Flow-mediated Arterial Dilatation, Hypertension, Endothelin-1 and sICAM-1 in Obese Adolescents

NCT05951894 | Completed

• 2 other identifiers: A NumberUA number
• Study Type: observational
• Target: 70
• Locations: 1 country
• Sites: 1

Brief Summary

Obesity in adolescents is associated with the development of cardiovascular disease and type 2 diabetes mellitus. In order to detect early development of cardiovascular disease, early detection of the endothelium of obese adolescents is needed. Endothelium dysfunction is an early stage of developing atherosclerosis, which can be a predictor of cardiovascular disease development in the future. Flow mediated dilatation (FMD) is a non-invasive method that can measure endothelium function and predict the risk of cardiovascular disease, which is not only able to measure artery diameter, but also provides function index of nitric oxide (NO) in the endothelium. FMD is negatively related to BMI. Meanwhile, Endothelin-1 (ET-1) is thought to play a role in the pathogenesis of insulin resistance, because when its levels increase, ET-1 can cause a condition of hyperinsulinemia. ET-1 was found to be high in patients with cardiovascular disorders, as well as in obese and diabetic subjects. Alternative methods for assessing endothelial function by measurement of biomarkers of activation and endothelial dysfunction such as soluble intercellular adhesion molecule-1 (sICAM-1). Levels of sICAM-1 have been found to be related positively to age, systolic and diastolic blood pressure, hypercholesterolemia, hypertriglyceridemia and inversely to estrogen. Furthermore, associations have been found between sICAM-1 and cardiovascular mortality in both healthy individuals and populations at high risk. The aim of the study was to evaluate FMD, concentrations of ET-1 and sICAM-1 in adolescents with a presence of obesity and hypertension and to compare these with controls (obesity and non hypertension), as well as to analyze the correlations between FMD, ET-1, sICAM-1 and blood pressure values.

Conditions

Obesity; Hypertension; Adolescent Obesity

Keywords

Obesity; Flow-mediated Arterial Dilatation; Hypertension; sICAM-1

Outcome Measures

Primary Outcomes (7)

• Body height

  Body height will be measured using Seca 213 stadiometer. The subjects were asked to step at the stadiometer base in an upright state, with the heel, the buttock, and the shoulder blade touching the scale pool. The chin up, look straight ahead. The head slider was lowered until it touches the cranium. Noted the body height in the data collection sheet (presenting in mean +/- SD, in cm). The subject must use light clothes without accessories or footwear, such as hats or hair ponytail.

  5 months

• Body weight

  Body weight will be measured using Tanita RD 953-BK digital scale (presenting in mean +/- SD, in kg). The subjects were asked to step at the scale in an upright state. The body weight appears on the screen and is then noted in the data collection sheet. The subject must use light clothes without accessories or footwear

  5 months

• Hip circumference (HC)

  Hip circumference will be measured using Seca 201 measuring tape (in cm), by asking the subjects to keep the feet together, then wrapping the measuring tape around the widest part of the hips, at the point of the greatest gluteal protuberance. The subjects were measured using light cloth without food wear and other accessories such as belts, hats, hair accessories, etc. The data will be presented as mean +/- SD

  5 months

• Waist circumference (WC)

  Waist circumference will be measured using Seca 201 measuring tape (in cm), Waist circumference was measured by wrapping the measuring tape around the subject's stomach, at the midpoint between the lowest rib and the endpoint of the iliac crest upon expiration, in line with the navel. The subjects were measured using light cloth without food wear and other accessories such as belts, hats, hair accessories, etc. The data will be presented as mean +/- standard deviation (SD)

  5 months

• Flow-mediated Arterial Dilatation diameter

  FMD was calculated as the maximum percentage increase in diameter of the brachial artery after ischemia of the forearm. The measurements were performed in supine position at the elbow of the right arm. The cuff was placed on the forearm, distally to the measurement site. The duration of ischemia of the forearm was 5 min. All lumen diameter measurements were done at end diastole by the use of the R-wave of the electrocardiogram. The ultrasound images were made by one technician with a 7.5 megahertz (MHz) linear array transducer of an Ultramark duplex scanner. All images were stored on flash-disk for off-line analysis. Measurement of the endothelium-independent vasodilatation using nitroglycerine, was not performed.

  5 months

• Endothelin-1

  Endothelin-1 will be analyzed using the Human Endothelin-1 Elisa kit (Bioassay Technology Laboratory) (in ng/ml). The data will be presented as mean +/- standard deviation (SD)

  5 months

• sICAM-1

  sICAM-1 will be analyzed using Human intercellular adhesion molecule 1 Elisa kit (Bioassay Technology Laboratory) (in ng/ml). The data will be presented as mean +/- standard deviation (SD)

  5 months

Secondary Outcomes (9)

• Body Mass Index (BMI)

  5 months

• Systolic blood pressure

  5 months

• Diastolic blood pressure

  5 months

• Fasting blood glucose

  5 months

• Total cholesterol

  5 months

Study Arms (3)

Hypertension

This group consists of obese adolescents with hypertension, defined as systole blood pressure \>130 mmHg or diastole blood pressure \>85 mmHg, or both

Non-hypertension

This group consists of obese adolescents without hypertension

Normal (non-obese)

This group consist of normal subjects (non-obese)

Eligibility Criteria

• Age: 13 Years - 18 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64)
• Sampling Method: Non-Probability Sample

Study Population

Obese adolescents aged 13-18 years old

You may qualify if:

• Obesity
• Healthy
• Study in Junior or Senior High School in Surabaja city

You may not qualify if:

• Smoking or consuming alcohol
• Suffering from infections, inflammation, autoimmune diseases, cancer, chronic diseases, and endocrine disorders
• consuming steroids or hormone therapy

Sponsors & Collaborators

• Universitas Airlangga: lead

Study Sites (1)

RS Bhayangkara Surabaya

Surabaya, East Java, 61318, Indonesia

Location

Related Publications (17)

• Zhao W, Mo L, Pang Y. Hypertension in adolescents: The role of obesity and family history. J Clin Hypertens (Greenwich). 2021 Dec;23(12):2065-2070. doi: 10.1111/jch.14381. Epub 2021 Nov 16.

  PMID: 34783422 BACKGROUND

• Koenen M, Hill MA, Cohen P, Sowers JR. Obesity, Adipose Tissue and Vascular Dysfunction. Circ Res. 2021 Apr 2;128(7):951-968. doi: 10.1161/CIRCRESAHA.121.318093. Epub 2021 Apr 1.

  PMID: 33793327 RESULT

• Bellamkonda K, Williams M, Handa A, Lee R. Flow Mediated Dilatation as a Biomarker in Vascular Surgery Research. J Atheroscler Thromb. 2017 Aug 1;24(8):779-787. doi: 10.5551/jat.40964. Epub 2017 Jul 1.

  PMID: 28674324 RESULT

• Weissgerber TL. Flow-mediated dilation: can new approaches provide greater mechanistic insight into vascular dysfunction in preeclampsia and other diseases? Curr Hypertens Rep. 2014 Nov;16(11):487. doi: 10.1007/s11906-014-0487-z.

  PMID: 25182159 RESULT

• Green DJ, Jones H, Thijssen D, Cable NT, Atkinson G. Flow-mediated dilation and cardiovascular event prediction: does nitric oxide matter? Hypertension. 2011 Mar;57(3):363-9. doi: 10.1161/HYPERTENSIONAHA.110.167015. Epub 2011 Jan 24.

  PMID: 21263128 RESULT

• Maruhashi T, Kajikawa M, Kishimoto S, Hashimoto H, Takaeko Y, Yamaji T, Harada T, Han Y, Aibara Y, Mohamad Yusoff F, Hidaka T, Kihara Y, Chayama K, Nakashima A, Goto C, Tomiyama H, Takase B, Kohro T, Suzuki T, Ishizu T, Ueda S, Yamazaki T, Furumoto T, Kario K, Inoue T, Koba S, Watanabe K, Takemoto Y, Hano T, Sata M, Ishibashi Y, Node K, Maemura K, Ohya Y, Furukawa T, Ito H, Ikeda H, Yamashina A, Higashi Y. Diagnostic Criteria of Flow-Mediated Vasodilation for Normal Endothelial Function and Nitroglycerin-Induced Vasodilation for Normal Vascular Smooth Muscle Function of the Brachial Artery. J Am Heart Assoc. 2020 Jan 21;9(2):e013915. doi: 10.1161/JAHA.119.013915. Epub 2020 Jan 8.

  PMID: 31910779 RESULT

• Jenkins HN, Rivera-Gonzalez O, Gibert Y, Speed JS. Endothelin-1 in the pathophysiology of obesity and insulin resistance. Obes Rev. 2020 Dec;21(12):e13086. doi: 10.1111/obr.13086. Epub 2020 Jul 6.

  PMID: 32627269 RESULT

• Yang L, Magnussen CG, Yang L, Bovet P, Xi B. Elevated Blood Pressure in Childhood or Adolescence and Cardiovascular Outcomes in Adulthood: A Systematic Review. Hypertension. 2020 Apr;75(4):948-955. doi: 10.1161/HYPERTENSIONAHA.119.14168. Epub 2020 Mar 2.

  PMID: 32114851 RESULT

• Dulskiene V, Kuciene R, Medzioniene J, Benetis R. Association between obesity and high blood pressure among Lithuanian adolescents: a cross-sectional study. Ital J Pediatr. 2014 Dec 10;40:102. doi: 10.1186/s13052-014-0102-6.

  PMID: 25492217 RESULT

• Widjaja NA, Irawan R, Prihaningtyas RA, Ardiana M, Hanindita MH. Carotid intima-media thickness, hypertension, and dyslipidemia in obese adolescents. Pan Afr Med J. 2019 Nov 7;34:134. doi: 10.11604/pamj.2019.34.134.18309. eCollection 2019.

  PMID: 33708303 RESULT

• Rundek T, Gardener H, Della-Morte D, Dong C, Cabral D, Tiozzo E, Roberts E, Crisby M, Cheung K, Demmer R, Elkind MS, Sacco RL, Desvarieux M. The relationship between carotid intima-media thickness and carotid plaque in the Northern Manhattan Study. Atherosclerosis. 2015 Aug;241(2):364-70. doi: 10.1016/j.atherosclerosis.2015.05.027. Epub 2015 Jun 3.

  PMID: 26071659 RESULT

• Rivera-Gonzalez O, Wilson NA, Coats LE, Taylor EB, Speed JS. Endothelin receptor antagonism improves glucose handling, dyslipidemia, and adipose tissue inflammation in obese mice. Clin Sci (Lond). 2021 Jul 30;135(14):1773-1789. doi: 10.1042/CS20210549.

  PMID: 34278410 RESULT

• Busjahn A, Knoblauch H, Knoblauch M, Bohlender J, Menz M, Faulhaber HD, Becker A, Schuster H, Luft FC. Angiotensin-converting enzyme and angiotensinogen gene polymorphisms, plasma levels, cardiac dimensions. A twin study. Hypertension. 1997 Jan;29(1 Pt 2):165-70. doi: 10.1161/01.hyp.29.1.165.

  PMID: 9039097 RESULT

• Giannini C, de Giorgis T, Scarinci A, Cataldo I, Marcovecchio ML, Chiarelli F, Mohn A. Increased carotid intima-media thickness in pre-pubertal children with constitutional leanness and severe obesity: the speculative role of insulin sensitivity, oxidant status, and chronic inflammation. Eur J Endocrinol. 2009 Jul;161(1):73-80. doi: 10.1530/EJE-09-0042. Epub 2009 May 7.

  PMID: 19423560 RESULT

• Witte DR, Broekmans WM, Kardinaal AF, Klopping-Ketelaars IA, van Poppel G, Bots ML, Kluft C, Princen JM. Soluble intercellular adhesion molecule 1 and flow-mediated dilatation are related to the estimated risk of coronary heart disease independently from each other. Atherosclerosis. 2003 Sep;170(1):147-53. doi: 10.1016/s0021-9150(03)00253-3.

  PMID: 12957693 RESULT

• Dzikowska-Diduch O, Domienik-Karlowicz J, Gorska E, Demkow U, Pruszczyk P, Kostrubiec M. E-selectin and sICAM-1, biomarkers of endothelial function, predict recurrence of venous thromboembolism. Thromb Res. 2017 Sep;157:173-180. doi: 10.1016/j.thromres.2017.07.027. Epub 2017 Jul 26.

  PMID: 28780342 RESULT

• Glowinska B, Urban M, Peczynska J, Florys B. Soluble adhesion molecules (sICAM-1, sVCAM-1) and selectins (sE selectin, sP selectin, sL selectin) levels in children and adolescents with obesity, hypertension, and diabetes. Metabolism. 2005 Aug;54(8):1020-6. doi: 10.1016/j.metabol.2005.03.004.

  PMID: 16092051 RESULT

Biospecimen

Retention: SAMPLES WITHOUT DNA

the samples in the form of blood for investigation: lipid profile, fasting blood glucose, fasting insulin, endothelin-1 adn sICAM-1

MeSH Terms

Conditions

Obesity; Hypertension; Pediatric Obesity

Condition Hierarchy (Ancestors)

Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Vascular Diseases; Cardiovascular Diseases

Study Officials

• Budi Santoso, Professor

  Universitas Airlangga

  STUDY CHAIR

• Achmad Tri Ludfy Avianto, MD

  Universitas Airlangga

  STUDY CHAIR

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: CROSS SECTIONAL
• Target Duration: 5 Months
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator on Nutrition and Metabolic Disease

Study Record Dates

• First Submitted: June 19, 2023
• First Posted: July 19, 2023
• Study Start: August 1, 2023
• Primary Completion: October 31, 2023
• Study Completion: October 31, 2023
• Last Updated: November 21, 2023

Record last verified: 2023-11

Data Sharing

• IPD Sharing: Will not share

Locations

ID (1)