From the Guidelines
Lp-PLA2 activity refers to the functional capacity of the enzyme to hydrolyze oxidized phospholipids on LDL particles, producing pro-inflammatory mediators that contribute to atherosclerotic plaque formation and instability. Lipoprotein-Associated Phospholipase A2 (Lp-PLA2) is an enzyme produced by inflammatory cells that circulates in the bloodstream bound primarily to LDL cholesterol particles. Lp-PLA2 activity is considered a marker of vascular inflammation and has been associated with increased risk of cardiovascular events, including heart attacks and strokes, as reported in studies such as 1 and 1. The enzyme plays a direct role in promoting inflammation within arterial walls by generating inflammatory mediators at sites of developing atherosclerotic plaques.
Some key points about Lp-PLA2 activity include:
- It is a proatherogenic enzyme produced by macrophages and lymphocytes, as described in 1.
- Lp-PLA2 hydrolyzes oxidized phospholipids in LDL, leading to the generation of lysophosphatidylcholine, oxidized nonesterified fatty acids, and other active phospholipids and inflammatory mediators.
- Elevated Lp-PLA2 activity is associated with increased risk of cardiovascular events, including heart attacks and strokes, with a modest incremental risk prediction information, as indicated in 1.
- Lp-PLA2 activity can be measured through blood tests, with higher levels potentially indicating greater cardiovascular risk independent of traditional risk factors.
- While some medications like statins may indirectly lower Lp-PLA2 levels, specific Lp-PLA2 inhibitors have been studied but have not demonstrated significant clinical benefit in reducing cardiovascular events despite lowering the enzyme's activity, as noted in 1.
Overall, elevated Lp-PLA2 activity is a significant risk factor for cardiovascular events, and its measurement may be useful in assessing cardiovascular risk, particularly in intermediate-risk patients, as suggested by 1 and 1.
From the Research
LP PLA2 Activity
LP PLA2, or Lipoprotein-Associated Phospholipase A2, is a vascular-specific inflammatory marker that plays a significant role in the development of atherosclerosis and cardiovascular disease. The following points summarize the key aspects of LP PLA2 activity:
- LP PLA2 is associated with low-density lipoprotein in plasma and is recognized as a risk marker in primary or secondary prevention of atherosclerosis 2.
- Elevated LP PLA2 levels are associated with an increased risk for cardiovascular events, even after multivariable adjustment for traditional risk factors 2, 3.
- LP PLA2 is involved in the hydrolysis of phospholipids in the arterial wall, contributing to the development of unstable disease 3.
- Inhibition of LP PLA2 with darapladib has been shown to reduce the development of advanced coronary atherosclerosis and decrease plaque area 4.
- Statin treatment can reduce LP PLA2 levels in both plasma and atherosclerotic plaques, attenuating the local inflammatory response and improving plaque stability 2, 5.
Mechanism of Action
The mechanism of LP PLA2 activity involves:
- The production of LP PLA2 by inflammatory cells, which then binds to LDL and other lipoproteins 3.
- The facilitation of hydrolysis of phospholipids in the arterial wall, leading to the development of atherosclerosis 3.
- The inhibition of LP PLA2 by darapladib, which reduces the development of advanced coronary atherosclerosis and decreases plaque area 4.
Clinical Implications
The clinical implications of LP PLA2 activity include:
- The use of LP PLA2 as a risk predictor for coronary and carotid events 3.
- The potential clinical benefit of pharmacologic inhibition of LP PLA2 in reducing the inflammatory nature of atherosclerosis and plaque vulnerability 5.
- The association of LP PLA2 antigen with risk of future congestive heart failure in older people, independent of CHF and coronary risk factors 6.