Dietary nitrate prevents progression of carotid subclinical atherosclerosis through blood pressure-independent mechanisms in patients with or at risk of type 2 diabetes mellitus

Morselli, F., Faconti, L., Mills, C. E. ORCID: https://orcid.org/0000-0002-8313-3700, Morant, S., Chowienczyk, P. J., Yeung, J. A., Cavarape, A., Cruickshank, J. K. and Webb, A. J. (2021) Dietary nitrate prevents progression of carotid subclinical atherosclerosis through blood pressure-independent mechanisms in patients with or at risk of type 2 diabetes mellitus. British Journal of Clinical Pharmacology, 87 (12). ISSN 0306-5251 doi: 10.1111/bcp.14897

Abstract/Summary

Aims To test if 6 months' intervention with dietary nitrate and spironolactone could affect carotid subclinical atherosclerosis and stiffness, respectively, vs. placebo/doxazosin, to control for blood pressure (BP). Methods A subgroup of participants in our double-blind, randomized-controlled, factorial VaSera trial had carotid imaging. Patients with hypertension and with/at risk of type 2 diabetes were randomized to active nitrate-containing beetroot juice or placebo nitrate-depleted juice, and spironolactone or doxazosin. Vascular ultrasound for carotid diameter (CD, mm) and intima–media thickness (CIMT, mm) was performed at baseline, 3- and 6-months. 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-model effect, adjusted for confounders. Results In total, 93 subjects had a baseline evaluation and 86% had follow-up data. No statistical interactions occurred between the juice and drug arms and BP was similar between the juices and between the drugs. Nitrate-containing vs. placebo juice significantly lowered CIMT (−0.06 [95% confidence interval −0.12, −0.01], P = .034), an overall difference of ~8% relative to baseline; but had no effect on CD or CS. Doxazosin appeared to reduce CS from baseline (−0.34 [−0.62, −0.06]) however, no difference was detected vs. spironolactone (−0.15 [−0.46, 0.16]). No differences were detected between spironolactone or doxazosin on CIMT and CD. Conclusions Our results show that 6 months' intervention with dietary nitrate influences vascular remodelling, but not carotid stiffness or diameter. Neither spironolactone nor doxazosin had a BP-independent effect on carotid structure and function.

Item Type	Article
URI	https://reading-clone.eprints-hosting.org/id/eprint/101982
Identification Number/DOI	10.1111/bcp.14897
Refereed	Yes
Divisions	Life Sciences > School of Chemistry, Food and Pharmacy > Department of Food and Nutritional Sciences > Human Nutrition Research Group
Publisher	Wiley-Blackwell
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