Br J Clin Pharmacol. 2021 May 13. doi: 10.1111/bcp.14897. Online ahead of print.
ABSTRACT
AIM: To test if 6 months’ intervention with dietary nitrate and spironolactone could affect carotid subclinical atherosclerosis and stiffness, respectively, versus 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 was analysed by modified intention to treat and using mixed-model effect, adjusted for confounders.
RESULTS: 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 versus placebo juice significantly lowered CIMT [-0.06 (95% Confidence Interval -0.12, -0.01), p=0.034], an overall difference of ~8% relative to baseline; but had no effect on carotid diameter (CD) or carotid stiffness (CS). Doxazosin appeared to reduce CS from baseline [-0.34 (-0.62, -0.06)] however, no difference was detected versus spironolactone [-0.15 (-0.46, 0.16)]. No differences were detected between spironolactone or doxazosin on CIMT and CD.
CONCLUSION: 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.
PMID:33982797 | DOI:10.1111/bcp.14897
