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.

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.