Plaque Inflammation and Dysfunctional HDL in AIM-HIGH

NCT ID: NCT00880178

Last Updated: 2018-05-14

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 324 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2008-05-31
• Study Completion Date: 2011-09-30

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.

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.

Conditions

Cardiovascular Diseases; Heart Diseases; Coronary Disease; Atherosclerosis; Myocardial Infarction

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

Simvastatin

Participants in the main AIM-HIGH study who are receiving simvastatin.

Simvastatin

Intervention Type: DRUG

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.

Simvastatin and Extended-Release niacin

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: 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.

Intervention Type: DRUG

Other Intervention Names

Simvastatin/Niacin

Eligibility Criteria

Inclusion Criteria

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

• Minimum Eligible Age: 45 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Heart, Lung, and Blood Institute (NHLBI)

NIH

Sponsor Role: collaborator

University of Washington

OTHER

Sponsor Role: lead

Responsible Party

Kevin O'Brien

Professor of Medicine, Cardiology

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Kevin D. O'Brien, MD

Role: PRINCIPAL_INVESTIGATOR

University of Washington

Locations

Cardiovascular Associates

Birmingham, Alabama, United States

Cardiovascular Consultants

Phoenix, Arizona, United States

Long Beach VA Medical Center

Long Beach, California, United States

Christiana Care Health Services

Newark, Delaware, United States

University of Maryland

Baltimore, Maryland, United States

University of Minnesota

Minneapolis, Minnesota, United States

HealthPartners Riverside Clinic

Minneapolis, Minnesota, United States

Mayo Clinic

Rochester, Minnesota, United States

Duke University

Durham, North Carolina, United States

Wake Forest University, Geriatrics

Greensboro, North Carolina, United States

Wake Forest University, Cardiology

Winston-Salem, North Carolina, United States

Wake Forest University, Endocrinology

Winston-Salem, North Carolina, United States

St. Vincent Charity Hospital

Cleveland, Ohio, United States

Portland VA Medical Center

Portland, Oregon, United States

Philadelphia VA Medical Center

Philadelphia, Pennsylvania, United States

Pennsylvania Cardiology Associates

Philadelphia, Pennsylvania, United States

Cardiology Consultants of Philadelphia

Philadelphia, Pennsylvania, United States

Baylor College of Medicine

Houston, Texas, United States

Kelsey Research Foundation

Houston, Texas, United States

Methodist Hospital

Houston, Texas, United States

McGuire VA Medical Center

Richmond, Virginia, United States

Harborview Medical Center

Seattle, Washington, United States

University of Washington

Seattle, Washington, United States

Puget Sound VA Medical Center, Seattle Campus

Seattle, Washington, United States

Heart Health Institute

Calgary, Alberta, Canada

University of Calgary

Calgary, Alberta, Canada

Vancouver General Hospital

Vancouver, British Columbia, Canada

University of Western Ontario

London, Ontario, Canada

St. Michael's Health Centre

Toronto, Ontario, Canada

Countries

United States; Canada

References

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(1):51. doi: 10.1186/s12968-014-0051-7.

Reference Type: RESULT

PMID: 25084698 (View on PubMed)

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.

Reference Type: RESULT

PMID: 25245415 (View on PubMed)

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.

Reference Type: RESULT

PMID: 26708287 (View on PubMed)

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.

Reference Type: RESULT

PMID: 26977429 (View on PubMed)

Sun J, Zhao XQ, Balu N, Neradilek MB, Isquith DA, Yamada K, Canton 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.

Reference Type: RESULT

PMID: 28279371 (View on PubMed)

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.

Reference Type: RESULT

PMID: 29301785 (View on PubMed)

Ronsein GE, Vaisar T, Davidson WS, Bornfeldt KE, Probstfield JL, O'Brien KD, Zhao XQ, Heinecke JW. Niacin Increases Atherogenic Proteins in High-Density Lipoprotein of Statin-Treated Subjects. Arterioscler Thromb Vasc Biol. 2021 Aug;41(8):2330-2341. doi: 10.1161/ATVBAHA.121.316278. Epub 2021 Jun 17.

Reference Type: DERIVED

PMID: 34134520 (View on PubMed)

Sun J, Zhao XQ, Balu N, Hippe DS, Hatsukami TS, Isquith DA, Yamada K, Neradilek MB, Canton 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.

Reference Type: DERIVED

PMID: 25216871 (View on PubMed)

Other Identifiers

R01HL089504

Identifier Type: NIH

Identifier Source: secondary_id

View Link

28201

Identifier Type: -

Identifier Source: org_study_id