Diagnostic Tests

What Physicians Need to Know

PLAC Test for Lp-PLA2 Activity to Predict Coronary Heart Disease

 

Am Fam Physician. 2020 Jan 1;101(1):44-46.

The PLAC test is a blood test used to measure serum activity of lipoprotein-associated phospholipase A2 (Lp-PLA2), an enzyme that breaks down oxidized low-density lipoprotein in the vascular wall. Higher levels of Lp-PLA2 activity are thought to promote atherosclerotic plaque formation.1 The PLAC test was approved by the U.S. Food and Drug Administration for this indication in 2014.2

Accuracy

In a prospective multiethnic cohort of 5,456 asymptomatic patients followed over a median of 10.2 years, Lp-PLA2 activity was associated with an increased risk of incident cardiovascular disease. Patients included persons with baseline subclinical vascular disease (n = 3,228 [450 events]; hazard ratio [HR] = 1.17 [95% CI, 1.06 to 1.30]) and without subclinical disease (n = 2,228 [66 events]; HR = 1.30 [95% CI, 1.01 to 1.68]), as determined by coronary artery calcium score and carotid intima-medial thickness. These associations persisted after adjustment for age, sex, race, and ethnicity. However, when further adjusted for body mass index, diabetes mellitus, smoking status, education, systolic blood pressure, use of antihypertensive medications, total and high-density lipoprotein cholesterol, use of lipid-lowering medications, and C-reaction protein, the associations were no longer significant.3 The analysis suggested that Lp-PLA2 activity does not add significant information to the standard cardiovascular risk assessment.

Contrast this with a 2010 collaborative analysis of 18 prospective studies of Lp-PLA2 activity. A subanalysis (12 studies), representing a heterogeneous population of 41,121 patients with and without a history of vascular disease and a total of 3,963 fatal and nonfatal cardiovascular events, showed an increased risk of coronary heart disease (CHD) per one standard deviation higher Lp-PLA2 activity (risk ratio [RR] = 1.10 [95% CI, 1.05 to 1.16]). This association persisted after adjusting for standard risk factors. Other subanalyses showed a similar risk-adjusted association between Lp-PLA2 activity and vascular death (n = 38,105 [nine studies; 2,689 events]; RR = 1.16 [95% CI, 1.09 to 1.24]) and nonvascular death (n = 37,084 [eight studies; 2,795 events]; RR = 1.10 [95% CI, 1.04 to 1.17]).4

There is less evidence to support risk assessment using the manufacturer’s suggested binary cut-off of 225 nmol per minute per mL or higher to define high Lp-PLA2 activity.5,6 The validation study referenced on the test website and package insert is a published abstract containing only a summary of data from a subanalysis case-cohort study (n = 5,025; including 771 participants with incident CHD and 4,254 without CHD) sampled from the REGARDS (Reasons for Geographic and Racial Differences in Stroke) trial.7,8 The abstract reports HRs for CHD using sex-specific cut-offs for elevated Lp-PLA2 activity (defined as greater than 80th percentile): 250 nmol per minute per mL for men and 200 nmol per minute per mL for women. Given that statistically significant differences in Lp-PLA2 activity between men and women have been demonstrated elsewhere, it is unclear why the PLAC test does not also have sex-specific cut-offs.9,10

A subanalysis of the JUPITER (Justification for the Use of Statins in Prevention: an Intervention Trial Evaluating Rosuvastatin) trial suggested that the PLAC test

Address correspondence to Jennifer G. Chang, MD, at jennifer.chang@usuhs.edu. Reprints are not available from the author.

Author disclosure: No relevant financial affiliations.


The opinions and assertions expressed herein are those of the author and do not necessarily reflect the official policy or position of the Uniformed Services University of the Health Sciences or the Department of Defense.

References

show all references

1. Epps KC, Wilensky RL. Lp-PLA2- a novel risk factor for high-risk coronary and carotid artery disease. J Intern Med. 2011;269(1):94–106....

2. U.S. Food and Drug Administration. 510(k) substantial equivalence determination decision summary assay only template. Accessed April 14, 2019. https://www.accessdata.fda.gov/cdrh_docs/reviews/K141575.pdf

3. Garg PK, McClelland RL, Jenny NS, et al. Lipoprotein-associated phospholipase A2 and risk of incident cardiovascular disease in a multi-ethnic cohort: the multi-ethnic study of atherosclerosis. Atherosclerosis. 2015;241(1):176–182.

4. Thompson A, Gao P, Orfei L, et al. Lipoprotein-associated phospholipase A2 and risk of coronary disease, stroke, and mortality: collaborative analysis of 32 prospective studies. Lancet. 2010;375(9725):1536–1544.

5. PLAC Activity. Enhanced cardiovascular risk assessment from your laboratory. Introducing the PLAC test for Lp-PLA2 activity (PLAC activity). Accessed online April 1, 2019 – May 25, 2019. http://www.placactivity.com/laboratory-professionals

6. Lp-PLA2 activity assay [package insert]. diaDexus, Inc.; 2019.

7. 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. Atherosclerosis. 2015;241(1):e9.

8. Howard VJ, McClure LA, Meschia JF, et al. High prevalence of stroke symptoms among persons without a diagnosis of stroke or transient ischemic attack in a general population: the REasons for Geographic and Racial Differences in Stroke (REGARDS) study. Arch Intern Med. 2006;166(18):1952–1958.

9. De Stefano A, Mannucci L, Massoud R, et al. Performance characteristics of lipoprotein-associated phospholipase A2 activity assay on the Dimension Vista analyser and preliminary study of a healthy Italian population. Biochem Med (Zagreb). 2017;27(3):030701.

10. Acevedo M, Varleta P, Kramer V, et al. Comparison of lipoprotein-associated phospholipase A2 and high sensitive C-reactive protein as determinants of metabolic syndrome in subjects without coronary heart disease: in search of the best predictor. Int J Endocrinol. 2015;2015:934681.

11. Ridker PM, MacFadyen JG, Wolfert RL, et al. Relationship of lipoprotein-associated phospholipase A2 mass 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(5):877–886.

12. White HD, Simes J, Stewart RAH, 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(5):e000360.

13. Hassan M. STABILITY and SOLID-TIMI 52: Lipoprotein-associated phospholipase A2 (Lp-PLA2) as a biomarker or risk factor for cardiovascular diseases. Glob Cardiol Sci Pract. 2015;2015:6.

14. Healthcare Bluebook. Lipoprotein-associated phospholipase A2. Accessed May 22, 2019. https://www.healthcarebluebook.com/page_ProcedureDetails.aspx?cftid=L1203&g=Lipoprotein-Associated%20Phospholipase%20A2&directsearch=true

15. Centers for Medicare and Medicaid Services. Clinical laboratory fee schedule. Accessed April 14, 2019. https://go.cms.gov/36hRPFG

16. Arnett DK, Blumenthal RS, Albert MA, et al. 2019 ACC/AHA guideline on the primary prevention of cardiovascular disease: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. J Am Coll Cardiol. 2019;74(10):e177–e232.

17. U.S. Preventive Services Task Force. Final recommendation statement: statin use for the primary prevention of cardiovascular disease in adults: preventive medication. November 2016. Accessed April 14, 2019. https://www.uspreventiveservicestaskforce.org/Page/Document/RecommendationStatementFinal/statin-use-in-adults-preventive-medication1

This series is coordinated by Kenny Lin, MD, MPH, deputy editor.

 

 

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