The big picture: Lp-PLA2 (Lipoprotein-associated Phospholipase A2) is an enzyme created by immune cells called macrophages and monocytes and are bound to lipoproteins. It is a specific marker for vascular inflammation. Those with high Lp-PLA2 are up to 11x more likely to have a stroke.

Lp-PLA2 participates in the breakdown of certain atherogenic lipoproteins.

Lipoproteins are particles that also transport cholesterol and triglycerides in the bloodstream.
About 70-80% of Lp-PLA2 are bound to a type of lipoprotein called LDL (low-density lipoprotein) and the remaining resides on HDLs (high-density lipoprotein), lipoprotein (a), and triglyceride-rich remnant lipoproteins.
When the LDLs penetrate the arterial walls, Lp-PLA2 breaks down the LDLs and releases pro-inflammatory and pro-atherogenic (plaque forming) metabolites.

Lp-PLA2 determines risk for heart disease and stroke in otherwise apparently healthy individuals.

The Rotterdam Study (n=7,983) showed that elevation in Lp-PLA2 activity confers approximately a 2-fold increase in both first and recurrent strokes.
A meta-analysis of 32 prospective studies (n=80,000) found a one standard deviation increment in Lp-PLA2 activity from baseline meant a 10-11% increased risk for coronary heart disease, 8-14% increased risk for stroke and 13-16% increased risk for mortality.

Elevated levels of both Lp-PLA2 and {{35|hs-CRP}} increases the risk of heart disease and stroke by 4x-11x.

hs-CRP is a non-specific marker for inflammation.
This increased risk for cardiovascular disease occurs even for individuals with low or moderately elevated LDL cholesterol.
Notably, in the ARIC Study (n=15,792), when both Lp-PLA2 and CRP were in the top tertile, the risks for coronary heart disease events and stroke increased 4-fold and 11-fold, respectively, compared with those in the lowest tertile for both markers.

Pharmacological lowering of Lp-PLA2 activity has not shown to reduce cardiovascular events but reducing inflammation is still important. In particular, Darapladib is a selective inhibitor of Lp-PLA2 that has been evaluated as a new therapeutic drug.

In two large trials (STABILITY trial and SOLID-TIMI study), while Darapladib reduced Lp-PLA2 levels by 66% and 65%, respectively, it failed to reduce coronary events compared with placebo.
These trials had limitations but at this time there are no treatments that are recommended at this time to singularly target Lp-PLA2.
But treatments aimed at reducing inflammation in general (e.g. dietary modification, omega-3 fatty acid supplementation, smoking cessation) are still important.