CT COMPARE: CT Coronary Angiography to Measure Plaque Reduction

In high risk patients undergoing invasive angiography, intravascular ultrasound (IVUS) has
shown reduction of plaque for patients treated with HMG-CoA reductase inhibitors (statins).
However, there is no accepted noninvasive method to determine if treatment for
atherosclerosis results in reduction of coronary artery plaque.

Coronary artery CT angiography (CCTA) is noninvasive and can accurately determine the degree
of coronary artery stenosis. In addition, the extent of calcified and noncalcified plaque may
be directly measured using this technology at low radiation dose using state-of-the-art CT
scanners. Several retrospective studies have previously suggested that CCTA may be able to
show plaque regression in the coronary arteries due to statin therapy.

The primary aim of this proposal is to determine the change in coronary artery plaque volume
in individuals treated with high intensity statin therapy as defined by 2013 ACC/AHA
Guideline on the Treatment of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular Risk
in Adults.

Men and women who meet the inclusion and exclusion criteria will undergo CCTA examination for
the presence or absence of coronary artery plaque. Individuals with evidence of noncalcified
coronary plaque by CCTA and who meet criteria for HMG-CoA reductase (statin) therapy will be
evaluated for a total of 36 months. The change of coronary artery plaque (progression or no
change, or regression) in individuals with noncalcified plaque at baseline will be measured
by CCTA at yearly intervals.

- INCLUSION CRITERIA:

A. Men greater than or equal to 45 and less than or equal to 75 years of age; women greater
than or equal to 50 and less than or equal to 75 years of age

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

C. Willing to start or modify statin therapy.

D. Able to understand and sign informed consent.

E. Eligible for primary prevention statin therapy

1. Eligible for at least moderate intensity statin according to 2013 ACC/AHA GRCR (i.e.,
greater than or equal to 5% 10 year cardiovascular risk,
https://my.americanheart.org/professional/StatementsGuidelines/Prevention-Guidelines_U
CM_457698_SubHomePage.jsp) OR

2. low (<5%) 10 year cardiovascular risk per 2013 ACC/ AHA and with coronary artery
calcium score greater than or equal to 300 Agatston units or greater than or equal to
75 percentile for age, sex, and ethnicity determined per MESA study

(http://www.mesa-nhlbi.org/calcium/input.aspx).

EXCLUSION CRITERIA:

A. Allergy or prior clinically relevant adverse reaction to Rosuvastatin (does not include
minor muscle pain).

B. High intensity statin treatment for more than 90 days prior to enrollment

C. LDL greater than or equal to 190 mg/ml

D. Physician-diagnosed heart attack

E. Physician-diagnosed angina or taking nitroglycerin

F. Physician-diagnosed stroke or TIA

G. Physician-diagnosed heart failure

H. Current atrial fibrillation

I. Having undergone procedures related to cardiovascular disease (CABG, angioplasty, valve
replacement, pacemaker or defibrillator implantation, any surgery on the heart or arteries)

J. Active treatment for cancer

K. Prior hypersensitivity reaction to iodinated contrast injection

L. Known hyperthyroidism.

M. Acute renal failure, renal transplant, dialysis and renal failure clinically diagnosed.

N. History of liver transplant or severe liver disease or unexplained elevation of baseline
ALT>3x upper limit of normal

O. Claustrophobia

P. Pregnancy and nursing

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

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

S. Individuals with hemoglobinopathies or severe asthma.

T. Severe renal excretory dysfunction, estimated glomerular filtration (eGFR) rate < 30
mL/min/1.73m2 body surface area according to the Modification of Diet in Renal Disease
criteria Glomerular filtration rate will be estimated using the MDRD 2005 revised study
formula: eGFR (mL/min/1.73m2) = 175 x (standardized serum creatinine)-1.154 x (age)-0.203 x
0.742 (if the subject is female) or x 1.212 (if the subject is black)