3 Months of Nitrate plus Exercise Training Improves Hemodynamic Profile in Peripheral Arterial Disease

Abstract

Peripheral artery disease (PAD) is a form of cardiovascular disease caused by atherosclerotic occlusions that impair blood flow to the lower extremities. It is characterized by endothelial dysfunction and an inability to endogenously produce nitric oxide (NO). NO bioavailability is essential for vascular health and can be increased exogenously via oral nitrate supplementation and its subsequent conversion to plasma nitrite and NO. We have previously shown changes in resting hemodynamics following chronic exercise training and after an acute oral nitrate beverage. PURPOSE: To determine the effects of 3 months of supervised exercise training plus chronic dietary provision of an inorganic nitrate (4.2mmol in the form of concentrated beetroot juice, BR) beverage (EX+BR) versus exercise training and placebo beverage (EX+PL) on resting hemodynamics and hyperemic blood flow in subjects with PAD. The study was a double-blind, randomized controlled trial (data is a subset of a larger clinical trial). METHODS: At baseline testing, all subjects underwent measures of resting ankle-brachial index (ABI), aortic blood pressures (ASBP) and calf muscle blood flow during reactive hyperemia following 5 minutes of ischemia (RHBF). Subjects were then randomized to either the EX+BR (n=11) or EX+PL (n=12) group. Exercise training involved 3 sessions per week consisting of at least 30 minutes walking at a moderate claudication pain level. Subjects consumed BR or PL 3 hours prior to each exercise session. The 3-month testing protocol was identical to baseline. Comparisons were made using a two-way ANOVA with repeated measures. RESULTS: There were no differences in baseline measures for ABI, ASBP or RHBF between groups. At 3M, ABI increased 0.10±0.15 (p=0.05) and 0.15±0.11 (p≤0.01), RHBF 0.74±2.80% (ns) and 2.44±2.77% (p≤0.05) for the EX+PL and EX+BR respectively (ES = -0.69, CI = -0.17 to +1.51). Resting ASBP were significantly lower at 3M for EX±BR versus EX+PL (128.45±17.31 v 147.67±23.27mmHg, p0.05, ES = -0.95, CI = -1.76 to -0.04). CONCLUSION: Chronic administration of a high nitrate drink plus supervised exercise training improved the hemodynamic profile in subjects with PAD more than exercise training alone.Supported by grants R21HL111972 and R21HL113717 to JDA