Emergent Cardiovascular Risk Factor: Homocysteine

Cindy J. Warren, MSN, RN


Prog Cardiovasc Nurs. 2002;17(1) 

In This Article

How Homocysteine is Measured

Fasting blood tests are usually the manner in which homocysteine is measured.[3] For standard reference purposes, total fasting plasma homocysteine is recommended.[3] A patient who has had a serious illness, such as a myocardial infarction or cerebrovascular accident, should not be tested for 8-12 weeks after the event because there is a potential for the homocysteine level to be abnormal during that time period.[12] The reason for this effect has not been elucidated. Before a blood sample is taken, the patient should be advised to fast for 10-12 hours.[23] Between 0.6 and 1.2 mL of blood is collected in a green-top or purple-top tube for total homocysteine assay. The blood should be centrifuged within 30 minutes[12] to 1 hour[23] of collection, and must be refrigerated[12] or frozen until the time of analysis.[23] Some studies with negative results have been criticized for using plasma samples that were stored in liquid nitrogen for extended periods.[18] Storing blood at room temperature may cause homocysteine levels to be falsely elevated due to the export of homocysteine from red blood cells[2] or hemolysis.[23] If the sample is sent to an outside laboratory for analysis, the serum should be shipped on dry ice, via overnight delivery.[23] The cost of fasting homocysteine analysis ranges from $50-$110. It is advisable to check with individual insurance and managed care companies to ask if they will pay for the screening test.

Similar to a glucose tolerance test for metabolic abnormality, a methionine loading test can be performed to assess methionine metabolism. In some laboratories a granulated form of 100 mg/kg of methionine is dissolved in a glass of fruit juice and given orally after 10 hours of fasting. Blood samples are obtained before and at 4, 8, 12, and 24 hours after loading.[24] In other laboratories, the post-loading sample is taken once at 6 hours and compared to the fasting value.[25] The methionine loading test is more expensive; however, the fasting homocysteine test can be made more sensitive by lowering the normative range criterion.[25] A methionine loading test is used by van der Griend et al.[25] to diagnose hyperhomocysteinemia because a considerable number of people with high homocysteine would remain undiagnosed with the determination of a fasting homocysteine level alone.[25] This test is not conducted on patients whose creatinine levels exceed 1.5 mg/dL, because elevated creatinine levels indicate malfunctioning kidneys that cannot effectively filter protein (in this case, methionine).[17] Comparisons of serum folic acid, vitamins B6 and B12, and creatinine should be measured at the same time as homocysteine.[17]

A total plasma homocysteine level of ≤12 µmol/L is considered optimal,[4] but the algorithm used by Drs. McBride and Stein[12] starts secondary prevention at ≥11 µmol/L and considers ≥14 µmol/L to require primary prevention.[12] Those numbers vary somewhat, depending on which study is being followed.[3] A concentration above 15 µmol/L is associated with a high risk of occlusive vascular disease.[4] If the homocysteine level is ≥100 µmol/L, the patient should be referred to a geneticist, especially if several members of the same family have hyperhomocysteinemia.[4]


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