Lp-PLA2 and Coronary Atherosclerosis in Humans
Condition: Coronary Atherosclerosis; Endothelial Dysfunction
MeSH terms: Atherosclerosis; Coronary Artery Disease; Myocardial Ischemia
Study type: Interventional

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.
    

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.
    

Intervention name(s): Blood sampling from the Coronary Sinus and Aorta; Intravascular Ultrasound of the coronary artery.
Intervention type(s): Other; Procedure
Intervention description(s): Blood samples will be obtained from the aorta and the coronary sinus during the clinically scheduled angiogram and endothelial function testing.; Intravascular Ultrasound will be completed for those subjects testing positive for coronary endothelial dysfunction during a clinically scheduled angiogram and endothelial function testing.
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Diagnostic
Keywords: coronary artery disease; coronary artery spasm; small vessel coronary artery disease