Abstract 111: Plasma Levels of Oxidative Stress Marker ADMA (Asymmetric Dimethylarginine) is Reduced by Successful PFO Closure

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Background: Patent foramen ovale (PFO) is an independent risk factor of ischemic stroke. It enables the mixing of venous and arterial blood and therefore serves as a conduit for venous clots and vasoactive factors to enter into arterial circulation and contribute to a prothrombotic status. Asymmetric dimethylarginine (ADMA), an endogenous competitive inhibitor of nitric oxide synthase, contributes to vascular disease and has been linked with increased levels of homocysteine, which creates additional oxidative stress by decreasing the production of dimethylarginine dimethlyaminohydrolase (DDAH) and further inhibiting the clearance of ADMA. We previously identified a significant reduction of homocysteine by PFO closure. Here we study the influence of PFO on ADMA levels, a marker of oxidative stress.

Method: 97 PFO-related stroke patients were prospectively recruited in accordance with IRB, of which 61 received PFO closure and 36 underwent medical therapy alone. Peripheral venous blood was collected at baseline (BL) and 1 year follow-up (FU) post treatments. Plasma ADMA was quantified by mass spectrometry.

Result: Compared to baseline, plasma ADMA levels were statistically significantly reduced post PFO closure (p = 0.0026), while no changes were observed for the patients treated with medications alone (p = 0.5500) (Figure 1A). Moreover, among the patients receiving PFO closure, the reduction of ADMA was only pronounced for those without residual shunting (p = 0.0009) but not for those with residual shunting (p = 0.4557) (Figure 1B, C).

Conclusion: PFO closure reduced oxidative stress marker ADMA in the circulation, but no changes were observed in patients on medical treatment only or those with residual shunting post PFO closure. Our results support the hypothesis that PFO-related right-to-left interatrial blood shunting may causally contribute to the high level of vasoactive factors in circulation. Further studies on an expanded cohort of PFO patients are ongoing.

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