Hyperhomocysteinemia and Cardiovascular Risk

Clinical Significance and Risk Assessment

Elevated total homocysteine levels are associated with a 2- to 3-fold increased risk of atherosclerotic vascular disease, stroke, and venous thromboembolism, and require evaluation to identify the underlying cause before initiating treatment with B vitamins 1, 2
For every 5 μmol/L increase in homocysteine, stroke risk increases by 59% (95% CI, 29-96%) 2
An increment of 5 mmol/L in total homocysteine confers equivalent coronary artery disease risk to a 20 mg/dL increase in plasma cholesterol 3, 2
Homocysteine accounts for up to 10% of the population's coronary artery disease risk 3, 2
Elevated levels are associated with increased carotid intima-media thickness and carotid artery stenosis 4, 2

Elevated homocysteine causes cardiovascular damage through multiple mechanisms, including endothelial dysfunction, eNOS uncoupling, pro-thrombotic state, and increased oxidative stress 3, 4

The American Heart Association/American Stroke Association suggests B-complex vitamins might be considered for prevention of ischemic stroke in patients with hyperhomocysteinemia (Class IIb; Level of Evidence B) 1, 2
The effectiveness of homocysteine-lowering therapy for reducing cardiovascular events remains controversial, with mixed evidence from trials such as NORVIT and HOPE-2 1, 2, 3, 4
However, the HOPE-2 study showed a 25% stroke reduction (RR 0.75; 95% CI, 0.59-0.97) with combination B6, B12, and folic acid therapy 2