Chronic antioxidant administration restores macrovascular function in patients with heart failure with reduced ejection fraction.

Heart failure with reduced ejection fraction (HFrEF) is characterized by macrovascular dysfunction and elevated oxidative stress that may be mitigated by antioxidant (AOx) administration. In this prospective study, we assessed flow-mediated dilatation (FMD) and reactive hyperaemia responses in 14 healthy, older control participants and 14 patients with HFrEF, followed by 30 days of oral AOx administration (1 g vitamin C, 600 I.U. vitamin E and 0.6 g α-lipoic acid) in the patient group. Blood biomarkers of oxidative stress (malondialdehyde) and AOx capacity (ferric reducing ability of plasma) were also assessed. Patients with HFrEF had a lower %FMD (2.63 ± 1.57%) than control participants (5.62 ± 2.60%), and AOx administration improved %FMD in patients with HFrEF (30 days, 4.90 ± 2.38%), effectively restoring macrovascular function to that of control participants. In a subset of patients, we observed a progressive improvement in %FMD across the treatment period (2.62 ± 1.62, 4.23 ± 2.69, 4.33 ± 2.24 and 4.97 ± 2.56% at days 0, 10, 20 and 30, respectively, n = 12) that was abolished 7 days after treatment cessation (2.99 ± 1.78%, n = 9). No difference in reactive hyperaemia was evident between groups or as a consequence of the AOx treatment. Ferric reducing ability of plasma levels increased (from 6.08 ± 2.80 to 6.70 ± 1.59 mm, day 0 versus 30) and malondialdehyde levels decreased (from 6.81 ± 2.80 to 6.22 ± 2.84 μm, day 0 versus 30) after treatment. These findings demonstrate the efficacy of chronic AOx administration in attenuating oxidative stress, improving AOx capacity and restoring macrovascular function in patients with HFrEF.