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CHRONICLES IN CHOLESTEROLAn Insiders Guide to State of The Art
Cardiovascular
Prevention Laboratory Testing Available From
Lp-PLA2 2 - The PLAC Test
What is the biomarker Lp-PLA2 2?
Lp-PLA2 is an enzyme that is found in LDL particles, as well as
on
HDL particles, lipoprotein (a) [Lp(a)], and triglyceride-rich
remnant
lipoproteins. It is produced by macrophages, monocytes, T
lymphocytes, and mast and liver cells. Lp-PLA2 activity has
been
shown to be up-regulated in atherosclerotic lesions and in
rupture-
prone fibrous caps. The Lp-PLA2 enzyme hydrolyzes oxidized
phospholipids on LDL particles within the arterial intima.
This
hydrolysis reaction produces two highly inflammatory
mediators,
lysophosphatidylcholine and oxidized fatty acids. These
products
result in a cascade of events that have been linked to
atherosclerotic plaque formation such as the up-regulation
of
adhesion molecules, expression of cytokines, and the
production
of foam cells through monocyte recruitment. Foam cells
aggregate to form the fatty streak of atherosclerosis.
CRP is an acute-phase reactant, and its elevation can be
caused
by acute infections, chronic inflammatory conditions and
obesity,
as well as certain medications such as oral estrogens. Lp-PLA2,
onthe other hand, appears to be related specifically to
vascular
inflammation and shows significantly less variability than
CRP.
Lp-PLA2 as a significant predictor of CV events and stroke.
Because the enzyme is produced in atherosclerotic plaques and
is
specifically linked to plaque inflammation, it is thought
that
measurement of this inflammatory biomarker might help
predict
patients at increased risk for these events.
In both primary and secondary prevention trials, elevations of
Lp-
PLA2 after multuivariate adjustment for traditional risk
factors,
predict Cardiovascular events and stroke independent and
complimentary to C reactive protein measurement.
December, 2011 VOL 1 ISSUE 5
In This Issue:Lipoprotein Phospholipase A2
In both primary and secondary
prevention trials, elevations of
LPPLA2 after multivariate
adjustment for traditional risk
factors, predict cardiovascular
events and stroke independent and
complimentary to C reactive protein
measurement.
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LpPLA2
y In the Atherosclerosis Risk in Communities Study
orARIC Study, the group with the highest elevations of
both Lp-PLA2 and CRP had a 4 fold higher incidence of
a CHD events and a 11 fold higher incidence of stroke.
y In separate studies, measurement of both LPPLA2 mass
and activity were both highly correlated with increased
risk of CHD events and stroke.
y The association between baseline Lp-PLA2and CHD risk
was similar in magnitude to those for non-HDL-C and
systolic blood pressure for CHD risk.
y Intermediate -risk patients with an elevated Lp-
PLA2 level (which was defined as >200 ng/mL) should
be reclassified as high risk, with a appropriateadjustment of
their LDL goal.
y In patients with known CHD or CHD risk equivalent,
such as diabetes or ischemic stroke, An elevated Lp-
PLA2 would up-classify these patients to the very high-
risk category.
y In preclinical studies, inhibition of Lp-PLA2 attenuates
the inflammatory response and slows atherosclerotic
plaque progression.
y Lipid-altering medications, including statins,
fenofibrate,ezetimibe, and prescription omega-3 fatty acids, as
well
as weight loss, have been shown to reduce inflammatory
markers, including Lp-PLA2
y To address the utility of lowering LPPLA2 directly, the
ongoing STABILITY trial will be address this issue. This
trial will add a specific LPPLA2 inhibitor, Darapladib to
patients aready on Atorvastatin therapy and assess
whether the additional lowering of LPPLA2 wil have
clinical benefit.
y The PLAC (Lp-PLA2) Test is the ONLY blood test
cleared by the FDA to aid in assessing risk for both
coronary artery disease and stroke.
By Spencer Kroll MD PhD
National Lipid Association Board Certified
Board of Directors, Northeast Lipid Association
December, 2011 VOL 1 ISSUE 5
