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Faconti L.; Mills, C.E.; Morant, S.; Gu, H.; Jiang, B.; Cruickshank, J.K.; Webb, A.J.
Journal of Hypertension: September 2016
doi: 10.1097/


Patients with type II diabetes (T2DM) are at 2–3 fold excess risk of heart failure. Its prevention and treatment are poor. Here we tested the hypothesis that spironolactone, perhaps by limiting myocardial fibrosis, and inorganic nitrate, which acutely affects myocardial dynamics, would improve cardiac structure and function beyond effects of blood pressure (BP) in these patients.

Design and method:

104 patients with or at risk of T2DM participated in a factorial design, double blind, randomised controlled trial (VaSera). Trans-thoracic cardiac ultrasound (echo) was performed at randomisation, 3 and 6 months after intervention of either < 50 mg spironolactone or <16 mg doxazosin (control), and beetroot juice (<11 mmol inorganic nitrate (NO3-)) or placebo (NO3- depleted). Data are ‘intention-to-treat’.


Baseline data (mean ± SD) were: age 57 ± 11y, 65% T2DM, BP 142/87 mmHg; left ventricular (LV) mass index (LVMI) 53.5 ± 13.3 g/m2.7, 89% had normal LV filling pressure (E/A 1.02 ± 0.41, E/E′ 7.8 ± 2.3). 82% had echos at 6 months’ follow up. Brachial BP change was similar between drugs (spiro/dox SBP 6.5/6.4 mmHg DBP 5.2/4.8 mmHg) unaffected by juice. Reduction in LVMI with spironolactone tended to be greater than doxazosin's (mean (95% CI): −1.48 (−2.08,−0.88) vs −0.63 (−1.28,0.01) g/m2.7, p = 0.064), but with overtly significant effects on mean differences in LV posterior wall (−0.3 (−0.4,−0.1) mm, p < 0.01) and relative wall thickness (−0.01 (−0.02,−0.0), p < 0.01). E/A ratio on spironolactone decreased by 0.12 (−0.19,−0.04) (p < 0.01) compared with doxazosin while S′ (a tissue Doppler index of systolic function) increased compared with doxazosin by 0.52 (0.05,1) cm/s, p < 0.05. No treatment altered the E/E′ ratio.

While NO3- did not affect the above parameters, active juice decreased LV end diastolic (ED) and systolic volume (6.3 (−11.1,−1.6) mL and 3.2 (−5.9,−0.5) mL, p = 0.01 and p = 0.02 respectively) and increased the ED mass/volume (M/V) ratio by 0.04 (0,0.7) g/mL (p < 0.05) compared to placebo.


Spironolactone influences myocardial remodelling and LV systo-diastolic function in patients with or at risk of T2DM. Inorganic nitrate decreases LV volumes with no changes in LV mass, which leads to increased M/V ratio suggesting a favourable effect on LV wall stress. The trial was funded by Fukuda Denshi.

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