Cardiovascular Disease Risk Tests

Coverage Summary

Coverage stance: mixed. Scope summary: UnitedHealthcare medical policy CS015.V governs coverage determinations for multiple cardiovascular disease risk tests including arterial compliance/waveform analysis, carotid intima-media thickness (CIMT), advanced lipoprotein analysis (including Lp(a), subfractions, particle number/size, apoB), Lp-PLA2, endothelial function testing (e.g., peripheral arterial tonometry, brachial artery flow-mediated dilation), and multi-protein algorithmic biomarker tests (examples: aptamer-based proteomic panels, multi-protein panels with algorithmic risk scores, LC-MS/MS HDL apolipoprotein/CEC assays).

Effective date: 2025-09-01.

High-level overview: The policy lists the tests above as unproven and not medically necessary due to insufficient evidence of clinical utility for determining risk or guiding management; it also lists multiple proprietary/PLA U-codes and CPT codes associated with these unproven services. Advanced lipoprotein analyses must be performed in CLIA-compliant laboratories.

Exclusions/limitations: This policy does not apply to listed states (Idaho, Indiana, Kansas, Kentucky, Louisiana, New Jersey, New Mexico, North Carolina, Ohio, Pennsylvania, Tennessee); refer to state-specific policies as indicated.

Notes: Several specific multi-protein and proprietary tests (listed PLA/U-codes) and select CPT codes are identified in the policy as not covered / not medically necessary.

Not Medically Necessary / Unproven Tests

Not Medically Necessary / Unproven

The following tests and multi-protein biomarker panels are considered not medically necessary / unproven due to insufficient evidence of clinical utility and improvement in health outcomes:

ALL of the following

Arterial compliance testing, using waveform analysis as a method to determine risk for cardiovascular disease.
Carotid intima-media thickness (CIMT) measurement as an effective screening tool for the management of cardiovascular disease.
Advanced lipoprotein analysis (e.g., lipoprotein(a), subfractions, or particle size) as a method to determine risk for cardiovascular disease.
Lipoprotein-associated phospholipase A2 (Lp-PLA2) enzyme as a method to determine risk for cardiovascular disease or ischemic stroke.
Endothelial function assessment using tools such as peripheral arterial tonometry (PAT) or brachial artery pressure ultrasound as a prognostic indicator to determine risk of cardiovascular disease.
Multi-protein diagnostic biomarker (examples listed)

Denial Risk

Claims for unproven tests are not medically necessary

Claims for the tests listed as not medically necessary/unproven will be subject to denial. Use guideline indications for ordering Lp(a) and apolipoprotein B (apoB) when considering testing; orders inconsistent with guideline-based indications may be denied as not medically necessary.

Affected CPT/HCPCS/PLA codes: 0019M, 0052U, 0308U, 0309U, 0377U, 0415U, 0541U, 83695 (Lp(a)), 83698 (Lp-PLA2), 83701, 83704, 93050, 93799, 93895, 93998
Code groups: not_covered

Clinical Utility Conclusions & Evidence Summary

Background summary: The policy reviews evidence across modalities (arterial compliance/waveform analysis, CIMT, advanced lipoprotein testing including Lp(a) and Lp-PLA2, endothelial function testing, cholesterol efflux capacity and multi-protein algorithmic biomarker tests) and concludes that evidence is insufficient to demonstrate clinical utility or that routine use alters patient management or improves outcomes for several of these modalities.

Key point: Studies show associations between some markers (e.g., Lp(a), Lp-PLA2, CEC, PWV, CIMT, proteomic scores) and cardiovascular outcomes, but heterogeneity, lack of standardized assays, limited prospective clinical utility studies, and absence of demonstrated impact on management or outcomes limit adoption.

Laboratory requirement: Advanced lipoprotein analyses and related assays must be performed in accordance with CLIA quality standards.

Study / Source	Key finding
Sequí-Dominguez et al. (2020)
cfPWV pooled diagnostic odds ratio 11.23 for cardiovascular mortality; HSROC AUC ~0.75; suggested cut-offs near 10.7–11.5; incremental clinical utility not reported
Willeit et al. (2020)
Meta-analysis of 119 RCTs: 10 μm/y slower CIMT progression associated with RR 0.91 for CVD; interventions reducing CIMT progression associated with lower CVD risk but role in altering clinical management not demonstrated
ACCELERATE trial subgroup (Shah et al. 2020)
Higher Lp(a) tertiles associated with increased composite cardiovascular events in a high-risk secondary prevention cohort (median Lp(a) 29.1 nmol/L); study did not address impact on clinical management
ATTICA cohort (Kouvari et al. 2019b)
Using threshold ≥50 mg/dL, Lp(a) ≥50 mg/dL associated with ~2x 10-year CVD risk (HR 2.18, 95% CI 1.11–4.28); effect modified by sex and other lipid factors
BiomarCaRE (Waldeyer et al. 2017)
Lp(a) levels >90th percentile associated with increased major coronary events and CVD (HRs up to ~1.49 and 1.44); supports association but not demonstrated clinical utility for changing outcomes
Lp-PLA2 meta-analyses (Hu 2019; Li 2017a; Tian 2017)
Elevated Lp-PLA2 activity and mass associated with modestly increased risk of stroke and CHD (pooled RRs modestly >1) but heterogeneity and limited evidence of clinical utility
Multi-protein tests (Hayes 2023; McCarthy 2020; Mohebi 2023; Neumann 2020)
Prognostic/prognostic discrimination reported in selected cohorts (AUCs ~0.77–0.86) for proteomic/multi-marker algorithms, but limited peer-reviewed evidence and no demonstrated impact on outcomes or management
Endothelial function (Cooper 2021; Schnabel 2021; van den Heuvel 2015)
PAT measures not associated with composite CVD events in community cohorts; PAT ratio associated with lower incident stroke risk in one study; overall routine screening or risk prediction not supported
NLA recommendation (Koschinsky et al. 2024; NLA statements)
NLA recommends measuring Lp(a) at least once in every adult for risk stratification and defines numeric thresholds (low <75 nmol/L ≈30 mg/dL; intermediate 75–125 nmol/L; high ≥125 nmol/L ≈50 mg/dL)
ACC/AHA statements (2010/2013/2019)
ACC/AHA: FMD/PAT not recommended for risk assessment in asymptomatic adults (Class III); Lp-PLA2 might be reasonable for intermediate-risk adults but evidence does not show clinical effectiveness for improving outcomes

Clinical Guidelines & Regulatory Statements

Applicable Codes

Listed Proprietary/Lab Test Codes (unproven)mixedNot Covered

0019M	Cardiovascular disease, plasma, analysis of protein biomarkers by aptamer-based microarray and algorithm reported as 4-year likelihood of coronary event in high-risk populations.
0052U	Lipoprotein, blood, high resolution fractionation and quantitation of lipoproteins, including all five major lipoprotein classes and subclasses of HDL, LDL, and VLDL by vertical auto profile ultracentrifugation.
0308U	Cardiology [coronary artery disease (CAD)], analysis of 3 proteins (hs troponin, adiponectin, KIM-1) with 3 clinical parameters, plasma, algorithm reported as a risk score for obstructive CAD.
0309U	Cardiology (cardiovascular disease), analysis of 4 proteins (NT-proBNP, osteopontin, TIMP-1, KIM-1), plasma, algorithm reported as a risk score for major adverse cardiac event.
0377U	Cardiovascular disease, quantification of advanced serum or plasma lipoprotein profile, by NMR spectrometry with report of a lipoprotein profile (including 23 variables).
0415U	Cardiovascular disease (ACS), IL-16, FAS, FASLigand, HGF, CTACK, EOTAXIN, and MCP-3 by immunoassay combined with age, sex, family history, and personal history of diabetes, blood, algorithm reported as a 5-year score for ACS.
0541U	Cardiovascular disease (HDL reverse cholesterol transport), cholesterol efflux capacity, LC-MS/MS, quantitative measurement of 5 distinct HDL-bound apolipoproteins (apolipoproteins A1, C1, C2, C3, and C4), serum, algorithm reported as prediction of pCAD score.

CPT/HCPCS / Laboratory Codes referencedmixedNot Covered

83695	Lipoprotein (a).
83698	Lipoprotein-associated phospholipase A2 (Lp-PLA2).
83701	Lipoprotein, blood; high resolution fractionation and quantitation of lipoproteins including lipoprotein subclasses when performed (e.g., electrophoresis, ultracentrifugation).
83704	Lipoprotein, blood; quantitation of lipoprotein particle number(s) (e.g., by NMR spectroscopy), includes lipoprotein particle subclass(es), when performed.
93050	Arterial pressure waveform analysis for assessment of central arterial pressures, includes obtaining waveform(s), digitization, and application of nonlinear mathematical transformations to determine central arterial pressures and augmentation index, with interpretation and report, upper extremity artery, non-invasive.
93799	Unlisted cardiovascular service or procedure.
93895	Quantitative carotid intima media thickness and carotid atheroma evaluation, bilateral.
93998	Unlisted noninvasive vascular diagnostic study.

Added CPT code (per Policy History)CPT

0541U

Added CPT code for quantitative measurement of 5 distinct HDL-bound apolipoproteins with algorithm reported as a risk score (per Policy History effective 09/01/2025).

Billing Rule

CPT 0541U addition

CPT code 0541U was added to the policy effective 2025-09-01. Use CPT 0541U for the specified LC-MS/MS assay that quantitatively measures five HDL-bound apolipoproteins (A1, C1, C2, C3, C4) and reports an algorithmic risk score where applicable. Record and bill this code for that specific test beginning on the effective date.

Effective date: 2025-09-01
Use CPT 0541U for quantitative LC-MS/MS measurement of 5 HDL-bound apolipoproteins with algorithmic risk score

Documentation Required

Laboratory quality compliance

Advanced lipoprotein analyses must be performed in accordance with Clinical Laboratory Improvement Amendments (CLIA) quality standards. Ensure testing laboratories are CLIA-compliant when ordering or submitting claims for advanced lipoprotein or HDL apolipoprotein LC-MS/MS assays.

Provider Actions & Billing Impact

Documentation Required

State-specific policy application

This policy does not apply to the following states; providers must follow the listed state-specific policy/guideline when servicing members in these states: Idaho, Indiana, Kansas, Kentucky, Louisiana, New Jersey, New Mexico, North Carolina, Ohio, Pennsylvania, Tennessee.

States excluded: Idaho; Indiana; Kansas; Kentucky; Louisiana; New Jersey; New Mexico; North Carolina; Ohio; Pennsylvania; Tennessee
Action: follow the state-specific policy/guideline for members in these states

Documentation Required

Consider Lp(a) measurement in guideline-specified settings

Consider measuring Lp(a) and apoB in patients per guideline-based indications. Indications include: clinical ASCVD (especially premature or recurrent despite LDL-C lowering), family history of premature ASCVD or known elevated Lp(a), individuals of South Asian or African ancestry with family history, primary prevention patients with 10-year ASCVD risk ≥ 10% for risk stratification, personal or family history of aortic valve stenosis, and refractory LDL-C elevation despite therapy. ApoB measurement is relatively indicated when triglycerides are elevated (e.g., ≥ 200 mg/dL) or in select patients per guidelines.

Definitions & FAQs

Lp(a): Lipoprotein(a) is a genetically determined lipoprotein particle associated with increased ASCVD risk; measurements expressed in mg/dL or nmol/L.

Lp-PLA2: Lipoprotein-associated phospholipase A2 is an enzyme linked to vascular inflammation; it can be measured as mass or activity and has been studied as a potential risk marker for CHD and ischemic stroke.

CEC: Cholesterol efflux capacity measures HDL functionality—the ability to remove cholesterol from macrophages—and has been associated with coronary artery disease in observational studies.

PAT: Peripheral arterial tonometry is a noninvasive device-based assessment of digital pulse amplitude/reactive hyperemia index used to evaluate endothelial function.

ApoB: Apolipoprotein B is a marker of atherogenic particle number and is a relative indication when triglycerides are elevated (guideline-recommended consideration).

Q: Are Lp-PLA2 or multi-protein algorithmic tests recommended for routine risk assessment?

A: No. Evidence is inconsistent or insufficient to support routine clinical use of Lp-PLA2 or multi-protein algorithmic biomarker tests to guide management or improve outcomes; these tests lack demonstrated clinical utility for routine risk assessment.

Revision History

2025-09-01addedLatest

CPT code 0541U was added to the Applicable Codes (quantitative measurement of 5 distinct HDL-bound apolipoproteins by LC-MS/MS with algorithm reported as prediction of pCAD score); coverage/coding update effective 09/01/2025. This is a material change.

2025-09-01revisedLatest

Clinical Evidence and References sections were updated and the list of unproven/not medically necessary services was revised to explicitly add cardiovascular disease (HDL reverse cholesterol transport), cholesterol efflux capacity (CEC) by LC-MS/MS measuring five HDL-bound apolipoproteins with algorithm and reported as a risk score. This is a material change.