The Efficacy Of Statin Administration On Vascular Function And Exercise Hyperemia In Patients With Heart Failure With Preserved Ejection Fraction

Background: Heart failure with preserved ejection fraction (HFpEF) is characterized by macro- and microvascular dysfunction resultant of disease-related derangements in inflammation, oxidative stress, and nitric oxide (NO) bioavailability. These impairments in vascular function contribute to a reduced hyperemic response to exercise and severe exercise intolerance in this patient population. Statins have been shown to exert pleiotropic effects including antioxidant and anti-inflammatory properties that improve NO bioavailability and endothelial function. However, whether statins improve peripheral vascular function and exercise hyperemia in patients with HFpEF has yet to be determined. Methods: Sixteen patients with HFpEF participated in a parallel, double-blind, placebo-controlled study in which patients were randomized to 30 days of statin (atorvastatin 10 mg, once daily) or placebo administration (Statin: n = 8, 74 ± 6 yr; Placebo: n = 8, 67 ± 9 yr). Conduit vessel function was assessed by sustained-stimulus flow-mediated dilation (SS-FMD) which was quantified by determining the slope of changes in brachial artery diameter across the range of shear rates during handgrip exercise. Exercising muscle blood flow was assessed by the change in forearm blood flow (∆FBF) and forearm vascular conductance (∆FVC) during rhythmic hand grip (HG) exercise (3 and 5 kg workloads, 1 Hz, 3 min per exercise stage). Results: The slope of brachial artery diameter to shear rate during progressive HG exercise increased (pre: 5.31 e-4 ± 3.85 e-4 cm/sec-1; post: 8.54 e-4 ± 4.98 e-4 cm/sec-1; P < 0.05) following statin administration, but was unchanged in the placebo group. In contrast, the hyperemic (∆FBF, pre, 3 kg: 137 ± 76 mL/min; 5 kg: 203 ± 102 mL/min; post, 3 kg: 131 ± 51 mL/min; 5 kg: 241 ± 93 mL/min; P > 0.05) and vasodilatory (∆FVC, pre, 3 kg: 107 ± 50 mL/min/mmHg; 5 kg: 162 ± 83 mL/min/mmHg; post, 3 kg: 119 ± 30 mL/min/mmHg; 5 kg: 215 ± 65 mL/min/mmHg; P > 0.05) response during HG exercise at 3 and 5 kg workloads was not different following statin administration. Conclusion: These data provide new evidence for the efficacy of low-dose statin administration to improve brachial artery endothelium-dependent vasodilation, but not exercising muscle blood flow, in patients with HFpEF. HL162856, HL139451, CX002152, IK2RX003670