Plaque Inflammation and Dysfunctional HDL in AIM-HIGH

Study Overview
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Brief Summary
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Coronary heart disease (CHD) is a serious health concern that affects millions of people in the United States. It is usually caused by atherosclerosis-a condition that occurs when fatty material and plaque build up on the walls of the arteries that supply blood and oxygen to the heart, causing the arteries to narrow. As the arteries narrow, blood flow to the heart can slow down or stop, which can cause chest pain, shortness of breath, heart attack, or heart failure. Another component of CHD events involves inflammatory changes that result in structural breakdown of atherosclerotic plaques. Adding niacin to statin medications may be an effective way to block inflammation in the atherosclerotic plaques. This study will examine magnetic resonance imaging (MRI) images and blood samples of participants in the AIM-HIGH study who are taking niacin plus statins or statins alone to determine the effect of these medications on inflammation in atherosclerotic plaques.

Detailed Description
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CHD is the leading cause of death in the United States. Preliminary research has shown that CHD is associated with oxidative and inflammatory changes in high-density lipoprotein (HDL) cholesterol, which is considered the good cholesterol. The inflammatory changes can impair HDL cholesterol's normal function, which is to remove excess cholesterol from the arteries and thereby slow the build-up of atherosclerotic plaque. Statins are cholesterol-lowering medications that are used to treat people with CHD. Taking niacin, a type of B vitamin, in combination with statins may stabilize atherosclerotic plaques better than statins alone, but more research is needed to examine how niacin may do this. By improving the ability of HDL cholesterol to repair inflammatory damage to atherosclerotic plaques, niacin may assist in preventing the inflammation that leads to plaque breakdown. The AIM-HIGH study (NCT00120289) is examining the use of niacin plus statins in people with vascular disease. Participants in the AIM-HIGH study are randomly assigned to receive either niacin plus simvastatin, which is a type of statin medication, or simvastatin alone. The purpose of this substudy is to determine whether niacin in combination with statins reduces atherosclerotic plaque inflammation and dysfunctional HDL cholesterol more than statins alone. The substudy will enroll participants who are participating in the AIM-HIGH study. At the AIM-HIGH baseline and Year 2 study visits, study researchers for this substudy will collect an additional blood sample from participants to examine the changes in HDL oxidation levels and protein composition at both time points. Study researchers will also analyze participants' MRI scans to examine changes in plaque inflammation during the study period; these MRI scans will be completed as part of another AIM-HIGH substudy, conducted by Dr. Xue-Qiao Zhao. There will be no additional study procedures or visits for participants in this substudy.

Official Title
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Plaque Inflammation and Dysfunctional HDL in AIM-HIGH

Conditions
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Cardiovascular Diseases, Heart Diseases, Coronary Disease, Atherosclerosis, Myocardial Infarction

Intervention / Treatment
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* Drug: Simvastatin and Extended-Release niacin
* Drug: Simvastatin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Eligible for main AIM-HIGH study (NCT00120289) Willing to provide informed consent for participation in this substudy

Ages Eligible for Study
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Minimum Age: 45 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Simvastatin<br>Participants in the main AIM-HIGH study who are receiving simvastatin. | Drug: Simvastatin<br>* Participants will be enrolled in this substudy only if they are candidates for the main AIM-HIGH study (NCT00120289). Participants will be randomly assigned to simvastatin or simvastatin plus niacin as a part of the main AIM-HIGH protocol, and adjustments in simvastatin and/or niacin doses will be made as per the protocol for the main AIM-HIGH study.<br>|
| Simvastatin and Extended-Release Niacin<br>Participants in the main AIM-HIGH study who are receiving simvastatin and extended-release niacin. | Drug: Simvastatin and Extended-Release niacin<br>* Participants will be enrolled in this substudy only if they are candidates for the main AIM-HIGH study (NCT00120289). Participants will be randomly assigned to simvastatin or simvastatin plus niacin as a part of the main AIM-HIGH protocol, and adjustments in simvastatin and/or niacin doses will be made as per the protocol for the main AIM-HIGH study.<br>* Other names: Simvastatin/Niacin;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in HDL oxidation and proteomics |  | Measured at Year 2 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Comparison of HDL oxidation and proteomics changes between participants receiving statins versus participants receiving statins plus niacin |  | Measured at Year 2 | 
| Comparison of change in an MRI marker of plaque inflammation between participants receiving statins versus participants receiving statins plus niacin |  | Measured at Year 2 | 
| Comparison of changes in HDL oxidation and proteomics with change in an MRI marker of plaque inflammation |  | Measured at Year 2 | 
| Change in an MRI marker of plaque inflammation |  | Measured at Year 2 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Simvastatin, Niacin, Vascular Disease, Magnetic Resonance Imaging, High Density Lipoprotein, Oxidation, Proteomics, Stroke, Cerebrovascular Accident