{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T21:13:57Z","timestamp":1783113237092,"version":"3.54.6"},"reference-count":56,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2018,11,13]],"date-time":"2018-11-13T00:00:00Z","timestamp":1542067200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Fukuda Denshi Ltd"},{"name":"NIHR Biomedical Research Centre based at\u00a0Guy's and St Thomas' NHS Foundation Trust and King's College London"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brit J Clinical Pharma"],"published-print":{"date-parts":[[2019,1]]},"abstract":"<jats:sec><jats:title>Aims<\/jats:title><jats:p>The aims of the present study were to explore whether a long\u2010term intervention with dietary nitrate [(NO<jats:sub>3<\/jats:sub><jats:sup>\u2212<\/jats:sup>), a potential tolerance\u2010free 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).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A subsample of participants in our double\u2010blind, randomized, factorial\u2010design intervention (VaSera) trial of active beetroot juice as a nitrate source (\u226411.2\u00a0mmol) or placebo (nitrate depleted) beetroot juice, and either \u226450\u00a0mg spironolactone or \u226416\u00a0mg doxazosin (control), had transthoracic cardiac ultrasounds at baseline (<jats:italic>n<\/jats:italic> = 105), and at 3\u00a0months and 6\u00a0months (<jats:italic>n<\/jats:italic> = 87) after the start of the intervention. Analysis was by modified intent\u2010to\u2010treat.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Nitrate\u2010containing juice (<jats:italic>n<\/jats:italic> = 40) decreased left ventricular (LV) end\u2010diastolic volume {\u22126.3 [95% confidence interval (CI) \u201311.1, \u20131.6] ml} and end\u2010systolic volume [\u22123.2 (95% CI \u22125.9, \u20130.5) ml], and increased end\u2010diastolic mass\/volume ratio [+0.04 (95% CI 0.00, 0.07)], relative to placebo juice (<jats:italic>n<\/jats:italic> = 47). Spironolactone (<jats:italic>n<\/jats:italic> = 44) reduced relative wall thickness compared with doxazosin (<jats:italic>n<\/jats:italic> = 43) [\u22120.01 (95% CI \u22120.02, \u20130.00)]. Although spironolactone reduced LV mass index relative to baseline [\u22121.48\u00a0(95% CI \u22122.08, \u20130.88) g m<jats:sup>\u20132.7<\/jats:sup>], there was no difference <jats:italic>vs<\/jats:italic>. doxazosin [\u22120.85 (95% CI \u22121.76, 0.05) g m<jats:sup>\u20132.7<\/jats:sup>]. Spironolactone also decreased the E\/A ratio [\u22120.12 (95% CI \u22120.19, \u20130.04)] and increased S\u2032 (a tissue\u2010Doppler systolic function index) by 0.52 (95% CI 0.05, 1.0) cm s<jats:sup>\u20131<\/jats:sup>. BP did not differ between the juices, or between the drugs.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Six months' dietary nitrate decreased LV volumes ~5%, representing new, sustained, BP\u2010independent benefits on cardiac structure, extending mechanisms characterized in preclinical models of heart failure. Spironolactone's effects on cardiac remodelling and systolic\u2013diastolic function, although confirmatory, were independent of BP.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bcp.13783","type":"journal-article","created":{"date-parts":[[2018,10,8]],"date-time":"2018-10-08T03:23:22Z","timestamp":1538969002000},"page":"169-180","source":"Crossref","is-referenced-by-count":30,"title":["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\u2010blind, randomized controlled VaSera trial"],"prefix":"10.1111","volume":"85","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1066-6899","authenticated-orcid":false,"given":"Luca","family":"Faconti","sequence":"first","affiliation":[{"name":"Department of Clinical Pharmacology School of Cardiovascular Medicine and Sciences, King's College London British Heart Foundation Centre  London UK"},{"name":"Department of Nutritional Sciences, School of Life Course Sciences King's College London  London UK"},{"name":"Biomedical Research Centre, Clinical Research Facility Guy's and St Thomas\u2019 NHS Foundation Trust  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8313-3700","authenticated-orcid":false,"given":"Charlotte Elizabeth","family":"Mills","sequence":"additional","affiliation":[{"name":"Department of Nutritional Sciences, School of Life Course Sciences King's College London  London UK"},{"name":"Biomedical Research Centre, Clinical Research Facility Guy's and St Thomas\u2019 NHS Foundation Trust  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Virginia","family":"Govoni","sequence":"additional","affiliation":[{"name":"Department of Nutritional Sciences, School of Life Course Sciences King's College London  London UK"},{"name":"Biomedical Research Centre, Clinical Research Facility Guy's and St Thomas\u2019 NHS Foundation Trust  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haotian","family":"Gu","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology School of Cardiovascular Medicine and Sciences, King's College London British Heart Foundation Centre  London UK"},{"name":"Biomedical Research Centre, Clinical Research Facility Guy's and St Thomas\u2019 NHS Foundation Trust  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven","family":"Morant","sequence":"additional","affiliation":[{"name":"Medicines Monitoring Unit (MEMO) University of Dundee  Dundee UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benju","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology School of Cardiovascular Medicine and Sciences, King's College London British Heart Foundation Centre  London UK"},{"name":"Biomedical Research Centre, Clinical Research Facility Guy's and St Thomas\u2019 NHS Foundation Trust  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8126-1760","authenticated-orcid":false,"given":"J. 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