Cardiovascular Evaluation of Patients With High Cholesterol and Normal Volunteers

Study Overview
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Brief Summary
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Homozygous familial hypercholesterolemia is a rare inherited disease of metabolism. It occurs in less than 1 in 1 million people within the United States. Patients with the disease are typically children and young adults who develop heart disease early in life. Children less than age 5 years with this disease have suffered heart attacks and death. The normal process that removes cholesterol particles from the blood stream does not work in patients with this disease. It causes cholesterol to build-up in the arteries and leads to hardening of the arteries (atherosclerosis). The goal of this study is to detect and measure atherosclerosis in these patients before it becomes permanent and potentially life threatening. Patients with this disease can participate in this study. Researchers plan to evaluate patients with homozygous familial hypercholesterolemia using new and standard methods for detecting atherosclerosis. Researchers plan to use information gathered during this study to develop new, promising treatments such as liver transplantation and gene therapy.

Detailed Description
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Familial hypercholesterolemia is an autosomal co-dominant disorder resulting in abnormal LDL receptor function, profoundly elevated concentrations of low density lipoproteins, accelerated atherosclerosis and death by early adulthood. This disease is heterogeneous in both the degree of LDL receptor dysfunction as well as the age of death. Liver transplantation has been demonstrated to virtually normalize plasma lipoprotein concentrations in homozygous FH and the recent cloning of a functional LDL receptor gene holds promise in the definitive treatment of this condition. We propose performing longitudinal sequential cardiologic studies utilizing noninvasive techniques in homozygous patients with well-characterized LDL receptor defects. Sequential cardiovascular study of these patients will not only characterize the progression of atherosclerosis heart disease in this disease, it may also permit the identification of individuals with would be likely to benefit from liver transplantation and/or genetic engineering.

Official Title
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Cardiovascular Evaluation of Homozygous Familial Hypercholesterolemia

Conditions
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Homozygous Familial Hypercholesterolemic

Participation Criteria
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Eligibility Criteria
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INCLUSION CRITERIA: Fasting cholesterol greater than 500 mg/dl, low density lipoprotein cholesterol greater than 400 mg/dl, and triglycerides less than mg/dl. Family history of hypercholesterolemia and/or cardiovascular disease before the age of 60 years. Tendinous and tuberous xanthomas. Arcus corneae before the age of 30.

Ages Eligible for Study
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Minimum Age: 2 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| 1<br>Longitudinal sequential cardiologic studies utilizing noninvasive techniques in homozygous patients with well-characterized LDL receptor defects | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| We propose performing longitudinal sequential cardiologic studies utilizing noninvasive techniques in homozygous patients with well-characterized LDL receptor defects. | Descriptive data | one year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Current work has focused on identifying new noninvasive measurements of CAD and quantitating atherosclerosis burden. | Current work has focused on identifying new noninvasive measurements of CAD and quantitating atherosclerosis burden. | one year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Natural History, Dyslipoproteinemia, Hypercholesterolemia, Atherosclerosis