Aims: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 (≤50 mg) vs doxazosin (control ≤16 mg) and 70 mL beetroot juice (Beet-It ≤11 mmol nitrate) vs nitrate-depleted juice (placebo; 0 mmol 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), 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 interval]; 0.25 [−0.3, 0.5] units, P = .080), firmer for PWVart (0.37 [0.01, 0.7] m/s, P = .045). There was no difference in systolic pressure reduction between spironolactone and doxazosin (0.7 [−4.8, 3.3] mmHg, P = .7). Circulating nitrate and nitrite increased on active vs placebo juice, with central systolic pressure lowered −2.6 [−4.5, − 0.8] mmHg, P = .007 more on the active juice, but did not reduce CAVI, PWVart or 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 < .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.PI statement: The authors confirm that the Principal Investigator for this paper is Professor J.K. Cruickshank and that he had direct clinical responsibility for patients.Clinical trial registration: ISRCTN registry: ISRCTN25003627
