Pilot Study-Magnetic Resonance Imaging for Global Atherosclerosis Risk Assessment

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.

Study Overview

• Status: Recruiting
• Conditions: Cardiovascular Disease; Atherosclerosis
• Intervention / Treatment: Other: MRI; Other: Laboratory blood test; Other: PET/MRI

Detailed Description

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.

1. 5 asymptomatic subjects with lower CVD risk (recent coronary artery calcium score [CACS] 10-299)
2. 5 asymptomatic subjects with higher CVD risk (CACS 300-1000)
3. 5 subjects with known coronary atherosclerosis and stable angina
4. 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.

• Study Type: Observational
• Enrollment (Anticipated): 20

Contacts and Locations

• Study Contact: Name: Denisse Barajas; Phone Number: 310-423-9666; Email: denisse.barajas@cshs.org

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90048
      • Recruiting
      • Cedars-Sinai Medical Center
      • Contact: Ying Mou, PhD; Phone Number: 310-248-7669; Email: ying.mou@cshs.org
      • Contact: Sophie Yoo, MS; Phone Number: 424-315-4306; Email: Jihye.Yoo@cshs.org

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

20 subjects with known coronary atherosclerosis but varying degrees of CVD risk

Description

Inclusion Criteria:

1. 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)
2. No planned revascularization procedures

Exclusion Criteria:

1. Contraindications to MRI
2. Pregnant and lactating women
3. Body mass index (BMI)>40
4. Active smoking
5. Resting heart rate>75 beats per minute
6. Arrhythmia
7. Prior carotid/coronary/peripheral revascularization
8. Life expectancy <5 years
9. Allergy to animal dander
10. Severe asthma

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

4

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Asymptomatic, CACS <300; 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; Noncontrast T1- and T2-weighted 3.0 T MRI of the bilateral carotid, coronary, and superficial femoral arteries; Other: Laboratory blood test; Cardiovascular biomarkers
Asymptomatic, CACS ≥300; 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; Noncontrast T1- and T2-weighted 3.0 T MRI of the bilateral carotid, coronary, and superficial femoral arteries; Other: Laboratory blood test; Cardiovascular biomarkers; Other: PET/MRI; Simultaneous 18F-NaF PET/MRI of the bilateral carotid, coronary, and superficial femoral arteries
Stable angina; 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; Noncontrast T1- and T2-weighted 3.0 T MRI of the bilateral carotid, coronary, and superficial femoral arteries; Other: Laboratory blood test; Cardiovascular biomarkers; Other: PET/MRI; Simultaneous 18F-NaF PET/MRI of the bilateral carotid, coronary, and superficial femoral arteries
Recent acute MI; 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; Noncontrast T1- and T2-weighted 3.0 T MRI of the bilateral carotid, coronary, and superficial femoral arteries; Other: Laboratory blood test; Cardiovascular biomarkers; Other: PET/MRI; Simultaneous 18F-NaF PET/MRI of the bilateral carotid, coronary, and superficial femoral arteries

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Cedars-Sinai Medical Center
• Investigators: Principal Investigator: Janet Wei, MD, Cedars-Sinai Medical Center; Principal Investigator: Noel Bairey Merz, MD, Cedars-Sinai Medical Center

Study record dates

Study Major Dates

• Study Start: September 1, 2014
• Primary Completion (Anticipated): October 1, 2024
• Study Completion (Anticipated): October 1, 2024

Study Registration Dates

• First Submitted: October 3, 2014
• First Submitted That Met QC Criteria: October 10, 2014
• First Posted (Estimate): October 15, 2014

Study Record Updates

• Last Update Posted (Actual): August 10, 2020
• Last Update Submitted That Met QC Criteria: August 6, 2020
• Last Verified: August 1, 2020

More Information

Terms related to this study

• Keywords: magnetic resonance imaging; positron emission tomography
• Additional Relevant MeSH Terms: Vascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Cardiovascular Diseases; Atherosclerosis
• Other Study ID Numbers: Pro00037025

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes