ARYA Atherosclerosis Journal

Investigation of flow-mediated vasodilatation (FMD) and comparison with carotid intima-media thickness (CIMT) in children with cyanotic congenital heart disease

Document Type : Original Article

Authors

Mehdi Ghaderian 1
Alireza Ahmadi 2
Narges Navabfar 3
Mohammad Reza Sabri 2
Bahar Dehghan 2
Chehreh Mahdavi 2

1 Associate professor of Pediatric Cardiology, Pediatric Cardiovascular Research Center, Cardiovascular Research Institute, Isfahan University of Medical Sciences, Isfahan, Iran

2 Pediatric Cardiovascular Research Center, Cardiovascular Research Institute, Isfahan University of Medical Sciences, Isfahan, Iran

3 Department of Pediatrics, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran

https://doi.org/10.48305/arya.2023.42047.2917
Abstract
BACKGROUND: There is a high mortality rate in cyanotic patients with congenital heart disease (CHD) due to cardiovascular complications. The cardiovascular prognosis is negatively affected by endothelium dysfunction, increased arterial stiffness, and impaired vascular system. This study aimed to determine carotid intimal mean thickness (CIMT) and flow-mediated dilatation (FMD) in a group of children with cyanotic CHD (CCHD).
METHODS: FMD and CIMT were evaluated for 45 children with CHKD and 38 patients who did not have CHKD over the period 2021 to 2022, as part of this case-control study. In terms of age and gender, the case group has been compared to controls.
RESULTS: Men accounted for 61.3% of the participants, with a mean standard deviation age of 7.8  5.39 years. In subjects with CCHD, CIMT increased non-significantly and FMD decreased significantly, but systolic blood pressure was significantly higher in patients than in the healthy group. (P=0.003).
CONCLUSION: FMD was reduced in children with CCHD, but in controls, systolic blood pressure and CIMT were lower. The risk of developing atherosclerosis in CCHD patients may be increased by an increase in CIMT and systolic blood pressure.

Keywords

Congenital Heart Defects
Flow-Mediated Dilatation
Cyanosis
Carotid Intimal-Media Thickness
Vascular Endothelium 
  1. Haas NA, Schirmer KR. Guidelines for the management of congenital heart diseases in childhood and adolescence. Cardiol Young. 2017;27(S3):S1-S105. https://doi.org/10.1017/S10 47951116001955
  2. Varma A, Sharma V, Damke S, Meshram R, Kher A, Vagha J. Clinical Presentation of cyanotic congenital heart diseases in the pediatric population. J Datta Meghe Inst Med Sci Univ. 2020;15(1):7-11.
    https://doi.org/10.4103/jdmimsu.jdmimsu_74_18
  3. Wu W, He J, Shao X. Incidence and mortality trend of congenital heart disease at the global, regional, and national level, 1990-2017. Medicine (Baltimore). 2020 Jun 5;99(23):e20593.
    https://doi.org/10.1097/MD.0000000000020593
  4. Sun R, Liu M, Lu L, Zheng Y, Zhang P. Congenital Heart Disease: Causes, Diagnosis, Symptoms, and Treatments. Cell Biochem Biophys. 2015 Jul;72(3):857-60. https://doi.org/10.1007/s12013-015-0551-6
  5. Cristina-Oliveira M, Meireles K, Gil S, Cavalcante Assis F, Geber-Júnior JC, Shinjo SK, et al. Carotid intima-media thickness and flow-mediated dilation do not predict acute in-hospital outcomes in patients hospitalized with COVID-19. Am J Physiol Heart Circ Physiol. 2022 Jun 1;322(6):H906-H13. https://doi.org/10.1152/ajpheart.00026.2022
  6. Rahul I, Krishnamurthy S, Satheesh S, Biswal N, Bobby Z, Lakshminarayanan S. Brachial artery flow-mediated dilatation and carotid intima medial thickness in pediatric nephrotic syndrome: a cross-sectional case-control study. Clin Exp Nephrol. 2015 Feb;19(1):125-32. https://doi.org/10.1007/s10157-014-0958-1
  7. Broxterman RM, Witman MA, Trinity JD, Groot HJ, Rossman MJ, Park S-Y, et al. Strong Relationship Between Vascular Function in the Coronary and Brachial Arteries. Hypertension. 2019 Jul;74(1):208-15. https://doi.org/10.1161/HYPERTENSIONAHA.119.12881
  8. Vlahos AP, Naka KK, Bechlioulis A, Theoharis P, Vakalis K, Moutzouri E, et al. Endothelial dysfunction, but not structural atherosclerosis, is evident early in children with heterozygous familial hypercholesterolemia. Pediatr Cardiol. 2014 Jan;35(1):63-70. https://doi.org/10.1007/s00246-013-0742-0
  9. Katz DL, Davidhi A, Ma Y, Kavak Y, Bifulco L, Njike VY. Effects of walnuts on endothelial function in overweight adults with visceral obesity: a randomized, controlled, crossover trial. J Am Coll Nutr. 2012 Dec;31(6):415-23. https://doi.org/10.1080/07315724.2012.10720468
  10. Xu S, Ilyas I, Little PJ, Li H, Kamato D, Zheng X, et al. Endothelial Dysfunction in Atherosclerotic Cardiovascular Diseases and Beyond: From Mechanism to Pharmacotherapies. Pharmacol Rev. 2021 Jul;73(3):924- 67. https://doi.org/10.1124/pharmrev.120.000096
  11. Dehghan B, Sabri MR, Hosseinzadeh M, Ahmadi A, Ghaderian M, Sarrafzadegan N, et al. The commencement of congenital heart diseases registry in Isfahan, Iran: Methodology and design. ARYA Atheroscler. 2020 Sep;16(5):244-47. https://doi.org/10.22122/arya.v16i5.1913
  12. Sorensen KE, Celermajer DS, Spiegelhalter DJ, Georgakopoulos D, Robinson J, Thomas O, et al. Non-invasive measurement of human endothelium dependent arterial responses: accuracy and reproducibility. Br Heart J. 1995 Sep;74(3):247-53. https://doi.org/10.1136/hrt.74.3.247
  13. Manganaro A, Ciracì L, Andrè L, Trio O, Manganaro R, Saporito F, et al. Endothelial dysfunction in patients with coronary artery disease: insights from a flow-mediated dilation study. Clin Appl Thromb Hemost. 2014 Sep;20(6):583-8. https://doi.org/10.1177/1076029614524620
  14. Oechslin E, Kiowski W, Schindler R, Bernheim A, Julius B, Brunner-La Rocca HP. Systemic endothelial dysfunction in adults with cyanotic congenital heart disease. Circulation. 2005 Aug 23;112(8):1106-12. https://doi.org/10.1161/CIRCULATIONAHA.105.534073
  15. Çiftel M, Şimşek A, Turan Ö, Kardelen F, Akçurin G, Ertuğ H. Endothelial dysfunction and atherosclerosis in children with irreversible pulmonary hypertension due to congenital heart disease. Ann Pediatr Cardiol. 2012 Jul;5(2):160-4. https://doi.org/10.4103/0974-2069.99619
  16. Cordina RL, Nakhla S, O’Meagher S, Leaney J, Graham S, Celermajer DS. Widespread endotheliopathy in adults with cyanotic congenital heart disease. Cardiol Young. 2015 Mar;25(3):511-9. https://doi.org/10.1017/S1047951114000262
  17. Tarp JB, Clausen P, Celermajer D, Christoffersen C, Jensen AS, Sørensen K, et al. Vascular function in adults with cyanotic congenital heart disease. Int J Cardiol Heart Vasc. 2020 Sep 15;30:100632. https://doi.org/10.1016/j.ijcha.2020.100632
  18. Pedersen CM, Schmidt MR, Mortensen B, Contractor H, Bøtker HE, Kharbanda RK, et al. Preserved flow-mediated dilation in adults with cyanotic congenital heart disease. Pediatr Cardiol. 2009 Oct;30(7):965-70. https://doi.org/10.1007/s00246-009-9489-z
  19. Sabri MR, Dehghan B, Yaghini O, Nasiri J, Mansourian M, Khalifehsoltani S. Endothelial dysfunction state in migraine headache and neutrally mediated syncope in children and young adults. J Res Med Sci. 2015 Aug;20(8):771-6. https://doi.org/10.4103/1735-1995.168384
  20. Giannakoulas G, Dimopoulos K, Engel R, Goktekin O, Kucukdurmaz Z, Vatankulu MA, et al. Burden of coronary artery disease in adults with congenital heart disease and its relation to congenital and traditional heart risk factors. Am J Cardiol. 2009 May 15;103(10):1445-50. https://doi.org/10.1016/j.amjcard.2009.01.353
  21. Mayyas F, Niebauer M, Zurick A, Barnard J, Gillinov AM, Chung MK, et al. Association of left atrial endothelin-1 with atrial rhythm, size, and fibrosis in patients with structural heart disease. Circ Arrhythm Electrophysiol. 2010 Aug;3(4):369-79. https://doi.org/10.1161/CIRCEP.109.924985
  22. Tarp JB, Jensen AS, Engstrøm T, Holstein-Rathlou N-H, Søndergaard L. Cyanotic congenital heart disease and atherosclerosis. Heart. 2017 Jun;103(12):897-900. https://doi.org/10.1136/hea rtjnl-2016-311012
  23. Fyfe A, Perloff JK, Niwa K, Child JS, Miner PD. Cyanotic congenital heart disease and coronary artery atherogenesis. Am J Cardiol. 2005 Jul 15;96(2):283-90. https://doi.org/10.1016/j.amj card.2005.03.060
  24. Sillesen H, Sartori S, Sandholt B, Baber U, Mehran R, Fuster V. Carotid plaque thickness and carotid plaque burden predict future cardiovascular events in asymptomatic adult Americans. Eur Heart J Cardiovasc Imaging. 2018 Sep 1;19(9):1042-1050. https://doi.org/10.1093/ehjci/jex239
  25. Mahdavi-Roshan M, Salari A, Doostdar-Sanaye M. Brachial endothelial function and carotid intima-media thickness in patients with coronary artery disease. Arch Adv Biosci. 2015;6(4):15-9. https://doi.org/10.22037/jps.v6i4.10622
  26. Bytyçi I, Shenouda R, Wester P, Henein MY. Carotid Atherosclerosis in Predicting Coronary Artery Disease: A Systematic Review
    and Meta-Analysis. Arterioscler Thromb Vasc Biol. 2021 Apr;41(4):e224-e237.https://doi.org/10.1161/ATVBAHA.120.315747
  27. Meyer A, Joharchi M, Kundt G, Schuff-Werner P, Steinhoff G, Kienast W. Predicting the risk of early atherosclerotic disease development in children after repair of aortic coarctation. Eur Heart J. 2005 Mar;26(6):617-22. https://doi.org/10.1093/eurheartj/ehi037
  28. Sabri MR, Kelishadi R. The thickness of the intimal and medial layers of the carotid arteries, and the index of left ventricular mass, in children of patients with premature coronary arterial disease. Cardiol Young. 2007 Dec;17(6):609-16. https://doi.org/10.1017/S1047951107001357
  29. Reiner B, Oberhoffer R, Häcker AL, Ewert P, Müller J. Carotid Intima-Media Thickness in Children and Adolescents With Congenital Heart Disease. Can J Cardiol. 2018 Dec;34(12):1618-23. https://doi.org/10.1016/j.cjca.2018.09.012
  30. de Groot PC, Thijssen D, Binkhorst M, Green DJ, Schokking M, Hopman MT. Vascular function in children with repaired tetralogy of Fallot. Am J Cardiol. 2010 Sep 15;106(6):851-5. https://doi.org/10.1016/j.amjcard.2010.05.009
  31. Goeder D, Oberhoffer-Fritz R, Brudy L, Willinger L, Meyer M, Ewert P, et al. Diminished Endothelial Function but Normal Vascular Structure in Adults with Tetralogy of Fallot. J Clin Med. 2022 Jan 19;11(3):493. https://doi.org/10.3390/jcm11030493
  32. Naessen T, Einarsson G, Henrohn D, Wikström G. Peripheral Vascular Ageing in Pulmonary Arterial Hypertension as Assessed by Common Carotid Artery Intima Thickness and Intima/Media Thickness Ratio: An Investigation Using Non-Invasive High-Resolution Ultrasound. Heart Lung Circ. 2023 Mar;32(3):338-347.
    https://doi.org/10.1016/j.hlc.2022.10.017
  33. Tarp JB, Sørgaard MH, Christoffersen C, Jensen AS, Sillesen H, Celermajer D, et al. Subclinical atherosclerosis in patients with cyanotic congenital heart disease. Int J Cardiol. 2019 Feb 15;277:97-103. https://doi.org/10.1016/j.ijcard.2018.08.104
  34. Giannini C, Diesse L, D’adamo E, Chiavaroli V, De Giorgis T, Di Iorio C, et al. Influence of the Mediterranean diet on carotid intima-media thickness in hypercholesterolaemic children: a 12-month intervention study. Nutr Metab Cardiovasc Dis. 2014 Jan;24(1):75-82. https://doi.org/10.1016/j.numecd.2013.04.005
  35. Eikendal AL, Groenewegen KA, Bots ML, Peters SA, Uiterwaal CS, den Ruijter HM. Relation Between Adolescent Cardiovascular Risk Factors and Carotid Intima-Media Echogenicity in Healthy Young Adults: The Atherosclerosis Risk in Young Adults (ARYA) Study. J Am Heart Assoc. 2016 May 12;5(5):e002941. https://doi.org/10.1161/JAHA.115.002941
  36. Kamel AS, AlGhawass MME, Sayed MA, Roby SA. Evaluation of carotid intima media thickness in children with idiopathic nephrotic syndrome. Ital J Pediatr. 2022 Dec 9;48(1):195. https://doi.org/10.1186/s13052-022-01383-7
  37. Ayer JG, Harmer JA, Nakhla S, Xuan W, Ng MK, Raitakari OT, et al. HDL-cholesterol, blood pressure, and asymmetric dimethylarginine are significantly associated with arterial wall thickness in children. Arterioscler Thromb Vasc Biol. 2009 Jun;29(6):943-9. https://doi.org/10.1161/ATVBAHA.109.184184
  38. Sabri MR, Daryoushi H, Gharipour M. Endothelial function state following repair of cyanotic congenital heart diseases. Cardiol Young. 2015 Feb;25(2):222-7. https://doi.org/10.1017/S104795111300187X
ARYA Atherosclerosis Journal
Volume 20, Issue 1
January and February 2024
Pages 1-8

Home

Guide for Authors

Submit Manuscript

Reviewers

Contact Us