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, randomized controlled VaSera trial

Luca Faconti, Charlotte Elizabeth Mills, Virginia Govoni, Haotian Gu, Steven Morant, Benju Jiang, J. Kennedy Cruickshank, Andrew James Webb (Lead / Corresponding author)

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Abstract

Aims: The aims of the present study were to explore whether a long-term intervention with dietary nitrate [(NO 3 ), a potential tolerance-free source of beneficial vasoactive nitric oxide] and spironolactone (to oppose aldosterone's potential deleterious cardiovascular effects) improve cardiac structure/function, independently of blood pressure (BP), in patients with/at risk of type 2 diabetes (a population at risk of heart failure).

Methods: A subsample of participants in our double-blind, randomized, 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 transthoracic cardiac ultrasounds at baseline (n = 105), and at 3 months and 6 months (n = 87) after the start of the intervention. Analysis was by modified intent-to-treat.

Results: Nitrate-containing juice (n = 40) decreased left ventricular (LV) end-diastolic volume {−6.3 [95% confidence interval (CI) –11.1, –1.6] ml} and end-systolic volume [−3.2 (95% CI −5.9, –0.5) ml], and increased end-diastolic mass/volume ratio [+0.04 (95% CI 0.00, 0.07)], relative to placebo juice (n = 47). Spironolactone (n = 44) reduced relative wall thickness compared with doxazosin (n = 43) [−0.01 (95% CI −0.02, –0.00)]. Although spironolactone reduced LV mass index relative to baseline [−1.48 (95% CI −2.08, –0.88) g m –2.7], there was no difference vs. doxazosin [−0.85 (95% CI −1.76, 0.05) g m –2.7]. Spironolactone also decreased the E/A ratio [−0.12 (95% CI −0.19, –0.04)] and increased S′ (a tissue-Doppler systolic function index) by 0.52 (95% CI 0.05, 1.0) cm s –1. BP did not differ between the juices, or between the drugs.

Conclusions: Six months' dietary nitrate decreased LV volumes ~5%, representing new, sustained, BP-independent benefits on cardiac structure, extending mechanisms characterized in preclinical models of heart failure. Spironolactone's effects on cardiac remodelling and systolic–diastolic function, although confirmatory, were independent of BP.

Original languageEnglish
Pages (from-to)169-180
Number of pages12
JournalBritish Journal of Clinical Pharmacology
Volume85
Issue number1
Early online date7 Oct 2018
DOIs
Publication statusPublished - 1 Jan 2019

Keywords

  • beetroot juice
  • cardiac remodelling
  • dietary nitrate
  • echocardiography
  • nitrate–nitrite–NO pathway
  • type 2 diabetes

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