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P1.12 Tetrahydrobiopterin (BH4) Improves Endothelial Function, But Not Aortic Stiffness in Patients with Rheumatoid Arthritis

Abstract

Background

Rheumatoid arthritis (RA) is a systemic inflammatory condition associated with increased cardiovascular risk. The aetiology is most likely multi-factorial, including endothelial dysfunction, caused by uncoupling of the endothelial nitric oxide synthase (eNOS). We hypothesised that oral tetrahydrobiopterin (BH4), an essential co-factor for eNOS, would lead to an improvement of endothelial function and subsequently, aortic stiffness.

Methods

This was a randomised, double-blinded crossover study, consisting of two separate regimes, 1: a single dose of BH4 400mg vs. placebo and 2: a one-week treatment with BH4 400mg OD vs. placebo. In study 1, aortic pulse wave velocity (aPWV), and flow mediated dilatation (FMD) were studied before and 3 hours after BH4 supplementation and placebo. In study 2, FMD and aPWV were assessed four times, separated by a week.

Results

A single dose of BH4, but not placebo, improved endothelial dysfunction (+3.57±4.14 vs.+0.05±1.17%, P = 0.03; n = 18). There was no change in aPWV following BH4 or placebo (−0.13±0.58 vs. −0.21±0.43m/s; P = 0.6). One-week treatment with BH4, improved endothelial function, whereas placebo did not (+3.69±4.90 vs. +0.19±2.51%, P = 0.02; n = 15). There was no change in aPWV following BH4 or placebo (−0.22±1.3 vs. −0.25±0.51m/s, P = 0.4) and no correlation between change in aPWVand FMD in either regime.

Conclusion

Both acute and chronic BH4 supplementation lead to an improvement of endothelial function, but did not reduce aortic stiffness. This suggests that there is no causality between endothelial function and aortic stiffness and that these conditions may just exist in parallel, both influences by common risk factors, such as inflammation.

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This is an open access article distributed under the CC BY-NC license http://creativecommons.org/licenses/by/4.0/.

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Maki-Petaja, K., Day, L., Hall, F. et al. P1.12 Tetrahydrobiopterin (BH4) Improves Endothelial Function, But Not Aortic Stiffness in Patients with Rheumatoid Arthritis. Artery Res 8, 132 (2014). https://doi.org/10.1016/j.artres.2014.09.093

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  • DOI: https://doi.org/10.1016/j.artres.2014.09.093