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Tetrahydrobiopterin Supplementation Improves Endothelial Function But Does Not Alter Aortic Stiffness in Patients With Rheumatoid Arthritis.


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Authors

Mäki-Petäjä, Kaisa M 
Day, Lisa 
Hall, Frances C 
Östör, Andrew JK 

Abstract

BACKGROUND: Rheumatoid arthritis is a systemic inflammatory condition associated with increased cardiovascular risk that may be due to underlying endothelial dysfunction and subsequent aortic stiffening. We hypothesized that supplementation with tetrahydrobiopterin (BH4) would recouple endothelial nitric oxide synthase and thus improve endothelial function and consequently reduce aortic stiffness. METHODS AND RESULTS: We conducted 2 randomized, double-blinded, placebo-controlled crossover studies examining 2 separate regimens: an acute regimen, with a single dose of BH4 400 mg versus placebo (n=18), and a short-term regimen, composed of a 1-week treatment with BH4 400 mg once daily versus placebo (n=15). Flow-mediated dilatation and aortic pulse wave velocity were studied 4 times, before and after each treatment phase. Acute BH4 supplementation led to an improvement of flow-mediated dilatation, whereas placebo had no effect (mean±SD of effect difference 2.56±4.79%; P=0.03). Similarly, 1-week treatment with BH4 improved endothelial function, but there was no change with placebo (mean±SD of effect difference 3.50±5.05%; P=0.02). There was no change in aortic pulse wave velocity following acute or short-term BH4 supplementation or placebo (mean±SD of effect difference: acute 0.09±0.67 m/s, P=0.6; short-term 0.03±1.46 m/s, P=0.9). CONCLUSION: Both acute and short-term supplementation with oral BH4 improved endothelial function but not aortic stiffness. This result suggests that BH4 supplementation may be beneficial for patients with rheumatoid arthritis by improving endothelial dysfunction and potentially reducing risk of cardiovascular disease. There appears to be no causal relationship between endothelial function and aortic stiffness, suggesting that they occur in parallel, although they may share common risk factors such as inflammation.

Description

Keywords

arteriosclerosis, endothelial function, inflammation, rheumatoid arthritis, tetrahydrobiopterin, Administration, Oral, Adult, Aged, Arthritis, Rheumatoid, Biomarkers, Biopterins, Cardiovascular Agents, Cross-Over Studies, Dietary Supplements, Double-Blind Method, Drug Administration Schedule, Endothelium, Vascular, England, Female, Humans, Inflammation Mediators, Male, Middle Aged, Nitric Oxide Synthase Type III, Pilot Projects, Pulse Wave Analysis, Time Factors, Treatment Outcome, Vascular Diseases, Vascular Stiffness, Vasodilation, Young Adult

Journal Title

J Am Heart Assoc

Conference Name

Journal ISSN

2047-9980
2047-9980

Volume Title

5

Publisher

Ovid Technologies (Wolters Kluwer Health)
Sponsorship
British Heart Foundation (None)
KMMP and IBW were funded by British Heart Foundation. IBW, JC and NS received funding from the Comprehensive Local Research Network and IBW and JC from the National Institute for Health Research: Cambridge Biomedical Research Centre.