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Lp-PLA2 and Coronary Atherosclerosis in Humans (AIM 1 and II)

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ClinicalTrials.gov Identifier: NCT01557088
Recruitment Status : Completed
First Posted : March 19, 2012
Last Update Posted : September 23, 2015
Information provided by (Responsible Party):

Study Description
Brief Summary:
The majority of the acute coronary events are caused by coronary artery segments with minimal luminal disease, but with potentially significant vascular wall inflammation and oxidative stress leading to plaque vulnerability. It has become apparent that an initial injury at the endothelial surface, is the primary site of the mechanisms involved and a role for vascular inflammation and the interaction with oxidative stress continues to emerge. Lipoprotein-associated phospholipase A2 (Lp-PLA2) is a novel biomarker for vascular wall inflammation that circulates in the blood bound to both low density (LDL) and high density (HDL) lipoprotein and promotes vascular inflammation. Circulating levels of Lp-PLA2 mass and activity are an independent risk factor for cardiovascular events. Recent studies, demonstrating that Lp-PLA2 is also associated with coronary endothelial dysfunction. However, the relationship between Lp-PLA2 and early atherosclerotic changes in the coronary arteries, and the contribution of lipoprotein binding to the deleterious potential of Lp- PLA2 have not been elucidated. Our working hypothesis is that the endogenous local activation of the Lp-PLA2 pathway plays an integral role in early coronary atherosclerosis and contributes to the mechanism of coronary endothelial dysfunction and the structural and mechanical properties reflecting plaque vulnerability. Thus, the current application will characterize prospectively the correlation between the functional, mechanical, and structural vascular wall properties, and the systemic as well as the coronary activity of the Lp-PLA2 pathway.

Condition or disease Intervention/treatment
Coronary Atherosclerosis Endothelial Dysfunction Other: Blood sampling from the Coronary Sinus and Aorta Procedure: Intravascular Ultrasound of the coronary artery.

Detailed Description:

Aim I: Hypothesis: The extent of endothelial dysfunction will correlate with production of Lp-PLA2 and oxidative stress and correlates with the tissue characteristics of plaque vulnerability. The investigators will define the systemic and coronary gradient and production of markers of inflammation and oxidative stress and the presence of coronary endothelial dysfunction in patients with early coronary atherosclerosis.

Aim II: Hypothesis: The distribution of Lp-PLA2 on the LDL is associated with greater coronary endothelial dysfunction and correlates with the degree coronary atherosclerosis and plaque vulnerability. The investigators will define the distribution of Lp-PLA2 in patients with early coronary atherosclerosis and endothelial dysfunction.

Study Design

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 166 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Diagnostic
Official Title: Lp-PLA2, Progenitor Cells and Coronary Atherosclerosis in Humans
Study Start Date : February 2009
Primary Completion Date : June 2015
Study Completion Date : June 2015

Resource links provided by the National Library of Medicine

U.S. FDA Resources

Arms and Interventions

Intervention Details:
    Other: Blood sampling from the Coronary Sinus and Aorta
    Blood samples will be obtained from the aorta and the coronary sinus during the clinically scheduled angiogram and endothelial function testing.
    Procedure: Intravascular Ultrasound of the coronary artery.
    Intravascular Ultrasound will be completed for those subjects testing positive for coronary endothelial dysfunction during a clinically scheduled angiogram and endothelial function testing.

Outcome Measures

Primary Outcome Measures :
  1. Lp-PLA2 Assessment [ Time Frame: baseline endothelial function assessment 6 months ]
    AIM 1: To assess the relationship between the 3 inflammatory measures of the Lp-PLA2 pathway (Lp-PLA2 mass, Lp-PLA2 activity and LysoPC) with endothelial function (as measured by the percent change in CAD (coronary artery disease) [Ach] and by the length of segments with endothelial dysfunction and plaque vulnerability (as measured by the necrotic core percent volume). AIM II: To assess the association between the percent of Lp-PLA2 residing on LDL and endothelial function (again measured by percent change in CAD [Ach], percent change in CBF (coronary blood flow)[Ach], and the length of endothelial dysfunction).

Eligibility Criteria

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Ages Eligible for Study:   18 Years to 85 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Patients undergoing coronary angiography including endothelial function testing
  • male and female
  • age 18 up to age 85

Exclusion Criteria:

  • Heart failure with ejection fraction less that 40%
  • unstable angina
  • myocardial infarction or angioplasty within 6 months prior to entry into the study
  • use of investigational agents within 1 month of entry into the study
  • patients who require treatment with positive inotropic agents other than digoxin during the study
  • patients with cerebrovascular accident within 6 months prior to entry into the study
  • significant endocrine, hepatic or renal disorders
  • local or systemic infectious disease within 4 weeks prior to entry into study
  • pregnancy or lactation (women of child-bearing age will have a pregnancy test prior to angiogram)
  • mental instability
  • federal medical center inmates
  • hemoglobin less than 12 mg/dL
  • severe asthma
Contacts and Locations

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To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01557088

United States, Minnesota
Mayo Clinic
Rochester, Minnesota, United States, 55905
Sponsors and Collaborators
Mayo Clinic
National Institutes of Health (NIH)
National Institute on Aging (NIA)
Principal Investigator: Amir Lerman, MD Mayo Clinic
More Information

Responsible Party: Amir Lerman, Professor of Medicine, Mayo Clinic
ClinicalTrials.gov Identifier: NCT01557088     History of Changes
Other Study ID Numbers: 08-008161
5R01HL92954-01A1-05 ( Other Grant/Funding Number: US NIH Grant )
1R01 AG31750-01A2-04 ( Other Grant/Funding Number: NIA )
First Posted: March 19, 2012    Key Record Dates
Last Update Posted: September 23, 2015
Last Verified: September 2015

Keywords provided by Amir Lerman, Mayo Clinic:
coronary artery disease
coronary artery spasm
small vessel coronary artery disease

Additional relevant MeSH terms:
Coronary Artery Disease
Myocardial Ischemia
Arterial Occlusive Diseases
Vascular Diseases
Cardiovascular Diseases
Coronary Disease
Heart Diseases