Abstract 2766: No Additional Improvement in Vascular Function With High Dose vs. Low Dose Folic Acid in Coronary Artery Disease - Implications for HOPE-2
Background: Folic acid (FA) appears to improve vascular function. However, the HOPE-2 study found no additional clinical benefit from folate therapy in patients from a folate-fortified population. We compared the effects of low and high dose folic acid treatment on vascular function in a non-folate fortified population using magnetic resonance imaging (MRI), and determined the relationships with both plasma and vascular tissue concentrations of 5-methyltetrahydrofolate (5MTHF), the active metabolite of FA.
Methods: In a double-blind placebo-controlled trial, 56 patients (mean age 63±1y) with coronary artery disease undergoing coronary bypass surgery were randomized to receive FA 400μg/d or 5mg/d, or placebo, for 6 weeks. Changes in aortic distensibility and brachial artery flow-mediated dilatation (FMD) were quantified by high-resolution cine MRI (1.5 tesla). 5MTHF levels were measured in plasma and in tissue samples of internal mammary artery (IMA) and saphenous vein (SV).
Results: Both aortic distensibility and FMD significantly improved after FA 400μg and 5mg/d, but not placebo (figs a, b⇓). Plasma 5MTHF was significantly increased in the 5mg/d-treated group compared to the 400μg/d group (fig c⇓). In contrast, vascular tissue 5MTHF levels were similarly increased in both treatment groups compared with placebo (fig d⇓).
Conclusion: Despite a large difference in plasma levels, vascular tissue 5MTHF levels are similar after both low and high dose FA treatment, leading to similar improvements in arterial stiffness and endothelial function. Low-dose FA supplementation may only be a useful therapeutic strategy in non-folate fortified vascular disease populations.