Dietary nitrate supplementation and cardiovascular risk outcomes in chronic obstructive pulmonary disease
File(s)
Author(s)
Alasmari, Ali Mubarak
Type
Thesis
Abstract
It has been shown that acute/short-term dietary nitrate supplementation improves cardiovascular (CV) risk outcomes. However, it is not clear if any long-term beneficial effect is present. So, the overall aim of this thesis was to investigate the effect of prolonged consumption of daily nitrate rich beetroot juice (NR-BRJ) on CV risks in patients with COPD over three months.
A pooled result from the meta-analysis I conducted at the start of my PhD has shown a reduction in BP due to short term consumption of nitrate supplement. However, the longest and largest study combined the intervention with pulmonary rehabilitation leading to inconclusive results.
Therefore, I undertook a 3-month randomised controlled trial (the ON-BC study) recruiting COPD patients with systolic blood pressure (SBP) ≥130 mmHg. We observed for the first time a sustained reduction in SBP in the (NR-BRJ) intervention group as compared to placebo (Pl-BRJ) median (IQR): Δ -4 mm Hg, (-6, -2), vs. Δ -1 mmHg (-2, 1); an estimated treatment effect -3 mm Hg, (-6, 1), P<0.001), respectively. This was associated with a clinically significant improvement in exercise capacity (6-minute walk distance).
To explore the potential mechanisms associated with the observed change in SBP, I studied several vascular markers. Novel findings in this section include a fall in plasma asymmetric dimethylarginine (ADMA), and an increase in the plasma L-arginine/ADMA ratio. Endothelial function assessed using peripheral arterial tonometry (PAT) improved following NR-BRJ supplement, but there was no change in platelet aggregation.
In summary, this thesis has shown that dietary nitrate supplementation in the form of NR-BRJ exerts a sustained (12 weeks) effect on blood pressure in people with COPD, accompanied by improvements in other markers of endothelial function and vascular risk. Further longer-term trials are needed to examine the effects of BRJ at CVD event rates and establish whether the effect on exercise capacity translates into a meaningful improvement in daily life physical activity.
A pooled result from the meta-analysis I conducted at the start of my PhD has shown a reduction in BP due to short term consumption of nitrate supplement. However, the longest and largest study combined the intervention with pulmonary rehabilitation leading to inconclusive results.
Therefore, I undertook a 3-month randomised controlled trial (the ON-BC study) recruiting COPD patients with systolic blood pressure (SBP) ≥130 mmHg. We observed for the first time a sustained reduction in SBP in the (NR-BRJ) intervention group as compared to placebo (Pl-BRJ) median (IQR): Δ -4 mm Hg, (-6, -2), vs. Δ -1 mmHg (-2, 1); an estimated treatment effect -3 mm Hg, (-6, 1), P<0.001), respectively. This was associated with a clinically significant improvement in exercise capacity (6-minute walk distance).
To explore the potential mechanisms associated with the observed change in SBP, I studied several vascular markers. Novel findings in this section include a fall in plasma asymmetric dimethylarginine (ADMA), and an increase in the plasma L-arginine/ADMA ratio. Endothelial function assessed using peripheral arterial tonometry (PAT) improved following NR-BRJ supplement, but there was no change in platelet aggregation.
In summary, this thesis has shown that dietary nitrate supplementation in the form of NR-BRJ exerts a sustained (12 weeks) effect on blood pressure in people with COPD, accompanied by improvements in other markers of endothelial function and vascular risk. Further longer-term trials are needed to examine the effects of BRJ at CVD event rates and establish whether the effect on exercise capacity translates into a meaningful improvement in daily life physical activity.
Version
Open Access
Date Issued
2022-06
Date Awarded
2022-12
Copyright Statement
Creative Commons Attribution NonCommercial Licence
License URL
Advisor
Hopkinson, Nicholas
Polkey, Michael
Sponsor
Taibah University
Saudi Arabia. Ministry of Higher Education
Publisher Department
National Heart & Lung Institute
Publisher Institution
Imperial College London
Qualification Level
Doctoral
Qualification Name
Doctor of Philosophy (PhD)