Atherosclerosis in Familial Hypercholesterolemia

Study Overview
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Brief Summary
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Familial hypercholesterolemia (FH) is a common inherited disorder with a frequency of 1 in 500 in the UK. Our aim is compare the carotid and coronary artery atherosclerosis in monogenic FH and polygenic hypercholesterolemia with means of a carotid ultrasound, a coronary CT angiogram and biochemical biomarkers.

Detailed Description
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Familial hypercholesterolemia (FH) is a common inherited disorder with a frequency of 1 in 500 in the UK. Previous Studies showed that risk of heart attack in these patients is at least 50% higher in men and 30% higher in women compared to the general population as they have high blood cholesterol since birth. We propose to develop a screening model based on non-invasive visualisation of the heart blood vessels (coronary arteries) by CT scan, ultrasound of the neck vessels (carotid arteries) and blood tests to access the extend of cholesterol deposit in the blood vessels in these patients. Participants with confirmed diagnosis of FH would be recruited from FH database registry at Royal Free Hospital. They would have a CT coronary angiogram, an ultrasound of carotid arteries and a blood test. The study is divided into overlapping stages of recruitment and data collection and data analysis. If CT scan shows more than 70% obstruction in their coronary arteries, they would be offered a coronary angiogram and an intracoronary Optical Coherence Tomography for assessment of their blood vessel blockage.

Official Title
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Incidence and Characteristics of Coronary Atherosclerosis in Asymptomatic Patients With Familial Hypercholesterolemia According to Monogenic Versus Polygenic Status

Conditions
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Familial Hypercholesterolemia

Intervention / Treatment
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* Other: CT coronary angiogram and carotid ultrasound


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: The subjects must give written informed consent to participate in the study, Male and female subjects ≥ 18 years old, documentation of clinical diagnosis of familial Hypercholesterolemia Exclusion Criteria: Estimated GFR <45, pregnant women, Atrial fibrillation or unstable heart rate, Established ischemic heart disease, previous Percutaneous Coronary Investigations (PCI) or Coronary Artery Bypass Surgery (CABG), Known allergy to iodine contrast

Ages Eligible for Study
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Minimum 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 |
| --- | --- |
| polygenic hypercholesterolemia<br>patients with high cholesterol level where no mutation was found in their FH-causing genes and had to gene score in their six LDL-C raising gene score undergo a carotid ultrasound, a CT coronary angiogram and a blood test | Other: CT coronary angiogram and carotid ultrasound<br>* Scans in addition to routine clinical care<br>|
| monogenic FH<br>patients with a mutation in FH-causing gene undergo a carotid ultrasound, a CT coronary angiogram and a blood test | Other: CT coronary angiogram and carotid ultrasound<br>* Scans in addition to routine clinical care<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| carotid Intima Media thickness measurement | done by carotid ultrasound to look for risk of atherosclerosis | 24 months |