Biomarkers of Cardiovascular Disorders - Applications of Biotechnology in Cardiovascular Therapeutics - page 112

Biomarkers of Risk Factors for Coronary Heart Disease
Antibody to Oxidized-LDL
Following rupture of the plaque oxidised-LDL (Ox-LDL), stored in the wall of the
plaque, sets off an immunological reaction in the blood stream and antibodies are
produced, which are directed against the exposed Ox-LDL molecules. These anti-
bodies can be measured in the laboratory as biomarkers. One particular form of
antibody is known to be particularly associated with the risk of a heart attack.
EG010 (Ark Therapeutics) has been specifically developed as an IVD and opti-
mized to detect this antibody. Initial trials data indicate that it predicted 81% of
patients with an acute coronary syndrome, comparing very favorably with CRP
testing, which only predicted 29%. Ark has completed the necessary clinical valida-
tion work to achieve CE marking status in Europe and will address the US position
once it has obtained CE marking in Europe.
Apolipoproteins as Risk Factors for Coronary Heart Disease
Apolipoproteins AI and B are structural components of lipoprotein particles, and
also determinants of the metabolic fate of the encapsulated lipid, cholesterol, and
triglyceride. Development of accurate assays for these apolipoproteins has opened
the way for their use as predictors of coronary heart disease risk. Interpretation of
AI and apo B levels is best undertaken with background knowledge of the meta-
bolic status of an individual, especially the lipolytic capacity as reflected in the
triglyceride concentration. Those with raised triglyceride, in general, not only have
an elevated apo B/apo AI ratio, but also apo B-containing lipoproteins with a pro-
longed residence time and hence ample opportunity for modification and damage
(Marcovina and Packard 2006 ). Assessment of apolipoprotein levels is an aid to
risk prediction and can be useful in tailoring treatment. An inverse relationship
between the concentration of high-density lipoprotein (HDL) cholesterol and the
risk of developing cardiovascular is well established. There are several documented
functions of HDLs that may contribute to a protective role of these lipoproteins.
These include the ability of HDLs to promote the efflux of cholesterol from mac-
rophages and foam cells in the artery wall and to anti-inflammatory/antioxidant
properties of these lipoproteins. The fact that the main apolipoprotein of HDLs,
apoA-I, plays a prominent role in each of these functions adds support to the view
that apoA-I should be measured as a component of the assessment of cardiovascu-
lar risk in humans (Barter and Rye 2006 ).
Results from recent epidemiological studies and statin trials suggest that apolipo-
protein B-100 (apoB), with or without apoA-I, is superior to LDL cholesterol in
predicting coronary events (Chan and Watts 2006 ). Measurements of apolipopro-
teins are internationally standardized, automated, cost-effective and more conve-
nient and precise than those for LDL cholesterol. ApoB may also be preferable to the
measurement of non-HDL cholesterol. Measurement of apolipoproteins (apoB and
possibly apoA-I) should be routinely added to the routine lipid profile (cholesterol,