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MP 2.04.32 Measurement of Lipoprotein-Associated Phospholipase A2 in the Assessment of Cardiovascular Risk

Medical Policy    
Section
Medicine 
Original Policy Date
10/9/03
Last Review Status/Date
Reviewed with literature search/6:2014
Issue
6:2014
  Return to Medical Policy Index

Disclaimer

Our medical policies are designed for informational purposes only and are not an authorization, or an explanation of benefits, or a contract.  Receipt of benefits is subject to satisfaction of all terms and conditions of the coverage.  Medical technology is constantly changing, and we reserve the right to review and update our policies periodically. 


Description 

Lipoprotein-associated phospholipase A2 (Lp-PLA2), also known as platelet-activating factor acetylhydrolase, is an enzyme that hydrolyzes phospholipids and is primarily associated with low-density lipoproteins (LDLs). Accumulating evidence has suggested that Lp-PLA2 is a biomarker of coronary artery disease (CAD) and may have a proinflammatory role in the progression of atherosclerosis.

Background

LDLs have been identified as the major atherogenic lipoproteins and have long been identified by the National Cholesterol Education Project (NCEP) as the primary target of cholesterol-lowering therapy. LDL particles consist of a surface coat composed of phospholipids, free cholesterol, and apolipoproteins, surrounding an inner lipid core composed of cholesterol ester and triglycerides. Traditional lipid risk factors such as low-density lipoprotein-cholesterol (LDL-C), while predictive on a population basis, are weaker markers of risk on an individual basis. Only a minority of subjects with elevated LDL and cholesterol levels will develop clinical disease, and up to 50% of cases of coronary artery disease (CAD) occur in subjects with ‘normal’ levels of total and LDL-C. Thus, there is considerable potential to improve the accuracy of current cardiovascular risk prediction models.

Lp-PLA2, also known as platelet-activating factor acetylhydrolase, is an enzyme that hydrolyzes phospholipids and is primarily associated with LDLs. Accumulating evidence has suggested that Lp-PLA2 is a biomarker of CAD and may have a proinflammatory role in the progression of atherosclerosis. The recognition that atherosclerosis represents, in part, an inflammatory process has created considerable interest in measurement of proinflammatory factors as part of cardiovascular disease risk assessment.

Regulatory Status

The U.S. Food and Drug Administration (FDA) cleared for marketing an enzyme-linked immunosorbent assay test, the PLAC test (diaDexus, San Francisco, CA), to measure levels of Lp-PLA2. FDA product code: NOE.


Policy

Measurement of lipoprotein A enzyme is a distinct laboratory test. Genetic testing for lipoprotein(s) variants is addressed in Policy No. 2.04.70.

Measurement of lipoprotein-associated phospholipase A2 (Lp-PLA2) is considered investigational.


Policy Guidelines

Effective January 1, 2007, there is a specific CPT code for this test:

83698: Lipoprotein-associated phospholipase A2 (Lp-PLA2).


Benefit Application 
BlueCard/National Account Issues

State or federal mandates (e.g., FEP) may dictate that all FDA-approved devices may not be considered investigational and thus these devices may be assessed only on the basis of their medical necessity. 


Rationale 

This policy was created in October 2003 and updated periodically with literature reviews. The most recent update with literature review covers the period from May 2013 through May 12, 2014.

A large body of literature has accumulated on the utility of risk factors in the prediction of future cardiac events. The evidence reviewed for this policy statement consists of large, prospective cohort studies that have evaluated the association of lipoprotein-associated phospholipase A2 (Lp-PLA2) with cardiovascular outcomes. A smaller amount of literature is available on the utility of Lp-PLA2 as a treatment target.

The National Cholesterol Education Program (NCEP) ATP-III guidelines(1) document notes that to determine their clinical significance, the emerging risk factors should be evaluated against the following criteria to determine their clinical significance:

  • Significant predictive power that is independent of other major risk factors
  • A relatively high prevalence in the population (justifying routine measurement in risk assessment)
  • Laboratory or clinical measurement must be widely available, well standardized, inexpensive, have accepted population reference values, and be relatively stable biologically.
  • Preferable, but not necessarily, modification of the risk factor in clinical trials will have shown reduction in risk.

A 2002 TEC Assessment(2) summarized the steps necessary to determine utility of a novel cardiac risk factor. Three steps were required:

  • Standardization of the measurement of the risk factor
  • Determination of its contribution to risk assessment. As a risk factor, it is important to determine whether the novel risk factor […] independently contributes to risk assessment compared with established risk factors.
  • Determination of how the novel risk assessment will be used in the management of the patient, compared with standard methods of assessing risk, and whether any subsequent changes in patient management result in an improvement in patient outcome.

Is the measurement of Lp-PLA2 standardized?

According to the FDA’s Summary of Safety and Effectiveness for the diaDexus’ lipoprotein-associated phospholipase A2 (Lp-PLA2) assay, the intra-assay precision for the assay was 7% coefficient of variability (CV), and the inter-assay precision was 9% CV, with a detection limit of 1.2 ng/mL. Reference intervals for the Lp-PLA2 assay were calculated from samples for 251 apparently healthy males and 174 apparently healthy females aged 40 to 70 years; the reference interval calculated from the samples (central 90%) was determined to be 120 to 342 ng/mL for females and 131 to 376 ng/mL for males.(3) FDA concluded that the assay demonstrated acceptable analytical performance.

Is Lp-PLA2 an independent risk factor for cardiovascular disease?

Lp-PLA2 as a predictor of cardiovascular disease.

Results of numerous, large-scale observational studies have examined whether Lp-PLA2 is an independent risk factor for cardiovascular disease. Some of these observational studies have been evaluated in systematic reviews and meta-analyses. A representative sample of some of the larger studies is given next.

Systematic Reviews. Several systematic reviews and meta-analyses have summarized the association between Lp-PLA2 and cardiovascular disease in general populations.

The Emerging Risk Factors Collaboration performed a patient-level meta-analysis of the association of novel lipid risk factors with cardiovascular risk.(4) Records from 37 prospective cohort studies enrolling 165,544 participants were combined to predict cardiovascular risk over a median follow-up of 10.4 years. The authors examined the independent association of markers with cardiovascular risk and the ability to reclassify risk into clinically relevant categories. For Lp-PLA2, there were 11 studies enrolling 32,075 participants that measured this factor. Overall, Lp-PLA2 was an independent risk factor for cardiovascular events with a hazard ratio (HR) of 1.12 (95% confidence interval [CI], 1.09 to 1.21) for each 1 SD increase in Lp-PLA2 activity. There was no significant improvement in risk reclassification following the addition of Lp-PLA2 to the reclassification model, with a net reclassification improvement of 0.21 (-0.45 to 0.86). The net reclassification improvement crossing 0.0 indicates that the addition of Lp-PLA2 to the model may result in either improvement or worsening of reclassification.

A number of systematic reviews have been published that summarize the observational studies on the association of Lp-PLA2 and CV disease.(5-7) For example, Garza et al(5) reviewed 14 observational studies enrolling 20,549 patients. This study reported the predictive ability of Lp-PLA2 levels for CV disease after adjustment for traditional cardiac risk factors. The combined odds ratio (OR) for an elevated Lp-PLA2 was reported as 1.60 (95% CI, 1.36 to 1.89) for the development of future cardiac events. A patient-level meta-analysis(6) evaluated the association between Lp-PLA2 levels, CAD, stroke, and mortality. A total of 79,036 participants from 32 prospective studies were included in this report. There were significant associations found between Lp-PLA2 and all 3 outcome measures. For every 1 SD increase in Lp-PLA2 levels, the risk ratio (RR) adjusted for conventional risk factors was 1.10 (95% CI, 1.04 to 1.17) for CAD, 1.08 (95% CI, 0.97 to 1.20) for stroke, and 1.16 (95% CI, 1.09 to 1.24) for vascular death. There was also a significant association found between Lp-PLA2 levels and nonvascular deaths (RR=1.10; 95% CI, 1.04 to 1.17). The authors estimated that this strength of association was similar to that seen for non-high-density lipoprotein (HDL) cholesterol and systolic blood pressure.

Nonrandomized Comparative Studies of Lp-PLA2 in General Populations. Some of the representative cohort and case-control studies evaluating the association between Lp-PLA2 and cardiovascular outcomes are described next.

The West of Scotland Coronary Prevention Study (WOSCOPS) was a 5-year, case control trial evaluating 6595 men with elevated cholesterol levels and no history of a heart attack.(8) Researchers looked at a smaller population of this study to determine if inflammatory markers such as Lp-PLA2 and high-sensitivity C-reactive protein (hsCRP) were correlated with coronary heart disease (CHD) events. The 580 men who went on to have a myocardial infarction (MI) or revascularization were compared with 1160 age- and smoking-matched men who did not have an event. The results showed that those with the highest levels of Lp-PLA2 had twice the risk of an event compared with those with the lowest levels, even after adjustment for traditional risk factors and other inflammatory mediators.

The Atherosclerosis Risk in Communities (ARIC) study(9) evaluated the various risk markers and their association with increased risk in a large, diverse population of more than 12,000 people. At enrollment in the study, patients were free of CHD and were followed up for the development of the disease for the next 9 years. The case-cohort component of the study examined 2 inflammatory markers, Lp-PLA2 and hsCRP, in a subset of 608 cases and 740 controls. The results showed that elevated levels of Lp-PLA2 are higher in incident CHD cases. In people with nonelevated low-density lipoprotein (LDL) levels (<130 mg/dL), Lp-PLA2 levels were independently associated with CHD, even after adjustment for traditional risk factors and CRP. Koenig et al(10) reported similar results in a study of 934 apparently healthy men aged 45 to 64 who were followed up between 1984 and 1998. During this period, 97 men experienced a coronary event. Elevated levels of Lp-PLA2 appeared to be predictive of future coronary events in middle-aged men with moderately elevated total cholesterol, independent of CRP.

Ballantyne et al(11) studied Lp-PLA2 in the 12,762 apparently healthy subjects participating in the ARIC study. Mean levels of both Lp-PLA2 and CRP were higher in the 194 stroke cases; the authors concluded that Lp-PLA2 levels may provide complementary information beyond traditional risk factors in identifying those at risk for ischemic stroke. As part of the PEACE study,(12) Lp-PLA2 levels were measured in 3766 patients with stable CAD followed up for a median of 4.8 years. After adjustment for other baseline risk factors, patients in the highest quartile of Lp-PLA2 were 1.4 times more likely (95% CI, 1.17 to 1.70; p<0.001) to experience an adverse cardiovascular outcome compared with patients in the lowest quartile. Winkler et al(13) studied 3232 consecutive patients referred for coronary angiography and reported that Lp-PLA2 levels were an independent predictor of cardiac mortality (HR=2.0; 95% CI, 1.4 to 3.1; p<0.001) after adjusting for established risk factors, including CRP and N-terminal b-natriuretic peptide. Persson et al(14) evaluated the relationship between Lp-PLA2 and the metabolic syndrome in 4480 nondiabetic patients without a history of CAD. Both Lp-PLA2 (RR=1.54; 95% CI, 1.07 to 2.24) and the metabolic syndrome (RR=1.42; 95% CI, 1.06 to 1.90) were significant predictors of a first cardiac event. The combination of both elevated Lp-PLA2 and metabolic syndrome conferred a further increase in risk (RR=1.97; 95% CI, 1.34 to 2.90).

The Rancho Bernardo Study(15) enrolled 1077 community-dwelling elderly people without known heart disease and followed-up patients a mean of 16 years for the development of heart disease. Lp-PLA2 was an independent predictor of cardiac events, with a RR for patients in the second, third, and fourth quartiles of 1.66, 1.80, and 1.89, respectively, compared with the first quartile.

Another study evaluated the discriminatory ability of Lp-PLA2 for incident CHD in 421 cases and 800 controls from the Nurses’ Health Study.(16) Lp-PLA2 was a significant predictor of CHD after adjustment for traditional risk factors with a RR of 1.75 (95% CI, 1.09 to 2.84). It also added significantly to the discriminatory ability, as judged by an increase in the area under the curve from 0.720 without Lp-PLA2 to 0.733 with Lp-PLA2, and improved the net reclassification improvement index for discriminating between patients with and without CHD (p=0.004).

Other studies have correlated Lp-PLA2 levels with different parameters of CV disease. Multiple publications have reported that Lp-PLA2 levels are associated with characteristics of “vulnerable atherosclerotic plaques,” both in the coronary (17) and in the carotid arteries(18). Subsequent publications also found an association between Lp-PLA2 levels and plaque rupture (19) and fibrous cap thickness in patients with acute coronary syndrome.(20) Muller et al reported that Lp-PLA2 levels are associated with low fractional flow reserve on cardiac catheterization in 197 patients with stable CAD.(21) Tehrani et al evaluated the association between Lp-PLA2 levels and the protective effect of high-density lipoprotein-cholesterol (HDL-C) on incident CHD among 3888 adults with known cardiovascular disease.(22) Among patients with the highest tertile of Lp-PLA2, the relationship between HDL-C and incident CHD was attenuated, although there was no consistent association of higher levels of Lp-PLA2 with CHD risk across HDL-C categories.

Most, but not all, observational studies reported a positive association of Lp-PLA2 with cardiovascular outcomes. Allison et al(23) studied 508 patients with peripheral vascular disease followed for an average of 6.7 years. While there was a modest univariate association of Lp-PLA2 with cardiovascular events, this association disappeared after adjustment for established risk factors. In the Rotterdam Coronary Calcification Study,(24) similar results were reported. This population-based study followed 520 patients for 7 years and evaluated the association between Lp-PLA2 and coronary calcification by electron beam computed tomography scan. The unadjusted OR for each SD increase in Lp-PLA2 was 1.6 (95% CI, 1.1 to 2.4); however, this association became nonsignificant after controlling for lipid levels.

Nonrandomized Comparative Studies of Lp-PLA2 in Subpopulations. Some studies have specifically evaluated Lp-PLA2 as a risk factor in the diabetic population. For example, Saremi et al(25) performed a substudy of the Veterans Affairs Diabetes trial examining risk factors that predicted the progression of coronary artery calcification over an average of 4.6 years of follow-up. Lp-PLA2 mass was 1 of 2 significant independent predictors that remained (p=0.01) after adjustment for standard risk factors. Hatoum et al(26) evaluated Lp-PLA2 as a risk factor for incident CHD in 1517 diabetic patients enrolled in the Health Profession Follow-Up Study. After adjustment for standard risk factors, the RR for incident CHD for the upper quartile of Lp-PLA2 activity compared with the lower quartile was 1.39 (95% CI, 1.01 to 1.90; p=0.03).

Section Summary

There is a large amount of evidence establishing that Lp-PLA2 levels are an independent predictor of cardiovascular risk factors, physiologic measures of cardiac disease, and CV events. This association has been demonstrated in a variety of clinical populations, in people both with and without CV disease. The evidence on the ability of Lp-PLA2 to reclassify patients into clinically relevant categories is less convincing, with the largest patient-level meta-analysis reporting no significant improvement.

Lp-PLA2 as treatment target.

Interventional studies involving Lp-PLA2 suggest that the level of Lp-PLA2 is modifiable by antihyperlipidemic drugs (eg, statins, fibrates, niacin). An ad hoc study of the PROVE IT-TIMI 22 (Pravastatin or Atorvastatin Evaluation and Infection Therapy—Thrombolysis In Myocardial Infarction) trial,(27) in which Lp-PLA2 levels were measured at baseline (n=3648) and at 30 days (n=3265) and patients were followed up for a mean of 24 months for death, MI, unstable angina, revascularization, or stroke suggested that patients randomized to atorvastatin 80 mg/d, but not pravastatin 40 mg/d, experienced a 20% reduction of Lp-PLA2 levels at 30 days, independent of other cardiac risk factors. The 30-day, Lp-PLA2 level was independently associated with an increased risk of CV events. Another ad hoc study from the DIACOR (Diabetes and Combined Lipid Therapy Regimen) trial(28) demonstrated improved Lp-PLA2 levels (overall 16.8% reduction) compared with baseline, with no difference found between treatment groups among the 300 patients with diabetes and mixed dyslipidemias randomized to either fenofibrate 160 mg/d, simvastatin 20 mg/d, or both, for 12 weeks.

Rosenson randomized 55 hyperlipidemic subjects with metabolic syndrome to fenofibrate or placebo.(29) Fenofibrate treatment was associated with a 13% reduction in Lp-PLA2 mass compared with placebo. Saougos et al studied the effect of 3 lipid-lowering agents, rosuvastatin, ezetimibe, and fenofibrate, on Lp-PLA2 levels.(30) All 3 agents significantly lowered Lp-PLA2 levels; fenofibrate also selectively increased HDL-associated Lp-PLA2 levels.

At least 2 clinical trials have examined the change in Lp-PLA2 levels in patients treated with statins versus placebo and evaluated whether the utility of Lp-PLA2 for risk stratification is modified by statin treatment.(31,32) Ridker et al analyzed the changes in Lp-PLA2 levels among patients in the JUPITER trial, a randomized controlled trial (RCT) of 17,802 subjects randomized to rosuvastatin or placebo.(31) Among patients assigned to rosuvastatin, Lp-PLA2 mass decreased by 33.8%. In the placebo group, Lp-PLA2 levels were predictive of subsequent cardiac events, but this was not true in the rosuvastatin group. In a similar analysis of the MIRACL RCT, Ryu et al analyzed 2587 patients treated with high-dose atorvastatin or placebo.(32) Atorvastatin reduced Lp-PLA2 levels in 2587 patients treated with high-dose atorvastatin or placebo. Atorvastatin reduced Lp-PLA2 mass by 32.1% and Lp-PLA2 activity by 29.5%. In the placebo group, Lp-PLA2 levels were predictive of adverse cardiac outcomes, but no relationship was found in the atorvastatin group. The authors estimated that treatment with statins reduced the attributable risk of death due to Lp-PLA2 by approximately 50%.

Section Summary

Levels of Lp-PLA2 decrease substantially following treatment with antilipid medications, including statins. However, there are not currently well-accepted thresholds for using Lp-PLA2 as a treatment target. Some studies have reported that treatment with statins eliminates the predictive ability of Lp-PLA2 as a treatment target; this may potentially reduce the potential of Lp-PLA2 for this purpose.

Will identification of Lp-PLA2 levels lead to changes in patient management, and will these changes in management lead to improved patient outcomes?

Multiple studies have identified Lp-PLA2 as an independent risk factor for CV events and CV disease and have suggested that medication treatment for hyperlipidemia is associated with changes in Lp-PLA2 levels. However, no studies were identified that addressed whether testing strategies that use Lp-PLA2 levels lead to changes in patient management.

Preliminary clinical trials of Lp-PLA2 inhibitors have been published, although none of the Lp-PLA2 inhibitors have been approved by FDA for any indication. Darapladib was the first drug of this class that was tested. In 2014, results of the STABILITY trial of darapladib were published.(33) This study was a double-blind, placebo-controlled randomized trial in which 15,828 patients with stable coronary disease were randomized to receive once-daily darapladib or placebo. Analysis was intention-to-treat. Over a median 3.7-year follow-up, the study’s primary end point of CV death, MI, or stroke, occurred in 769 of 7924 (9.7%) of the darapladib group and in 819 of 7904 (10.4%) of those in the placebo group (HR for darapladib, 0.94; 95% CI, 0.85 to 1.03; p=0.20). Darapladib was associated with improvements in the rates of major coronary events (9.3% vs 10.3%; HR=0.90; 95% CI, 0.82 to 1.00; p=0.045) and all coronary events (14.6% vs 16.1%; HR=0.91; 95% CI, 0.84 to 0.98; p=0.02).

The Stabilization of plaques using Darapladib – Thrombolysis in Myocardial Infarction 52 (SOLID-TIMI 52) trial will enroll approximately 11,500 participants within 30 days of acute MI. Participants will be randomized to darapladib or placebo and followed for 3 years for the outcomes of CV death, nonfatal MI, or stroke. Results of this trial are expected to be presented in 2014.

Earlier studies compared darapladib with placebo in smaller study populations. Mohler et al randomized 959 patients with hyperlipidemia receiving atorvastatin to placebo or 1 of 3 doses of darapladib.(34) Dose-dependent inhibition of Lp-PLA2 was noted, ranging from 43% to 66% compared with placebo. The inflammatory markers interleukin-6 and hsCRP were also reduced by 12.3% and 13%, respectively. Serruys et al randomized 330 patients with documented CAD to darapladib or placebo and reported the impact of 12 months of treatment with darapladib on Lp-PLA2 levels, hsCRP levels, and coronary plaque composition, as measured by intravascular ultrasound.(35) This study found no difference in plaque deformability but a reduction in plaque necrotic core was reported for the darapladib group. Lp-PLA2 levels were decreased by 59%, but there were no significant differences in hsCRP levels between groups.

A second phospholipase A2 inhibitor, varespladib, is also being tested in clinical trials. The FRANCIS-ACS trial is a randomized double-blind, placebo-controlled trial of varespladib for patients with acute coronary syndrome. This trial is projected to enroll 700 patients, with follow-up for at least 24 weeks and report on the primary end point of major cardiovascular events.

Section Summary

Studies have not identified whether a testing strategy that uses Lp-PLA2 levels improves health outcomes.

Inhibitors of Lp-PLA2 have been developed and tested in clinical trials, but no trials have demonstrated an improvement in health outcomes with these inhibitors. Further phase 3 clinical trials are ongoing.

Ongoing Clinical Trials

A search of online database ClinicalTrials.gov with the search terms “lipoprotein-associated phospholipase A2,” “Lp-PLA2”, and “platelet-activating factor acetylhydrolase,” identified the following studies using Lp-PLA2 as an intervention or an outcome and currently enrolling patients.

  • Lp-PLA2 and Coronary Atherosclerosis in Humans (AIM 1 and II) (NCT01557088) – This is a single-group study designed to evaluate the role of Lp-PLA2 in the development of early coronary atherosclerosis and coronary endothelial dysfunction among adult patients undergoing coronary angiography including endothelial function testing. Enrollment is planned for 200 subjects; the planned study completion date is January 2015.
  • Lp-PLA2, Progenitor Cells and Coronary Atherosclerosis in Humans AIM III (NCT01067339) – This is a randomized double-blinded, phase 3 trial to quantify the effect of the Lp-PLA2 inhibitor darapladib on coronary endothelial function, progression of coronary atherosclerosis as determined by IVUS, and atherosclerosis in patients with early atherosclerosis. Patients will be randomized to darapladib or placebo for 6 months. Enrollment is planned for 80 subjects; the planned study completion date is January 2015.

Summary

There is a large body of literature evaluating lipoprotein-associated phospholipase A2 (Lp-PLA2) as a predictor of cardiovascular risk. These studies demonstrate that Lp-PLA2 is an independent predictor of cardiovascular disease but do not demonstrate that health outcomes are improved as a result of measuring Lp-PLA2. Improved risk prediction does not by itself result in improved health outcomes. To improve outcomes, clinicians must have the tools to incorporate emerging risk factors into existing risk prediction models, and these models should demonstrate improved classification into risk categories that will lead to more appropriate treatment. These tools are not currently available to the practicing clinician for Lp-PLA2. As a result, use of Lp-PLA2 for risk stratification for cardiovascular disease is considered investigational.

Clinical trials of Lp-PLA2 inhibitors are a new line of research with therapeutic potential. However, the available trials are preliminary, reporting only on physiologic outcomes such as reduction in high-sensitivity C-reactive protein, and use a pharmacologic agent that is not yet approved for use in the U.S. One phase 3 clinical trial of an Lp-PLA2 inhibitor demonstrated no significant improvements in the study’s primary outcome, but other trials are still in progress. Therefore, Lp-PLA2 has not demonstrated improved outcomes as a treatment target and is considered investigational for this purpose.

Practice Guidelines and Position Statements

The American College of Cardiology Foundation and American Heart Association published joint guidelines on the assessment of cardiovascular risk in asymptomatic patients in 2010.(36) The guidelines contained the following statement concerning testing for Lp-PLA2:

  • Lipoprotein-associated phospholipase A2 might be reasonable for cardiovascular risk assessment in intermediate-risk asymptomatic adults. (Class IIb recommendation; Level of Evidence B)

The American Association of Clinical Endocrinologists published guidelines for the management of dyslipidemia and prevention of atherosclerosis in 2012.(37) These guidelines made the following recommendations for Lp-PLA2 testing:

  • Assess markers of inflammation in patients where further stratification of risk is necessary. Highly sensitive CRP (hsCRP) and Lp-PLA2 provide useful information in these instances and appear to be synergistic in predicting risk of CVD and stroke. (Grade B recommendation; best level of evidence 1)
  • Measure Lp-PLA2, which in some studies has demonstrated more specificity than hsCRP, when it is necessary to further stratify a patient’s CVD risk, especially in the presence of systemic highly sensitive CRP elevations (Grade B recommendation; best level of evidence 2).

In 2012, the European Society of Cardiology and Other Societies on Cardiovascular Disease Prevention in Clinical Practice issued guidelines on cardiovascular disease prevention.(38) These guidelines include the following statements about Lp-PLA2 testing:

  • LpPLA2 may be measured as part of a refined risk assessment in patients at high risk of a recurrent acute atherothrombotic event (Class IIb recommendation; Level of Evidence B; weak evidence).

References:

  1. National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. Adult Treatment Panel III guidelines. 2001. Available online at: http://www.nhlbi.nih.gov/guidelines/cholesterol/atp3xsum.pdf. . Last accessed May 12, 2014.
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  3. FDA. 510(K) Summary -- diaDexus PLAC Test. 2013. Available online at: http://www.accessdata.fda.gov/cdrh_docs/pdf3/K030477.pdf. Last accessed May 22, 2014.
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  20. Gu X, Hou J, Yang S et al. Is lipoprotein-associated phospholipase A2 activity correlated with fibrous-cap thickness and plaque volume in patients with acute coronary syndrome? Coron. Artery Dis. 2014; 25(1):10-5.
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  38. Members: ATF, Perk J, De Backer G et al. European Guidelines on cardiovascular disease prevention in clinical practice (version 2012): The Fifth Joint Task Force of the European Society of Cardiology and Other Societies on Cardiovascular Disease Prevention in Clinical Practice (constituted by representatives of nine societies and by invited experts)Developed with the special contribution of the European Association for Cardiovascular Prevention & Rehabilitation (EACPR). Eur. Heart J. 2012; 33(13):1635-701.

 

Codes

Number

Description

CPT 

83698 Lipoprotein-associated phospholipase A2 (Lp-PLA2)
ICD-9-CM Diagnosis   Investigational for all diagnoses
ICD-10-CM (effective 10/1/15)    Investigational for all diagnoses
ICD-10-PCS (effective 10/1/15)   Not applicable. No ICD procedure codes for laboratory tests.

 


Index

Cardiac Risk Factor, Lp-PLA2
Lipoprotei-associated Phospholipase A2, Cardiac Risk Factor
Lp-PLA2, Cardiac Risk Factor
PLAC, Laboratory Test


Policy History

Date Action Reason
10/09/03 Add policy to Medicine section, Pathology/ Laboratory subsection New policy
04/1/05 Replace policy Policy updated; reference numbers 2 and 4 added; no change in policy statement
04/25/06 Replace policy Policy updated with literature search; policy statement unchanged; reference numbers 5 and 6 added 
12/12/06 Replace policy Policy updated with literature search and new coding; no changes to policy statement. Reference numbers 7-13 added. CPT coding updated 
12/13/07 Replace policy Policy updated with literature search; no changes to policy statement. Reference numbers 14-19 added.
10/07/08 Replace policy  Policy updated with literature search; no changes to policy statement. Reference numbers 20-26 added
06/10/10 Replace policy Policy updated with literature search; no changes to policy statement. Policy rationale extensively condensed and revised. Reference numbers 2, 15, and 22 added
6/9/11 Replace policy Policy updated with literature search through April 2011; no changes to policy statement. References 16-18 and 26 were added.
06/14/12 Replace policy Policy updated with literature search through April 2012; no changes to policy statement. References 15-17, 20, 26 and 27 were added.
6/13/13 Replace policy Policy updated with literature search through May 15, 2013, references 22,23 added. No change to policy statement.
6/12/14 Replace policy
Policy updated with literature review through May 12, 2014. References 3, 21-22, 33, and 38 added. Rationale reorganized. No changes to policy statement.