Cardiovascular Risk Panels

Number 2.04.509

Effective Date October 14, 2013

Revision Date(s) N/A

Replaces N/A


Cardiovascular risk panels, consisting of multiple individual biomarkers intended to assess cardiac risk (other than simple lipid panels- see Policy Guidelines), are considered not medically necessary.

Related Policies


Ultrasonographic Measurement of Carotid Intimal-Medial Thickness as an Assessment of Subclinical Atherosclerosis


Measurement of Lipoprotein-Associated Phospholipase A2 (Lp-PLA2) in the Assessment of Cardiovascular Risk


Genotyping for 9p21 Single Nucleotide Polymorphisms to Predict Risk of Cardiovascular Disease or Aneurysm


Gene Expression Testing to Predict Coronary Artery Disease

Policy Guidelines

A simple lipid panel is generally composed of the following lipid measures:

  • Total cholesterol
  • LDL cholesterol
  • HDL cholesterol
  • Triglycerides

Certain calculated ratios, such as the total/HDL cholesterol may also be reported as part of a simple lipid panel.

Other types of lipid testing, i.e. apolipoproteins, lipid particle number or particle size, lipoprotein (a), etc., are not considered to be components of a simple lipid profile.


Cardiovascular risk panels refer to different combinations of cardiac markers that are intended to evaluate risk of cardiovascular disease. There are numerous commercially available risk panels that include different combinations of lipids, non-cardiac biomarkers (e.g. troponin, BNP), measures of inflammation, radiologic measures and/or genetic markers. Risk panels report the results of multiple individual tests, as distinguished from quantitative risk scores that combine the results of multiple markers into one score.


Cardiovascular disease remains the single largest cause of morbidity and mortality in the developed world. As a result, accurate prediction of cardiovascular risk is a component of medical care that has the potential to focus and direct preventive and diagnostic activities. Current methods of risk prediction in use in general clinical care are not highly accurate, and as a result there is a potential unmet need for improved risk prediction instruments.

Components of cardiovascular risk include family history, cigarette smoking, hypertension, and lifestyle factors such as diet and exercise. In addition, numerous laboratory tests have been associated with CV risk, most prominently lipids such as LDL and HDL. These clinical and lipid factors are often combined into simple risk prediction instruments, such as the Framingham risk sore (FRS). (1) The Framingham risk score provides an estimate of the 10 year risk for developing cardiac disease, and is currently used in clinical care to determine the aggressiveness of risk factor intervention, such as the decision to treat hyperlipidemia with statins.

Many additional biomarkers, genetic factors and radiologic measures, have been associated with increased risk of CV disease. Over 100 emerging risk factors have been proposed as useful for refining estimates of cardiovascular risk. (2-4) Some general categories of these potential risk factors are as follows:

  • Lipid markers. In addition to LDL and HDL, other lipid markers may have predictive ability, including the apolipoproteins, Lipoprotein (a), lipid subfractions, and/or other measures.
  • Inflammatory markers. Many measures of inflammation have been linked to the likelihood of CV disease. High sensitivity CRP is one example of an inflammatory markers, other include fibrinogen, interleukins, and
  • Metabolic syndrome biomarkers. Measures associated with metabolic syndrome, such as specific dyslipidemic profiles or serum insulin levels, have been associated with increased risk of CV disease.
  • Radiologic measures. Carotid artery CMT and coronary artery calcium scores are two radiologic measures that have been associated with increased risk.
  • Genetic markers. A number of mutations that associated with increased thrombosis risk, such as the MHTFR mutation or the prothrombin gene mutations, have been associated with increased CV risk. In addition, numerous single-nucleotide polymorphisms (SNP’s) have been associated with CV disease in large genome-wide studies.

CV risk panels may contain measures from one or all of the above categories. Some cardiovascular risk panels are relatively limited, including a few markers in addition to standard lipids. Others include a wide variety of potential risk factors from a number of different categories, often including both genetic and non-genetic risk factors. Other panels are composed entirely of genetic markers.

Some examples of commercially available CV risk panels are as follows:

  • Health Diagnostics Cardiac Risk Panel: MTHFR gene analysis, common variants; Vitamin D; 1, 25 dihydroxy ; BNP; Lp-PLA2; Myeloperoxidase; Apolipoprotein, each; Immune complex assay; Lipoprotein, blood; electrophoretic separation and quantitation; Very long chain fatty acids; Total cholesterol; HDL; LDL; triglycerides; (hsCRP); Lipoprotein (a); Insulin, total; Fibrinogen; apolipoprotein analysis; multiple SNP’s associated with CAD;
  • Boston Heart Advanced Risk Markers Panel: small dense LDL, Lipoprotein (a), apolipoprotein B, hsCRP, Lipoprotein-Associated Phospholipase A2, Homocysteine
  • Genova Diagnostics CV Health Plus Genomics™ Panel: Apo E; Prothrombin; Factor V Leiden; Fibrinogen; HDL; HDL size; HDL particle number; Homocysteine; LDL; LDL size; LDL particle number; Lipoprotein (a); LP-PLA2; MTHFR gene; Triglycerides, VLDL; VLDL size; vitamin D; hs-CRP.
  • Metametrix Cardiovascular Health Profile; Total cholesterol, HDL, LDL, triglycerides, lipoprotein (a), ferritin, fibrinogen, hsCRP, coenzyme Q, vitamin E, lipid peroxides, homocysteine, RBC magnesium, insulin, testosterone, sex hormone binding globulin, free androgen index.
  • Cleveland HeartLab CVD Inflammatory Profile: hs-CRP, urinary microalbumin, myeloperoxidase, Lp-PLA2, F2-isoprostanes.
  • Applied Genetics Cardiac Panel: Genetic mutations associated with: cytochrome p450 (2C19, 2C9/VKORC1, 2D6, 3A4/3A5), Factor V Leiden, Prothrombin gene, MTHFR gene, Apo-E gene.
  • Genetiks Genetic Diagnosis and Research Center Cardiovascular Risk Panel: Factor V Leiden, Factor V R2, Prothrombin gene, Factor XIII, Fibrinogen -455, PAI-1, GPIIIs (HPA-1), MTHFR, ACE I/D, Apo B, Apo E.


Medical policies are systematically developed guidelines that serve as a resource for Company staff when determining coverage for specific medical procedures, drugs or devices. Coverage for medical services is subject to the limits and conditions of the member benefit plan. Members and their providers should consult the member benefit booklet or contact a customer service representative to determine whether there are any benefit limitations applicable to this service or supply.

Benefit Application



This policy was created in October 2013, with review of the literature through July 31, 2013.

There is a large amount of literature on the association of individual risk factors with cardiovascular disease. The vast majority of this literature evaluates correlations between individual biomarkers and the presence of, or future development of, cardiovascular disease. A framework for evaluation the clinical utility of risk factor assessment includes the following steps:

  1. Standardization of the measurement of the risk factor.
  2. 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 to established risk factors. In addition, as there are many potential novel risk factors that could be incorporated into existing CV risk panels, it is important to understand the relationship of each individual risk factor with other risk factors.
  3. Determination of how the novel risk assessment will be used in the management of the patient, compared to standard methods of assessing risk, and whether any subsequent changes in patient management result in an improvement in patient outcome.

Helfand et al (2) have suggested a similar framework for evaluating the utility of risk factors that includes the concept of reclassifying patients into clinically relevant risk factors. These suggested criteria are as follows:

  • Risk factor should be easily and reliably measured.
  • Risk factor should be an independent predictor of major CV events in patients with an intermediate risk of CV disease and no history of CV disease.
  • Risk factor should reclassify a substantial portion of intermediate risk patients as high-risk
  • Reclassified individuals should be managed differently than they otherwise would have been
  • If other risk factors provide similar prognostic information, then convenience, availability, cost and safety should be considered in choosing among them.

Literature Review

No published studies were identified that evaluated the use of commercially available cardiovascular risk panels as risk prediction instruments in clinical care. Some studies have attempted to incorporate novel risk markers into an overall quantitative risk score, (5, 6) but these risk scores are not the same as CV risk panels, which report the results of individual risk factors.

There is a large evidence base on the association of individual risk markers with cardiovascular risk. Many observational studies have established that individual risk markers are independent predictors of cardiac risk. (2, 4) Other studies have demonstrated that risk markers can be used to reclassify patients into different risk categories. However, there is there is no convincing evidence that addition of any individual risk marker, or combination or risk markers, leads to clinically meaningful changes in management that improve outcomes. In the available studies, the improvement in risk prediction has generally been of a small magnitude, and/or has not been found to be associated with clinically meaningful management changes.(2, 7, 8).

Because of this uncertain impact on management, the clinical utility for any of the individual risk markers is either low or uncertain. For some of the individual factors, there are existing medical policies (see Related Policies). In all cases where individual risk factors have been evaluated, the individual risk factors did not meet the criteria for medical necessity.

The available evidence on individual risk markers is only of limited value in evaluating CV risk panels. It is difficult to extrapolate the results of single risk factors to panels given the variable composition of panels. Ideally, panels should be evaluated individually as to their impact on clinical decision making

Furthermore, there are no standardized methods for combining multiple individual risk factors with each other, or with established risk prediction instruments such as the Framingham risk score. Therefore, there is a potential for both overestimation and underestimation of the true cardiac risk. This may lead to management decisions that are based on an inaccurate risk assessment. As a result of these deficiencies, it is not possible to make a reliable assessment of the impact of using CV risk panels on health outcomes.

Clinical Input Received through Physician Specialty Societies and Academic Medical Centers



Numerous cardiovascular (CV) risk panels are commercially available. These panels report results for multiple individual CV risk markers, and have wide variability in the risk factors included in the panel. While the individual risk factors have in most cases been associated with increased risk of CV disease, it is not clear how the results of individual risk factors impact management changes, so it is also not certain how the panels will impact management decisions. Given the lack of evidence for clinical utility of any individual risk factor beyond simple lipid measures, it is unlikely that the use of CV risk panels improves outcome. As a result, the use of cardiac risk panels for predicting risk of CV disease is considered not medically necessary.

Practice Guidelines and Position Statements


Medicare National Coverage



  1. D'Agostino RB, Sr., Grundy S, Sullivan LM et al. Validation of the Framingham coronary heart disease prediction scores: results of a multiple ethnic groups investigation. JAMA : the journal of the American Medical Association 2001; 286(2):180-7.
  2. Helfand M, Buckley DI, Freeman M et al. Emerging risk factors for coronary heart disease: a summary of systematic reviews conducted for the U.S. Preventive Services Task Force. Annals of internal medicine 2009; 151(7):496-507.
  3. Brotman DJ, Walker E, Lauer MS et al. In search of fewer independent risk factors. Archives of internal medicine 2005; 165(2):138-45.
  4. Greenland P, Alpert JS, Beller GA et al. 2010 ACCF/AHA guideline for assessment of cardiovascular risk in asymptomatic adults: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Journal of the American College of Cardiology 2010; 56(25):e50-103.
  5. Ridker PM, Buring JE, Rifai N et al. Development and validation of improved algorithms for the assessment of global cardiovascular risk in women: the Reynolds Risk Score. JAMA : the journal of the American Medical Association 2007; 297(6):611-9.
  6. Zethelius B, Berglund L, Sundstrom J et al. Use of multiple biomarkers to improve the prediction of death from cardiovascular causes. The New England journal of medicine 2008; 358(20):2107-16.
  7. Emerging Risk Factors C, Di Angelantonio E, Gao P et al. Lipid-related markers and cardiovascular disease prediction. JAMA : the journal of the American Medical Association 2012; 307(23):2499-506.
  8. Paynter NP, Chasman DI, Pare G et al. Association between a literature-based genetic risk score and cardiovascular events in women. JAMA : the journal of the American Medical Association 2010; 303(7):631-7.













New policy. Policy created with literature review through July 31, 2013. Cardiovascular risk panels consisting of multiple individual markers intended to assess cardiac risk are considered not medically necessary.

Disclaimer: This medical policy is a guide in evaluating the medical necessity of a particular service or treatment. The Company adopts policies after careful review of published peer-reviewed scientific literature, national guidelines and local standards of practice. Since medical technology is constantly changing, the Company reserves the right to review and update policies as appropriate. Member contracts differ in their benefits. Always consult the member benefit booklet or contact a member service representative to determine coverage for a specific medical service or supply. CPT codes, descriptions and materials are copyrighted by the American Medical Association (AMA).
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