Carotid Plaque Characteristics by MRI in AIM-HIGH (Carotid MRI Substudy)

NCT ID: NCT01178320

Last Updated: 2018-02-09

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 230 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2008-03-31
• Study Completion Date: 2015-02-28

Brief Summary

Heart attacks and strokes caused by the unstable atherosclerotic plaques remain the leading cause of death in the United States. Unstable plaques often have more fat than stable plaques. This study will investigate if a treatment with LDL-lowering plus HDL-raising compared with LDL-lowering alone would more effectively reduce the plaque fat content assessed by magnetic resonance imaging (MRI), therefore, further reducing heart attacks and strokes.

Detailed Description

Although studies have suggested that plaque morphology and composition are important determinants of plaque stability, our understanding on plaque tissue components is mainly from histological studies until recent development in MRI technique. A low level of HDL is associated with higher risk of cardiovascular events and increased amount of lipid content in the carotid plaques. Treatment with LDL-lowering plus HDL-raising compared with LDL-lowering alone more effectively protects against atherosclerosis progression. It is widely believed that HDL or its apolipoproteins mediate the removal of excess free cholesterol from peripheral cells and the cholesterol is delivered via either LDL or HDL to the liver for excretion into the bile. However, it has not been tested and approved in human atherosclerotic condition in vivo. The NIH/Abbott-funded multi-center AIM-HIGH trial is designed to compare the clinical efficacy of LDL-lowering alone with statin versus LDL-lowering plus HDL-raising with statin plus nicotinic acid combination therapy in patients with established vascular disease and high triglycerides and low HDL.

We propose to conduct a carotid MRI sub-study in 220 subjects enrolled in AIM-HIGH to investigate the important vascular biological mechanisms of HDL-raising therapy. Image collection will occur at 3 timepoints. The hypotheses and specific aims are:

• (1) To test the primary hypothesis that compared with LDL-lowering alone, intensive LDL-lowering plus HDL-raising therapy decreases the mean plaque lipid composition in carotid arteries assessed by MRI.
• (2) To test the hypothesis that compared with LDL-lowering alone, intensive LDL-lowering plus HDL-raising therapy decreases the plaque burden including volume and wall thickness.
• (3) To test the hypothesis that increased plaque lipid composition or vessel wall thickness by MRI is associated with increased risk of cardiovascular events.
• (4)To test a hypothesis that LDL-lowering plus HDL-raising, compared to LDL-lowering alone, will promote more rapid plaque lipid depletion. And determine the time-course of atherosclerotic plaque lipid depletion during lipid therapy.
• (5) To examine the association of clinical risk factors, lipids, lipoprotein heterogeneity, inflammatory markers and carotid plaque characteristics.

This MRI sub-study offers a unique opportunity to investigate the effectiveness of LDL-lowering plus HDL-raising therapy on human atherosclerotic plaque in vivo, to examine the association of plaque characteristics both lipid composition and volume assessed by MRI and cardiovascular outcome, and to gain novel insights in our understanding of atherosclerotic plaque pathology and the mechanisms of intensive lipid management in preventing cardiovascular events.

Conditions

Coronary Artery Disease; Carotid Artery Diseases; Atherosclerosis

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, simvastatin plus 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.

Simvastatin and Extended-Release Niacin

Participants in the main AIM-HIGH study who are receiving simvastatin and extended-release niacin.

Simvastatin, simvastatin plus 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, simvastatin plus 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

Other Intervention Names

simvastatin; Zocor; niacin; Niaspan

Eligibility Criteria

Inclusion Criteria

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

Exclusion Criteria

• Uses pacemaker or has metallic implants
• History of bilateral carotid endarterectomy
• Glomerular filtration rate less than 60 mL/min/1.73 m^2

• 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

Xue-Qiao Zhao

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Xue-Qiao Zhao, MD

Role: PRINCIPAL_INVESTIGATOR

University of Washington

Locations

Cardiovascular Consultants

Phoenix, Arizona, United States

Long Beach VA Medical Center

Long Beach, California, United States

University of Southern California

Los Angeles, California, United States

University of Maryland

Baltimore, Maryland, United States

Johns Hopkins University

Baltimore, Maryland, United States

Mayo Clinic

Rochester, Minnesota, United States

Duke University

Durham, North Carolina, United States

Wake Forest University

Winston-Salem, North Carolina, United States

Philadelphia VA Medical Center

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

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

Countries

United States; Canada

References

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)

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: RESULT

PMID: 25216871 (View on PubMed)

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)

Zhao XQ, Sun J, Hippe DS, Isquith DA, Canton G, Yamada K, Balu N, Crouse JR 3rd, Anderson TJ, Huston J 3rd, O'Brien KD, Hatsukami TS, Yuan C; AIM-HIGH Carotid MRI Substudy Investigators. Magnetic Resonance Imaging of Intraplaque Hemorrhage and Plaque Lipid Content With Continued Lipid-Lowering Therapy: Results of a Magnetic Resonance Imaging Substudy in AIM-HIGH. Circ Cardiovasc Imaging. 2022 Nov;15(11):e014229. doi: 10.1161/CIRCIMAGING.122.014229. Epub 2022 Nov 15.

Reference Type: DERIVED

PMID: 36378778 (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: DERIVED

PMID: 26708287 (View on PubMed)

Other Identifiers

R01HL088214

Identifier Type: NIH

Identifier Source: secondary_id

View Link

627

Identifier Type: -

Identifier Source: org_study_id