From the Guidelines
Homocysteine levels should be checked in patients with premature cardiovascular disease without traditional risk factors, recurrent venous thromboembolism, or a family history of early-onset atherosclerosis, as recommended by the most recent guidelines 1. Testing is also recommended for individuals with certain genetic disorders like homocystinuria, patients with vitamin B12 or folate deficiency, those with chronic kidney disease, and in cases of unexplained neurological disorders. The test helps identify elevated homocysteine levels, which are associated with increased cardiovascular risk through mechanisms including endothelial dysfunction, oxidative stress, and promotion of thrombosis, as supported by studies on the relationship between homocysteine and cardiovascular disease 1. Elevated levels can be addressed through supplementation with B vitamins (particularly B6, B12, and folate) at standard doses, though routine screening in the general population is not recommended due to limited evidence that treating elevated levels significantly reduces cardiovascular events. Fasting before the test is typically required for accurate results, and certain medications like methotrexate, anticonvulsants, and metformin may affect homocysteine levels. Some key points to consider when checking homocysteine levels include:
- The definition of hyperhomocysteinemia as a fasting total plasma homocysteine level > 15 mM, with graded increased risks for persons with levels of 10–15 mM 1
- The importance of precise sample collection, immediate separation and freezing of plasma, and referral to a specialized laboratory for accurate measurement of total plasma homocysteine 1
- The complex etiologies of hyperhomocysteinemia, involving both genetic and environmental factors, and the need to identify the cause prior to treatment 1
From the Research
When to Check Homocysteine Levels
Homocysteine levels should be checked in the following situations:
- In patients with unexplained thrombotic tendencies 2
- In young patients who develop coronary events or disease without the usual predisposing factors such as hypertension, smoking, hypercholesterolemia, or diabetes 2
- In patients with known cardiovascular disease or who are at high risk 3
- In patients with chronic kidney disease or end-stage renal disease, as they experience tremendous cardiovascular risk 4
- In adults with total homocysteine values of 11 μmol/L or above, as values above this level may justify intervention 5
Specific Conditions that May Require Homocysteine Level Checks
- Coronary disease 2
- Venous thromboembolism 2, 3
- Stroke 3, 5
- Cognitive impairment in the elderly 5
- Macular degeneration 5
- Neural tube defects 5
- Impaired childhood cognition 5
Considerations for Checking Homocysteine Levels
- Elevated plasma homocysteine is associated with an increased risk of myocardial infarction, stroke, and venous thromboembolism 3
- Folic acid and other B vitamins can lower plasma homocysteine levels, but whether this therapy confers a clinical benefit has yet to be determined 3
- The link between hyperhomocysteinemia and cardiac disease has not been conclusively shown to be causal as yet 2