arterial stiffness in young normotensive patients with Turner syndrome: associations with vascular biomarkers. Clin Endocrinol 82:719–727CrossRef
17.
go back to reference Guven B, Can M, Mungan G, Acіkgoz S (2013) Reference values for serum levels of insulin-like growth factor 1 (IGF-1) and IGF-binding protein 3 (IGFBP-3) in the West Black Sea region of Turkey. Scand J Clin Lab Invest 73(2):135–140CrossRefPubMed Guven B, Can M, Mungan G, Acіkgoz S (2013) Reference values for serum levels of insulin-like growth factor 1 (IGF-1) and IGF-binding protein 3 (IGFBP-3) in the West Black Sea region of Turkey. Scand J Clin Lab Invest 73(2):135–140CrossRefPubMed
18.
go back to reference Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC (1985) Homeostasis model assessment: insulin resistance and b-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 28:412–419CrossRefPubMed Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC (1985) Homeostasis model assessment: insulin resistance and b-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 28:412–419CrossRefPubMed
19.
go back to reference Keskin M, Kurtoglu S, Kendirci M, Atabek ME, Yazici C (2005) Homeostasis model assessment is more reliable than the fasting glucose/insulin ratio and quantitative insulin sensitivity check index for assessing insulin resistance among obese children and adolescents. Pediatrics 115:e500–e503CrossRefPubMed Keskin M, Kurtoglu S, Kendirci M, Atabek ME, Yazici C (2005) Homeostasis model assessment is more reliable than the fasting glucose/insulin ratio and quantitative insulin sensitivity check index for assessing insulin resistance among obese children and adolescents. Pediatrics 115:e500–e503CrossRefPubMed
20.
go back to reference Zimmet P, Alberti KG, Kaufman F, Tajima N, Silink M, Arslanian S, Wong G, Bennett P, Shaw J, Caprio S, IDF Consensus Group (2007) The metabolic syndrome in children and adolescents–an IDF consensus report. Pediatr Diab 8, 299–306CrossRef Zimmet P, Alberti KG, Kaufman F, Tajima N, Silink M, Arslanian S, Wong G, Bennett P, Shaw J, Caprio S, IDF Consensus Group (2007) The metabolic syndrome in children and adolescents–an IDF consensus report. Pediatr Diab 8, 299–306CrossRef
21.
go back to reference Urbina E, Alpert B, Flynn J et al (2008) Ambulatory blood pressure monitoring in children and adolescents: recommendations for standard assessment: a scientific statement from the American Heart Association Atherosclerosis, Hypertension, and Obesity in Youth Committee of the Council on Cardiovascular Disease in the Young and the Council for High Blood Pressure Research. Hypertension 52:433–444CrossRefPubMed Urbina E, Alpert B, Flynn J et al (2008) Ambulatory blood pressure monitoring in children and adolescents: recommendations for standard assessment: a scientific statement from the American Heart Association Atherosclerosis, Hypertension, and Obesity in Youth Committee of the Council on Cardiovascular Disease in the Young and the Council for High Blood Pressure Research. Hypertension 52:433–444CrossRefPubMed
22.
go back to reference Verdecchia P, Schillaci G, Guerrieri M et al (1990) Circadian blood pressure changes and left ventricular hypertrophy in essential hypertension. Circulation 81:528–536CrossRefPubMed Verdecchia P, Schillaci G, Guerrieri M et al (1990) Circadian blood pressure changes and left ventricular hypertrophy in essential hypertension. Circulation 81:528–536CrossRefPubMed
23.
go back to reference Haycock GB, Schwartz GJ, Wisotsky DH (1978) Geometric method for measuring body surface area: a height-weight formula validated in infants, children, and adults. J Pediatr 93(1):62–66CrossRefPubMed Haycock GB, Schwartz GJ, Wisotsky DH (1978) Geometric method for measuring body surface area: a height-weight formula validated in infants, children, and adults. J Pediatr 93(1):62–66CrossRefPubMed
24.
go back to reference Mahabala C, Kamath P, Bhaskaran U, Pai ND, Pai AU (2013) Antihypertensive therapy: nocturnal dippers and nondippers. Do we treat them differently? Vasc Health Risk Manag 9:125–133CrossRefPubMedPubMedCentral Mahabala C, Kamath P, Bhaskaran U, Pai ND, Pai AU (2013) Antihypertensive therapy: nocturnal dippers and nondippers. Do we treat them differently? Vasc Health Risk Manag 9:125–133CrossRefPubMedPubMedCentral
25.
go back to reference Sas TC, de Muinck Keizer-Schrama SM, Stijnen T, Aanstoot HJ, Drop SL (2000) Carbohydrate metabolism during long-term growth hormone (GH) treatment and after discontinuation of GH treatment in girls with Turner syndrome participating in a randomized dose-response study. Dutch Advisory Group on Growth Hormone. J Clin Endocrinol Metab 85:769–775PubMed Sas TC, de Muinck Keizer-Schrama SM, Stijnen T, Aanstoot HJ, Drop SL (2000) Carbohydrate metabolism during long-term growth hormone (GH) treatment and after discontinuation of GH treatment in girls with Turner syndrome participating in a randomized dose-response study. Dutch Advisory Group on Growth Hormone. J Clin Endocrinol Metab 85:769–775PubMed
26.
go back to reference Van den Berg J, Bannink EM, Wielopolski PA, Pattynama PM, de Muinck Keizer-Shrama SM, Helbing WA (2006) Aortic distensibility and dimensions and the effects of growth hormone treatment in the Turner syndrome. Am J Cardiol 97:1644–1649CrossRefPubMed Van den Berg J, Bannink EM, Wielopolski PA, Pattynama PM, de Muinck Keizer-Shrama SM, Helbing WA (2006) Aortic distensibility and dimensions and the effects of growth hormone treatment in the Turner syndrome. Am J Cardiol 97:1644–1649CrossRefPubMed
27.
go back to reference Bolar K, Hoffman AR, Maneatis T, Lippe B (2008) Long term safety of recombinant human growth hormone in Turner syndrome. J Clin Endocrinol Metab 93:344–351CrossRefPubMed Bolar K, Hoffman AR, Maneatis T, Lippe B (2008) Long term safety of recombinant human growth hormone in Turner syndrome. J Clin Endocrinol Metab 93:344–351CrossRefPubMed
28.
go back to reference Bondy CA, Van PL, Bakalov VK, Ho VB (2006) Growth hormone treatment and aortic dimensions in Turner syndrome. J Clin Endocrinol Metab 91:1785–1788CrossRefPubMed Bondy CA, Van PL, Bakalov VK, Ho VB (2006) Growth hormone treatment and aortic dimensions in Turner syndrome. J Clin Endocrinol Metab 91:1785–1788CrossRefPubMed
29.
go back to reference Ungvari Z, Gautam T, Koncz P, Henthorn JC, Pinto JT, Ballabh P, Yan H, Mitschelen M, Farley J, Sonntag WE, Csiszar A (2010) Vasoprotective effects of life span-extending peripubertal GH replacement in Lewis dwarf rats. J Gerontol A 65:1145–1156CrossRef Ungvari Z, Gautam T, Koncz P, Henthorn JC, Pinto JT, Ballabh P, Yan H, Mitschelen M, Farley J, Sonntag WE, Csiszar A (2010) Vasoprotective effects of life span-extending peripubertal GH replacement in Lewis dwarf rats. J Gerontol A 65:1145–1156CrossRef
30.
go back to reference Ungvari Z, Sosnowska D, Podlutsky A, Koncz P, Sonntag WE, Csiszar A (2011) Free radical production, antioxidant capacity, and oxidative stress response signatures in fibroblasts from Lewis dwarf rats: effects of life span extending peripubertal GH treatment. J Gerontol A 66:501–510CrossRef Ungvari Z, Sosnowska D, Podlutsky A, Koncz P, Sonntag WE, Csiszar A (2011) Free radical production, antioxidant capacity, and oxidative stress response signatures in fibroblasts from Lewis dwarf rats: effects of life span extending peripubertal GH treatment. J Gerontol A 66:501–510CrossRef
31.
32.
go back to reference Castillo C, Cruzado M, Ariznavarreta C, Gil-Loyzaga P, Lahera V, Cachofeiro V, Tresguerres JA (2005) Effect of recombinant human growth hormone administration on body composition and vascular function and structure in old male Wistar rats. Biogerontology 6:303–312CrossRefPubMed Castillo C, Cruzado M, Ariznavarreta C, Gil-Loyzaga P, Lahera V, Cachofeiro V, Tresguerres JA (2005) Effect of recombinant human growth hormone administration on body composition and vascular function and structure in old male Wistar rats. Biogerontology 6:303–312CrossRefPubMed
33.
go back to reference Lombardi G, Galdiero M, Auriemma RS, Pivonello R, Colao A (2006) Acromegaly and the cardiovascular system. Neuroendocrinology 83:211–217CrossRefPubMed Lombardi G, Galdiero M, Auriemma RS, Pivonello R, Colao A (2006) Acromegaly and the cardiovascular system. Neuroendocrinology 83:211–217CrossRefPubMed
34.
go back to reference Cintron D, Rodriguez-Gutierrez R, Serrano V, Latortue-Albino P, Erwin PJ, Murad MH (2017) Effect of estrogen replacement therapy on bone and cardiovascular outcomes in women with Turner syndrome: a systematic review and meta-analysis. Endocrine 55(2):366–375CrossRefPubMed Cintron D, Rodriguez-Gutierrez R, Serrano V, Latortue-Albino P, Erwin PJ, Murad MH (2017) Effect of estrogen replacement therapy on bone and cardiovascular outcomes in women with Turner syndrome: a systematic review and meta-analysis. Endocrine 55(2):366–375CrossRefPubMed
35.
go back to reference Lazo M, Young JH, Brancati LF, Coresh J, Whelton S, Ndumele CE, Hoogeveen R, Ballantyne CM, Selvin E (2013) NH2-terminal pro-brain natriuretic peptide and risk of diabetes. Diabetes 62:3189–3193CrossRefPubMedPubMedCentral Lazo M, Young JH, Brancati LF, Coresh J, Whelton S, Ndumele CE, Hoogeveen R, Ballantyne CM, Selvin E (2013) NH2-terminal pro-brain natriuretic peptide and risk of diabetes. Diabetes 62:3189–3193CrossRefPubMedPubMedCentral
36.
go back to reference Wang TJ, Larson MG, Levy D, Benjamin EJ, Leip EP, Omland T, Wolf PA, Vasan RS (2004) Plasma natriuretic peptide levels and the risk of cardiovascular events and death. N Engl J Med 350:655–663CrossRefPubMed Wang TJ, Larson MG, Levy D, Benjamin EJ, Leip EP, Omland T, Wolf PA, Vasan RS (2004) Plasma natriuretic peptide levels and the risk of cardiovascular events and death. N Engl J Med 350:655–663CrossRefPubMed
37.
go back to reference Habashi JP, Judge DP, Holm TM, Cohn RD, Loeys BL, Cooper TK, Myers L, Klein EC, Liu G, Calvi C, Podowski M, Neptune ER, Halushka MK, Bedja D, Gabrielson K, Rifkin DB, Carta L, Ramirez F, Huso DL, Dietz HC (2006) Losartan, an AT1 antagonist, prevents aortic aneurysm in a mouse model of Marfan syndrome. Science 312(5770):117–121CrossRefPubMedPubMedCentral Habashi JP, Judge DP, Holm TM, Cohn RD, Loeys BL, Cooper TK, Myers L, Klein EC, Liu G, Calvi C, Podowski M, Neptune ER, Halushka MK, Bedja D, Gabrielson K, Rifkin DB, Carta L, Ramirez F, Huso DL, Dietz HC (2006) Losartan, an AT1 antagonist, prevents aortic aneurysm in a mouse model of Marfan syndrome. Science 312(5770):117–121CrossRefPubMedPubMedCentral
Metadata
Title
Determinants of Increased Aortic Diameters in Young Normotensive Patients With Turner Syndrome Without Structural Heart Disease
Authors
A. Uçar
Melike Tuğrul
Bülent Oğuz Erol
Ensar Yekeler
Banu Aydın
Seher Yıldız
Kemal Nişli
Firdevs Baş
Şükran Poyrazoğlu
Feyza Darendeliler
Nurçin Saka
Aylin Yetim Şahin
Yasin Yılmaz
Rüveyde Bundak
Publication date
01-04-2018
Publisher
Springer US
Published in
Pediatric Cardiology / Issue 4/2018
Print ISSN: 0172-0643
Electronic ISSN: 1432-1971
DOI
https://doi.org/10.1007/s00246-018-1821-z

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