Research Overview
Differences in Vascular Compliance in Pediatric Patients at Risk for Cardiovascular Disease as Measured by EndoPAT Technology
Endothelial dysfunction (ED) is a vascular marker for underlying subclinical cardiovascular disease. In the adult population, endothelial dysfunction has been observed in a variety of pathologic conditions, such as obesity, type 2 diabetes mellitus, hypertension, and atherosclerotic cardiovascular disease. Numerous studies have established the validity of the Endo-PAT technique when compared to flow mediated dilation (FMD) measurement of the brachial artery, intracoronary acetylcholine infusion, and, to a limited extent, carotid Intima-Media Thickness (IMT). Recent pediatric population studies of obese, hypertensive, diabetic, as well as Kawasaki patients have demonstrated abnormalities in endothelial function noninvasively. Recently, a less cumbersome and user-independent technique to assess endothelial function has been developed by Itamar Corporation using the Endo-PAT technology. Currently, many large adult cardiovascular programs have replaced FMD with the Endo-PAT technique.
We propose a pilot observational and feasibility study to measure the utility of Endo-PAT in the pediatric population, and ultimately incorporate its utilization into our overall pediatric cardiovascular preventive program. We plan to concurrently measure carotid artery intimal-medial thickness (IMT), as it is a standard of experimental design for assessing preliminary subclinical atherosclerosis anatomically in conjunction with physiologic assessment by Endo-PAT.
EndoPAT is a new, noninvasive technique to measure the stiffness and endothelial function of the arteries. A new and safe method to measure the health of the arteries (blood vessels that carry blood with oxygen) has been developed. Arteries may become stiffer with age or other conditions such as: overweight, high blood pressure, high cholesterol (fat) in the blood, or fatty liver.
The Endo-PAT is a non-invasive machine that is similar to a blood pressure machine. A small soft rubber cup is placed on the middle finger of each hand. One arm will have a blood pressure cuff inflated (squeezed) above the elbow for 5 minutes and then released. The machine will record the pulse waves in the finger tips on the computer. The test will be performed once in a quiet area at the time of enrollment and should take approximately 60 minutes. An automated computer software program will immediately analyze the information. The child will have this measurement repeated between 3-6 months and 12 months later. After completion of the Endo-PAT test, an ultrasound picture of the thickness of the walls of the main arteries in the neck (carotid arteries) will be obtained at the time of enrollment and repeated 12 months later. We hope to be able to use this new non-invasive test to detect whether the child’s arteries are healthy or not and whether the treatment received, such as diet, exercise, or medication, improves his/her condition. This test could be a way of detecting early changes in the arteries of children and adolescents that may lead to significant cardiovascular disease in adulthood.
Hypothesis and Specific Aims
Primary Objectives
Primary Aims: To demonstrate the feasibility of Endo-PAT technology to measure 1) endothelial function (EF) as reflected in changes in peripheral arterial tone (PAT) and 2) arterial stiffness (Augmentation Index) non-invasively in pediatric patients at high risk for early cardiovascular disease.
Secondary Objectives
Secondary Aims:
- To observe changes (and/or improvements) in PAT after interventions (treatments) appropriately tailored for each cohort:
- Overweight: reduction in BMI or weight as the result of a comprehensive weight management program intervention.
- Familial hypercholesterolemia and dyslipidemia: pre-and post-LDL apheresis, diet, and/or statin therapy.
- Nonalcoholic Fatty Liver Disease (NAFLD): pre-and post-vitamin E treatment.
- To correlate PAT with carotid intimal medial thickness (IMT).
- To correlate PAT with risk factors for vascular disease (markers of abnormal lipid, glucose and vitamin D metabolism, inflammation, blood clotting, blood pressure, family history).
Patient Recruitment
Study Groups
We will measure reactive hyperemia and augmentation index in four groups, ages 8 to 21.
Group 1) Healthy males (10) and females (10).
Group 2) Children who are overweight at ≥ 95th percentile for weight, or body mass index (BMI).
Group 3) Children with abnormal fat content in their blood (elevated LDL cholesterol, Lpa, and/or elevated triglycerides or low HDL cholesterol).
80 patients will be studied distributed evenly at 20 patients in each group. Each group will be matched on gender, race, and Tanner staging of sexual development (Stages 1-5; roughly correlative with age; see appendix).
