Novel Biomarkers in Risk Assessment and Management of Cardiovascular Disease
A standard lipid panel calculates LDL, HDL, triglycerides and total cholesterol. New laboratory tests have been developed to address non-standard lipid and non-lipid markers either individually or as part of a panel. These novel biomarkers include:
B-type natriuretic peptide (BNP)
Some cardiovascular risk panels are relatively limited, including a few markers in addition to standard lipids. Others include both genetic and nongenetic risk factors while some are composed entirely of genetic markers. Some examples of commercially available cardiovascular risk panels are as follows:
Health Diagnostics Cardiac Risk Panel: MTHFR gene analysis, common variants; vitamin D, 1,25 dihydroxy; B-type natriuretic peptide; lipoprotein-associated phospholipase A2 (Lp-PLA2); myeloperoxidase; apolipoprotein; immune complex assay; lipoprotein, blood; electrophoretic separation and quantitation; very long chain fatty acids; total cholesterol; HDL; LDL; triglycerides; hs-CRP; Lp(a); insulin, total; fibrinogen; apolipoprotein analysis; multiple SNPs associated with coronary artery disease (CAD).
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; Lp(a); Lp-PLA2; MTHFR gene; triglycerides; very-low-density lipoprotein (VLDL); VLDL size; vitamin D; hs-CRP.
Genova Diagnostics CV Health Plus™ Panel: fibrinogen; HDL; HDL size; HDL particle number; homocysteine; LDL; LDL size; LDL particle number; lipid panel; Lp(a); Lp-PLA2; triglycerides; VLDL; VLDL size; vitamin D; hs-CRP.
Cleveland Heartlab CVD Inflammatory Profile: hs-CRP, urinary microalbumin, myeloperoxidase, Lp-PLA2, F2 isoprostanes.
Applied Genetics Cardiac Panel: genetic mutations associated with CAD: cytochrome p450 mutations associated with metabolism of clopidogrel, ticagrelor, warfarin, beta-blockers, rivaroxaban, prasugrel (2C19, 2C9/VKORC1, 2D6, 3A4/3A5), factor V Leiden, prothrombin gene, MTHFR gene, APOE 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.
Singulex® Cardiac-Related Test Panels: Several panels of markers related to cardiac dysfunction, vascular inflammation and dysfunction, dyslipidemia, and cardiometabolic status are offered by Singulex (Alameda, CA). Some of these panels are offered in conjunction with a CV disease testing and wellness management service. The test panels use an immunoassay method referred to as “Proprietary high-precision Single Molecule Counting [SMC] technology.”
Cardiac Dysfunction panel: SMC™ cTnl (high-sensitivity troponin), N-terminal pro-B-type natriuretic peptide
Vascular Inflammation and Dysfunction panel: SMC™ IL-6, SMC™ IL-17A, SMC™ TNFα, SMC™ Endothelin, Lp-PLA2, hs-CRP, homocysteine, vitamin B12, folate.
Dyslipidemia panel: total cholesterol, LDL-C (direct), apo B, small dense LDL, HDL cholesterol, apo AI, HDL2b, triglycerides, Lp(a).
Cardiometabolic panel: parathyroid , vitamin D, calcium, magnesium, leptin, adiponectin, ferritin, cortisol, cystatin C, hemoglobin A1c, glucose, insulin, thyroid-stimulating hormone (TSH), T3 and free T4, uric acid, liver panel, renal panel, thyroid peroxidase antibody, thyroglobulin antibody.
When a standardized test is billed alone (e.g., BNP test, LDL, HDL), and is not part of a novel biomarker risk assessment, this policy should not be used to deny that test.
The use of panels that include non-standard lipid and non-lipid cardiovascular risk markers is considered investigational.
Measurement of novel lipid and nonlipidbiomarkers (e.g., apolipoprotein A-I, apolipoprotein B, apolipoprotein E, B-type natriuretic peptide, cystatin C, fibrinogen, HDL subclass, LDL subclass, leptin, lipoprotein[a]) as an adjunct to LDL cholesterol in the risk assessment and management of cardiovascular disease is considered investigational.
Any specific products referenced in this policy are just examples and are intended for illustrative purposes only. It is not intended to be a recommendation of one product over another, and is not intended to represent a complete listing of all products available. These examples are contained in the parenthetical e.g. statement.
We develop Medical Policies to provide guidance to Members and Providers. This Medical Policy relates only to the services or supplies described in it. The existence of a Medical Policy is not an authorization, certification, explanation of benefits, or a contract for the service (or supply) that is referenced in the Medical Policy. For a determination of the benefits that a Member is entitled to receive under his or her health plan, the Member's health plan must be reviewed. If there is a conflict between the Medical Policy and a health plan, the express terms of the health plan will govern.
Published data are inadequate to determine how novel biomarker measurements should guide treatment decisions and whether these treatment decisions result in beneficial outcomes.
American Association of Clinical Endocrinologists. American College of Endocrinology. (2017). American Association of Clinical Endocrinologists and American College of Endocrinology guidelines for management of dyslipidemia and prevention of cardiovascular disease. Retrieved March 9, 2017 from https://www.aace.com/files/lipid-guidelines.pdf.
American Heart Association. Scientific Statement. (2011) Nontraditional risk factors and biomarkers for cardiovascular disease: mechanistic, research, and clinical considerations for youth. Retrieved March 9, 2017 from http://circ.ahajournals.org/content/circulationaha/123/23/2749.full.pdf.
BlueCross BlueShield Association. Evidence Positioning System. (12:2018). Novel biomarkers in risk assessment and management of cardiovascular disease (2.04.65). Retrieved October 18, 2018 from http://www.evidencepositioningsystem.com/. (126 articles and/or guidelines reviewed)
BlueCross BlueShield Association. Medical Policy Reference Manual. (12:2017). Cardiovascular Risk Panels (2.04.100) Retrieved October 18, 2018 from http://www.evidencepositioningsystem.com/. (25 articles and/or guidelines reviewed)
Boekholdt, S. M., Arsenault, B. J., Mora, S., Pedersen, T. R., LaRosa, J. C., Nestel, P. J., et al. (2012). Association of LDL cholesterol, non-HDL cholesterol, and apolipoprotein B levels with risk of cardiovascular events among patients treated with statins. A meta-analysis. JAMA, 307 (12), 1302-1309. (Level 1 evidence)
CMS.gov: Center for Medicare & Medicaid Services. Palmetto, GBA. (2018, October) MolDX: Biomarkers in Cardiovascular Risk Assessment (LCD ID L36129). Retrieved October 18, 2018 from https://www.cms.gov.
Di Angelantonio, E., Gao, P., Pennells, L., Kaptoge, S., Caslake, M., Thompson, A., et al. (2012). Lipid-related markers and cardiovascular disease prediction. JAMA, 307 (23), 2499-2506. (Level 2 evidence)
National Institute for Health and Care Excellence. (2014; last update search September, 2016). Cardiovascular disease: risk assessment and reduction, including lipid modification. Retrieved March 9, 2017 from www.nice.org.uk/guidance.
Wang, J., Tan, G., Han, L., Bai, Y., He, M., & Liu, H. (2017). Novel biomarkers for cardiovascular risk prediction. Journal of geriatric Cardiology, 14, 135-150. (Level 2 evidence)
ORIGINAL EFFECTIVE DATE: 12/12/2011
MOST RECENT REVIEW DATE: 1/10/2019
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