{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,18]],"date-time":"2026-07-18T05:30:01Z","timestamp":1784352601417,"version":"3.55.0"},"reference-count":50,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2021,5,29]],"date-time":"2021-05-29T00:00:00Z","timestamp":1622246400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brit J Clinical Pharma"],"published-print":{"date-parts":[[2021,12]]},"abstract":"<jats:sec><jats:title>Aims<\/jats:title><jats:p>To test if 6\u00a0months' intervention with dietary nitrate and spironolactone could affect carotid subclinical atherosclerosis and stiffness, respectively, <jats:italic>vs<\/jats:italic>. placebo\/doxazosin, to control for blood pressure (BP).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A subgroup of participants in our double\u2010blind, randomized\u2010controlled, factorial VaSera trial had carotid imaging. Patients with hypertension and with\/at risk of type 2 diabetes were randomized to active nitrate\u2010containing beetroot juice or placebo nitrate\u2010depleted juice, and spironolactone or doxazosin. Vascular ultrasound for carotid diameter (CD, mm) and intima\u2013media thickness (CIMT, mm) was performed at baseline, 3\u2010 and 6\u2010months. Carotid local stiffness (CS, m\/s) was estimated from aortic pulse pressure (Arteriograph) and carotid lumen area. Data were analysed by modified intention to treat and using mixed\u2010model effect, adjusted for confounders.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In total, 93 subjects had a baseline evaluation and 86% had follow\u2010up data. No statistical interactions occurred between the juice and drug arms and BP was similar between the juices and between the drugs. Nitrate\u2010containing <jats:italic>vs<\/jats:italic>. placebo juice significantly lowered CIMT (\u22120.06 [95% confidence interval \u22120.12, \u22120.01],\u00a0<jats:italic>P<\/jats:italic> =\u2009.034), an overall difference of ~8% relative to baseline; but had no effect on CD or CS. Doxazosin appeared to reduce CS from baseline (\u22120.34 [\u22120.62, \u22120.06]) however, no difference was detected <jats:italic>vs<\/jats:italic>. spironolactone (\u22120.15 [\u22120.46, 0.16]). No differences were detected between spironolactone or doxazosin on CIMT and CD.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Our results show that 6\u00a0months' intervention with dietary nitrate influences vascular remodelling, but not carotid stiffness or diameter. Neither spironolactone nor doxazosin had a BP\u2010independent effect on carotid structure and function.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bcp.14897","type":"journal-article","created":{"date-parts":[[2021,5,13]],"date-time":"2021-05-13T09:50:21Z","timestamp":1620899421000},"page":"4726-4736","source":"Crossref","is-referenced-by-count":10,"title":["Dietary nitrate prevents progression of carotid subclinical atherosclerosis through blood pressure\u2010independent mechanisms in patients with or at risk of type 2 diabetes mellitus"],"prefix":"10.1111","volume":"87","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6186-4780","authenticated-orcid":false,"given":"Franca","family":"Morselli","sequence":"first","affiliation":[{"name":"Department of Clinical Pharmacology King's College London British Heart Foundation Centre, School of Cardiovascular Medicine and Sciences  UK"},{"name":"Dipartimento di Area Medica, Clinica Medica Universita\u2019 degli Studi di Udine  Udine Italy"},{"name":"Biomedical Research Centre, Clinical Research Facility, 4th Floor, North Wing St Thomas' Hospital, Guy's and St Thomas' NHS Foundation Trust  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1066-6899","authenticated-orcid":false,"given":"Luca","family":"Faconti","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology King's College London British Heart Foundation Centre, School of Cardiovascular Medicine and Sciences  UK"},{"name":"Biomedical Research Centre, Clinical Research Facility, 4th Floor, North Wing St Thomas' Hospital, Guy's and St Thomas' NHS Foundation Trust  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8313-3700","authenticated-orcid":false,"given":"Charlotte E.","family":"Mills","sequence":"additional","affiliation":[{"name":"King's College London, Department of Nutritional Sciences School of Life Course Sciences  London UK"},{"name":"Department of Food and Nutritional Sciences, School of Chemistry, Food and Pharmacy University of Reading  Reading UK"},{"name":"Biomedical Research Centre, Clinical Research Facility, 4th Floor, North Wing St Thomas' Hospital, Guy's and St Thomas' 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  UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4507-038X","authenticated-orcid":false,"given":"Philip J.","family":"Chowienczyk","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology King's College London British Heart Foundation Centre, School of Cardiovascular Medicine and Sciences  UK"},{"name":"King's College London, Department of Nutritional Sciences School of Life Course Sciences  London UK"},{"name":"Biomedical Research Centre, Clinical Research Facility, 4th Floor, North Wing St Thomas' Hospital, Guy's and St Thomas' NHS Foundation Trust  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joshua Au","family":"Yeung","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology King's College London British Heart Foundation Centre, School of Cardiovascular Medicine and Sciences  UK"},{"name":"Biomedical Research Centre, Clinical Research Facility, 4th Floor, North Wing St Thomas' Hospital, Guy's and St Thomas' NHS Foundation Trust  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandro","family":"Cavarape","sequence":"additional","affiliation":[{"name":"Dipartimento di Area Medica, Clinica Medica Universita\u2019 degli Studi di Udine  Udine Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8126-1760","authenticated-orcid":false,"given":"J. 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