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

Mayo Clinic

Status

Completed

Conditions

Endothelial Dysfunction

Coronary Atherosclerosis

Treatments

Procedure: Intravascular Ultrasound of the coronary artery.

Other: Blood sampling from the Coronary Sinus and Aorta

Study type

Interventional

Funder types

Other

NIH

Identifiers

NCT01557088

1R01 AG31750-01A2-04 (Other Grant/Funding Number)

5R01HL92954-01A1-05 (Other Grant/Funding Number)

08-008161

Details and patient eligibility

About

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.

Full 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.

Enrollment

166 patients

Sex

All

Ages

18 to 85 years old

Volunteers

No Healthy Volunteers

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