487artery disease. A genotype score of nine validated SNPs that are associated with
modulation in levels of LDL or HDL cholesterol is an independent risk factor for
incident cardiovascular disease (Kathiresan et al. 2008 ). The score does not improve
risk discrimination but modestly improves clinical risk reclassifi cation for individ-
ual subjects beyond standard clinical factors.
Fifteen genetic markers of twelve loci have been genotyped in three studies of
diabetic patients: the prospective Nurses’ Health Study, Health Professional
Follow-up Study and the cross-sectional Joslin Heart Study (Qi et al. 2011 ). Only
fi ve SNPs – rs4977574, rs12526453, rs646776, rs2259816, and rs11206510 –
showed directionally consistent associations with coronary heart disease (CHD) in
the three studies. A genetic risk score (GRS) was created by combining the risk
alleles of the fi ve signifi cantly associated loci. Prediction of CHD was signifi cantly
improved when the GRS was added to a model including clinical predictors in the
combined samples.
Testing in Coronary Heart Disease
In ischemic heart disease, the patient’s arteries have narrowed and the heart cannot
pump normally because blood fl ow (and thus oxygen) is often restricted to the heart
muscle. In nonischemic forms of the disease, the heart cannot pump normally
because the heart muscle has often enlarged for other reasons, such as physical
deformity or alcohol abuse. Both conditions can lead to cardiac arrest or more grad-
ual heart failure as the muscle weakens over time. Differentiation between the two
types is important for planning the management. The next step is to develop a test
that can be used in a clinical setting. Ischemic patients need to be monitored more
closely in case they develop drug resistance and require surgery to unblock clogged
arteries. Knowing which patients to treat and how closely to monitor them could
signifi cantly improve how well physicians manage the disease and, consequently,
improve health outcomes.
Lp-PLA2 (lipoprotein-associated phospholipase A2) is an enzyme that is impli-
cated in the vascular infl ammatory pathway that leads to plaque formation and ath-
erosclerosis. Previous hypotheses on the cause of coronary heart disease focused
around lipid accumulation within the arterial walls. Increasing evidence now sug-
gests that atherosclerosis is largely an infl ammatory disease. The MONICA
(MONItoring of trends and determinants in CArdiovascular disease) study showed
a statistically signifi cant relationship between elevated Lp-PLA2 and the risk of a
coronary event (Koenig et al. 2004 ). Among individuals in the MONICA popula-
tion, each standard deviation increase in Lp-PLA2 levels resulted in a 37 % increase
in the risk of a coronary event. This study also showed that Lp-PLA2 and C-reactive
protein, a biomarker of infl ammation, may be additive in their ability to predict risk
of coronary heart disease.
Routine cholesterol tests account for only about 50 % of the predictability in heart
disease risk. A test based on Vertical Auto Profi le (VAP, Atherotech Inc) technology
for density gradient ultracentrifugation, which directly measures the cholesterol
Role of Diagnostics in Personalized Management of Cardiovascular Disease