Randomized Trial of Imaging Versus Risk Factor-Based Therapy for Plaque Regression

• INCLUSION CRITERIA:

A. Men and Women greater than or equal to 55 years of age

B. Candidates for lipid lowering therapy under NCEP ATP III guidelines without contraindication to statin therapy

C. Willing to modify therapy to enroll in the study

D. Willing to travel to the NIH for follow-up visits.

E. Able to understand and sign informed consent

F. Lab Eligibility parameters:

• eGFR > 45 mL/min/m2
• For age > 60 test GFR within 1 week prior to contrast; For age less than or equal to 60 test within 4 weeks

INCLUSION CRITERIA FOR THE PET SUBSTUDY:

Patients will be selected who fall about the 50th percentile of plaque burden based on carotid MRI.

INCLUSION CRITERIA FOR THE REPRODUCIBILITY SUBSTUDY:

Patients will be selected who had a one RR interval initial CT scan with less that 10.5 mSv estimated radiation dosage and who will not be participating in the PET Substudy.

EXCLUSION CRITERIA:

A. Ineligibility for MR imaging due to:

• Previous pacemaker implantation
• Automatic implantable cardioverter-defibrillator (AICD)
• Metal implants or other ferromagnetic devices, or
• Foreign material

B. Claustrophobia

C. Contra-indication or allergy to statin medications.

D. Current statin therapy at or above the maximum dosage permitted per study protocol (section 1.3,above).

E. Use of fibrates, ezetimibe, niacin, or bile acid binding agents within 6 months of screening visit.

F. Pregnancy and nursing.

G. Liver failure defined clinically and by laboratory data.

H. Mental, neurologic or social condition preventing understanding of the rationale, procedures, risks and potential benefits associated with the trial.

I. Any other conditions that precludes safety for MRI and/or CT imaging per the researcher's evaluation.

Exclusion for participation for Gadolinium contrast: Participants may still undergo all other study evaluations.

(Inclusive of the above exclusion criteria):

1. Allergy to gadolinium for scans using contrast; will be eligible for non-contrast scans.
2. Acute renal failure, renal transplant, dialysis and renal failure (eGFR < 45 mL/min/m2 and/or clinically diagnosed).
3. Individuals with a history of liver transplant or severe liver disease.
4. Individuals with hemoglobinopathies or severe asthma.

Exclusion for participation for iodinated contrast: Participants may still undergo all other study evaluations

Prior hypersensitivity reaction to iodinated contrast injection, renal dysfunction (defined as eGFR < 45 mL/min/ m2) or a current clinical diagnosis of renal failure.

EXCLUSION CRITERIA FOR THE PET SUBSTUDY:

Patients who are unable or unwilling to comply with the dietary modifications or physical activity restrictions prior to FDG PET scanning will be excluded. Due to the need for dietary manipulation and the maintenance of strict glycemic control we will exclude diabetic patients from our initial study sample. Blood glucose measurements before injection must be within normal limits, less than 200 mg/dL (11 mmol/L).

EXCLUSION CRITERIA FOR THE REPRODUCIBILITY

Patients who did not have a one RR interval initial CT scan. Patients who will participate in the PET Substudy.