ModifiedUnitedHealthcarePolicy CS015.V

Cardiovascular Disease Risk Tests

Defines UnitedHealthcare's stance on various cardiovascular disease risk tests (e.g., arterial compliance, CIMT, advanced lipoprotein analysis, Lp-PLA2, multi-protein biomarker panels) and identifies tests considered unproven or not medically necessary; applies to members except where state-specific policies override.

Policy Summary

PayerUnitedHealthcare

PolicyCardiovascular Disease Risk Tests

Policy CodePolicy CS015.V

Change TypeMaterial coverage updatesnew unproven tests added and CPT code 0541U added

Effective DateSep 1, 2025

Next Review DateN/A

Key ActionVerify plan-specific prior authorization requirements (including any for newly listed CPT 0541U) before ordering advanced CVD risk tests.

SourceLink

POLICY UPDATE CHANGES

Revised list of unproven and not medically necessary services; added '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), with algorithm and reported as a risk score'.

Added CPT code 0541U to Applicable Codes.

Updated Clinical Evidence and References sections to reflect the most current information.

Removed content/language pertaining to the state of Louisiana.

Added language to indicate this Medical Policy does not apply to the state of Nebraska; refer to the state-specific policy version.

multiple testslisted as unproven / not medically necessary

≥7CPT/PLA codes provided

30+

Trek Health ingests and normalizes Transparency in Coverage data and payer policy updates to give provider organizations a clear view of how commercial reimbursement behaves across markets, payers, and services. Our platform transforms raw payer disclosures into structured intelligence that supports contract evaluation, payer negotiations, and service line strategy. By combining market benchmarks with ongoing policy visibility, Trek helps teams identify variability, risk, and opportunity in commercial reimbursement. The result is faster insight, stronger negotiating positions, and more informed financial decisions.

1new CPT code added (0541U)

NC listedstate-specific policy exists

states modifiedstate applicability edits

Coverage Criteria and Evidence Conclusions

Not medically necessary / Unproven

The following tests are considered unproven and not medically necessary due to insufficient evidence of efficacy:

Unproven tests: Arterial compliance testing using waveform analysis; Carotid intima-media thickness (CIMT) measurement for screening or management of cardiovascular disease; Advanced lipoprotein analysis (including lipoprotein(a) subfractions, particle size, NMR, or other high-resolution fractionation methods) as a method to determine CVD risk; Lipoprotein-associated phospholipase A2 (Lp-PLA2) enzyme testing as a method to determine risk for cardiovascular disease or ischemic stroke; Endothelial function assessment (e.g., peripheral arterial tonometry [PAT] or brachial artery flow-mediated dilation/ultrasound) as a prognostic indicator to determine CVD risk; Multi-protein diagnostic biomarker panels and algorithm-reported risk scores (including aptamer-based protein microarray algorithms, HDL reverse cholesterol transport/cholesterol efflux capacity LC-MS/MS assays measuring five HDL-bound apolipoproteins reported with an algorithm, 3-protein panels [hs-troponin, adiponectin, KIM-1], 4-protein panels [NT-proBNP, osteopontin, TIMP-1, KIM-1], and 7-protein panels [IL-16, FAS, FASLigand, HGF, CTACK, EOTAXIN, MCP-3]).

Policy cites insufficient evidence that use of these tests changes management or improves clinical outcomes.

Evidence conclusions

Evidence-based findings and conclusions in the provided sections:

CIMT comparative performance: Coronary artery calcium (CAC) scoring outperforms CIMT and carotid plaque for risk discrimination in asymptomatic low-to-intermediate risk individuals; CIMT yields only modest incremental reclassification beyond traditional risk factors and heterogeneity of CIMT measures limits generalizability.

Systematic review and cohort/meta-analyses (Azcui Aparicio et al.; Den Ruijter et al.)

CIMT as surrogate and association with events: Slower CIMT progression is associated with reduced CVD risk in pooled randomized trials (e.g., a 10 μm/y slower CIMT progression associated with RR ~0.91), but trials varied in interventions and comorbidities and did not demonstrate that integrating CIMT measurement into care alters management or outcomes.10 μm/y

Willeit et al. meta-analysis

Advanced lipoprotein testing overall stance: Advanced lipoprotein tests (apoB, Lp(a), Lp-PLA2, particle measures) show associations with CVD in observational studies, but results are inconsistent, assays and modalities lack standardization, and there is no consistent evidence that these tests add incremental predictive value beyond standard lipids or change clinical management to improve outcomes.

Emerging Risk Factors Collaboration and other systematic reviews

Lp(a) associations: Elevated Lp(a) levels are associated with increased risk of MACE and other cardiovascular outcomes in cohort studies (associations by percentile and thresholds such as ≥50 mg/dL), but the incremental value for risk prediction and impact on management remain unproven.Lp(a) ≥50 mg/dL; high percentiles (e.g., >90th)

Large cohort and retrospective analyses

Lp-PLA2 associations and utility: Elevated Lp-PLA2 activity or mass is associated with higher stroke and cardiovascular risk in meta-analyses, but overall evidence quality and assay heterogeneity limit conclusions and clinical utility has not been established to guide treatment or improve outcomes.one SD increase associated with RR ~1.07-1.11

Hu et al., Tian et al., Li et al.

Coverage rationale and evidence synthesis

Coverage stance derived from evidence summaries in these sections:

General coverage rationale: Although multiple observational studies and meta-analyses report associations between biomarkers (including Lp-PLA2) or physiologic tests (arterial stiffness, endothelial function, multi-protein panels) and cardiovascular outcomes, limitations such as small event counts, heterogeneous assays/definitions, retrospective designs, and lack of prospective studies demonstrating that test-guided management improves outcomes prevent demonstration of clinical utility; therefore these tests are not supported for routine coverage absent evidence of benefit to patient management.

Evidence synthesis across systematic reviews and cohort studies

Multi-protein panels and risk scores: Multi-marker panels and algorithm-reported risk scores may show discrimination in derivation or retrospective validation cohorts, but available studies are observational and do not evaluate whether use of the test changes management or improves patient-centered outcomes; clinical utility is unproven.

Hayes 2023 evidence brief; Mohebi et al.; McCarthy; Neumann

Endothelial function testing: Noninvasive endothelial function assessments (PAT, brachial FMD) demonstrate inconsistent associations with incident CVD and mortality and have not been shown to effectively stratify risk or guide treatment decisions in routine practice; routine coverage is not supported.

Guideline-driven coverage contexts

Use of advanced lipoprotein tests and endothelial/peripheral vascular function tests varies by guideline and is generally limited to specified clinical contexts rather than routine screening.

Contexts where Lp(a) measurement is reasonable/considered: Measurement of Lp(a) is recommended or considered at least once in adults by some societies (e.g., NLA recommends measurement at least once) and is advised in selected situations such as family history of premature ASCVD, unexplained or premature ASCVD, very high inherited Lp(a) levels, for risk reclassification in borderline cases, or in patients with aortic valve stenosis; thresholds such as ≥50 mg/dL (≥125 nmol/L) or much higher values (e.g., >180 mg/dL) are referenced by different societies.see guideline thresholds

AACE/AACE 2020; NLA; ACC/AHA; ESC/EAS

ApoB measurement contexts: ApoB measurement may be recommended for risk assessment in individuals at increased risk (including diabetes) and when triglycerides are elevated (e.g., triglycerides ≥200 mg/dL); guideline-based apoB target goals vary by risk category.apoB goals <90, <80, <70 mg/dL depending on risk; TG ≥200 mg/dL as relative indication

AACE; ACC/AHA; ESC/EAS

This Medical Policy does not apply to all UHC members in every state. Refer to the state-specific policy when applicable; the policy lists exceptions for the following states: Idaho, Indiana, Kansas, Kentucky, Nebraska, New Jersey, New Mexico, North Carolina, Ohio, Pennsylvania, and Tennessee (see state-specific policy versions for coverage determinations).

Several evidence summaries and meta-analyses note a key limitation: studies of tests such as CIMT, Lp(a), Lp-PLA2, and advanced lipoprotein assays generally report associations with outcomes but do not evaluate whether integrating these measurements into clinical care changes management decisions or improves patient outcomes. For example, the Willeit et al. meta-analysis and other reviews explicitly state they did not assess how incorporating CIMT measurements into clinical care alters management or clinical outcomes.

Multi-protein biomarker panels reported as algorithm-derived risk scores (including tests evaluated in the Hayes evidence brief and other observational studies) and noninvasive endothelial function assessments (e.g., PAT or brachial artery ultrasound) lack sufficient quality evidence demonstrating clinical utility. As a result, routine use of multi-protein blood tests with algorithm-reported risk scores and endothelial function assessments is considered unsupported for screening or management of cardiovascular disease.

Guideline and regulatory sources advise caution for peripheral endothelial testing. The ACC/AHA guidelines state that peripheral arterial flow-mediated dilation (FMD) studies are not recommended (Class III) for cardiovascular risk assessment in asymptomatic adults. Endothelial function measures overall show inconsistent associations with incident CVD and mortality, and routine use has not been demonstrated to inform management decisions. Device-specific systems used for these assessments (for example, PAT and brachial artery ultrasound platforms) have limited, context-specific roles described in the literature.

The EndoPAT 2000 device has FDA 510(k) clearance as a diagnostic aid for detection of coronary artery endothelial dysfunction using a reactive hyperemia procedure in symptomatic patients being evaluated for coronary disease. The FDA clearance summary explicitly states the device is not intended for use as a screening test in the general patient population.

Available evidence does not demonstrate that carotid intima-media thickness (CIMT) or noninvasive arterial compliance testing provides actionable incremental benefit over traditional risk assessment to guide management. Systematic reviews and meta-analyses conclude that CIMT and arterial compliance measures have heterogeneous definitions and modest incremental value, and they do not show that use of these measures in clinical practice alters patient management or outcomes.

Advanced lipoprotein analyses (including particle sizing, NMR, and detailed fractionation), measurement of Lp-PLA2, and many multi-protein biomarker panels demonstrate associations with cardiovascular outcomes in observational studies, but the evidence is inconsistent and does not establish that these tests improve clinical management or outcomes. Consequently, these tests are considered unproven and not medically necessary for routine cardiovascular risk assessment.

In several sections the document reports that the literature indicates a lack of established clinical utility rather than furnishing explicit, prospective outcome trials showing benefit. Multiple systematic reviews and pooled analyses conclude that while biomarkers such as apoB, Lp(a), and Lp-PLA2 are associated with risk, the studies do not demonstrate incremental predictive value over standard lipids or that testing these markers changes care—supporting a stance of insufficient evidence for routine clinical use.

Routine measurement of Lp-PLA2, multi-protein biomarker panels reported as algorithmic risk scores, and endothelial function testing (PAT or flow-mediated dilation) is not recommended for routine cardiovascular risk assessment due to insufficient evidence that these tests improve patient-centered outcomes or meaningfully alter management.

Measurement of arterial compliance (e.g., pulse wave velocity or central arterial waveform analysis) and many advanced lipid tests (particle sizing, NMR spectrometry, and similar assays) are not recommended for routine clinical use outside research settings. Professional society guidance (ASCP, ACC/AHA) advises against routine ordering of expanded lipid panels and indicates limited or no benefit for these measures in broad, asymptomatic populations.

The policy was revised to expand the list of services considered unproven and not medically necessary. The update added testing for HDL reverse cholesterol transport / cholesterol efflux capacity using LC-MS/MS quantitative measurement of five HDL-bound apolipoproteins (A1, C1, C2, C3, and C4) with algorithm-reported risk scoring to the list of unproven services and also added CPT code 0541U to the applicable codes.

Applicable Codes, Cutoffs, and Regulatory Identifiers

Applicable CPT/PLA/HCPCS Codesmixed

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 autoprofile ultracentrifugation.
0308U	Cardiology [coronary artery disease (CAD)], analysis of 3 proteins [high sensitivity (hs) troponin, adiponectin, and kidney injury molecule-1 (KIM-1)] with 3 clinical parameters (age, sex, history of cardiac intervention), plasma, algorithm reported as a risk score for obstructive CAD.
0309U	Cardiology (cardiovascular disease), analysis of 4 proteins [NT-proBNP, osteopontin, tissue inhibitor of metalloproteinase-1 (TIMP-1), and kidney injury molecule-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 nuclear magnetic resonance (NMR) spectrometry with report of a lipoprotein profile (including 23 variables).
0415U	Cardiovascular disease [acute coronary syndrome (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 (deleted risk) 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 coronary artery disease (pCAD) score.
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).

1–10 of 15

1/2

No coding groups in these chunksmixed

No codes listed

FDA product codes (informational)mixed

DXN	FDA product code for non-invasive blood pressure measurement system products (informational)
IYO	FDA product code for B-mode ultrasound equipment (informational)
DFC	FDA product code for products used to measure lipoprotein(a) (informational)
NOE	FDA product code for products for the measurement of Lp-PLA2 (informational)
JJX	FDA product code for products for the measurement of Lp-PLA2 (informational)

FDA 510(k) identifiersmixed

K032519	EndoPAT 2000 510(k) clearance
K001852	Predicate device PAT 1000 RD (Itamar Medical) referenced in clearance
K122129	SphygmoCor XCEL 510(k) clearance (example of arterial waveform device)
K070795	SphygmoCor CVMS predicate 510(k) clearance

Applicable CPT Codes (added)CPT

0541U

CPT code added to Applicable Codes (document lists addition without full descriptor in this chunk)

cfPWV cutoffs discussed

cfPWV cutoffs associated with mortalityClosest cut-off points reported ~10.7 m/s (cardiovascular mortality) and ~11.5 m/s (all-cause mortality) in pooled cfPWV analyses

cfPWV performance metricsPooled diagnostic odds ratios: 11.23 for cardiovascular mortality and 6.52 for all-cause mortality; HSROC AUCs ~0.75–0.78

Population and limitationsNine studies (n = 3,170) included; limitations noted—publication bias, small sample size, technique differences, and lack of incremental clinical utility data

CIMT diagnostic cutoff

CIMT diagnostic cutoffSubgroup analyses identified a 1.0 mm IMT cutoff as more accurate for diagnosing coronary artery disease (sensitivity 0.66; specificity 0.79; AUC 0.80)

Billing, Prior Authorization, and Documentation Guidance

Prior Authorization

Prior authorization and benefit determination

Follow the member's benefit terms and the plan's prior authorization processes; inclusion of a code in this policy does not guarantee coverage. Prior authorization and benefit determination must be confirmed with the applicable federal, state, or contractual plan documents before ordering or billing tests.

Listing of a code in this policy does not imply coverage or a right to reimbursement.
Verify benefit coverage and prior authorization requirements with the member's plan or payer portal before ordering services.

Note

Prior authorization not specified in provided sections

No specific prior authorization requirements are specified in the provided policy sections for most listed tests; however, the absence of a stated prior authorization rule in this document does not replace plan-specific verification.

When no prior authorization information is listed here, check the member's contract and payer portal for plan-specific rules.

Background and Clinical Context

Cardiovascular diseases such as coronary artery disease, stroke, and hypertension are leading causes of morbidity and mortality. Proposed diagnostic and prognostic tests (including arterial compliance measures, CIMT, advanced lipoprotein analyses, Lp-PLA2, endothelial function testing, and multi-protein biomarker panels) aim to detect subclinical disease or refine risk estimates, but the policy summarizes that evidence is variable and, for many tests, insufficient to support routine clinical use or to demonstrate improved patient outcomes.

Key Definitions and Test Descriptions

Carotid intima-media thickness (CIMT) definition

DefinitionCarotid intima‑media thickness (CIMT) — a noninvasive ultrasound measurement of carotid artery wall thickness used as a marker of subclinical atherosclerosis and predictor of CVD events

MethodCIMT uses ultrasound imaging and software analysis to quantify thickness of the carotid artery intima‑media complex

Intended use and limitationsProposed for risk stratification but evidence is heterogeneous and clinical utility for changing management is unproven

Arterial compliance / pulse wave analysis definition

DefinitionArterial compliance / pulse wave analysis — noninvasive assessment of arterial stiffness using techniques such as pulse wave velocity, augmentation index, and blood pressure waveform analysis

Measurement approaches

Policy Summary

PayerUnitedHealthcare

PolicyCardiovascular Disease Risk Tests

Policy CodePolicy CS015.V

Change TypeMaterial coverage updatesnew unproven tests added and CPT code 0541U added

Effective DateSep 1, 2025

Next Review DateN/A

Key ActionVerify plan-specific prior authorization requirements (including any for newly listed CPT 0541U) before ordering advanced CVD risk tests.

SourceLink

On This Page

Cooper 2021; Schnabel 2021; Van den Heuvel; Rubinshtein 2010; Hamburg 2008

Endothelial function testing (PAT/FMD) stance: ACC/AHA does not recommend peripheral arterial FMD for cardiovascular risk assessment in asymptomatic adults (Class III); EndoPAT 2000 has FDA 510(k) clearance as a diagnostic aid for symptomatic evaluation of endothelial dysfunction but is not intended for general population screening.FDA intended-use limits

ACC/AHA guidelines; FDA clearance summary

Lp-PLA2 and other inflammatory markers: Some guideline statements indicate Lp-PLA2 might be reasonable to consider in select intermediate-risk asymptomatic adults or to further stratify risk, but routine use is not established and guidelines note lack of evidence that Lp-PLA2 measurement changes management or outcomes.none specified

ACC/AHA; AACE; ASCP statements

Overall diagnostic performancePooled sensitivity and specificity for IMT diagnosing CAD: 0.68 and 0.70 respectively; overall AUC 0.74

Study limitationsIncluded 22 articles with heterogeneity across populations (fewer Asian studies) and variability in IMT measurement methods; clinical utility for outcomes not addressed

CIMT cutoff and Lp(a) threshold referenced

CIMT cutoff valueCIMT cutoff of 1.0 mm referenced as a subgroup cutoff with improved diagnostic accuracy for CAD

Lp(a) threshold referencedRecommended Lp(a) threshold of 50 mg/dL used to define abnormal Lp(a) status in cohort analyses

Context and limitationsAnalyses support association with CAD/CVD risk but do not demonstrate that measurement alters management or improves outcomes

Lp(a) risk thresholds

Lp(a) low/intermediate/high ranges (NLA)Low: <75 nmol/L (~30 mg/dL); Intermediate: 75–125 nmol/L (30–50 mg/dL); High: ≥125 nmol/L (~50 mg/dL)

ACC/AHA risk-enhancing thresholdLp(a) ≥50 mg/dL (≥125 nmol/L) constitutes a risk‑enhancing factor per ACC/AHA guidance

ESC very high inherited risk thresholdESC notes levels >180 mg/dL (>430 nmol/L) indicate very high inherited risk

Clinical contextElevated Lp(a) is associated with increased CVD risk in cohort studies, but incremental clinical utility for management is not established

Triglyceride threshold for apoB consideration

Triglyceride threshold prompting apoB considerationTriglyceride ≥ 200 mg/dL cited as a relative indication for measuring apolipoprotein B (apoB)

ApoB risk contextElevated apoB (≥130 mg/dL) noted as a risk-enhancing factor; apoB measurement considered when TGs are high or to refine risk

Guideline framingACC/AHA lists apoB and triglyceride thresholds within risk-enhancing factors and measurement contexts

Prior Authorization

Verify prior authorization per plan

Always verify prior authorization requirements on a per-plan basis. Newly listed or updated tests (for example, CPT 0541U) may require plan-specific prior authorization or pre-determination.

Confirm prior authorization for new or uncommon codes (e.g., 0541U) with the payer.
Document clinical indication and intended device use when submitting requests (especially for device-based tests).

Denial Risk

Potential denial for unproven CVD risk tests

Claims for tests considered unproven or not medically necessary (for example, multi-protein risk panels, advanced lipoprotein analysis for general risk determination, arterial compliance testing, CIMT as screening, Lp-PLA2 for routine risk determination, endothelial function tests) may be denied.

The policy lists certain tests as unproven/not medically necessary and subject to denial.
Denial risk is higher when evidence does not demonstrate clinical utility or change in management.

Note

No explicit authorization/coverage action in policy

This policy provides informational guidance but does not itself establish coverage — there are no explicit authorization/coverage actions listed for every code. Providers must consult the member's benefit terms and administrative requirements for explicit authorization steps.

Use this policy as informational only; refer to contractual documents for final coverage decisions.
UnitedHealthcare may use third-party tools (e.g., InterQual®) to assist in benefit administration.

Denial Risk

Insufficient evidence may prompt denial

Insufficient evidence for clinical utility may prompt claim denial. For many multi-marker panels and certain endothelial function tests, the literature shows correlation with risk but lacks demonstration that test use improves patient management or outcomes.

Tests lacking evidence of improved clinical outcomes are considered experimental/unproven and may be not medically necessary.
Provide supporting clinical documentation if seeking authorization for tests with limited evidence.

Documentation Required

Reference benefit terms / Benefit requirement conflicts

Coverage determinations must reconcile the policy with federal, state, or contractual benefit terms; in case of conflict, the applicable benefit contract or law governs.

Reference the member's contract and applicable laws when making coverage decisions.
When policy guidance conflicts with contract terms, follow the federal/state/contractual requirements.

Documentation Required

Coding and documentation note

Inclusion of a procedure or diagnosis code in the policy is for reference only and does not imply coverage. Ensure coding and documentation support medical necessity; provide test indication and relevant clinical data with claims or prior authorization requests.

List of codes in this policy is not exhaustive and does not guarantee reimbursement.
Document clinical indication, prior therapies, and pertinent lab/imaging results when submitting requests.

Documentation Required

Studies report Lp(a) measured in nmol/L (and mg/dL)

Lp(a) results in cited studies are reported using nmol/L and mg/dL; when documenting or communicating results, include the unit of measure (e.g., nmol/L) and applicable thresholds noted by guidelines (for example, ≥ 125 nmol/L or ≥ 50 mg/dL as high risk in some guidance).

Report Lp(a) with units (nmol/L or mg/dL) and clarify threshold used when submitting clinical documentation.
Be aware that guideline-recommended thresholds vary (e.g., 75 nmol/L = 30 mg/dL considered low risk; ≥125 nmol/L = 50 mg/dL considered high risk per NLA).

Documentation Required

Regulatory and documentation notes

Document device intended use, FDA clearance/510(k) status, and test methodology when submitting prior authorization or claims for device-based or regulated tests. FDA clearance alone does not ensure coverage; policies are informational only.

Include device name and 510(k) number (when available) and intended patient population in submissions (e.g., EndoPAT 2000 510(k) K032519).
Advanced lipoprotein testing must comply with CLIA quality standards.

Step Therapy

No step-therapy requirements described / Step therapy not specified

There are no step-therapy requirements described in the reviewed policy sections for the listed tests. Providers should not assume any step-therapy or sequencing rules beyond standard clinical practice; verify plan-specific utilization management requirements.

Policy does not define step therapy for Lp-PLA2, multi-protein assays, or advanced lipoprotein testing.
Ensure standard lipid testing is performed and documented before pursuing advanced lipoprotein testing when clinically appropriate.

Step Therapy

Stepwise use of advanced lipoprotein testing

When considering advanced lipoprotein testing (e.g., Lp(a), LDL particle number, NMR profiles), follow a stepwise approach: perform standard lipid panel first, evaluate clinical risk factors and guideline-recommended risk enhancers, and reserve advanced testing for scenarios where results would change management.

Perform standard lipid panel and assess LDL-C/non-HDL-C before ordering advanced assays.
Reserve advanced lipoprotein testing for selected patients (e.g., strong family history, unexplained premature ASCVD, discrepant clinical picture) where guideline recommendations or specialist consultation support its use.

Direct methods: MRI and ultrasound; Indirect methods: pulse wave velocity (e.g., cfPWV), augmentation index, and waveform-derived indices

Clinical noteNo single gold standard; indices are proposed as early indicators of CVD but incremental clinical utility is not established

Advanced lipoprotein analysis / NMR definition

DefinitionAdvanced lipoprotein analysis / NMR — laboratory methods (e.g., NMR spectrometry, ultracentrifugation, vertical auto profile) that quantify lipoprotein subclasses, particle numbers, and advanced lipid metrics

Examples of methods/codesNMR spectrometry (0377U), high‑resolution fractionation/ultracentrifugation (0052U, 83701, 83704) are used to characterize HDL, LDL, VLDL subclasses and particle counts

Clinical noteThese tests characterize lipid particles beyond conventional lipids but evidence of incremental utility for routine risk management is inconsistent

CIMT short definition

Short definitionCIMT — ultrasound measurement of the carotid artery wall thickness used as a marker of atherosclerosis

PurposeUsed as a surrogate for coronary atherosclerosis severity and proposed for risk stratification

Evidence noteSystematic reviews show heterogeneity of CIMT measures and limited data that measurement changes clinical outcomes

Lp(a) definition — LDL-like particle measured mg/dL or nmol/L

DefinitionLipoprotein(a) [Lp(a)] — an LDL‑like particle with an additional apolipoprotein(a) moiety; measured in mg/dL or nmol/L and associated with increased ASCVD risk

Measurement units and thresholdsMeasured in mg/dL or nmol/L; guideline thresholds include ≥50 mg/dL (≥125 nmol/L) as a risk‑enhancing level and NLA stratifications (e.g., <75, 75–125, ≥125 nmol/L)

Clinical implicationGenetically determined; measurement may inform risk stratification in selected contexts though routine clinical utility is not fully established

Lp-PLA2 definition (mass/activity) — inflammatory biomarker association with stroke/CVD

DefinitionLipoprotein‑associated phospholipase A2 (Lp‑PLA2) — a vascular inflammatory enzyme measured as mass or activity and studied as a biomarker associated with stroke and cardiovascular events

Measurement formatsReported as activity or mass; studies report associations of higher Lp‑PLA2 with increased CHD and IS risk (RRs modestly >1 per SD)

Evidence and limitationsMeta‑analyses show associations but evidence quality is low and tests have not demonstrated clear clinical utility to change management

Lp-PLA2 alternate definition (mass/activity)

Alternate phrasingLp‑PLA2 — circulating enzyme measured as mass or activity investigated as an emerging marker of vascular inflammation and CVD risk

Association metricsMeta‑analyses report RRs for stroke and CHD comparing highest vs lowest Lp‑PLA2 categories (e.g., pooled HRs ~1.26–1.56 for stroke/CHD in some analyses)

Clinical recommendationAdditional well‑designed trials are needed; routine measurement for risk stratification is not established

Multi-protein blood test with algorithm — definition and output (risk score)

DefinitionMulti‑protein blood test with algorithm — laboratory assays measuring multiple biomarkers combined with clinical parameters via an algorithm to produce a risk score for obstructive CAD or future cardiovascular events

Reported outputsReported outputs include algorithmic risk scores and predicted probabilities or categorical risk levels (examples: HART CADhs, Mohebi et al. panel with C‑statistic reporting)

Evidence noteStudies report discrimination (AUC/C‑statistics) in derivation/validation cohorts but do not establish that use of these panels improves clinical outcomes or management

Peripheral arterial tonometry (PAT) definition

DefinitionPeripheral arterial tonometry (PAT) — a noninvasive test measuring fingertip pulse amplitude response to reactive hyperemia to assess microvascular endothelial function

MeasurementPAT records finger arterial pulse wave amplitude before and after occlusion; results often reported as a ratio or reactive hyperemia index (RHI)

Clinical evidenceCohort studies show inconsistent associations with composite CVD events; PAT may relate to stroke risk but not consistently to overall CVD outcomes

EndoPAT/Reactive Hyperemia Index (RHI) definition and intended use

EndoPAT / RHI definitionEndoPAT reactive hyperemia index (RHI) — device output derived from fingertip PAT after reactive hyperemia, reported as an index to assess endothelial function

Intended useEndoPAT 2000 has FDA 510(k) clearance as a diagnostic aid to detect coronary artery endothelial dysfunction in symptomatic patients undergoing evaluation for coronary disease

Screening limitationEndoPAT is not intended for use as a screening test in the general patient population per its 510(k) clearance summary

EndoPAT device brief — non-invasive diagnostic aid not for general screening

EndoPAT device briefEndoPAT 2000 — a noninvasive device cleared by FDA (K032519) as a diagnostic aid for detecting coronary artery endothelial dysfunction using a reactive hyperemia procedure

Intended populationCleared for symptomatic patients being evaluated for ischemic heart disease where angiography lacks obstructive CAD; not intended for general population screening

Regulatory noteClearance summary lists predicate device PAT 1000 RD (K001852); device intended‑use statements should be documented when claiming testing

SphygmoCor System definition — central arterial waveform analysis devices with 510(k) clearances

SphygmoCor system definitionSphygmoCor System — a series of noninvasive devices for central arterial pressure waveform analysis and arterial stiffness measurement; specific models (e.g., XCEL) have FDA 510(k) clearances

Regulatory examplesSphygmoCor XCEL cleared November 2012 (K122129); predicate device SphygmoCor CVMS (K070795) also cited

Clinical useIntended to assist clinicians managing hypertensive/pre‑hypertensive patients by providing central arterial BP and arterial stiffness calculations