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Location: Jean Mayer Human Nutrition Research Center On Aging

Title: Non-invasive detection of aortic and coronary atherosclerosis in homozygous familial hypercholesterolemia by 64 slice multi-detector row computed tomography angiography

item Santos, Raul
item Miname, Marcio
item Martinez, Lilton
item Rochitte, Carlos
item Chacra, Ana
item Nakandakare, Edna
item Chen, David
item Schaefer, Ernst

Submitted to: Atherosclerosis
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 8/2/2007
Publication Date: 4/4/2008
Citation: Santos, R.D., Miname, M.H., Martinez, L.R., Rochitte, C.E., Chacra, A.P., Nakandakare, E.R., Chen, D., Schaefer, E. 2008. Non-invasive detection of aortic and coronary atherosclerosis in homozygous familial hypercholesterolemia by 64 slice multi-detector row computed tomography angiography. Atherosclerosis. 197(2):910-915.

Interpretive Summary: The major cholesterol carrying particles in the bloodstream are known as low density lipoproteins or LDL. High levels of LDL cholesterol have been associated with an increased risk of heart disease, a leading cause of death and disability in our society. High LDL cholesterol levels (>160 mg/dl) have been associated with diets high in animal fat and cholesterol (as found in eggs), but can also be inherited. When elevated LDL cholesterol runs in families it can cause cholesterol deposits in the tendons, and is usually due to defects in the receptor that breaks down the LDL found in the bloodstream. This receptor is known as the LDL receptor, and mutations in this receptor are the cause of familial hypercholesterolemia or FH. People that inherit one defective LDL receptor gene from each parent have LDL cholesterol levels that are more than four fold elevated (>500 mg/dl) and they are known as FH homozygotes. FH homozygotes if not treated generally develop heart disease prior to age 20 years, and often die suddenly outside the hospital. We studied 5 FH homozygotes (mean age 20 years) with a mean LDL cholesterol of 618 mg/dl. All had normal exercise tolerance tests. However when we measured the amount of calcium in their heart as assessed by computed tomography or CT, we found that they all had alot of calcium in their hearts (very high heart calcium score). Furthermore when they had this procedure repeated after injection of dye into their arm veins, 2 of the 5 patients had severe narrowing of their coronary arteries requiring bypass surgery. Therefore this non-invasive procedure also known as CT angiography in these very high patients allows for the detection of severe heart disease requiring therapy, and is potentially life-saving. It has clearly been shown that lowering elevated blood cholesterol (>240 mg/dl) and elevated low density lipoprotein (LDL) cholesterol (>160 mg/dl) with diet and statin medications can reduce the risk of heart disease. However there are some people that inherit very high levels of total cholesterol (>600 mg/dl) and LDL cholesterol (>500 mg/dl). These people have inherited defects in the receptor that breaks down LDL. Despite aggressive treatment, they may develop heart disease before age 20 years, and what we have shown here is that following the amount of calcium in their heart using computed tomography (CT), and then following up with CT angiography in those with high heart calcium scores by intravenous injection of dye (quite non-invasive) can pick up life threatening disease. This approach allows for treatment prior to heart attack or sudden death.

Technical Abstract: Homozygous familial hypercholesterolemia (HoFH) is a rare disorder characterized by the early onset of atherosclerosis, often at the ostia of coronary arteries. In this study we document for the first time that aortic and coronary atherosclerosis can be detected using 64 slice multiple detector row computed tomographic coronary angiography (CTCA). We studied five HoFH patients (three females, two males, mean age 19.8±2.9 years, age range 15–23 years, with a mean low density lipoprotein (LDL) cholesterol 618±211 mg/dL) using 64 slice CTCA. None of the patients showed evidence of ischemia with standard exercise testing. Calcified and mixed atherosclerotic plaques adjacent to or compromising the coronary artery ostia were found in all study subjects. Coronary plaques causing significant obstruction were found in one patient, who had previously undergone coronary artery bypass surgery and aortic valve replacement. Two other patients were noted to have non-obstructive calcified, mixed and non-calcified coronary artery plaques. Our data suggest that CTCA could be a useful non-invasive method for detection of early aortic and coronary atherosclerosis specifically affecting the coronary ostia in HoFH subjects.