Effects of Ezetimibe, Simvastatin, and Vytorin on Reducing L5 a Subfraction of LDL in Patients With Metabolic Syndrome.

Epidemiological evidence indicates that metabolic syndrome (MS) is a strong predisposing
condition for atherosclerosis. Elevation of plasma low-density lipoprotein (LDL)
cholesterol(LDL-C) concentration is the most important risk factor for atherosclerosis;
however, LDL-C elevation is not a criterion for metabolic syndrome, raising the question of
LDL's role in the syndrome's association with atherosclerosis. L5, a highly electronegative
and mildly oxidized LDL subfraction that we recently isolated from hypercholesterolemic
human plasma, may provide a key to answering this question. In cultured vascular endothelial
cells (EC), L5 inhibits proliferation and induces apoptosis and monocyte-EC adhesion. In our
preliminary studies, L5 could also be detected in patients with MS without elevated LDL-C.
Because other LDL subfractions were harmless to EC, the presence of MS-L5 prompted us to
hypothesize that the atherogenic role of LDL is not solely determined by plasma LDL-C
concentration, but more importantly, by its composition. The proposed study is designed to
test this hypothesis. The first question we will address is what lipid factor determines the
prevalence of L5 in MS.

Subsequently, we will examine whether treatment with selected medicines can effectively
reduce L5 in MS patients by correcting the factor favorable for L5 formation.

We are in the process of identifying the active components of L5 to fully characterize the
atherogenic role of L5 in MS,. In the current proposal, we focus our interest on the
efficacy of Ezetimibe, Simvastatin, and Vytorin in reducing L5 from the plasma of MS
patients.

Inclusion Criteria:

- Participants who meet 3 or more of the 5 criteria specified in the ATPIII guidelines
will be recruited.

- The 5 criteria are:

1. abdominal obesity (men>40 inches, women >35 inches);

2. TG> 150mg/dL;

3. low HDL-C (men < 40mg/dL, women < 50 mg/dL);

4. high blood pressure (>or=130/>or=85 mmHg);

5. fasting glucose > or = 110mg/dL.

- People with different ethnic backgrounds will be included.

Exclusion Criteria:

- symptomatic coronary artery disease

- peripheral vascular disease

- cerebral ischemia (stroke)

- smoking

- hypothyroidism

- kidney diseases

- consumption of antioxidation supplements/drugs or use of lipid-lowering drugs in the
last 3 months

- women who are pregnant, nursing, or planning to become pregnant