Regional Activation of Leukocytes in Coronary artery disease And Diabetes mellitus (REAL-CAD)

Atherosclerosis is one of the major causes of death in the world. Lipoproteins,
triglycerides (TG), fatty acids and glucose are able to induce leukocyte
activation in vitro and in vivo, which is obligatory for the development of
atherosclerosis. Therefore, inhibition of leukocyte activation and/or
endothelial cell activation is a promising target for intervention in the
struggle against atherosclerosis. Complement component 3 (C3) and Mannose
Binding Lectin (MBL) are other inflammatory factors which plays a role in the
process of atherosclerosis as both have been linked to CAD.
Our knowledge concerning these inflammatory factors and the relation to
atherogenesis is limited. In recent studies regional differences in leukocyte
activation was found during catheterization in subjects with unstable angina
compared to patients with stable angina and healthy subjects. Higher leukocyte
activation has also been shown in type 2 diabetics compared to healthy
controls.
There are no data available on the mechanism behind the (regional) differences
in leukocyte activation. In addition, only a few publications have been
released on the role of neutrophils in the process of atherosclerosis. Most
groups have studied monocytes and lymphocytes because these are the cells that
are present in the plaque.
We propose that the activation of neutrophils is one of the earliest events in
the process of atherosclerosis and that complement activation and regional
differences in lipoprotein and glucose concentrations may be involved.

1. The primary aim of REAL CAD is to determine regional differences of
leukocyte
activation in different vascular beds in vivo.
2. The secondary aim is to investigate differences in leukocyte activation
between
diabetic and CAD subjects and patients suffering from both.
3. The third aim is to investigate the relationship between complement
components, triglycerides and leukocyte activation markers in order to gain
more insight into the causative processes leading to activation of
leukocytes.
4. The fourth aim is to get more insight in the MBL genotypes and serum levels
of
CAD and/or diabetic patients and the *healthy* groups included in our
study.

Patients, who visit the outpatient clinics of the department of cardiology and
are scheduled to undergo a diagnostic coronary catheterization, will be asked
to participate in this study. Written informed consent will be obtained from
each participant. Subjects must give a separate consent for the DNA blood
sampling. Patients will not be paid for participation in this study.
The patients will be asked to visit the laboratory for blood sampling in order
to determine baseline characteristics and to obtain DNA. Subsequently, they
will be scheduled for catheterization, which they will undergo after a 10 hrs
fasting period. During catheterization blood sampling shall occur at five
different regions, which are the abdominal aorta just above the bifurcation,
aorta ascendens, both coronaries and a peripheral vein in the left or right
arm.

Except for the risks of coronary catheterization there are no/little risks for
the patients in this study. The patients are already scheduled to undergo a
coronary catheterization and by means of the catheter blood sampling can occur.
However, there shall be an intravenous blood sample in a peripheral vene in the
arm.
The time burden will also be minimal; during the visit in which the
cardiologist and the patient decide to do a catheterization, the patient will
be asked to participate. If they agree on participation, the investigator will
come to the patient in order to ask the family history and the medication as
well as to determine the blood pressure, weight, length, waist. This shall take
15 minutes.