Cardiac effects of 6 months' dietary nitrate and spironolactone in patients with hypertension and with/at risk of type 2 diabetes, in the factorial design, double-blind, randomised-controlled, VASERA TRIAL

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Abstract

Aims
To explore whether long‐term intervention with dietary nitrate ((NO3‐), a potential tolerance‐free source of beneficial vasoactive nitric oxide) and spironolactone (to oppose aldosterone's potential deleterious cardiovascular effects) improve cardiac structure/function, independent of blood pressure (BP), in patients with/at risk of type 2 diabetes (a population at risk of heart failure).

Methods
A sub‐sample of participants in our double‐blind, randomised, factorial‐design intervention (VaSera) trial of active beetroot juice as a nitrate source (≤11.2 mmol) or placebo (nitrate‐depleted) beetroot juice, and either ≤50 mg spironolactone or ≤16 mg doxazosin (control), had trans‐thoracic cardiac ultrasounds at baseline (n=105), 3 and 6 months (n=87) of intervention. Analysis was by modified intention‐to‐treat.

Results
Nitrate‐containing juice (n=40) decreased left ventricular (LV) end diastolic volume: ‐6.3 mL (95% confidence intervals (CI) ‐11.1,‐1.6), and end systolic volume: ‐3.2 mL (‐5.9,‐0.5), and increased end diastolic mass/volume ratio: +0.04 (0.00,0.07), relative to placebo juice (n=47). Spironolactone (n=44) reduced relative wall thickness compared to doxazosin (n=43): ‐0.01 (‐0.02,‐0.00). Whilst spironolactone reduced LV mass index relative to baseline: ‐1.48 g/m2.7 (‐2.08,‐0.88), there was no difference versus doxazosin: ‐0.85 g/m2.7 (‐1.76,0.05). Spironolactone also decreased the E/A ratio: ‐0.12 (‐0.19,‐0.04) and increased S' (a tissue‐Doppler systolic function index) by 0.52 (0.05,1.0 cm/s). BP did not differ between the juices, or between the drugs.

Conclusions
6 months' dietary nitrate decreased LV volumes ~5%, representing new, sustained, BP‐independent benefits on cardiac structure, extending mechanisms characterised in pre‐clinical models of heart failure. Spironolactone's effects on cardiac remodeling and systo‐diastolic function whilst confirmatory, were independent of BP.
Original languageEnglish
JournalBritish Journal of Clinical Pharmacology
Early online date13 Nov 2018
DOIs
Publication statusE-pub ahead of print - 13 Nov 2018

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