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

Study Overview
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Brief Summary
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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.

Detailed Description
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This study is cross sectional study with observational analytic that evaluates FMD, ET-1 dan sICAM-1 in obese adolescents with hypertension compared to obese adolescents without hypertension and normal adolescents. The subjects are 70 adolescents (obese and normal) aged 13-18 years, healthy, not undergoing any medication, not smoking and not drinking alcohol, which are further divided into 3 groups: obesity with hypertension, obesity without hypertension and normal. Examination includes blood pressure examination, brachial ultrasound and blood sampling to measure levels of profile lipid, blood glucose, ET-1, and sICAM-1. Blood sample of subjects were taken by laboratory employee of the general hospital in Surabaja, Indonesia.

Official Title
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Flow-mediated Arterial Dilatation, Hypertension, Endothelin-1 (ET-1) and Soluble Intercellular Adhesion Molecule (sICAM-1) in Obese Adolescents

Conditions
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Obesity, Hypertension, Adolescent Obesity

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Obesity Healthy Study in Junior or Senior High School in Surabaja city Exclusion Criteria: Smoking or consuming alcohol Suffering from infections, inflammation, autoimmune diseases, cancer, chronic diseases, and endocrine disorders consuming steroids or hormone therapy

Ages Eligible for Study
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Minimum Age: 13 Years
Maximum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Hypertension<br>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<br>This group consists of obese adolescents without hypertension | |
| Normal (non-obese)<br>This group consist of normal subjects (non-obese) | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Body Mass Index (BMI) | BMI was calculated by dividing body weight (in kg) by body height square (in m) [body weight (kg)/body height2 (m2)], in kg/m2 unit. The data will be presented as mean +/- standard deviation (SD) | 5 months | 
| Systolic blood pressure | Systolic blood pressure was measure using Omron Automatic Blood Pressure Monitor (Omron Health Care Co., Ltd, Japan) (in mmHg), by placing the cuff on the right arm, then pull and tighten it according to the size if the arm. After it was installed correctly (fasten and did not move), the power button on the digital tension tool was pressed, and then the microprocessor started to drive air pressure into the cuff, and then the value of blood pressures will appear in the manometer tube column. Systolic blood pressure measurement was performed in a sitting position after the subject had rested for 10 minutes. The data will be presented as mean +/- standard deviation (SD) | 5 months | 
| Diastolic blood pressure | Diastolic blood pressure was measure using Omron Automatic Blood Pressure Monitor (Omron Health Care Co., Ltd, Japan) (in mmHg), by placing the cuff on the right arm, then pull and tighten it according to the size if the arm. After it was installed correctly (fasten and did not move), the power button on the digital tension tool was pressed, and then the microprocessor started to drive air pressure into the cuff, and then the value of blood pressures will appear in the manometer tube column. Diastolic blood pressure measurement was performed in a sitting position after the subject had rested for 10 minutes. The data will be presented as mean +/- standard deviation (SD) | 5 months | 
| Fasting blood glucose | Blood samples were collected at 08.00-09.00 after the subject fasted for 12 hours through the median cubital vein. Ten ml of blood was taken. The blood sample collection was done by a laboratory's employers or a nurse who had been hired by the researchers. After the blood was taken, it was placed into a tube containing ethylenediaminetetraacetic acid (EDTA) for further analysis of fasting blood glucose (FBG). After that, the tube containing blood samples was placed in a cooling box for transport to the lab. The data will be presented as mean +/- SD, in mg/dL. | 5 months | 
| Total cholesterol | Blood samples were collected at 08.00-09.00 after the subject fasted for 12 hours through the median cubital vein. Ten ml of blood was taken. The blood sample collection was done by a laboratory's employers or a nurse who had been hired by the researchers. After the blood was taken, it was placed into a tube containing ethylenediaminetetraacetic acid (EDTA) for further analysis of Total cholesterol. After that, the tube containing blood samples was placed in a cooling box for transport to the lab. The data will be presented as mean +/- SD, in mg/dL. | 5 months | 
| HDL-c | Blood samples were collected at 08.00-09.00 after the subject fasted for 12 hours through the median cubital vein. Ten ml of blood was taken. The blood sample collection was done by a laboratory's employers or a nurse who had been hired by the researchers. After the blood was taken, it was placed into a tube containing ethylenediaminetetraacetic acid (EDTA) for further analysis of High-density lipoprotein cholesterol (HDL-c). After that, the tube containing blood samples was placed in a cooling box for transport to the lab. The data will be presented as mean +/- SD, in mg/dL. | 5 months | 
| LDL-c | Blood samples were collected at 08.00-09.00 after the subject fasted for 12 hours through the median cubital vein. Ten ml of blood was taken. The blood sample collection was done by a laboratory's employers or a nurse who had been hired by the researchers. After the blood was taken, it was placed into a tube containing ethylenediaminetetraacetic acid (EDTA) for further analysis of Low-density lipoprotein cholesterol (LDL-c). After that, the tube containing blood samples was placed in a cooling box for transport to the lab. The data will be presented as mean +/- SD, in mg/dL. | 5 months | 
| Triglyceride | Blood samples were collected at 08.00-09.00 after the subject fasted for 12 hours through the median cubital vein. Ten ml of blood was taken. The blood sample collection was done by a laboratory's employers or a nurse who had been hired by the researchers. After the blood was taken, it was placed into a tube containing ethylenediaminetetraacetic acid (EDTA) for further analysis of Triglycerides After that, the tube containing blood samples was placed in a cooling box for transport to the lab. The data will be presented as mean +/- SD, in mg/dL. | 5 months | 
| Fasting insulin | Blood samples were collected at 08.00-09.00 after the subject fasted for 12 hours through the median cubital vein. Ten ml of blood was taken. The blood sample collection was done by a laboratory's employers or a nurse who had been hired by the researchers. After the blood was taken, it was placed into a tube containing ethylenediaminetetraacetic acid (EDTA) for further analysis of Fasting insulin (FI). After that, the tube containing blood samples was placed in a cooling box for transport to the lab. The data will be presented as mean +/- SD, in μU/mL. | 5 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Obesity, Flow-mediated Arterial Dilatation, Hypertension, sICAM-1