What is the LP (Lipoprotein) PLA2 (Phospholipase A2) test?

Lipoprotein-Associated Phospholipase A2 (Lp-PLA2) Test

The Lp-PLA2 test is a cardiovascular biomarker that measures the activity or mass of lipoprotein-associated phospholipase A2, a proatherogenic enzyme that serves as a "second-line" marker for cardiovascular risk assessment, particularly useful in patients at intermediate risk. 1

What is Lp-PLA2?

Lp-PLA2 (also known as platelet-activating factor acetylhydrolase) is an enzyme:

• Produced by macrophages and lymphocytes
• Primarily bound to LDL cholesterol (with smaller amounts bound to HDL)
• Hydrolyzes oxidized phospholipids in LDL, generating inflammatory mediators
• Plays a critical role in atherogenesis and plaque inflammation
• Associated with increased cardiovascular risk independent of traditional risk factors 1, 2

Clinical Significance

Cardiovascular Risk Assessment

• Lp-PLA2 is associated with increased cardiovascular risk with an adjusted odds ratio of 1.60 (95% CI 1.36-1.89) 1
• Higher levels correlate with:
  • Advanced age
  • Male sex
  • Smoking status
  • LDL cholesterol levels
  • Inversely associated with HDL cholesterol 1
• Risk prediction remains significant even after adjusting for C-reactive protein and standard cardiovascular risk factors 1

Incremental Value in Risk Prediction

• Provides modest incremental risk prediction information beyond traditional risk factors
• Studies show statistically significant but small improvements in area under the curve (AUC):
  • ARIC study: 0.774 increased to 0.780
  • Rancho Bernardo study: 0.595 to 0.617 1

Clinical Application

When to Consider Testing

• Most appropriate for patients at intermediate cardiovascular risk
• May help refine risk assessment when traditional risk factors provide borderline results
• Particularly useful in patients with:
  • Metabolic syndrome
  • Diabetes
  • Intermediate Framingham risk score 1, 2

Limitations

• Considered a "second-line" marker for cardiovascular risk estimation
• Limited information about predictive capability in ethnic minorities (most studies conducted in whites of European ancestry)
• Ethnic differences in Lp-PLA2 concentrations have been observed (higher in white and Hispanic participants than in black participants) 1
• Test is more expensive compared to classical biological risk factors (blood glucose and lipids) 1

Therapeutic Implications

• Currently no evidence that Lp-PLA2 testing improves patient motivation or outcomes
• Lipid-lowering therapies (particularly statins) reduce Lp-PLA2 levels
• Specific Lp-PLA2 inhibitors have been developed and shown to lower Lp-PLA2 activity and inflammatory markers, but clinical benefit remains unproven 1, 2

Key Considerations

• Lp-PLA2 should not replace traditional cardiovascular risk assessment but can supplement it in specific cases
• Interpretation of Lp-PLA2 levels requires consideration of cardiac parameters and treatments (especially statins and ACE inhibitors/ARBs)
• The test provides additional value primarily in refining risk assessment for patients at moderate or undefined cardiovascular risk 1