Carotid Plaque Regression With Statin Treatment Assessed by High Field Magnetic Resonance Imaging (MRI)

Atherosclerotic vascular disease is the leading cause of death in the United States.
Atherosclerosis develops with increasing plaque burden and eccentric arterial wall expansion
or remodeling, later leading to luminal obstruction. More than 90% of patients with CAD have
carotid plaques. Statins have been shown to cause plaque regression in the carotid and
coronary arteries. However, there is ongoing controversy about how low the target LDL should
be in atherosclerotic patients. The benefits of aggressive LDL lowering with higher statin
doses are counterbalanced by the potential for liver and muscle toxicity. High field (3
Tesla) MRI is a promising new modality for measuring plaque volume with high spatial
resolution. It is not clear whether increasing statin dose will lead to plaque volume
reduction in the short-term (6 months) that can be measured by this new modality.

The primary aim of the study is to determine if LDL lowering using statins in vascular
disease patients with carotid plaque will be associated with measurable reduction in carotid
plaque volume in the short term (6 months) using 3T MRI.

The four secondary aims of the study are as follows:

To compare the short term carotid plaque volume change using high field MRI in vascular
disease patients whose statin dose was increased (dose increased) versus those whose statin
dose was maintained (dose maintained).

To determine if increasing statin dose in patients with carotid plaque will lead to
measurable change in carotid plaque composition in the short term (6 months) using 3T MRI.

To compare the carotid plaque volume change using 3T MRI with change in plaque burden score
using carotid ultrasound .

To determine the relationship between change in plaque volume with change in lipid levels
(total cholesterol, LDL, HDL) and change in inflammatory markers (cytokines, high
sensitivity CRP).

The study is significant because it will provide insight into optimal statin treatment for
atherosclerotic disease. It will also test a new modality for measurement of plaque burden.
A reliable and sensitive test with high spatial resolution that accurately measures change
in plaque volume will be helpful in assessing response to treatment and as a tool for future
clinical trials in assessing efficacy of new treatment modalities that may reduce the need
for expensive, long term studies that rely on clinical events for outcome measurement.

Inclusion criteria:

- Adult (> 21 years old) patients.

- Diagnosed with coronary artery disease or suspected cerebrovascular accident.

- For dose increased subjects, patients whose statin dose or LDL lowering therapy is
doubled or increased from standard dose to high dose (see table).

- For dose maintained subjects, patients whose statin dose or LDL lowering therapy is
maintained at standard dose (see table).

- Standard Dose (reported LDL↓ < 40% from literature)

- Drug Daily Dose/s: (md/day)

- atorvastatin 10

- simvastatin 5, 10, 20

- pravastatin 10, 20, 40, 80

- fluvastatin 20, 40, 80

- lovastatin 10, 20, 40

- High Dose (reported LDL↓ > 40% from literature)

- Drug Daily Dose/s (mg/day)

- atorvastatin 40, 80

- simvastatin 40, 80

- lovastatin 80

- rosuvastatin 5, 10, 20, 40

- Addition of non-statin lipid transfer (tx) (e.g., ezetimibe, fibrate, niacin) to
standard statin dose

Exclusion criteria:

- severe claustrophobia causing inability to undergo MRI implanted ferromagnetic
materials (pacemakers, defibrillators, TENS units, aneurysm clips, etc.) that are not
suitable for MRI in the clinical setting

- patients anticipated to undergo carotid stenting or surgery in next 6 months

- patients unable to lie flat for 1 hour

- patients requiring supplemental oxygen

- pregnant women

- patients who could not be followed up for 6 months