Lipoprotein - associated phospholipase A2 (Lp - PLA2) and cardiovascular risk

• lipoprotein-associated phospholipase A2 (Lp-PLA2) is an inflammatory biomarker that offers several advantages relative to other markers, including specificity for vascular inflammation, minimal biovariability, and stability in states of myocardial ischemia
• Lp-PLA2
  • is a secreted calcium-independent member of the phospholipase A2 superfamily produced mainly, if not exclusively, by monocytes, macrophages, T-lymphocytes and mast cells
  • Lp-PLA2 activity has been shown to be upregulated in atherosclerotic lesions - this association is particularly in more complex plaques with co-localising with macrophages
  • however the positive association of plasma Lp-PLA2 with CHD is not fully explained by this enhanced expression
    • for example, unlike Lp-PLA2, elevated CRP levels that reflect ongoing inflammation were not identified in WOSCOPS as a strong independent risk factor of future cardiovascular disease
      • also Lp-PLA2 does play an active role during the oxidation of LDL
    • Lp-PLA2 levels are not solely a reflection of atherosclerotic burden - thus Lp-PLA2 is differentiated from other inflammatory components of atherosclerosis
    • about two-thirds of Lp-PLA2 in plasma resides on LDL, with the remainder distributed across high-density lipoprotein and very low-density lipoprotein (1)
      • Lp-PLA2 and oxidised LDL
        • one of the consequences of LDL oxidation is the rapid degradation of oxidised phosphatidylcholines generating substantial quantities of lysophosphatidylcholine (lyso-PC) and free oxidised fatty acids - the cleavage of oxidised phosphatidylcholines within modified LDL-particles is carried out solely by Lp-PLA2
          • Lp-PLA2 remains latent until LDL undergoes oxidative damage
          • lyso-PC and free oxidised fatty acids highly effective inflammatory mediators capable of attracting monocytes and exacerbating the atherogenic process
• observational studies carried out in primary prevention settings have shown a relationship between Lp-PLA2 and cardiovascular risk, although the magnitude of the association has varied
• with respect to secondary prevention setting
  • among community subjects presenting with MI, increased Lp-PLA2 levels measured early after MI are strongly and independently associated with mortality and provide incremental value in risk discrimination over traditional predictors (2)
  • increased concentrations of Lp-PLA2 predict future cardiovascular events in patients with manifest CHD independent of a variety of potential risk factors including markers of inflammation, renal function, and hemodynamic stress (3)

Reference:

1. Atherosclerosis 2000; 150:413-9.
2. Gerber Y et al. Lipoprotein-associated phospholipase A2 and prognosis after myocardial infarction in the community. Arterioscler Thromb Vasc Biol. 2006 Nov;26(11):2517-22
3. Koenig W et al. Lipoprotein-associated phospholipase A2 predicts future cardiovascular events in patients with coronary heart disease independently of traditional risk factors, markers of inflammation, renal function, and hemodynamic stress. Arterioscler Thromb Vasc Biol. 2006 Jul;26(7):1586-93. Epub 2006 Apr 20.