Accessibility navigation


A randomised, factorial trial to reduce arterial stiffness independently of blood pressure: proof of concept? The ‘VaSera’ trial testing dietary nitrate and spironolactone

Mills, C. E., Govini, V., Faconti, L., Casagrande, M.-L., Morant, S. V., Crickmore, H., Iqbal, F., Maskell, P., Masani, A., Nanino, E., Webb, A. J. and Cruickshank, J. K. (2020) A randomised, factorial trial to reduce arterial stiffness independently of blood pressure: proof of concept? The ‘VaSera’ trial testing dietary nitrate and spironolactone. British Journal of Clinical Pharmacology. ISSN 0306-5251

[img] Text - Accepted Version
· Restricted to Repository staff only until 22 February 2021.

380kB

It is advisable to refer to the publisher's version if you intend to cite from this work. See Guidance on citing.

To link to this item DOI: 10.1111/bcp.14194

Abstract/Summary

Aim To test if spironolactone or dietary nitrate from beetroot juice could reduce arterial stiffness as aortic pulse wave velocity (PWVart), a potential treatment target, independently of blood pressure. Methods Daily spironolactone (≤50mg) versus doxazosin (control ≤16mg) and 70mL beetroot juice (‘Beet-It’ ≤11mmol nitrate) versus nitrate-depleted juice (placebo; 0mmol nitrate) were tested in people at risk or with type-2 diabetes using a double-blind, 6-month factorial trial. Vascular indices (baseline, 12, 24 weeks) were cardiac-ankle vascular index (‘CAVI’), a nominally pressure-independent stiffness measure (primary outcome), pulse wave velocity (PWVart) secondary, central systolic pressure and augmentation. Analysis was intention-to-treat, adjusted for systolic pressure differences between trial arms. Results Spironolactone did not reduce stiffness, with evidence for reduced CAVI on doxazosin rather than spironolactone (mean difference [95% confidence intervals]; 0.25[-0.3, 0.5] units, p=0.080), firmer for PWVart (0.37[0.01, 0.7] ms-1, p=0.045). There was no difference in systolic pressure reduction between spironolactone and doxazosin (0.7[-4.8, 3.3]mmHg, p=0.7). Circulating nitrate and nitrite increased on active versus placebo juice, with central systolic pressure lowered -2.6[-4.5, - 0.8]mmHg, p=0.007 more on the active juice, but did not reduce CAVI, PWVart, nor peripheral pressure. Change in nitrate and nitrite concentrations were 1.5-fold [1.1-2.2] and 2.2-fold [1.3, 3.6] higher on spironolactone than on doxazosin respectively; both p<0.05. Conclusion Contrary to our hypothesis, in at-risk/type-2 diabetes patients, spironolactone did not reduce arterial stiffness, rather PWVart was lower on doxazosin. Dietary nitrate elevated plasma nitrite, selectively lowering central systolic pressure, observed previously for nitrite.

Item Type:Article
Refereed:Yes
Divisions:Faculty of Life Sciences > School of Chemistry, Food and Pharmacy > Department of Food and Nutritional Sciences > Human Nutrition Research Group
ID Code:88068
Publisher:Wiley-Blackwell

University Staff: Request a correction | Centaur Editors: Update this record

Page navigation