Oral nitrate supplementation improves cardiovascular risk markers in COPD: ON-BC, a randomised controlled trial

Abstract

Background: Short-term studies suggest that dietary nitrate (NO₃ ^-) supplementation may improve the cardiovascular risk profile, lowering blood pressure (BP) and enhancing endothelial function. It is not clear if these beneficial effects are sustained and whether they apply in people with COPD, who have a worse cardiovascular profile than those without COPD. Nitrate-rich beetroot juice (NR-BRJ) is a convenient dietary source of nitrate.

Methods: The ON-BC trial was a randomised, double-blind, placebo-controlled parallel group study in stable COPD patients with home systolic BP (SBP) measurement ≥130 mmHg. Participants were randomly allocated (1:1) using computer-generated, block randomisation to either 70 mL NR-BRJ (400 mg NO₃ ^-) (n=40) or an otherwise identical nitrate-depleted placebo juice (0 mg NO₃ ^-) (n=41), once daily for 12 weeks. The primary end-point was between-group change in home SBP measurement. Secondary outcomes included change in 6-min walk distance (6MWD) and measures of endothelial function (reactive hyperaemia index (RHI) and augmentation index normalised to a heart rate of 75 beats·min^-1 (AIx75)) using an EndoPAT device. Plasma nitrate and platelet function were also measured.

Results: Compared with placebo, active treatment lowered SBP (Hodges-Lehmann treatment effect -4.5 (95% CI -5.9- -3.0) mmHg), and improved 6MWD (30.0 (95% CI 15.7-44.2) m; p<0.001), RHI (0.34 (95% CI 0.03-0.63); p=0.03) and AIx75 (-7.61% (95% CI -14.3- -0.95%); p=0.026).

Conclusions: In people with COPD, prolonged dietary nitrate supplementation in the form of beetroot juice produces a sustained reduction in BP, associated with an improvement in endothelial function and exercise capacity.

FIGURE 1

CONSORT flow diagram for the Oral Nitrate for Blood pressure in COPD (ON-BC) trial. NR-BRJ: nitrate-rich beetroot juice; Pl-BRJ: placebo beetroot juice; COVID-19: coronavirus disease 2019; AECOPD: acute exacerbation of COPD; PAT: peripheral arterial tonometry; 6MWT: 6-min walk test.

FIGURE 2

Effect of dietary nitrate supplementation on blood pressure (BP) parameters. Change in home-monitored BP parameters in placebo beetroot juice (Pl-BRJ; n=34) versus nitrate-rich beetroot juice (NR-BRJ; n=36) subjects with COPD. Data are presented as mean±sd. HSBP: home systolic BP; HDBP: home diastolic BP; HMAP: home mean arterial pressure (calculated as MAP∼(SBP+(DBP×2))/3).

FIGURE 3

Effect of dietary nitrate supplementation on exercise capacity and endothelial function. a) 6-min walk distance (6MWD) in placebo beetroot juice (Pl-BRJ; n=20) and nitrate-rich beetroot juice (NR-BRJ; n=24) COPD individuals. b, c) Endothelial function assessed, in Pl-BR (n=19) compared with NR-BRJ (n=21), as b) reactive hyperaemia index (RHI) and c) augmentation index normalised to a heart rate of 75 beats·min⁻¹ (AIx75). Data are presented as mean±sd.

FIGURE 4

Effect of dietary nitrate supplementation on plasma nitrogen oxides (NO_x) concentrations in individuals with COPD. Data are presented as median (interquartile range); whiskers indicate minimum–maximum range. Pl-BRJ: placebo beetroot juice; NR-BRJ: nitrate-rich beetroot juice.