Background: Homocysteine is an independent risk factor of ischemic stroke by promoting vascular endothelial dysfunction and thrombotic process through oxidative stress. We previously found that PFO closure may reduce total homocysteine level (tHcy) in plasma. Here, we compare the effect of PFO closure and medical treatment in reducing mild homocysteinemia in PFO-related stroke patients.
Method: 28 PFO-related stroke patients with mildly elevated tHcy (>12 μmol/l) were prospectively recruited in accordance with IRB. 14 received PFO closure and 14 were treated by medical therapy (antiplatelet/anticoagulant) alone. None of the patients were on folate or vitamin B supplementation. Plasma was collected at baseline and 1 year follow-up after treatment. tHcy level was determined by selected reaction monitoring using mass spectrometry.
Result: Compared to medical therapy, PFO closure resulted in a lower tHcy level during follow-up (PFO closure: 11.13 ± 3.94 μmol/L, medical therapy: 15.48 ± 3.55 μmol/L, p = 0.006), with no difference at baseline (PFO closure: 17.77 ± 4.39 μmol/L, medical therapy: 16.47 ± 7.50 μmol/L, p = 0.575). Mild hyperhomocysteinemia patients post PFO closure had a significant reduction of tHcy by 37.34% (p = 0.0005), with 71.43% of the patients (10 of 14) having tHcy levels back to normal (<12 μmol/l), while most of medically treated patients (13 of 14) stayed abnormal (p = 0.4820) (χ2-test, adjusted p = 0.002).
Conclusion: We found that compared with routine medical therapy, PFO closure reduced tHcy level in patients with mild hyperhomocysteinemia. Since PFO stroke patients tend to be younger, the life-time risk of even mildly elevated tHcy may be relevant for future thrombotic risk. Understanding the mechanism of PFO-related tHcy changes is important in optimizing medical treatment (e.g. folate replacement); studies are ongoing.