Pilot Study-Magnetic Resonance Imaging for Global Atherosclerosis Risk Assessment

Study Overview
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Brief Summary
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Cardiovascular disease (CVD) remains the leading cause of death in the United States, and improved CVD risk assessment is needed for personalized medicine. Atherosclerosis measures including plaque volume and adverse plaque features have prognostic value. Novel techniques have been developed for assessing carotid, coronary, and femoral atherosclerosis using magnetic resonance imaging (MRI) methods that are rapid and reproducible, have improved spatial resolution, and do not require contrast media, making atherosclerosis assessment in multiple vascular beds feasible during a single MRI session. This pilot research will provide preliminary data to develop an innovative global atherosclerosis measure including carotid, coronary, and femoral vascular beds, for assessing cardiovascular risk and for monitoring atherosclerosis response to therapy. 20 participants will be recruited in one year.

Detailed Description
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There are up to 2 study visits in this study. During the first visit, the investigators will obtain non-contrast MRI (carotid, coronary, and femoral) in 20 subjects with known coronary atherosclerosis but varying degrees of CVD risk. 5 asymptomatic subjects with lower CVD risk (recent coronary artery calcium score [CACS] 10-299) 5 asymptomatic subjects with higher CVD risk (CACS 300-1000) 5 subjects with known coronary atherosclerosis and stable angina 5 subjects with known atherosclerosis and recent acute myocardial infarction The investigators will measure plaque volume and assess adverse plaque features (intra-plaque hemorrhage, positive remodeling, lesion eccentricity) in the three vascular beds. Eight of these subjects with evidence of large plaque burden by MRI will be asked to return for a simultaneous positron emission tomography (PET)-MRI imaging with 18F-sodium fluoride (18F-NaF) of their carotid, coronary, and femoral arteries, in which 18F-NaF uptake in plaque will represent micro-calcifications, which is associated with high-risk plaque. In all 20 subjects, the investigators will also measure the following biomarkers which have been shown to be useful for CVD risk assessment of atherosclerosis: LDL, HDL, lipoprotein(a), apolipoprotein B/A-1 ratio, hemoglobin A1c, adiponectin, and highly sensitive C-reactive protein. The investigators will also calculate their estimated 10-year and lifetime atherosclerotic CVD risk (American Heart Association), Framingham 10-year CVD risk, and Reynolds 10-year CVD risk scores. We aim to obtain the second scan within 3 months of the first visit; thus, the subjects will participate in the study for approximately 3 months. All the procedures are research-related. The research visit will take approximately 3 hours, and there will be maximum two visits. There are no collaborations with other sites.

Official Title
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Pilot Study-Magnetic Resonance Imaging for Global Atherosclerosis Risk Assessment

Conditions
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Cardiovascular Disease, Atherosclerosis

Intervention / Treatment
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* Other: MRI
* Other: PET/MRI
* Other: Laboratory blood test


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Men and women with evidence of coronary atherosclerosis based on a recent CACS 10-1000 or an invasive or CT coronary angiogram (within 6 weeks of recruitment) No planned revascularization procedures Exclusion Criteria: Contraindications to MRI Pregnant and lactating women Body mass index (BMI)>40 Active smoking Resting heart rate>75 beats per minute Arrhythmia Prior carotid/coronary/peripheral revascularization Life expectancy <5 years Allergy to animal dander Severe asthma

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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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Asymptomatic, CACS <300<br>5 asymptomatic subjects with low CVD risk, defined as recent coronary artery calcium score (CACS) <300 Noncontrast MRI of the bilateral carotid, coronary, and superficial femoral arteries; Laboratory blood test (cardiovascular biomarkers) | Other: MRI<br>* Noncontrast T1- and T2-weighted 3.0 T MRI of the bilateral carotid, coronary, and superficial femoral arteries<br>Other: Laboratory blood test<br>* Cardiovascular biomarkers<br>|
| Asymptomatic, CACS ≥300<br>5 asymptomatic subjects with increased CVD risk, defined as a recent coronary artery calcium score (CACS) ≥300 Noncontrast MRI of the bilateral carotid, coronary, and superficial femoral arteries; Laboratory blood test (cardiovascular biomarkers); Simultaneous 18F-NaF PET/MRI of the bilateral carotid, coronary, and superficial femoral arteries | Other: MRI<br>* Noncontrast T1- and T2-weighted 3.0 T MRI of the bilateral carotid, coronary, and superficial femoral arteries<br>Other: PET/MRI<br>* Simultaneous 18F-NaF PET/MRI of the bilateral carotid, coronary, and superficial femoral arteries<br>Other: Laboratory blood test<br>* Cardiovascular biomarkers<br>|
| Stable angina<br>5 subjects with stable angina and evidence of coronary atherosclerosis based on a recent invasive or CT coronary angiogram Noncontrast MRI of the bilateral carotid, coronary, and superficial femoral arteries; Laboratory blood test (cardiovascular biomarkers); Simultaneous 18F-NaF PET/MRI of the bilateral carotid, coronary, and superficial femoral arteries | Other: MRI<br>* Noncontrast T1- and T2-weighted 3.0 T MRI of the bilateral carotid, coronary, and superficial femoral arteries<br>Other: PET/MRI<br>* Simultaneous 18F-NaF PET/MRI of the bilateral carotid, coronary, and superficial femoral arteries<br>Other: Laboratory blood test<br>* Cardiovascular biomarkers<br>|
| Recent acute MI<br>5 subjects with a recent acute myocardial infarction (within 1 month) and evidence of coronary atherosclerosis based on invasive or CT coronary angiogram Noncontrast MRI of the bilateral carotid, coronary, and superficial femoral arteries; Laboratory blood test (cardiovascular biomarkers); Simultaneous 18F-NaF PET/MRI of the bilateral carotid, coronary, and superficial femoral arteries | Other: MRI<br>* Noncontrast T1- and T2-weighted 3.0 T MRI of the bilateral carotid, coronary, and superficial femoral arteries<br>Other: PET/MRI<br>* Simultaneous 18F-NaF PET/MRI of the bilateral carotid, coronary, and superficial femoral arteries<br>Other: Laboratory blood test<br>* Cardiovascular biomarkers<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Plaque Volume | Quantitative plaque measurement using MRI software (VesselMass) | 24 hours | 
| Adverse plaque features | Presence of positive remodeling, lesion eccentricity, and intraplaque hemorrhage of plaque, on MRI | 24 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 18F-NaF PET uptake | Measured as maximum tissue/background ratio (TBR), to assess for high-risk plaque | 3-6 months | 
| Laboratory biomarkers | Measured as levels of LDL-C, HDL-C, lipoprotein(a), ApoB/ApoA-1 ratio, hemoglobin A1c, plasma adiponectin, hsCRP | 24 hours | 
| Clinical risk scores | Measured as (1) ACC/AHA 10-year and lifetime atherosclerotic CVD risk, (2) Framingham 10-year CVD risk, and (3) Reynolds Risk 10-year CVD risk | 24 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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magnetic resonance imaging, positron emission tomography