Homocysteine Testing in the Screening, Diagnosis, and Management of Dyslipidemia and Cardiovascular Disease
DESCRIPTION
Homocysteine is a sulfur-containing amino acid that is rapidly oxidized into homocystine and cysteine-homocysteine disulfide within the plasma. It is normally found in the body and the metabolism of homocysteine is linked to that of several vitamins, especially folic acid, B6, and B12. Deficiencies of these vitamins may cause elevated levels of homocysteine. Individuals with rare inherited defects of methionine metabolism can develop severe hyperhomocystinemia (plasma levels>100 mumol/liter). In contrast to severe hyperhomocystinemia, mild to moderate elevations of homocysteine (plasma levels>15 mumol/liter) are common in general populations, primarily due to insufficient dietary intake of folic acid. Measurement of total plasma homocysteine is the sum of homocysteine and its oxidized forms. The homocysteine blood test determines the homocysteine concentration in the plasma.
Plasma levels of homocysteine have been actively researched as a risk factor for cardiovascular disease. The assumption was initially based on the observation that individuals with hereditary homocystinuria, an inborn error of metabolism associated with high plasma levels of homocysteine, had a markedly increased risk of cardiovascular disease. The interest in homocysteine as a risk factor was further stimulated by the fact that plasma levels of homocysteine would be considered a modifiable risk factor; i.e., plasma levels may be modified by diet, specifically by increased intake of vitamin B12 and B6 and folate.
POLICY
Homocysteine testing in the screening, diagnosis, and management of dyslipidemia and cardiovascular disease is considered investigational.
See also: Lipid Risk Factors in Risk Assessment and Management of Cardiovascular Disease
IMPORTANT REMINDER
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.
ADDITIONAL INFORMATION
Observational evidence supoorts a relationship between homocysteine and cardiovascular disease,especially in those individuals with pre-existing vascular disease; however randomized clinical trials show no benefit in cardiac and lack of certainty in stroke for homocysteine testing.
SOURCES
American Heart Association. AHA Recommendation. (2007). Homocysteine, folic acid and cardiovascular disease. Retrieved December 1, 2009 from http://www.americanheart.org/presenter.jhtml?identifier=4677.
Armitage J., Bowman, L., Clarke, R., Wallendszus, K., Bulbulia, R., Rahimi, K., et al. (2010). Effects of homocysteine-lowering with folic acid plus vitamin B12 vs placebo on mortality and major morbidity in myocardial infarction survivors: a randomized trial. JAMA, 303 (24), 2486 - 2494. (Level 1 Evidence - Industry supported)
Bazzano, L. A., Reynolds, K., Holder, K. N., & He, J. (2006). Effect of folic acid supplementation on risk of cardiovascular diseases: A meta-analysis of randomized controlled trials. JAMA, 296 (22), 2720-2726. (Level 4 Evidence - Industry sponsored)
BlueCross BlueShield Association. Medical Policy Reference Manual. (4:2011) Homocysteine testing in the screening, diagnosis, and management of cardiovascular disease (2.04.23). Retrieved August 17, 2011 from BlueWeb. (27 articles and/or guidelines reviewed)
Clarke, R., Armitage, J., Lewington, S., Collins, R., & B-Vitamin Treatment Trialists’ Collaboration. (2007). Homocysteine-lowering trials for prevention of cardiovascular events: a review of the design and power of the large randomized trials. Clinical Chemistry and Laboratory Medicine, 45 (12), 1575-1581. Abstract retrieved April 8, 2008 from PubMed database. (Level 1 Evidence)
Jamison, R., Hartigan, P., Kaufman, J., Goldfarb, D. S., Warren, S. R., Guarino, P., Gaziano, J. M., & Veterans Affairs Site Investigators. (2007). Effect of homocysteine lowering on mortality and vascular disease in advanced chronic kidney disease and end-stage renal disease: A randomized controlled trial. JAMA, 298 (10), 1163-1170. (Level 1 Evidence - Industry sponsored)
Kropf, S., Domröse, U., Westphal, S., Borucki, K., Luley, C., Neumann, K., et al. (2010). B vitamins and the risk of total mortality and cardiovascular disease in end-stage renal disease: results of a randomized controlled trial. Circulation, 121 (12), 1432 -1438. ( Level 1 Evidence - Independent)
Maron, B. A., & Loscalzo, J. (2006). Homocysteine. Clinics in Laboratory Medicine, 26 (3), 591-609.
Myers, G., Christenson, R., Cushman, M., Ballantyne, C., Cooper, G., Grundy, S. et al. (2006). National Academy of Clinical Biochemistry Laboratory Medicine practice guidelines, Emerging biomarkers of cardiovascular disease and stroke. Retrieved August 24, 2011 from http:// www.guideline.gov.
Nerbass, F. B., Draibe, S. A., Feiten, S. F., Chiarello, P. G., Vannucchi, H., & Cuppari, L. (2006). Homocysteine and its determinants in non-dialyzed chronic kidney disease patients. Journal of the American Dietetic Association, 106 (2), 267-270. (Level 3 Evidence - Industry sponsored)
Ray, J. G., Kearon, C., Yi, Q., Sheridan, P., & Lonn, E. (2007). Homocysteine-lowering therapy and risk for venous thromboembolism. Annals of Internal Medicine, 146 (11), 761-767. (Level 1 Evidence - Industry sponsored)
Soinio, M., Marniemi, J., Laakso, M., Lehto, S., & Ronnemaa, T. (2004). Elevated plasma homocysteine level is an independent predictor of coronary heart disease events in patients with type 2 diabetes mellitus. Annals of Internal Medicine, 140 (2), 94-100. (Level 1 Evidence - Industry sponsored)
U. S. Food and Drug Administration. (2004, February). Center for Devices and Radiological Health. 510(k) Premarket Notification Database. K033706. Retrieved April 8, 2008 from http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpmn/pmn.cfm?ID=13741.
U. S. Food and Drug Administration. (2006, October). Center for Devices and Radiological Health. 510(k) Premarket Notification Database. K062808. Retrieved April 8, 2008 from http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpmn/pmn.cfm?ID=22817.
ORIGINAL EFFECTIVE DATE: 1/1/2002
MOST RECENT REVIEW DATE: 10/13/2011
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