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Lp-PLA2 (Lipoprotein-Associated Phospholipase A2)

Lp-PLA2 (Lipoprotein-Associated Phospholipase A2)

Test Summary

Lp-PLA2 (Lipoprotein-Associated Phospholipase A2)

  

Clinical Use

  • Assess risk of coronary artery disease

  • Assess risk of stroke

Clinical Background

Coronary artery disease is associated with the severity of atherosclerosis, which is an inflammatory disease. But although helpful for guiding treatment and improving prognosis, standard approaches for assessing a person’s risk do not include inflammatory markers.1 So, individuals with a moderate risk, as determined by standard approaches, may actually be at greater risk of a myocardial infarction or stroke than predicted.2 High-sensitivity C-reactive protein (hs-CRP) is a marker of systemic inflammation that can improve risk stratification; however, it is not specific for cardiovascular disease. On the other hand, lipoprotein-associated phospholipase A2 (Lp-PLA2) is a specific marker of vascular inflammation associated with atherosclerosis.3 Following production by inflammatory cells, this enzyme cleaves oxidized phospholipids, generating pro-inflammatory molecules and oxidized fatty acids.

Increased blood levels of Lp-PLA2 have been linked to increased risk for: 1) cerebral thrombosis,4 2)
first5 and recurrent6 coronary events, 3) adverse prognosis after acute coronary syndrome,7 and 4) cardiovascular disease associated with metabolic syndrome.8 A metaanalysis including more than 25 prospective studies found an approximate doubling of the risk for coronary artery disease and quadrupling of the risk for ischemic stroke when comparing Lp-PLA2 values in the top quintile versus the bottom quintile.9 The predictive value remained after adjustment for low-density lipoprotein (LDL)-cholesterol level and other established cardiovascular disease risk factors.9

A 2008 consensus panel recommended testing Lp-PLA2 as an adjunct to traditional risk factor assessment in individuals with moderate or high risk of cardiovascular disease as defined by Framingham risk scores.2 The panel found that an Lp-PLA2 level >200 ng/mL indicates an individual’s risk is actually higher than that determined using Framingham risk scores, and more intensive therapy is appropriate.2 For example, an individual with a moderate Framingham risk score and an elevated Lp-PLA2 may be reclassified as being at high risk. The LDL-cholesterol goal would then be reduced from <130 mg/dL to <100 mg/dL, and more intensive life-style changes would be recommended. Similarly, in individuals with an elevated Lp-PLA2 and high Framingham risk score, the LDL-cholesterol goal would be reduced from <100 mg/dL to <70 mg/dL.2 Though the consensus panel only recommended Lp-PLA2 measurement in moderate- or high-risk individuals, studies have shown that elevated Lp-PLA2 also predicts coronary artery disease and ischemic stroke in the general population.10,11

Subsequent to the 2008 consensus panel recommendations, other studies have shown that elevated Lp-PLA2 levels are predictive of cardiovascular events including myocardial infarction and ischemic stroke.12-14 Furthermore, a 2010 metaanalysis of 32 prospective studies showed a log-linear association between Lp-PLA2 level and risk of coronary artery disease and total vascular mortality.15 Lastly, studies have shown that the predictive value of Lp-PLA2 is independent of, and additive to, that of hs-CRP.4,5,9

Individuals Suitable for Testing2

  • Individuals with moderate risk of cardiovascular disease (≥2 risk factors and Framingham 10-year risk score ≤20%)

  • Individuals with high risk of cardiovascular disease (Framingham 10-year risk score >20%)

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

  • Individuals with moderate risk of stroke

Method

  • Enzyme-linked immunosorbent assay (ELISA) using 2 anti-Lp-PLA2 monoclonal antibodies to measure Lp-PLA2 concentration (mass, not enzyme activity)

  • Standardized using recombinant Lp-PLA2

  • Analytical sensitivity: 2.3 ng/mL

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

Interpretive Information

Increased Lp-PLA2 levels are associated with increased risk of cardiovascular disease and stroke. The preponderance of evidence suggests that a concentration <200 ng/mL is optimal, a concentration from 200-234 ng/mL is associated with a moderate risk of cardiovascular disease and stroke, and a concentration >234 ng/mL is associated with a high risk of cardiovascular disease and stroke.2,11,12,15 Risk is independent of age and gender. Patients with elevated levels may benefit from intensified lipid-lowering therapy and lifestyle changes.2

References

  1. Third report of the National Cholesterol Education Program (NCEP) expert panel on detection, evaluation, and treatment of high blood cholesterol in adults (Adult Treatment Panel III) final report. Circulation. 2002;106:3143-3421.

  2. 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.

  3. Zalewski A, Macphee C. Role of lipoprotein-associated phospholipase A2 in atherosclerosis: biology, epidemiology, and possible therapeutic target. Arterioscler Thromb Vasc Biol. 2005;25:923-331.

  4. Ballantyne CM, Hoogeveen RC, Bang H, et al. Lipoprotein-associated phospholipase A2, high-sensitivity C-reactive protein, and risk for incident ischemic stroke in middle-aged men and women in the Arthrosclerosis Risk in Communities (ARIC) study. Arch Intern Med. 2005;165:2479-2484.

  5. Koenig W, Khuseyinova N, Löwel H, et al. Lipoprotein-associated phospholipase A2 adds to risk prediction of incident coronary events by C-reactive protein in apparently healthy middle-aged men from the general population. Results from the 14-year follow-up of a large cohort from southern Germany. Circulation. 2004;110:1903-1908.

  6. 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

  7. Möckel M, Müller R, Vollert JO, et al. Lipoprotein-associated phospholipase A2 for early risk stratification in patients with suspected acute coronary syndrome: a multi-parameter approach. Clin Res Cardiol. 2007;96:604-612.

  8. 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.

  9. Corson MA, Jones PH, Davidson MH. Review of the evidence for the clinical utility of lipoprotein-associated phospholipase A2 as a cardiovascular risk marker. Am J Cardiol. 2008;101 (suppl):41F-50F.

  10. 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.

  11. Daniels LB, Laughlin GA, Sarno MJ, et al. Lipoprotein-associated phospholipase A2 is an independent predictor of incident coronary heart disease in an apparently healthy older population: The Rancho Bernardo Study. J Am Coll Cardiol. 2008;51:913-919.

  12. 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.

  13. 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.

  14. Robins SJ, Collins D, Nelson JJ, et al. Cardiovascular events with increased lipoprotein-associated  phospholipase A(2) and low high-density lipoprotein-cholesterol: The Veterans Affairs HDL Intervention Trial. Arterioscler Thromb Vasc Biol. 2008;28:1172-1178.

  15. Lp-PLA(2) Studies Collaboration,Thompson A, Gao P, Orfei L, et al. Lipoprotein-associated phospholipase A(2) and risk of coronary disease, stroke, and mortality: Collaborative analysis of 32 prospective studies. Lancet. 2010;375:1536-1544.
     

Content reviewed 06/2014

 

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