Plaque Inflammation and Dysfunctional HDL in AIM-HIGH (HDL Proteomics)

• ClinicalTrials.gov Identifier: NCT00880178
• Recruitment Status: Completed
• First Posted: April 13, 2009
• Last Update Posted: May 14, 2018
• Sponsor: University of Washington
• Collaborator: National Heart, Lung, and Blood Institute (NHLBI)
• Information provided by (Responsible Party): Kevin O'Brien, University of Washington

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment
Cardiovascular Diseases; Heart Diseases; Coronary Disease; Atherosclerosis; Myocardial Infarction	Drug: Simvastatin and Extended-Release niacin; Drug: Simvastatin

Detailed Description:

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.

Study Design

• Study Type: Observational
• Actual Enrollment: 324 participants
• Observational Model: Cohort
• Time Perspective: Prospective
• Official Title: Plaque Inflammation and Dysfunctional HDL in AIM-HIGH
• Study Start Date: May 2008
• Actual Primary Completion Date: August 2011
• Actual Study Completion Date: September 2011

Groups and Cohorts

Group/Cohort	Intervention/treatment
Simvastatin; Participants in the main AIM-HIGH study who are receiving simvastatin.	Drug: Simvastatin; 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.
Simvastatin and Extended-Release Niacin; Participants in the main AIM-HIGH study who are receiving simvastatin and extended-release niacin.	Drug: Simvastatin and Extended-Release niacin; 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.; Other Name: Simvastatin/Niacin

Outcome Measures

Primary Outcome Measures :

1. Change in HDL oxidation and proteomics [ Time Frame: Measured at Year 2 ]

Secondary Outcome Measures :

1. Comparison of HDL oxidation and proteomics changes between participants receiving statins versus participants receiving statins plus niacin [ Time Frame: Measured at Year 2 ]
2. Comparison of change in an MRI marker of plaque inflammation between participants receiving statins versus participants receiving statins plus niacin [ Time Frame: Measured at Year 2 ]
3. Comparison of changes in HDL oxidation and proteomics with change in an MRI marker of plaque inflammation [ Time Frame: Measured at Year 2 ]
4. Change in an MRI marker of plaque inflammation [ Time Frame: Measured at Year 2 ]

Biospecimen Retention:   Samples Without DNA

Plasma for HDL isolation

Eligibility Criteria

• Ages Eligible for Study: 45 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No
• Sampling Method: Probability Sample

Study Population

Participants in the main AIM-HIGH study (NCT00120289)

Criteria

Inclusion Criteria:

• Eligible for main AIM-HIGH study (NCT00120289)
• Willing to provide informed consent for participation in this substudy

Contacts and Locations

Locations

United States, Alabama

Cardiovascular Associates

Birmingham, Alabama, United States, 35213

United States, Arizona

Cardiovascular Consultants

Phoenix, Arizona, United States, 85032

United States, California

Long Beach VA Medical Center

Long Beach, California, United States, 90822

United States, Delaware

Christiana Care Health Services

Newark, Delaware, United States, 19718

United States, Maryland

University of Maryland

Baltimore, Maryland, United States, 21201

United States, Minnesota

University of Minnesota

Minneapolis, Minnesota, United States, 55414

HealthPartners Riverside Clinic

Minneapolis, Minnesota, United States, 55454

Mayo Clinic

Rochester, Minnesota, United States, 55905

United States, North Carolina

Duke University

Durham, North Carolina, United States, 27710

Wake Forest University, Geriatrics

Greensboro, North Carolina, United States, 27157

Wake Forest University, Cardiology

Winston-Salem, North Carolina, United States, 27157

Wake Forest University, Endocrinology

Winston-Salem, North Carolina, United States, 27157

United States, Ohio

St. Vincent Charity Hospital

Cleveland, Ohio, United States, 44115

United States, Oregon

Portland VA Medical Center

Portland, Oregon, United States, 97239

United States, Pennsylvania

Philadelphia VA Medical Center

Philadelphia, Pennsylvania, United States, 19104

Pennsylvania Cardiology Associates

Philadelphia, Pennsylvania, United States, 19106

Cardiology Consultants of Philadelphia

Philadelphia, Pennsylvania, United States, 19148

United States, Texas

Baylor College of Medicine

Houston, Texas, United States, 77030

Kelsey Research Foundation

Houston, Texas, United States, 77030

Methodist Hospital

Houston, Texas, United States, 77030

United States, Virginia

McGuire VA Medical Center

Richmond, Virginia, United States, 23249

United States, Washington

Harborview Medical Center

Seattle, Washington, United States, 98104

University of Washington

Seattle, Washington, United States, 98105

Puget Sound VA Medical Center, Seattle Campus

Seattle, Washington, United States, 98108

Canada, Alberta

Heart Health Institute

Calgary, Alberta, Canada, T2E-7C5

University of Calgary

Calgary, Alberta, Canada, T2N-2T9

Canada, British Columbia

Vancouver General Hospital

Vancouver, British Columbia, Canada, V5Z-1M9

Canada, Ontario

University of Western Ontario

London, Ontario, Canada, N6A-5A5

St. Michael's Health Centre

Toronto, Ontario, Canada, M5C-2T2

Sponsors and Collaborators

University of Washington

National Heart, Lung, and Blood Institute (NHLBI)

Investigators

• Principal Investigator: Kevin D. O'Brien, MD; University of Washington

More Information

Publications of Results:

Chen H, Sun J, Kerwin WS, Balu N, Neradilek MB, Hippe DS, Isquith D, Xue Y, Yamada K, Peck S, Yuan C, O'Brien KD, Zhao XQ. Scan-rescan reproducibility of quantitative assessment of inflammatory carotid atherosclerotic plaque using dynamic contrast-enhanced 3T CMR in a multi-center study. J Cardiovasc Magn Reson. 2014 Aug 1;16:51. doi: 10.1186/s12968-014-0051-7.

Zhao XQ, Hatsukami TS, Hippe DS, Sun J, Balu N, Isquith DA, Crouse JR 3rd, Anderson T, Huston J 3rd, Polissar N, O'Brien K, Yuan C; AIM-HIGH Carotid MRI Sub-study Investigators. Clinical factors associated with high-risk carotid plaque features as assessed by magnetic resonance imaging in patients with established vascular disease (from the AIM-HIGH Study). Am J Cardiol. 2014 Nov 1;114(9):1412-9. doi: 10.1016/j.amjcard.2014.08.001. Epub 2014 Aug 13.

O'Brien KD, Hippe DS, Chen H, Neradilek MB, Probstfield JL, Peck S, Isquith DA, Canton G, Yuan C, Polissar NL, Zhao XQ, Kerwin WS. Longer duration of statin therapy is associated with decreased carotid plaque vascularity by magnetic resonance imaging. Atherosclerosis. 2016 Feb;245:74-81. doi: 10.1016/j.atherosclerosis.2015.11.032. Epub 2015 Dec 1.

O'Brien KD, Hippe DS, Chen H, Neradilek MB, Probstfield JL, Peck S, Isquith DA, Canton G, Yuan C, Polissar NL, Zhao XQ, Kerwin WS. Summary of clinical and laboratory data of study subjects with and without DCE-MRI plaque measurements in the AIM-HIGH clinical trial. Data Brief. 2016 Jan 2;6:476-81. doi: 10.1016/j.dib.2015.12.030. eCollection 2016 Mar.

Sun J, Zhao XQ, Balu N, Neradilek MB, Isquith DA, Yamada K, Cantón G, Crouse JR 3rd, Anderson TJ, Huston J 3rd, O'Brien K, Hippe DS, Polissar NL, Yuan C, Hatsukami TS. Carotid Plaque Lipid Content and Fibrous Cap Status Predict Systemic CV Outcomes: The MRI Substudy in AIM-HIGH. JACC Cardiovasc Imaging. 2017 Mar;10(3):241-249. doi: 10.1016/j.jcmg.2016.06.017.

Hippe DS, Phan BAP, Sun J, Isquith DA, O'Brien KD, Crouse JR, Anderson T, Huston J, Marcovina SM, Hatsukami TS, Yuan C, Zhao XQ. Lp(a) (Lipoprotein(a)) Levels Predict Progression of Carotid Atherosclerosis in Subjects With Atherosclerotic Cardiovascular Disease on Intensive Lipid Therapy: An Analysis of the AIM-HIGH (Atherothrombosis Intervention in Metabolic Syndrome With Low HDL/High Triglycerides: Impact on Global Health Outcomes) Carotid Magnetic Resonance Imaging Substudy-Brief Report. Arterioscler Thromb Vasc Biol. 2018 Mar;38(3):673-678. doi: 10.1161/ATVBAHA.117.310368. Epub 2018 Jan 4.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Sun J, Zhao XQ, Balu N, Hippe DS, Hatsukami TS, Isquith DA, Yamada K, Neradilek MB, Cantón G, Xue Y, Fleg JL, Desvigne-Nickens P, Klimas MT, Padley RJ, Vassileva MT, Wyman BT, Yuan C. Carotid magnetic resonance imaging for monitoring atherosclerotic plaque progression: a multicenter reproducibility study. Int J Cardiovasc Imaging. 2015 Jan;31(1):95-103. doi: 10.1007/s10554-014-0532-7. Epub 2014 Sep 13.

• Responsible Party: Kevin O'Brien, Professor of Medicine, Cardiology, University of Washington
• ClinicalTrials.gov Identifier: NCT00880178
• Other Study ID Numbers: 28201; R01HL089504 ( U.S. NIH Grant/Contract )
• First Posted: April 13, 2009
• Last Update Posted: May 14, 2018
• Last Verified: February 2018

Keywords provided by Kevin O'Brien, University of Washington:

Simvastatin; Niacin; Vascular Disease; Magnetic Resonance Imaging; High Density Lipoprotein; Oxidation; Proteomics; Stroke; Cerebrovascular Accident

Additional relevant MeSH terms:

Cardiovascular Diseases; Myocardial Infarction; Heart Diseases; Atherosclerosis; Coronary Disease; Inflammation; Infarction; Pathologic Processes; Ischemia; Necrosis; Myocardial Ischemia; Vascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Niacin; Niacinamide; Nicotinic Acids; Simvastatin; Anticholesteremic Agents; Hypolipidemic Agents; Antimetabolites; Molecular Mechanisms of Pharmacological Action; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Enzyme Inhibitors; Vasodilator Agents; Vitamin B Complex; Vitamins; Micronutrients; Nutrients