Chronotropic Incompetence During Exercise in Obese Adolescents: Clinical Implications and Pathophysiology

Study Overview
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Brief Summary
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A reduction in peak heart rate (HR) and suppressed HR response during exercise is highly prevalent in obese populations. This phenomenon is also known as chronotropic incompetence (CI). In adult obese individuals, CI is independently related to elevated risk for major adverse cardiovascular events and premature death. Despite the established association between CI and prognosis in adult populations, the prognostic relevance of CI in adolescents with obesity has however deserved no attention, but is important. CI during exercise testing may indicate various, yet undetected anomalies, such as altered blood catecholamine and/or potassium concentrations during exercise, structural myocardial abnormalities or ventricular stiffness, impaired baroreflex sensitivity and cardiovascular autonomic dysfunction, atherosclerosis, or cardiac electrophysiological anomalies, which all have been detected in obese children and adolescents. However, whether CI during exercise testing may be a sensitive and specific indicator for these anomalies in obese adolescents has not been studied yet. In addition, the exact physiology behind obesity and development of heart disease remains to be studied in greater detail in obese adolescents. In this project, we examine the prevalence of CI (during maximal cardiopulmonary exercise testing, CPET) in 60 obese adolescents (aged 12-16 years) vs. 60 lean adolescents, and study the association between CI and changes in CPET parameters, lactate, catecholamine and potassium concentrations during CPET, biochemical variables, and cardiac electrophysiology (by ECG recording). In addition, the relation between CI and cardiac function (echocardiography) will be examined in a subgroup (29 lean and 29 obese) of these adolescents. In this regard, the diagnostic value of HR (responses) during maximal exercise testing will be clarified in obese adolescents, and the physiology behind the elevated risk for heart disease in obese adolescents can be explored.

Official Title
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Chronotropic Incompetence During Exercise and Relations With Development of Cardiovascular Disease in Obese Adolescents

Conditions
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Obesity, Adolescent Obesity

Intervention / Treatment
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* Other: the prevalence of chronotropic incompetence CI during maximal cardiopulmonary exercise testing, CPET


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: aged 12-16 years obese or lean (based on extended international (IOTF) body mass index cut-offs for thinness, overweight and obesity) Parental permission Exclusion Criteria: - Chronic cardiovascular, renal, pulmonary and orthopedic disease

Ages Eligible for Study
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Minimum Age: 12 Years
Maximum Age: 16 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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Design Details

Primary Purpose: Other
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Obese adolescents<br> | Other: the prevalence of chronotropic incompetence CI during maximal cardiopulmonary exercise testing, CPET<br> <br> |
| Other: Lean adolescents<br> | Other: the prevalence of chronotropic incompetence CI during maximal cardiopulmonary exercise testing, CPET<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Heart rate (HR) | Assessed using a 12-lead ECG device | day 1 | 
| Ventilatory function | Determined during maximal cardiopulmonary exercise testing. | day 1 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| height |  | day 1 | 
| weight |  | day 1 | 
| body composition |  | day 1 | 
| PAQ-A (Physical Activity Questionaire for Adolescents) | physical activity determined using the validated Dutch physical activity questionnaire for adolescents | day1 | 
| Tanner scale | Puberty stage (ranging from 1 to 5) will be assessed in all participants by the pediatric endocrinologist using Tanner staging criteria. Boys - development of external genitalia Girls - breast development Boys and girls - pubic hair | day 1 | 
| Plasma glucose | blood analyses | day 1 | 
| iron | blood analyses | day 1 | 
| aspartate aminotransferase | blood analyses | day 1 | 
| alanine aminotransferase | blood analyses | day 1 | 
| gamma-glutamyl transpeptidase | blood analyses | day 1 | 
| alkaline phosphatase | blood analyses | day 1 | 
| uric acid | blood analyses | day 1 | 
| calcium | blood analyses | day 1 | 
| blood total cholesterol | blood analyses | day 1 | 
| high-density lipoprotein cholesterol | blood analyses | day 1 | 
| low-density lipoprotein cholesterol | blood analyses | day 1 | 
| proteins | blood analyses | day 1 | 
| triglyceride concentrations | blood analyses | day 1 | 
| c-reactive proteine | blood analyses | day 1 | 
| thyroid-stimulating hormone | blood analyses | day 1 | 
| free thyroxine | blood analyses | day 1 | 
| cortisol and serum insulin | blood analyses | day 1 | 
| serum leptin concentration | blood analyses | day 1 | 
| blood haemoglobin | blood analyses | day 1 | 
| haematocrit | blood analyses | day 1 | 
| leukocytes | blood analyses | day 1 | 
| Echocardiography | Assessment left ventricular structure and systolic and diastolic function | day 1 |