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Lp-PLA2 Activity

Lp-PLA2 Activity

Test Summary

Lp-PLA2 Activity

  

Clinical Use

  • Assess risk of coronary artery disease

  • Assess risk of stroke

Clinical Background

Lipoprotein-associated phospholipase A2 (Lp-PLA2) is an enzymatic, specific marker of atherosclerosis-related vascular inflammation.1,2 Lp-PLA2 accumulates in atherosclerotic plaques and is believed to contribute to plaque development and rupture by cleaving oxidized phospholipids, which produces pro-inflammatory molecules and oxidized fatty acids.2

Lp-PLA2 levels in blood can be determined by measuring concentration (ie, mass) or enzyme activity. Enzyme activity is believed to be superior as activity values are less prone to variability from sample handling and preparation, are more reproducible,3 and are not affected by the presence of inactive enzyme. Mass and activity values are not interchangeable. Additionally, activity levels must be interpreted in light of the cut point used by each specific laboratory, due to method differences.

Increased Lp-PLA2 activity has been linked to increased risk for: 1) first4-6 and recurrent7 coronary events; 2) adverse prognosis after acute coronary syndrome8; 3) stroke9; 4) cardiovascular disease associated with metabolic syndrome10; and 5) peripheral arterial disease.11 Individuals with elevated Lp-PLA2 activity are twice as likely to experience a myocardial infarction, coronary revascularization, and coronary heart disease-related death at 5 years after identification of elevated Lp-PLA2 activity.6 Similarly, they are almost twice as likely to develop coronary heart disease at 7 years, regardless of non-high–density lipoprotein (HDL) cholesterol levels.9 The predictive value of Lp-PLA2 activity is independent of, and additive to, that of hs-CRP.5,7

A 2008 consensus panel recommended Lp-PLA2 testing as an adjunct to traditional risk factor assessment in individuals with moderate or high risk of cardiovascular disease, as defined by Framingham risk scores.1 The panel found that individuals with an elevated Lp-PLA2 level have a higher risk of cardiovascular disease than that determined using Framingham scores, and more intensive therapy is appropriate.1 Though the 2008 panel only recommended Lp-PLA2 measurement in moderate- or high-risk individuals, elevated activity also predicts coronary artery disease and ischemic stroke in the general population.9 The 2013 ACC/AHC Guideline on the Assessment of Cardiovascular Risk, however, did not review the use of Lp-PLA2 and thus offered no opinion regarding its use in risk stratification.12

Individuals Suitable for Testing

  • Individuals with moderate to high risk of cardiovascular disease

  • Individuals with coronary artery disease or risk equivalents (ie, symptomatic carotid artery disease, peripheral artery disease, abdominal aortic aneurysm, diabetes mellitus)

  • Individuals with moderate to high risk of stroke

Method

  • Enzymatic reaction dependent on Lp-PLA2 activity; results calculated based on substrate concentration before and after reaction

  • Analytical sensitivity: 5 nmol/min/mL

  • Aliases: lipoprotein-associated phospholipase A2, platelet-activating factor acetylhydrolase (PAF-AH)

Interpretive Information

Individuals with elevated Lp-PLA2 activity are at an increased risk of coronary artery disease and stroke. These patients may benefit from intensified lipid-lowering therapy, blood pressure control, and lifestyle changes.1

Note that statin therapy has been shown to decrease Lp-PLA2 activity in select patient populations.8,13 Early data show that this reduction in activity may decrease the risk of coronary heart disease events.14

References

  1. Davidson MH, Corson MA, Alberts MJ, et al. Consensus panel recommendation for incorporating lipoprotein-associated phospholipase A2 testing into cardiovascular disease risk assessment guidelines. Am J Cardiol. 2008;101(suppl):51F-57F.

  2. Gonçalves I, Edsfeldt A, Ko NY, et al. Evidence supporting a key role of Lp-PLA2-generated lysophosphatidylcholine in human atherosclerotic plaque inflammation. Arterioscler Thromb Vasc Biol. 2012;32:1505-1512.

  3. Donato LJ, Meeusen JW, Callanan H, et al. Advantages of the lipoprotein-associated phospholipase A2 activity assay. Clin Biochem. 2016;49:172-175.

  4. Tsimikas S, Willeit J, Knoflach M, et al. Lipoprotein-associated phospholipase A2 activity, ferritin levels, metabolic syndrome, and 10-year cardiovascular and non-cardiovascular mortality: Results from the Bruneck study. Eur Heart J. 2009;30:107-115.

  5. Jenny NS, Solomon C, Cushman M, et al. Lipoprotein-associated phospholipase A(2) (Lp-PLA(2)) and risk of cardiovascular disease in older adults: Results from the Cardiovascular Health Study. Atherosclerosis. 2010;209:528-532.

  6. Cushman M, Judd S, Kissela B, et al. Lipoprotein-associated phospholipase A2 (Lp-PLA2) activity and coronary heart disease risk in a biracial cohort: The reasons for geographic and racial differences in stroke (REGARDS) cohort [abstract EAS-0541]. Atherosclerosis. 2015; 241: e1-e31

  7. Koenig W, Twardella D, Brenner H, 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;26:1586-1593.

  8. O'Donoghue M, Morrow DA, Sabatine MS, et al. Lipoprotein-associated phospholipase A2 and its association with cardiovascular outcomes in patients with acute coronary syndromes in the PROVE IT-TIMI 22 (PRavastatin Or atorVastatin Evaluation and Infection Therapy-Thrombolysis In Myocardial Infarction) trial. Circulation. 2006;113:1745-1752.

  9. Oei HH, van der Meer IM, Hofman A, et al. Lipoprotein-associated phospholipase A2 activity is associated with risk of coronary heart disease and ischemic stroke: The Rotterdam Study. Circulation. 2005;111:570-575.

  10. Persson M, Hedblad B, Nelson JJ, et al. Elevated Lp-PLA2 levels add prognostic information to the metabolic syndrome on incidence of cardiovascular events among middle-aged nondiabetic subjects. Arterioscler Thromb Vasc Biol. 2007;27:1411-1416.

  11. Garg PK, Arnold AM, Hinckley Stukovsky KD, et al. Lipoprotein-associated phospholipase A2 and incident peripheral arterial disease in older adults: The Cardiovascular Health Study. Arterioscler Thromb Vasc Biol. 2016;36:750-756.

  12. Goff DC Jr, Lloyd-Jones DM, Bennett G, et al. 2013 ACC/AHA guideline on the assessment of cardiovascular risk: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation. 2014;129:S49-S73.

  13. Ridker PM, MacFadyen JG, Wolfert RL, et al. Relationship of lipoprotein-associated phospholipase A₂mass and activity with incident vascular events among primary prevention patients allocated to placebo or to statin therapy: an analysis from the JUPITER trial. Clin Chem. 2012;58:877-886.

  14. White HD, Simes J, Stewart RA, et al. Changes in lipoprotein-associated phospholipase A2 activity predict coronary events and partly account for the treatment effect of pravastatin: results from the Long-Term Intervention with Pravastatin in Ischemic Disease study. J Am Heart Assoc. 2013;2:e000360. doi: 10.1161/JAHA.113.000360.
     

This test was developed and its analytical performance characteristics have been determined by Quest Diagnostics Nichols Institute. It has not been cleared or approved by the FDA. This assay has been validated pursuant to the CLIA regulations and is used for clinical purposes.

Content reviewed 09/2016

 

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