Written By Dr. Cheryl Burdette,
Director of Clinical Support & Education For Doctor's Choice
Markers Included on the Doctor’s Choice Comprehensive Cardiovascular Panel:
Lipoprotein-associated phospholipase A2 (Lp-PLA2) also known as platelet-activating factor acetylhydrolase (PAF-AH) is a phospholipase A2 enzyme. Its two main sources are Lp-PLA2 that is brought into the intima bound to LDL from circulation and that which is synthesized de novo by plaque inflammatory cells including macrophages, T cells, and mast cells. Lp-PLA2 has two main activities. First, it inactivates the prominent proinflammatory mediator PAF-AH. Second, Lp-PLA2 hydrolyzes oxidatively modified polyunsaturated fatty acids producing lysophosphatidylcholine and oxidized non-esterified fatty acids. OxNEFA have potent monocyte chemotactic activity and LysoPC upregulates inflammatory mediators, including cytokines, adhesion molecules and the chemotactic mediator MCP-1. Whereas the first activity may be considered antiatherogenic, the prevailing consensus is that Lp-PLA2 is positively associated with coronary disease. In the blood, it travels mainly with low-density lipoprotein (LDL). Only 20% of Lp-PLA2 travels with as high-density lipoprotein.
Lp-PLA2 is quite specific to cardiovascular disease. While triggered by white blood cells it is not increased or influenced by acute illness such as a cold or flu, as can occur with CRP. It is a reliable marker, and is only skewed in the case of very high HDL, or levels greater than 110. In terms of predicting a reoccurrence of heart disease, Lp-PLA2 is highly indicative. Even in patients deemed high risk, they only have a 5% chance of having a cardiovascular event in the next four to six years when Lp-PLA2 is in a low range. By measuring this marker at regular intervals one will know when plaques have become more stable and less likely to contribute to a heart attack or stroke. Lp-PLA2 modulates with the state of inflammation in the body, and therefore measuring it periodically allows one to capture a patient that begins to experience an increase in risk. Regular monitoring is important.
While the particle size of lipids is important, it is not the entire story. Particle size lets us know which lipid is more susceptible to oxidation. Lp-PLA2 lets us know when inflammation has triggered release of inflammatory enzymes that damage LDL. Understanding how resistant the lipid is as well as knowing how much inflammation is occurring to decrease plaque stability are both important. LDL can be elevated for years, but not until Lp-PLA2 becomes elevated is there a change that will decrease the stability of a plaque and increase the chance of it rupturing. PLA2 gives status of the health of the arterial wall and will allow detection of stabilized arterial plaque.
The National Heart Lung and Blood Institute’s Atherosclerosis Risk in Communities (ARIC) study, which involved more than 1,300 patients showed that individuals with high levels of Lp-PLA2 have twice the risk of atherosclerotic stroke over the next six to eight years compared with individuals with normal Lp-PLA2 levels. The study also found that individuals with high levels of both C-reactive protein and Lp-PLA2 had the highest risk for future coronary events and stroke, after adjusting for traditional risk factors.
Although the units measuring Lp-PLA2 levels are different from those used to measure total cholesterol, the ranges associated with different levels of risk are similar. Predictive Lp-PLA2 levels for acute cardiovascular events are:
Low risk: <200 ng/mL
Borderline risk: 200-235 ng/mL
High risk: >235 ng/mL
Levels over 200 or 220 ng/mL are very highly correlated with endothelial dysfunction, which in turn is highly correlated with cardiovascular events and predisposition to atherosclerosis. This is particularly pronounced in African American females.
Lp-PLA2 testing can help physicians determine whether someone is at the high end of the low-risk group or at moderate risk. If they have a low Lp-PLA2, less aggressive management strategies may be indicated, while those with a higher level of Lp-PLA2 would more likely need intensive treatment, and frequent monitoring.
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