Homocysteine is commonly used as a screen for people at high risk for heart attack or stroke. It may be useful in patients who have a family history of coronary artery disease but no other known risk factors. However, its utility for this purpose continues to be questioned because the role, if any, that homocysteine plays in the progression of cardiovascular disease (CVD) has not been established. Routine screening, such as that done for total cholesterol, is not yet recommended.

A physician may also order a homocysteine test to determine if a patient has B12 or folate deficiency. The homocysteine concentration may be elevated in patients before B12 and folate tests are abnormal. Some doctors may recommend homocysteine testing in malnourished patients, such as the elderly (who often absorb less vitamin B12 from their diets), and those with drug or alcohol addictions.

A doctor may order both a urine and blood homocysteine to help diagnose homocystinuria if they suspect that an infant may have this inherited disorder. In some states, babies are tested for excess methionine as part of their newborn screening. If a baby’s test is positive, then urine and blood homocysteine tests are often performed to confirm the findings.

Urine and/or blood homocysteine concentrations may be ordered at intervals to monitor the effectiveness of treatment in patients who are being treated for elevated homocysteine.

Homocysteine may be ordered as part of a cardiac risk assessment, depending on the patient’s age and other risk factors. It may also be ordered following a heart attack or stroke to help guide treatment. It may also be ordered when a doctor suspects that a patient may have a B12 and/or folate deficiency or when a baby has signs or symptoms that suggest that they may have homocystinuria.

Recent studies have suggested that people who have elevated homocysteine levels have a much greater risk of heart attack or stroke than those with average levels. At present, however, the American Heart Association has not established a direct correlation between homocysteine levels and heart attacks but does acknowledge strong evidence of a relationship between homocysteine levels and heart attack/stroke survival rates. Blockage of a coronary artery, a precursor to a heart attack, occurs with more than double the average frequency in people with homocysteine levels in the highest 25% as compared to those in the lowest 25%.

Since measuring homocysteine levels to determine cardiac risk is a relatively new use for the test, a standardized interpretation of the measured value has yet to be determined. In many people, homocysteine levels can be decreased by taking extra levels of folic acid, vitamin B12, and vitamin B6 - three B-complex vitamins that drive homocysteine metabolism. The elderly are especially vulnerable and may need these supplements to keep their homocysteine levels low.

Greatly increased concentrations of homocysteine in the urine and blood mean that it is likely that an infant has homocystinuria and indicate the need for further testing to confirm the cause of the increase.

When test results suggest homocystinuria, liver or skin biopsy samples are sometimes tested to determine whether the enzyme cystathionine beta synthase (CBS) is present. The absence of this enzyme is the most common cause of homocystinuria. Genetic tests may be ordered to test for one or more of the most common gene mutations. If the patient has a strong family history of early atherosclerosis or a family member has been diagnosed with homocystinuria, then the patient should be tested for the gene mutation that was found in the family member.

Homocysteine levels can increase with age, when a patient smokes, and with the use of drugs such as carbamazepine, methotrexate, and phenytoin.