Aspirin Dose and Atherosclerosis in Patients With Metabolic Syndrome

Study Overview
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Brief Summary
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The purpose of the study is to test higher versus lower doses of aspirin on markers of atherosclerosis in patients at risk of a first heart attack.

Detailed Description
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Aspirin reduces risks of heart attacks, strokes, and deaths from cardiovascular causes in patients who have survived a prior event as well as during an acute heart attack. Aspirin also prevents a first heart attack. Low dose aspirin is sufficient to achieve complete inhibition of platelet aggregability, or stickiness, and this is the mechanism whereby aspirin prevents formation of blood clots. Our research is designed to explore whether higher doses of aspirin provide additional benefits on markers of atherosclerosis.

Official Title
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A Randomized, Double-Blind Trial to Test Higher- Versus Lower-Doses of Aspirin on Inflammatory Markers and Platelet Biomarkers and Nitric Oxide Formation in High Risk Primary Prevention (Patients With Metabolic Syndrome)

Conditions
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Cardiovascular Diseases, Metabolic Syndrome X, Atherosclerosis

Intervention / Treatment
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* Drug: Aspirin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 1. Age 40 to 80 years, inclusive. 2. No previous heart attack or a stroke, or other forms of these diseases. 3. Have at least three of the five characteristics listed below, indicating presence of metabolic syndrome, as defined by NCEP-III: waist measuring more than 40 inches (for men) or more than 35 inches (for women), high density lipoprotein (HDL) cholesterol levels lower than 40 milligrams per deciliter (mg/dl) in men or 50 mg/dl in women, triglyceride (TG) levels above 150 mg/dl, blood pressure greater than 130 millimeters of mercury (mmHg) systolic or 85 mmHg diastolic, fasting blood sugar greater than 110 mg/dl Exclusion Criteria: Patients taking greater than 81mg aspirin daily. Patients taking anti-platelet drugs such as clopidogrel or non-steroidal anti-inflammatory drugs (NSAIDs) or anticoagulant drugs such as warfarin, during the last two weeks. Patients taking any of the following medications for less than 3 months, or who plan to take them for the first time during the next 3 months: ACE-inhibitors, angiotensin receptor blockers, calcium channel blockers, or statins. Patients who are currently cigarette smokers. Women patients who are pregnant, planning to become pregnant, nursing a child, or taking hormone replacement therapy. Patients with any coagulation, bleeding or blood disorders. Patients who are sensitive or allergic to aspirin. Patients with documented history of any gastrointestinal disorders, including bleeding ulcers. Patients with any evidence of cancer or history of significant cardiovascular disease (including heart attack, stroke or drop attacks termed transient ischemic attacks (TIAs), or blockages of the arteries in the legs termed peripheral arterial disease (PAD)), kidney, liver, lung, blood, or brain disorders. Patients with asthma, rhinitis, or nasal polyps. Patients with any abnormal laboratory value or physical finding that, in the view of the responsible clinician, may interfere with interpretation of the study results, be indicative of an underlying disease state, or compromise the safety. Patients with Class IV heart failure. Patients with severe aortic insufficiency, or aortic regurgitation. Patients with hearing loss or tinnitus. Patients with tremors which cause them not to be able to remain motionless for approximately 30 seconds.

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 1<br>81 mg Aspirin | Drug: Aspirin<br>* Dosage<br>|
| Active Comparator: 2<br>162 mg Aspirin | Drug: Aspirin<br>* Dosage<br>|
| Active Comparator: 3<br>325 mg Aspirin | Drug: Aspirin<br>* Dosage<br>|
| Active Comparator: 4<br>650 mg Aspirin | Drug: Aspirin<br>* Dosage<br>|
| Active Comparator: 5<br>1300 mg Aspirin | Drug: Aspirin<br>* Dosage<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Nitric Oxide Formation From Baseline to 3 Months | Changes in Heme oxygenase (HO-1) a downstream target of nitric oxide (NO) formation. | Baseline to 3 Months (90-97 days) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Primary prevention, Cardiovascular diseases, Aspirin, Metabolic Syndrome X, Atherosclerosis