Clinical trial NCT00880178: Plaque Inflammation and Dysfunctional HDL in AIM-HIGH
Official title: Plaque Inflammation and Dysfunctional HDL in AIM-HIGH
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Cardiovascular Diseases
Heart Diseases
Coronary Disease
Atherosclerosis
Myocardial Infarction
Keywords: Simvastatin
Niacin
Vascular Disease
Magnetic Resonance Imaging
High Density Lipoprotein
Oxidation
Proteomics
Stroke
Cerebrovascular Accident
Lead sponsor: University of Washington
Sponsor class: OTHER
Collaborators: name: National Heart, Lung, and Blood Institute (NHLBI)
First posted: 2009-04-13
Enrollment: 324
Sex: ALL
Minimum age (years): 45
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Participants in the main AIM-HIGH study (NCT00120289)

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.

Eligibility criteria: Inclusion Criteria:

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

Primary outcomes:
measure: Change in HDL oxidation and proteomics
timeFrame: Measured at Year 2
Secondary outcomes:
measure: Comparison of HDL oxidation and proteomics changes between participants receiving statins versus participants receiving statins plus niacin
timeFrame: Measured at Year 2
measure: Comparison of change in an MRI marker of plaque inflammation between participants receiving statins versus participants receiving statins plus niacin
timeFrame: Measured at Year 2
measure: Comparison of changes in HDL oxidation and proteomics with change in an MRI marker of plaque inflammation
timeFrame: Measured at Year 2
measure: Change in an MRI marker of plaque inflammation
timeFrame: Measured at Year 2
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Cardiovascular Associates
state: Alabama
city: Phoenix
country: United States
facility: Cardiovascular Consultants
state: Arizona
city: Long Beach
country: United States
facility: Long Beach VA Medical Center
state: California
city: Newark
country: United States
facility: Christiana Care Health Services
state: Delaware
city: Baltimore
country: United States
facility: University of Maryland
state: Maryland
city: Minneapolis
country: United States
facility: University of Minnesota
state: Minnesota
city: Minneapolis
country: United States
facility: HealthPartners Riverside Clinic
state: Minnesota
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Durham
country: United States
facility: Duke University
state: North Carolina
city: Greensboro
country: United States
facility: Wake Forest University, Geriatrics
state: North Carolina
city: Winston-Salem
country: United States
facility: Wake Forest University, Cardiology
state: North Carolina
city: Winston-Salem
country: United States
facility: Wake Forest University, Endocrinology
state: North Carolina
city: Cleveland
country: United States
facility: St. Vincent Charity Hospital
state: Ohio
city: Portland
country: United States
facility: Portland VA Medical Center
state: Oregon
city: Philadelphia
country: United States
facility: Philadelphia VA Medical Center
state: Pennsylvania
city: Philadelphia
country: United States
facility: Pennsylvania Cardiology Associates
state: Pennsylvania
city: Philadelphia
country: United States
facility: Cardiology Consultants of Philadelphia
state: Pennsylvania
city: Houston
country: United States
facility: Baylor College of Medicine
state: Texas
city: Houston
country: United States
facility: Kelsey Research Foundation
state: Texas
city: Houston
country: United States
facility: Methodist Hospital
state: Texas
city: Richmond
country: United States
facility: McGuire VA Medical Center
state: Virginia
city: Seattle
country: United States
facility: Harborview Medical Center
state: Washington
city: Seattle
country: United States
facility: University of Washington
state: Washington
city: Seattle
country: United States
facility: Puget Sound VA Medical Center, Seattle Campus
state: Washington
city: Calgary
country: Canada
facility: Heart Health Institute
state: Alberta
city: Calgary
country: Canada
facility: University of Calgary
state: Alberta
city: Vancouver
country: Canada
facility: Vancouver General Hospital
state: British Columbia
city: London
country: Canada
facility: University of Western Ontario
state: Ontario
city: Toronto
country: Canada
facility: St. Michael's Health Centre
state: Ontario
Study officials:
affiliation: University of Washington
name: Kevin D. O'Brien, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.