Dietary nitrate prevents progression of carotid subclinical atherosclerosis through blood pressure-independent mechanisms in patients with or at risk of type 2 diabetes mellitus.
arterial stiffness
beetroot juice
blood pressure
carotid
dietary nitrate
intima media thickness
Journal
British journal of clinical pharmacology
ISSN: 1365-2125
Titre abrégé: Br J Clin Pharmacol
Pays: England
ID NLM: 7503323
Informations de publication
Date de publication:
12 2021
12 2021
Historique:
revised:
30
04
2021
received:
07
09
2020
accepted:
09
05
2021
pubmed:
14
5
2021
medline:
11
3
2022
entrez:
13
5
2021
Statut:
ppublish
Résumé
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). 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. 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. 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.
Substances chimiques
Nitrates
0
Banques de données
ISRCTN
['ISRCTN25003627']
Types de publication
Journal Article
Randomized Controlled Trial
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
4726-4736Informations de copyright
© 2021 The Authors. British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.
Références
Folsom A, Kronmal R, Detrano R, et al. Coronary artery calcification compared with carotid intimamedia thickness in prediction of cardiovascular disease incidence: the Multi-Ethnic study of Atherosclerosis (MESA). Arch Intern Med. 2008;168(12):1333-1339. https://doi.org/10.1001/archinte.168.12.1333
Newman A, Naydeck B, Ives D, et al. Coronary artery calcium, carotid artery wall thickness and cardiovascular disease outcomes in adults 70 to 99 years old. Am J Cardiol. 2008;101(2):186-192. https://doi.org/10.1016/j.amjcard.2007.07.075
Cosentino F, Grant PJ, Aboyans V, et al. 2019 ESC Guidelines on diabetes, pre-diabetes, and cardiovascular diseases developed in collaboration with the EASD diseases of the European Society of Cardiology (ESC) and the European Association for the Study of Diabetes (EASD). Eur Heart J. 2020;255-323. https://doi.org/10.1093/eurheartj/ehz486
Malik S, Budoff MJ, Katz R, et al. Impact of subclinical atherosclerosis on cardiovascular disease events in individuals with metabolic syndrome and diabetes. Diabetes Care. 2011;34(10):2285-2290. https://doi.org/10.2337/dc11-0816
van Sloten TT, Stehouwer CDA. Carotid stiffness: a novel cerebrovascular disease risk factor. Pulse. 2016;4(1):24-27. https://doi.org/10.1159/000445354
Lorenz MW, Markus HS, Bots ML, Rosvall M, Sitzer M. Prediction of clinical cardiovascular events with carotid intima-media thickness: A systematic review and meta-analysis. Circulation. 2007;115(4):459-467. https://doi.org/10.1161/CIRCULATIONAHA.106.628875
Centurión OA. Carotid intima-media thickness as a cardiovascular risk factor and imaging pathway of atherosclerosis. Crit Pathw Cardiol. 2016;15(4):152-160. https://doi.org/10.1097/HPC.0000000000000087
Nezu T, Hosomi N, Aoki S, Matsumoto M. Carotid Intima-media thickness for atherosclerosis. J Atheroscler Thromb. 2016;23(1):18-31. https://doi.org/10.5551/jat.31989
Naqvi TZ, Lee MS. Carotid intima-media thickness and plaque in cardiovascular risk assessment. JACC Cardiovasc Imaging. 2014;7(10):1025-1038. https://doi.org/10.1016/j.jcmg.2013.11.014
Förstermann U, Xia N, Li H. Roles of vascular oxidative stress and nitric oxide in the pathogenesis of atherosclerosis. Circ Res. 2017;120(4):713-735. https://doi.org/10.1161/CIRCRESAHA.116.309326
Khatri J, Mills CE, Maskell P, Odongerel C, Webb AJ. It is rocket science - why dietary nitrate is hard to ‘beet’! Part I: twists and turns in the realization of the nitrate-nitrite-NO pathway. Br J Clin Pharmacol. 2017;83(1):129-139. https://doi.org/10.1111/bcp.12913
Mills CE, Khatri J, Maskell P, Odongerel C, Webb AJ. It is rocket science - why dietary nitrate is hard to ‘beet’! Part II: further mechanisms and therapeutic potential of the nitrate-nitrite-NO pathway. Br J Clin Pharmacol. 2017;83(1):140-151. https://doi.org/10.1111/bcp.12918
Velmurugan S, Gan JM, Rathod KS, et al. Dietary nitrate improves vascular function in patients with hypercholesterolemia: A randomized, double-blind, placebo-controlled study. Am J Clin Nutr. 2016;103(1):25-38. https://doi.org/10.3945/ajcn.115.116244
Rammos C, Hendgen-Cotta UB, Pohl J, et al. Modulation of circulating macrophage migration inhibitory factor in the elderly. Biomed Res Int. 2014;2014:1-8. https://doi.org/10.1155/2014/582586
Lidder S, Webb AJ. Vascular effects of dietary nitrate (as found in green leafy vegetables and beetroot) via the nitrate-nitrite-nitric oxide pathway. Br J Clin Pharmacol. 2013;75(3):677-696. https://doi.org/10.1111/j.1365-2125.2012.04420.x
Alef MJ, Vallabhaneni R, Carchman E, et al. Nitrite-generated NO circumvents dysregulated arginine/NOS signaling to protect against intimal hyperplasia in Sprague-Dawley rats. J Clin Invest. 2011;121(4):1-11. https://doi.org/10.1172/JCI44079DS1
Marsch E, Theelen TL, Janssen BJA, et al. The effect of prolonged dietary nitrate supplementation on atherosclerosis development. Atherosclerosis. 2016;245:212-221. https://doi.org/10.1016/j.atherosclerosis.2015.11.031
Bakker JR, Bondonno NP, Gaspari TA, et al. Low dose dietary nitrate improves endothelial dysfunction and plaque stability in the ApoE−/− mouse fed a high fat diet. Free Radic Biol Med. 2016;99:189-198. https://doi.org/10.1016/j.freeradbiomed.2016.08.009
Khambata RS, Ghosh SM, Rathod KS, et al. Antiinflammatory actions of inorganic nitrate stabilize the atherosclerotic plaque. Proc Natl Acad Sci U S A. 2017;114(4):E550-E559. https://doi.org/10.1073/pnas.1613063114
Peng R, Luo M, Tian R, Lu N. Dietary nitrate attenuated endothelial dysfunction and atherosclerosis in apolipoprotein E knockout mice fed a high-fat diet: A critical role for NADPH oxidase. Arch Biochem Biophys. 2020;689:108453. https://doi.org/10.1016/j.abb.2020.108453
Bondonno CP, Blekkenhorst LC, Prince RL, et al. Association of Vegetable Nitrate Intake with Carotid Atherosclerosis and Ischemic Cerebrovascular Disease in Older Women. Stroke. 2017;48(7):1724-1729. https://doi.org/10.1161/STROKEAHA.117.016844
Blekkenhorst LC, Bondonno CP, Lewis JR, et al. Association of dietary nitrate with atherosclerotic vascular disease mortality: A prospective cohort study of older adult women. Am J Clin Nutr. 2017;106(1):207-216. https://doi.org/10.3945/ajcn.116.146761
Jackson JK, Patterson AJ, MacDonald-Wicks LK, et al. Vegetable nitrate intakes are associated with reduced self-reported cardiovascular-related complications within a representative sample of middle-aged australian women, prospectively followed up for 15 years. Nutrients. 2019;11(2):1-19. https://doi.org/10.3390/nu11020240
Sekiya M, Sato M, Funada J, Ohtani T, Akutsu H, Watanabe K. Effects of the long-term administration of nicorandil on vascular endothelial function and the progression of arteriosclerosis. J Cardiovasc Pharmacol. 2005;46(1):63-67. https://doi.org/10.1097/01.fjc.0000162771.00174.a8
Vukusich A, Kunstmann S, Varela C, et al. A randomized, double-blind, placebo-controlled trial of spironolactone on carotid intima-media thickness in nondiabetic hemodialysis patients. Clin J Am Soc Nephrol. 2010;5(8):1380-1387. https://doi.org/10.2215/CJN.09421209
Matsuda Y, Kawate H, Matsuzaki C, et al. Eplerenone improves carotid intima-media thickness (IMT) in patients with primary aldosteronism. Endocr J. 2016;63(3):249-255. https://doi.org/10.1507/endocrj.EJ15-0362
Holaj R, Rosa J, Zelinka T, et al. Long-termeffect of specific treatment of primary aldosteronismon carotid intima-media thickness. J Hypertens. 2015;33(4):874-882. https://doi.org/10.1097/HJH.0000000000000464
Mills CE, Govoni V, Faconti L, et al. A randomised, factorial trial to reduce arterial stiffness independently of blood pressure: Proof of concept? The VaSera trial testing dietary nitrate and spironolactone. Br J Clin Pharmacol. 2020;86(5):891-902. https://doi.org/10.1111/bcp.14194
Mills CE, Govoni V, Faconti L, Casagrande ML, Morant SV, Webb AJ. Reducing arterial stiffness independently of blood pressure. JACC. 2017;70(13):1683-1684. https://doi.org/10.1016/j.jacc.2017.07.765
Faconti L, Mills CE, Govoni V, et al. 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. Br J Clin Pharmacol. 2019;85(1):169-180. https://doi.org/10.1111/bcp.13783
BIHS. Measuring blood pressure using automated monitors, 2017. https://bihsoc.org/resources/bp-measurement/measure-blood-pressure/
Oates CP, Naylor AR, Hartshorne T, et al. Joint Recommendations for Reporting Carotid Ultrasound Investigations in the United Kingdom. Eur J Vasc Endovasc Surg. 2009;37(3):251-261. https://doi.org/10.1016/j.ejvs.2008.10.015
Simova I. Intima-media thickness: appropriate evaluation and proper measurement. E-Journal Cardiology Pract. 2015, [Online]. Available:13(21). https://www.escardio.org/Journals/E-Journal-of-Cardiology-Practice/Volume-13/Intima-media-thickness-Appropriate-evaluation-and-proper-measurement-described
Bruno RM, Cartoni G, Stea F, et al. Carotid and aortic stiffness in essential hypertension and their relation with target organ damage: The CATOD study. J Hypertens. 2017;35(2):310-318. https://doi.org/10.1097/HJH.0000000000001167
Mills CE, Govoni V, Casagrande ML, Faconti L, Webb AJ, Cruickshank JK. Design and progress of a factorial trial testing the effect of spironolactone and inorganic nitrate on arterial function in people at risk of or with type 2 diabetes ScienceDirect Design and progress of a factorial trial testing the effect of spironolacto. Artery Research. 2019;12:48-53.
Ring A, Schall R, Loke YK, Day S. Statistical reporting of clinical pharmacology research. Br J Clin Pharmacol. 2017;83(6):1159-1162. https://doi.org/10.1111/bcp.13254
Borghi C, Tsioufis K, Agabiti-Rosei E, et al. Nutraceuticals and blood pressure control: A European Society of Hypertension position document. J Hypertens. 2020;38(5):799-812. https://doi.org/10.1097/HJH.0000000000002353
Borghi C, Cicero AFG. Nutraceuticals with a clinically detectable blood pressure-lowering effect: a review of available randomized clinical trials and their meta-analyses. Br J Clin Pharmacol. 2017;83(1):163-171. https://doi.org/10.1111/bcp.12902
Bahadoran Z, Mirmiran P, Kabir A, Azizi F, Ghasemi A. The nitrate-independent blood pressure-lowering effect of beetroot juice: a systematic review and meta-analysis. Adv Nutr an Int Rev J. 2017;8(6):830-838. https://doi.org/10.3945/an.117.016717
Jackson JK, Patterson AJ, MacDonald-Wicks LK, Oldmeadow C, McEvoy MA. The role of inorganic nitrate and nitrite in cardiovascular disease risk factors: A systematic review and meta-analysis of human evidence. Nutr Rev. 2018;76(5):348-371. https://doi.org/10.1093/nutrit/nuy005
Blekkenhorst LC, Bondonno CP, Lewis JR, et al. Cruciferous and total vegetable intakes are inversely associated with subclinical atherosclerosis in older adult women. J Am Heart Assoc. 2018;7(8):1-13. https://doi.org/10.1161/JAHA.117.008391
Hughan KS, Helbling NL, Anthony SJ, Delany J, Goodpaster BH, Gladwin M. Oral Sodium Nitrite Improves Insulin Sensitivity, Blood Pressure, and Arterial Thickening in Adults with Uncontrolled Hypertension and Metabolic Syndrome. Hypertension. 2020;67(76):874. https://doi.org/10.1161/HYPERTENSIONAHA.120.14930
Omar SA, Fok H, Tilgner KD, et al. Paradoxical normoxia-dependent selective actions of inorganic nitrite in human muscular conduit arteries and related selective actions on central blood pressures. Circulation. 2015;131(4):381-389. https://doi.org/10.1161/CIRCULATIONAHA.114.009554
Paini A, Boutouyrie P, Calvet D, Tropeano AI, Laloux B, Laurent S. Carotid and aortic stiffness determinants of discrepancies. Hypertension. 2006;47(3):371-376. https://doi.org/10.1161/01.HYP.0000202052.25238.68
O'Gallagher K, Borg Cardona S, Hill C, et al. Grapefruit juice enhances the systolic blood pressure-lowering effects of dietary nitrate-containing beetroot juice. Br J Clin Pharmacol. 2021;87(2):577-587. https://doi.org/10.1111/bcp.14420
Piepoli MF, Hoes AW, Agewall S, et al. 2016 European Guidelines on cardiovascular disease prevention in clinical practice. Eur Heart J. 2016;37(29):2315-2381. https://doi.org/10.1093/eurheartj/ehw106
Goff DC, Lloyd-Jones DM, Bennett G, et al. 2013 ACC/AHA guideline on the assessment of cardiovascular risk: A report of the American college of cardiology/American heart association task force on practice guidelines. Circulation. 2014;129(25 SUPPL. 1):49-73. https://doi.org/10.1161/01.cir.0000437741.48606.98
Khanna NN, Jamthikar AD, Araki T, et al. Nonlinear model for the carotid artery disease 10-year risk prediction by fusing conventional cardiovascular factors to carotid ultrasound image phenotypes: A Japanese diabetes cohort study. Echocardiography. 2019;36(2):345-361. https://doi.org/10.1111/echo.14242
Blekkenhorst LC, Prince RL, Ward NC, et al. Development of a reference database for assessing dietary nitrate in vegetables. Mol Nutr Food Res. 2017;61(8):1-13. https://doi.org/10.1002/mnfr.201600982
Floyd CN, Shahed F, Ukah F, et al. Acute Blood Pressure-Lowering Effects of Nitrogen Dioxide Exposure from Domestic Gas Cooking via Elevation of Plasma Nitrite Concentration in HealthyIndividuals. Circ Res. 2020;127(6):10-13. https://doi.org/10.1161/circresaha.120.316748