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Plasma levels of homocysteine have been actively researched as a risk factor for cardiovascular disease, initially based on the observation that patients with hereditary homocystinuria, an inborn error of metabolism associated with high plasma levels of homocysteine, had a markedly increased risk of cardiovascular disease. Subsequently, prospective epidemiologic studies were conducted to determine if an elevated plasma level of homocysteine was an independent risk factor for cardiovascular disease, and could be used to improve current risk prediction models.

Interest in homocysteine as a potentially modifiable risk factor has been stimulated by the epidemiologic finding that levels of homocysteine are inversely correlated with levels of folate. This finding has raised the possibility that treatment with folic acid might lower homocysteine levels and, in turn, reduce the risk of coronary artery disease (CAD). Therefore, homocysteine has potential utility both as a risk predictor and as a target of treatment.

Determination of homocysteine may be offered as a component of a comprehensive cardiovascular risk assessment that may include evaluation of small-density lipoproteins, subclassification of high-density lipoproteins, evaluation of lipoprotein (a), high-sensitivity C-reactive protein, and genotyping of apolipoprotein E. These components are addressed in separate policies.

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Investigative service is defined as the use of any treatment procedure, facility, equipment, drug, device, or supply not yet recognized by certifying boards and/or approving or licensing agencies or published peer review criteria as standard, effective medical practice for the treatment of the condition being treated and as such therefore is not considered medically necessary.

The coverage guidelines outlined in the Medical Policy Manual should not be used in lieu of the Member's specific benefit plan language.

7/11/2001: Code Reference section updated

2/13/2002: Investigational definition added

5/8/2002: Type of Service and Place of Service deleted

8/8/2002: CPT code 82172 description revised, hyperlink added

3/31/2005: Reviewed by MPAC, Lipoprotein-associated phospholipase A2 (Lp-PLA2) is considered investigational, CPT code 82172 Note in Code Reference section “Apolipoprotein B (apo B) and Apolipoprotein E (apo E) testing is considered investigational.  Apolipoprotein A (apo A) is covered.  See Measurement of Small Low Density Lipoprotein (LDL) Particles medical policy.” deleted

5/12/2005: Code Reference section reviewed, ICD-9 diagnosis code 272.0-272.9, 410-414, 440.0-440.9, V12.50-V12.59, V17.3-V17.4, V77.91, V81.0-V81.2 deleted non-covered codes

5/9/2006: Policy reviewed, no changes

1/3/2007: Code reference section updated per the 2007 CPT/HCPCS revisions

4/4/2007: Policy reviewed, and updated. Homocysteine, apolipoprotein B (apo B), apolipoprotein E, and lipoprotein-associated phospholipase A2 (Lp-PLA2) separated into individual policies. Previously addressed in combination in the Tests used for Screening, Diagnosis, and Management of Dyslipidemia and Cardiovascular Disease policy

4/24/2009: Policy reviewed, no changes.

06/21/2011: Policy reviewed; no changes.

05/09/2012: Policy reviewed; no changes.

All codes billed for this procedure are considered investigational and not eligible for coverage.

Non-Covered Codes

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