Cardiovascular Risk Panels
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.
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.
This policy does not address the use of panels of biomarkers in the diagnosis of acute myocardial infarction (MI).
There is no specific CPT code for cardiovascular risk panels. If there are CPT codes for the component tests in the panel and there is no algorithmic analysis used.
Some examples of commercially available CV risk panels include but are not limited to the following (see Description):
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, metabolic parameters, genetic markers, and/or radiologic measures. 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 (CV) remains the single largest cause of morbidity and mortality in the developed world. As a result, accurate prediction of CV 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 CV 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:
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 follow:
Multiple assay methods for cardiac risk marker components, such as lipid panels and other biochemical assays, have clearance for marketing through the FDA 510(k) process. Other components of testing panels are laboratory-developed tests. Laboratory-developed tests performed by laboratories licensed for high-complexity testing under the Clinical Laboratory Improvement Amendments (CLIA) act do not require clearance from FDA for marketing.
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. This medical policy does not apply to Medicare Advantage.
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, CV disease. A framework for evaluation the clinical utility of risk factor assessment includes the following steps:
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:
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)
In 2013, van Holten et al conducted a systematic review of meta-analyses of prospective studies evaluating the association between serologic biomarkers and primary CV events (ie, CV disease events and stroke in CV disease-naïve populations) and secondary CV events (ie, CV disease events and stroke in populations with a history of CV disease).7 The final data synthesis included 85 studies published from 1988 to 2011. Sixty-five meta-analyses reported biomarkers’ association with primary CV events and 43 reported associations with secondary CV events. Eighteen meta-analyses reported biomarkers’ association with ischemic stroke in patients with a history of CV disease. Only 2 meta-analyses that reported associations with ischemic stroke in patients with no history of CV disease were identified, and results were not reported. CV disease risks for markers with the strongest associations are summarized in Table 1.
Table 1. Serum Biomarkers and Cardiovascular Risk in van Holten et al (2013)
Apo: apolipoprotein; CRP: C-reactive protein; cTn: cardiac troponin; CV: cardiovascular; HDL: high density lipoprotein; HR; hazard radio; OR: odds ratio; RR: relative risk
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, 8, 9).
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.
Ongoing and Unpublished Clinical Trials
A search of online database ClinicalTrials.gov in September 2014 identified multiple studies designed to reduce cardiovascular risks, but no interventional studies to evaluate the utility of cardiac risk panels. One observational study evaluating a comprehensive cardiac risk panel in a case control design was identified:
Summary of Evidence
Numerous 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 included in CV risk panels 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
American College of Cardiology (ACC) and American Heart Association (AHA)
In 2013, the ACC and the AHA issued guidelines on the assessment of CV risk. (10) These guidelines recommend that age- and sex-specific pooled cohort equations which include total cholesterol and HDL to predict the 10-year risk of a first hard atherosclerotic CV disease event be used in non-Hispanic blacks and non-Hispanic whites age between 40 and 79 years (AHA/ACC class of recommendation: I; AHA/ACC level of evidence: B). Regarding newer risk markers after quantitative risk assessment, the guidelines state the following: “If, after quantitative risk assessment, a risk-based treatment decision is uncertain, assessment of ≥1 of the following—family history, hs-CRP, CAC [coronary artery calcium] score, or ABI [ankle-brachial index]—may be considered to inform treatment decision-making” (class of recommendation: IIb; level of evidence: B). The guidelines do not recommend other novel cardiac risk factors or panels of cardiac risk factors.
U.S. Preventive Services Task Force Recommendations
No recommendations specific to the use of cardiovascular risk panels were identified. In 2009, USPSTF made the following recommendation about using nontraditional risk factors in coronary heart disease risk assessment::
The U.S. Preventive Services Task Force (USPSTF) concludes that the evidence is insufficient to assess the balance of benefits and harms of using the nontraditional risk factors discussed in this statement to screen asymptomatic men and women with no history of CHD to prevent CHD events (select "Clinical Considerations" for suggestions for practice when evidence is insufficient). Grade: I
The nontraditional risk factors included in this recommendation are hsCRP, ABI, leukocyte count, fasting blood glucose level, periodontal disease, carotid intima-media thickness, coronary artery calcification score on electron beam computed tomography, homocysteine level, and lipoprotein (a) level.
Medicare National Coverage
There is no national coverage determination (NCD). In the absence of an NCD, coverage decisions are left to the discretion of local Medicare carriers.
Lipoprotein-associated Phospholipase A2 (Lp-PLA2)
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.
Clarification. Additional cardiovascular risk panels added to the list of panel examples: Berkeley Heart Lab Cardio IQ™ Lipid Panel and Atherotech® Diagnostics Lab CVD Risk Panel and VAP Lipid Panel. Add Related Policy 12.04.509.
Annual Review. Added examples of commercially available CV risk panels to Policy Guidelines. Policy updated with literature review through September 29, 2014. Added Clinical Trials section. Added Practice Guidelines from ACC and AHA. Added U.S. Preventive Services Task Force Recommendations Section. References 7 and 10 added; others renumbered. Policy statement unchanged.
Interim Review. CardioVIP added to list of CV risk panels in Policy Guidelines.
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).